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2,333,600 |
PEGylated fluorescent carbon nanoparticles for noninvasive heart imaging.
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Fluorescent carbon nanoparticles (CNP) have gained much attention due to their unique fluorescent properties and safety. In this study, we evaluated the potential application of CNP and PEGylated CNP (PEG-CNP) in noninvasive heart imaging. CNP was prepared by hydrothermal treatment of silk. The particle size and zeta potential of CNP were 121.8 nm and -3.7 mV, respectively, which did not change significantly after PEGylation with a PEG density of 4.43 ± 0.02 μg/mg CNP. FTIR and XPS showed that CNP possessed several functional groups, such as -COOH, -OH, and NH2, which could be utilized for PEGylation and other modifications. CNP displayed strong blue fluorescence after excitation at the wavelength of 375 nm. PEG-CNP displayed better serum stability compared to CNP. The hemolysis rate of PEG-CNP was lower than that of CNP, suggesting PEGylation could enhance the hemocompatibility of CNP. Both CNP and PEG-CNP showed higher uptake capacity by H9c2 cells (a heart cell line) than that by human umbilical vein endothelial cells (HUVEC), suggesting the particles tend to be selectively taken up by heart cells. Both CNP and PEG-CNP were proven to be taken up through endosome-mediated pathway, and the colocalization of nanoparticles with mitochondria was also observed. In vivo results demonstrated that CNP could target heart with much higher fluorescent intensity than liver and spleen. Although PEGylation could decrease the distribution in heart, it remained high for PEG-CNP. In conclusion, CNP could be used for heart imaging, and moreover, PEGylation could improve the stability and biocompatibility of CNP.
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2,333,601 |
Comparison of dexmedetomidine and epinephrine as an adjuvant to 1% mepivacaine in brachial plexus block.
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Dexmedetomidine extends the duration of nerve block when administered perineurally together with local anesthetics by central and/or peripheral action. In this study, we compared the duration of nerve block between dexmedetomidine and epinephrine as an adjuvant to 1% mepivacaine in infraclavicular brachial plexus block.</AbstractText>Thirty patients, scheduled for upper limb surgery were assigned randomly to 3 groups of 10 patients each. We performed brachial plexus block using a nerve stimulator. In the control group (group C), patients received 40 ml of 1% mepivacaine. In group E, patients received 40 ml of 1% mepivacaine containing 200 µg of epinephrine as an adjuvant. In group D, patients received 40 ml of 1% mepivacaine containing 1 µg/kg of dexmedetomidine as an adjuvant. Sensory block duration, motor block duration, time to sense pain, and onset time were assessed. We also monitored blood pressure, heart rate, oxygen saturation and bispectral index.</AbstractText>In group D and group E, sensory block duration, motor block duration and time to sense first pain were prolonged significantly compared to group C. However, there was no significant difference between group D and group E.</AbstractText>Perineural 1 µg/kg of dexmedetomidine similarly prolonged nerve block duration compared to 200 µg of epinephrine, but slowed heart rate. Thus, dexmedetomidine is expected to be a good alternative as an adjuvant to local anesthesia in patients who are cautioned against epinephrine.</AbstractText>
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2,333,602 |
Adaptive techniques in electrical impedance tomography reconstruction.
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We present an adaptive algorithm for solving the inverse problem in electrical impedance tomography. To strike a balance between the accuracy of the reconstructed images and the computational efficiency of the forward and inverse solvers, we propose to combine an adaptive mesh refinement technique with the adaptive Kaczmarz method. The iterative algorithm adaptively generates the optimal current patterns and a locally-refined mesh given the conductivity estimate and solves for the unknown conductivity distribution with the block Kaczmarz update step. Simulation and experimental results with numerical analysis demonstrate the accuracy and the efficiency of the proposed algorithm.
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2,333,603 |
Addition of dexmedetomidine to bupivacaine in transversus abdominis plane block potentiates post-operative pain relief among abdominal hysterectomy patients: A prospective randomized controlled trial.
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Dexmedetomidine is an alpha 2 adrenergic agonist, prolongs analgesia when used in neuraxial and peripheral nerve blocks. We studied the effect of addition of dexmedetomidine to bupivacaine to perform transversus abdominis plane (TAP) block.</AbstractText>A total of 50 patients scheduled for abdominal hysterectomy were divided into two equal groups in a randomized double-blinded way. Group B patients (n = 25) received TAP block with 20 ml of 0.25% bupivacaine and 2 ml of normal saline while Group BD (n = 25) received 0.5 mcg/kg (2 ml) of dexmedetomidine and 20 ml of 0.25% bupivacaine bilaterally. Time for first analgesic administration, totally used doses of morphine, pain scores, hemodynamic data and side-effects were recorded.</AbstractText>Demographic and operative characteristics were comparable between the two groups. The time for the first analgesic dose was longer in Group BD than Group B (470 vs. 280 min, P < 0.001) and the total doses of used morphine were less among Group BD patients in comparison to those in Group B (19 vs. 29 mg/24 h, P < 0.001). Visual analog scores were significantly lower in Group BD in the first 8 h post-operatively when compared with Group B, both at rest and on coughing (P < 0.001). In Group BD, lower heart rate was noticed 60 min from the induction time and continued for the first 4 h post-operatively (P < 0.001).</AbstractText>The addition of dexmedetomidine to bupivacaine in TAP block achieves better local anesthesia and provides better pain control post-operatively without any major side-effects.</AbstractText>
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2,333,604 |
Comparing the analgesic effect of caudal and ilioinguinal iliohypogastric nerve blockade using bupivacaine-clonidine in inguinal surgeries in children 2-7 years old.
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We compared the analgesic effects of caudal and ilioinguinal-iliohypogastric nerve block using bupivacaine-clonidine performed in children undergoing inguinal hernia repair. The ilioinguinal-iliohypogastric nerve block provides excellent pain relief for operations on the inguinal region, including emergency procedures (e.g. strangulated inguinal hernia with intestinal obstruction). It should be preferred to caudal block for these procedures.</AbstractText>After local ethics committee approval and written parental consent, 67 ASA class I - II patients aged between 2-7 years old scheduled for elective inguinal hernia repair were allocated randomly into two groups after general anesthesia with same drugs in both groups. Group C received caudal block with 1 ml/kg bupivacaine 0.25% combined with 1 μg/kg clonidine, and group I received ilioinguinal- iliohypogastric nerve block with 0.3 ml /kg bupivacaine 0.25% combined with 1 μg/kg clonidine. Blood pressure and heart rate were documented every 5 minutes. Post-operative analgesia, analgesic use and side-effects were assessed during first 24 hours.</AbstractText>In group C, 7 / 34 and in group I, 12/33 patients required post-operative analgesia (P = 0.174). Five patients (15.5%) in group I and one patient (2.94%) in group C had severe pain after operation. Systolic and diastolic blood pressure decreased during operation, but the differences between two groups were not significant (P = 0.176, P = 0.111). Heart rate changes between two groups were insignificant (P = 0.182).</AbstractText>It seems that in children, caudal epidural block and ilioinguinal - iliohypogastric nerve block using bupivacaine-clonidine have comparable effects on analgesia, severity of pain and hemodynamic changes during and after surgery on inguinal region.</AbstractText>
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2,333,605 |
Feto-maternal outcome in pregnancies complicated by isolated fetal congenital complete heart block.
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A retrospective analysis of eleven pregnancies complicated by isolated fetal congenital complete heart block (CCHB) in anti-SSA/Ro antibody positive women was carried out at a tertiary hospital in India to study the perinatal outcome. The mean gestational age at the time of detection of fetal CCHB was 24.5 ± 3.1weeks. Six mothers were asymptomatic; two had Sjögren's syndrome and three had systemic lupus erythematosus. Oral dexamethasone was given to all the patients after the diagnosis was made. There was one case of intrauterine death. Seven (63.6%) neonates needed a permanent pacemaker. There was no significant difference in the perinatal outcome in asymptomatic women with fetal CCHB and in women with connective tissue disorder and fetal CCHB. To conclude, fetal CCHB is associated with high morbidity but the presence of underlying connective disorder in the mother does not worsen the prognosis of the affected neonate.
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2,333,606 |
Bupivacaine-sufentanil versus bupivacaine-fentanyl in spinal anesthesia of patients undergoing lower extremity surgery.
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The addition of intrathecal opioids to local anesthetics seems to improve the quality of analgesia and prolong the duration of analgesia, when using a subarachnoid block in Iranian patients with their specific pain tolerance.</AbstractText>The aim of this study was to evaluate the effects of adding fentanyl or sufentanil, to intrathecal bupivacaine, in terms of the onset and duration of; sensory block, motor block, hemodynamic effects and postoperative pain relief.</AbstractText>This randomized clinical trial included 90 patients who underwent orthopedic lower limb surgeries. Subjects were divided into experimental groups; intrathecal fentanyl 25 µg (F), and sufentanil 2.5 µg (S), along with a placebo 0.5 mL normal saline (C) group, which were added to bupivacaine 0.5%, 15 mg. Duration of complete and effective analgesia was recorded (by a visual analogue scale-VAS). The pain scores were assessed postoperatively. Intraoperative mean arterial pressure (MAP), heart rate and oxygen saturation (SPO(2)) were recorded. The incidence of side effects such as; nausea, vomiting, pruritus, shivering, bradycardia and hypotension were also recorded.</AbstractText>MAP and heart rate results showed no significant changes at the designated time points among the three groups (P > 0.05). However, SPO2 and VAS showed significant changes at the designated time points among the three groups (P < 0.05). The duration of complete and effective analgesia was also significantly longer in the sufentanil group (P < 0.05). Motor block did not exhibit any significant difference (P = 0.67). Only pruritus as a side effect was significantly higher in the sufentanil group (P < 0.05), while all other evaluated side effects were significantly lower in the sufentanil group (P < 0.05).</AbstractText>The addition of 2.5-3 mcg sufentanil to 15 mg 0.05% bupivacaine maintained the patient's hemodynamic stability similar to fentanyl. Intrathecal sufentanil added to bupivacaine,when compared with fentanyl, may lead to prolonged duration of analgesia, facilitate the spread of the sensory block, increase mean SPO2 levels, and reduce overall side effects.</AbstractText>
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2,333,607 |
Analgesic efficacy of paravertebral bupivacaine during percutaneous nephrolithotomy: an observer blinded, randomized controlled trial.
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A unilateral paravertebral (PVB) block with catheter can provide extendable analgesia without physiological changes. The objective of this study was to assess the efficacy of PVB bupivacaine for providing perioperative pain relief in adults undergoing percutaneous nephrolithotomy (PCNL) under general anesthesia.</AbstractText>Fifty American Society of Anesthesiologists Grade I, II patients, aged 18 to 65 years, were included in this prospective, randomized, controlled, observer blinded trial. PVB group patients received preinduction 20 mL of 0.5% bupivacaine in the T9-10 paravertebral space and a catheter in addition to general anesthesia. Control group patients received only general anesthesia. All patients received intravenous fentanyl (2 μg/kg on induction, 0.5 μg/kg on 20% increase in heart rate or mean blood pressure) and paracetamol every 6 hours. Postoperative pain was assessed using the visual analog scale (VAS) (0-10 cm) at rest and movement by a blinded observer at 0, 1, 2, 4, 6, 12, and 24 hours postoperatively.</AbstractText>Data of 48 patients were analyzed. Intraoperative fentanyl requirement was higher in the control group (2.74±0.75 μg/kg [95 % confidence interval (CI) 2.42, 3.05]) than the PVB group (2.07±0.26 μg/kg [95 % CI 1.96, 2.18]), (P=0.0001). Time to first postoperative analgesic requirement was longer in the PVB group (120 min [30-570]) than the control group (30 min [0-180]), (P=0.0000). The VAS on rest (0, 1, 2, and 12 h) and movement (all time points) were significantly lower in the PVB group. Postoperative fentanyl consumption was lower in this group (175 μg [25-475]) compared with the control group (525 μg[(150-1275]), (P=0.0000).</AbstractText>Unilateral PVB block with catheter provided effective perioperative analgesia for PCNL.</AbstractText>
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2,333,608 |
Tumor targeting by pH-sensitive, biodegradable, cross-linked N-(2-hydroxypropyl) methacrylamide copolymer micelles.
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Increasing the molecular weight of N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers by using micellar structures could result in more pronounced enhanced permeability and retention effect, thus increase the tumor accumulation of drug. However, most micellar formulations are relatively unstable and release their drug non-specifically. To improve on these disadvantages, we developed a micellar drug delivery system based on self-assembly of HPMA copolymers. Amphiphilic conjugates were synthesized by conjugating the hydrophobic drug doxorubicin and hydrophobic β-sitosterol to the hydrophilic HPMA polymer backbone via pH-sensitive hydrazone linkages. This linkage is quite stable at physiological pH but hydrolyzes easily at acidic pH. After conjugates self-assembly into micelles, HPMA copolymer side chains were cross-linked through the hydrazone linkages to ensure micelle stability in the blood. Using this approach, cross-linked micelles were obtained with molecular weight of 1030 KD and diameter of 10-20 nm. These micelles remained stable with undetectable doxorubicin release at pH 7.4 or mouse plasma, whereas collapsed quickly with 80% of the drug released at pH 5 which corresponds to the pH of lyso/endosome compartments of tumor cells. Both cross-linked and non-cross-linked micelles displayed similar in vitro anti-tumor activity as linear copolymer conjugates in Hep G2 and A549 cancer cell lines with internalization mechanism by caveolin, clathrin, and giant macropinocytosis. In vivo studies in an H22 mouse xenograft model of hepatocarcinoma showed the tumor accumulation (1633 μCi/L*h) and anti-tumor rate (71.8%) of cross-linked micelles were significantly higher than non-cross-linked ones (698 μCi/L*h, 64.3%). Neither type of micelle showed significant toxicity in heart, lung, liver, spleen or kidney. These results suggest that cross-linked HPMA copolymer micelles with pH-sensitivity and biodegradability show excellent potential as carriers of anti-cancer drugs.
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2,333,609 |
Defining phenotypes in asthma: a step towards personalized medicine.
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Asthma is a common disease with a complex pathophysiology. It can present in various clinical forms and with different levels of severity. Unbiased cluster analytic methods have unravelled several phenotypes in cohorts representative of the whole spectrum of severity. Clusters of severe asthma include those on high-dose corticosteroid treatment, often with both inhaled and oral treatment, usually associated with severe airflow obstruction. Phenotypes with concordance between symptoms and sputum eosinophilia have been reported, including an eosinophilic inflammation-predominant group with few symptoms and late-onset disease who have a high prevalence of rhinosinusitis, aspirin sensitivity, and exacerbations. Sputum eosinophilia is also a biomarker that can predict therapeutic responses to antibody-based treatments to block the effects of the T-helper (Th)-2 cytokine, interleukin (IL)-5. Low Th2-expression has been predictive of poor therapeutic response to inhaled corticosteroid therapy. Current asthma schedules emphasise a step-up approach to treating asthma in relation to increasing severity, but, in more severe disease, phenotyping or endotyping of asthma will be necessary to determine new treatment strategies as severe asthma is recognized as being a particularly heterogeneous disease. Much less is known about 'non-eosinophilic' asthma. Phenotypic characterisation of corticosteroid insensitivity and chronic airflow obstruction of severe asthma is also needed. Phenotype-driven treatment of asthma will be further boosted by the advent of transcriptomic and proteomic technologies, with the application of systems biology or medicine approaches to defining phenotypes and biomarkers of disease and therapeutic response. This will pave the way towards personalized medicine and healthcare for asthma.
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2,333,610 |
Virtual screening for cholesterol absorption inhibitors.
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Cholesterol, derived from two different sources of endogenous synthesis and diet, is essential for the growth and maintenance of mammalian cells. However, elevated level of serum cholesterol is among the associated risk factors for the coronary heart disease. Statins can reduce endogenous sterol synthesis by inhibiting HMG-CoA reductase, whereas cholesterol absorption inhibitors, such as ezetimibe, can block cholesterol uptake from dietary sources by blocking Niemann- Pick C1-like 1 (NPC1L1).</AbstractText>The present review focuses on the main research progress of cholesterol absorption inhibitors, the structure of NPC1L1 and discovery of novel chemical entities by virtual screening.</AbstractText>Studies on the structure-activity relationship reveal that azetidinone is important to maintain activity in azetidinone derivatives and the novel heterocyclic compounds with replacement of β-lactam scaffold by oxazolidinone also show similar activity as ezetimibe. Moreover, virtual screening is a computer-aided molecular design tool to propose novel cholesterol absorption inhibitors.</AbstractText>
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2,333,611 |
A new technique for the estimation of cardiac motion in echocardiography based on transverse oscillations: a preliminary evaluation in silico and a feasibility demonstration in vivo.
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Quantification of regional myocardial motion and deformation from cardiac ultrasound is fostering considerable research efforts. Despite the tremendous improvements done in the field, all existing approaches still face a common limitation which is intrinsically connected with the formation of the ultrasound images. Specifically, the reduced lateral resolution and the absence of phase information in the lateral direction highly limit the accuracy in the computation of lateral displacements. In this context, this paper introduces a novel setup for the estimation of cardiac motion with ultrasound. The framework includes an unconventional beamforming technique and a dedicated motion estimation algorithm. The beamformer aims at introducing phase information in the lateral direction by producing transverse oscillations. The estimator directly exploits the phase information in the two directions by decomposing the image into two 2-D single-orthant analytic signals. An in silico evaluation of the proposed framework is presented on five ultra-realistic simulated echocardiographic sequences, where the proposed motion estimator is contrasted against other two phase-based solutions exploiting the presence of transverse oscillations and against block-matching on standard images. An implementation of the new beamforming strategy on a research ultrasound platform is also shown along with a preliminary in vivo evaluation on one healthy subject.
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2,333,612 |
Depression, dietary habits, and cardiovascular events among women with suspected myocardial ischemia.
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Dietary habits and depression are associated with cardiovascular disease risk. Patients with depression often report poor eating habits, and dietary factors may help explain commonly observed associations between depression and cardiovascular disease.</AbstractText>From 1996 to 2000, 936 women were enrolled in the Women's Ischemia Syndrome Evaluation at 4 US academic medical centers at the time of clinically indicated coronary angiography and then assessed (median follow-up, 5.9 years) for adverse outcomes (cardiovascular disease death, heart failure, myocardial infarction, stroke). Participants completed a protocol including coronary angiography (coronary artery disease severity) and depression assessments (Beck Depression Inventory scores, antidepressant use, and depression treatment history). A subset of 201 women (mean age, 58.5 years; standard deviation, 11.4) further completed the Food Frequency Questionnaire for Adults (1998 Block). We extracted daily fiber intake and daily servings of fruit and vegetables as measures of dietary habits.</AbstractText>In separate Cox regression models adjusted for age, smoking, and coronary artery disease severity, Beck Depression Inventory scores (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.01-1.10), antidepressant use (HR, 2.4; 95% CI, 1.01-5.9), and a history of treatment for depression (HR, 2.4; 95% CI, 1.1-5.3) were adversely associated with time to cardiovascular disease outcomes. Fiber intake (HR, 0.87; 95% CI, 0.78-0.97) and fruit and vegetable consumption (HR, 0.36; 95% CI, 0.19-0.70) were associated with a decreased time to cardiovascular disease event risk. In models including dietary habits and depression, fiber intake and fruit and vegetable consumption remained associated with time to cardiovascular disease outcomes, whereas depression relationships were reduced by 10% to 20% and nonsignificant.</AbstractText>Among women with suspected myocardial ischemia, we observed consistent relationships among depression, dietary habits, and time to cardiovascular disease events. Dietary habits partly explained these relationships. These results suggest that dietary habits should be included in future efforts to identify mechanisms linking depression to cardiovascular disease.</AbstractText>Published by Elsevier Inc.</CopyrightInformation>
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2,333,613 |
BDNF polymorphism and differential rTMS effects on motor recovery of stroke patients.
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The brain-derived neurotrophic factor (BDNF) gene often shows a single nucleotide polymorphism that is thought to influence synaptic plasticity. It also affects the modulatory effects of repetitive transcranial magnetic stimulation (rTMS) on motor cortex excitability.</AbstractText>This study investigated whether BDNF polymorphism influences the effect of rTMS on the motor recovery of patients with stroke.</AbstractText>Forty-four patients (mean age 53.8 years) experiencing unilateral motor weakness after stroke were recruited. rTMS was applied over the primary motor cortex of the affected hemisphere at 10 Hz with 1000 pulses/day for 10 days. Each patient's motor functions were assessed using the Fugl-Meyer assessment (FMA) and the box and block test (BBT) before, immediately after and 2 months after the intervention. BDNF genotyping was performed via PCR assays of whole blood samples. The patients' data were grouped and analysed into Val/Val and Met allele groups according to the presence or absence of the BDNF polymorphism.</AbstractText>Nine patients (20.5%) were classified into the Val/Val group, and thirty-seven patients (79.5%) were classified into the Met allele group. The patients' baseline motor functions did not differ between the two groups. The FMA and BBT scores showed significant improvement immediately after and 2 months after rTMS in both groups. In addition, the time and groups were found to interact significantly, with the Val/Val group improving to a greater extent than the Met allele group in terms of their FMA and BBT scores.</AbstractText>The findings suggest that the BDNF gene polymorphism negatively influences the effect of rTMS on the motor recovery of upper extremities in stroke patients.</AbstractText>Copyright © 2014 Elsevier Inc. All rights reserved.</CopyrightInformation>
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2,333,614 |
Antenatal exercise in overweight and obese women and its effects on offspring and maternal health: design and rationale of the IMPROVE (Improving Maternal and Progeny Obesity Via Exercise) randomised controlled trial.
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Obesity during pregnancy is associated with adverse outcomes for the offspring and mother. Lifestyle interventions in pregnancy such as antenatal exercise, are proposed to improve both short- and long-term health of mother and child. We hypothesise that regular moderate-intensity exercise during the second half of pregnancy will result in improved maternal and offspring outcomes, including a reduction in birth weight and adiposity in the offspring, which may be protective against obesity in later life.</AbstractText><AbstractText Label="METHODS/DESIGN" NlmCategory="METHODS">The IMPROVE (Improving Maternal and Progeny Risks of Obesity Via Exercise) study is a two-arm parallel randomised controlled clinical trial being conducted in Auckland, New Zealand. Overweight and obese women (BMI ≥25 kg/m2) aged 18-40 years, with a singleton pregnancy of <20 weeks of gestation, from the Auckland region, are eligible for the trial. Exclusion criteria are ongoing smoking or medical contra-indications to antenatal exercise.Participants are randomised with 1:1 allocation ratio to either intervention or control group, using computer-generated randomisation sequences in variable block sizes, stratified on ethnicity and parity, after completion of baseline assessments. The intervention consists of a 16-week structured home-based moderate-intensity exercise programme utilising stationary cycles and heart rate monitors, commencing at 20 weeks of gestation. The control group do not receive any exercise intervention. Both groups undergo regular fetal ultrasonography and receive standard antenatal care. Due to the nature of the intervention, participants are un-blinded to group assignment during the trial.The primary outcome is offspring birth weight. Secondary offspring outcomes include fetal and neonatal body composition and anthropometry, neonatal complications and cord blood metabolic markers. Maternal outcomes include weight gain, pregnancy and delivery complications, aerobic fitness, quality of life, metabolic markers and post-partum body composition.</AbstractText>The results of this trial will provide valuable insights on the effects of antenatal exercise on health outcomes in overweight and obese mothers and their offspring.</AbstractText>Australian New Zealand Clinical Trials Registry ACTRN12612000932864.</AbstractText>
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2,333,615 |
PPARβ/δ attenuates palmitate-induced endoplasmic reticulum stress and induces autophagic markers in human cardiac cells.
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Chronic endoplasmic reticulum (ER) stress contributes to the apoptotic cell death in the myocardium, thereby playing a critical role in the development of cardiomyopathy. ER stress has been reported to be induced after high-fat diet feeding in mice and also after saturated fatty acid treatment in vitro. Therefore, since several studies have shown that peroxisome proliferator-activated receptor (PPAR)β/δ inhibits ER stress, the main goal of this study consisted in investigating whether activation of this nuclear receptor was able to prevent lipid-induced ER stress in cardiac cells.</AbstractText>Wild-type and transgenic mice with reduced PPARβ/δ expression were fed a standard diet or a high-fat diet for two months. For in vitro studies, a cardiomyocyte cell line of human origin, AC16, was treated with palmitate and the PPARβ/δ agonist GW501516. Our results demonstrate that palmitate induced ER stress in AC16 cells, a fact which was prevented after PPARβ/δ activation with GW501516. Interestingly, the effect of GW501516 on ER stress occurred in an AMPK-independent manner. The most striking result of this study is that GW501516 treatment also upregulated the protein levels of beclin 1 and LC3II, two well-known markers of autophagy. In accordance with this, feeding on a high-fat diet or suppression of PPARβ/δ in knockout mice induced ER stress in the heart. Moreover, PPARβ/δ knockout mice also displayed a reduction in autophagic markers.</AbstractText>Our data indicate that PPARβ/δ activation might be useful to prevent the harmful effects of ER stress induced by saturated fatty acids in the heart by inducing autophagy.</AbstractText>Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.</CopyrightInformation>
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2,333,616 |
Comparison of unilateral spinal anesthesia and L₁ paravertebral block combined with psoas compartment and sciatic nerve block in patients to undergo partial hip prosthesis.
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Just as hip prosthesis, most of the patients undergoing orthopedic lower extremity surgery (OLES) belong to the advanced age group. Sciatic nerve block combined with psoas compartment block is used as a technique alternative to central neuraxial block and GA. In geriatric patients that will undergo partial hip prosthesis, the effects of the methods of unilateral spinal anesthesia (SA) and L1 paravertebral block combined with psoas compartment block (PCB) and sciatic nerve block (PCSL) on peroperative hemodynamic parameters and the duration of need for postoperative analgesia were studied.</AbstractText>Fifty patients from the ASA III-IV group were randomly divided into two groups. Group SA was administered spinal anesthesia with hyperbaric bupivacaine (2 ml, 0.5%) from the selected intervertebral distance (L4-L5 or L3-L4) in lateral position. Group PCSL was administered L1 paravertebral block combined with PCB and sciatic nerve block with bupivacaine hydrochloride (total 35 ml). Hemodynamic parameters (HR: heart rate and MAP: mean artery pressure) were recorded in pre- and post-intervention 5-minute intervals. The initial time of the need for analgesia of patients were evaluated postoperatively.</AbstractText>Any failure in methods implemented on patients in either group was not observed. Times of anesthesia and surgical preparation of patients were observed to have significantly prolonged in the PCSL compared to Group SA (p < 0.005). Hundred and 5th and 110th min. mean arterial pressures of patients was found to be significantly higher in Group SA compared to Group PCSL (p < 0.05). The initial time of the need for analgesia was observed to be significantly prolonged in Group PCSL (432.80 ± 236.77 min) compared to Group SA (185.40 ± 171.40 min) (p < 0.001).</AbstractText>Unilateral SA conducted with bupivacaine hydrochloride and PCSL block technique provided a hemodynamically similar activity in the perioperative period in patients that underwent partial hip operation. However, PCSL block implementation extended the initial time of the need for analgesia in postoperative period. PCSL method could be selected in cases belonging to such group of patients. PCSL block can be a alternative anesthetic tecniques in patients that underwent partial hip operation.</AbstractText>
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2,333,617 |
Sodium channelopathy underlying familial sick sinus syndrome with early onset and predominantly male characteristics.
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Sick sinus syndrome (SSS) is a common arrhythmia often associated with aging or organic heart diseases but may also occur in a familial form with a variable mode of inheritance. Despite the identification of causative genes, including cardiac Na channel (SCN5A), the pathogenesis and molecular epidemiology of familial SSS remain undetermined primarily because of its rarity.</AbstractText>We genetically screened 48 members of 15 SSS families for mutations in several candidate genes and determined the functional properties of mutant Na channels using whole-cell patch clamping. We identified 6 SCN5A mutations including a compound heterozygous mutation. Heterologously expressed mutant Na channels showed loss-of-function properties of reduced or no Na current density in conjunction with gating modulations. Among 19 family members with SCN5A mutations, QT prolongation and Brugada syndrome were associated in 4 and 2 individuals, respectively. Age of onset in probands carrying SCN5A mutations was significantly less (mean±SE, 12.4±4.6 years; n=5) than in SCN5A-negative probands (47.0±4.6 years; n=10; P<0.001) or nonfamilial SSS (74.3±0.4 years; n=538; P<0.001). Meta-analysis of SSS probands carrying SCN5A mutations (n=29) indicated profound male predominance (79.3%) resembling Brugada syndrome but with a considerably earlier age of onset (20.9±3.4 years).</AbstractText>The notable pathophysiological overlap between familial SSS and Na channelopathy indicates that familial SSS with SCN5A mutations may represent a subset of cardiac Na channelopathy with strong male predominance and early clinical manifestations.</AbstractText>© 2014 American Heart Association, Inc.</CopyrightInformation>
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2,333,618 |
Sox7 is regulated by ETV2 during cardiovascular development.
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Vasculogenesis/angiogenesis is one of the earliest processes that occurs during embryogenesis. ETV2 and SOX7 were previously shown to play a role in endothelial development; however, their mechanistic interaction has not been defined. In the present study, concomitant expression of Etv2 and Sox7 in endothelial progenitor cells was verified. ETV2 was shown to be a direct upstream regulator of Sox7 that binds to ETV2 binding elements in the Sox7 upstream regulatory region and activates transcription. We observed that SOX7 over-expression can mimic ETV2 and increase endothelial progenitor cells in embryonic bodies (EBs), while knockdown of Sox7 is able to block ETV2-induced increase in endothelial progenitor cell formation. Angiogenic sprouting was increased by ETV2 over-expression in EBs, and it was significantly decreased in the presence of Sox7 shRNA. Collectively, these studies support the conclusion that ETV2 directly regulates Sox7, and that ETV2 governs endothelial development by regulating transcriptional networks which include Sox7.
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2,333,619 |
Prenatal anti-Ro antibody exposure, congenital complete atrioventricular heart block, and high-dose steroid therapy: impact on neurocognitive outcome in school-age children.
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To determine the impact of prenatal exposure to maternal anti-Ro antibodies, slow fetal heart rate, and/or prolonged dexamethasone therapy for immune-mediated congenital atrioventricular heart block (CAVB) on the cognitive and academic performance of these children at school age.</AbstractText>We performed a prospective, blinded assessment of the cognitive functioning of 3 cohorts of children ages 6-16 years with in utero exposure to maternal anti-Ro antibodies in the following groups: no CAVB and no prenatal dexamethasone treatment (n = 14), CAVB without prenatal treatment (n = 10), and CAVB with prenatal dexamethasone treatment (n = 16). Domains assessed included intelligence, visual perceptual and visual motor skills, auditory and visual attention, verbal learning and memory, visual memory, executive function, and behavior.</AbstractText>All cohorts scored within the normal range and were not significantly different in terms of intelligence scores, verbal comprehension, perceptional reasoning, working memory, and processing speed. For children with CAVB who were treated prenatally, there were no significant associations between the neurocognitive function scores, the minimal fetal heart rate (range 47-80 beats per minute), and either the duration (range 2-15 weeks) or dosage (range 56-824 mg) of dexamethasone therapy.</AbstractText>CAVB and transplacental treatment with dexamethasone was not associated with neurocognitive impairment in school-age children. Larger numbers of children are needed to validate our observation, and assessment of other cognitive abilities is warranted.</AbstractText>Copyright © 2014 by the American College of Rheumatology.</CopyrightInformation>
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2,333,620 |
Dose-escalation study for cardiac radiosurgery in a porcine model.<Pagination><StartPage>590</StartPage><EndPage>598</EndPage><MedlinePgn>590-8</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.ijrobp.2014.02.036</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S0360-3016(14)00280-6</ELocationID><Abstract><AbstractText Label="PURPOSE" NlmCategory="OBJECTIVE">To perform a proof-of-principle dose-escalation study to radiosurgically induce scarring in cardiac muscle tissue to block veno-atrial electrical connections at the pulmonary vein antrum, similar to catheter ablation.</AbstractText><AbstractText Label="METHODS AND MATERIALS" NlmCategory="METHODS">Nine mini-pigs underwent pretreatment magnetic resonance imaging (MRI) evaluation of heart function and electrophysiology assessment by catheter measurements in the right superior pulmonary vein (RSPV). Immediately after examination, radiosurgery with randomized single-fraction doses of 0 and 17.5-35 Gy in 2.5-Gy steps were delivered to the RSPV antrum (target volume 5-8 cm(3)). MRI and electrophysiology were repeated 6 months after therapy, followed by histopathologic examination.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">Transmural scarring of cardiac muscle tissue was noted with doses ≥32.5 Gy. However, complete circumferential scarring of the RSPV was not achieved. Logistic regressions showed that extent and intensity of fibrosis significantly increased with dose. The 50% effective dose for intense fibrosis was 31.3 Gy (odds ratio 2.47/Gy, P<.01). Heart function was not affected, as verified by MRI and electrocardiogram evaluation. Adjacent critical structures were not damaged, as verified by pathology, demonstrating the short-term safety of small-volume cardiac radiosurgery with doses up to 35 Gy.</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">Radiosurgery with doses >32.5 Gy in the healthy pig heart can induce circumscribed scars at the RSPV antrum noninvasively, mimicking the effect of catheter ablation. In our study we established a significant dose-response relationship for cardiac radiosurgery. The long-term effects and toxicity of such high radiation doses need further investigation in the pursuit of cardiac radiosurgery for noninvasive treatment of atrial fibrillation.</AbstractText><CopyrightInformation>Copyright © 2014 Elsevier Inc. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Blanck</LastName><ForeName>Oliver</ForeName><Initials>O</Initials><AffiliationInfo><Affiliation>Department of Radiation Oncology, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck, Germany; CyberKnife Center Northern Germany, Guestrow, Germany. Electronic address: [email protected].</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bode</LastName><ForeName>Frank</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Medical Department II, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gebhard</LastName><ForeName>Maximilian</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Institute of Pathology, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hunold</LastName><ForeName>Peter</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Department of Radiology and Nuclear Medicine, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Brandt</LastName><ForeName>Sebastian</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Anaesthesiology and Intensive Care Medicine, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bruder</LastName><ForeName>Ralf</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Institute for Robotics and Cognitive Systems, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Grossherr</LastName><ForeName>Martin</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Anaesthesiology and Intensive Care Medicine, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vonthein</LastName><ForeName>Reinhard</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Institute of Medical Biometry and Statistics, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rades</LastName><ForeName>Dirk</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Department of Radiation Oncology, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dunst</LastName><ForeName>Juergen</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Radiation Oncology, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck, Germany; University Copenhagen, Denmark.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2014</Year><Month>04</Month><Day>18</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Int J Radiat Oncol Biol Phys</MedlineTA><NlmUniqueID>7603616</NlmUniqueID><ISSNLinking>0360-3016</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="ErratumIn"><RefSource>Int J Radiat Oncol Biol Phys. 2014 Dec 1;90(5):1264</RefSource></CommentsCorrections></CommentsCorrectionsList><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002921" MajorTopicYN="N">Cicatrix</DescriptorName><QualifierName UI="Q000209" MajorTopicYN="Y">etiology</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004562" MajorTopicYN="N">Electrocardiography</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005355" MajorTopicYN="N">Fibrosis</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006321" MajorTopicYN="N">Heart</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName><QualifierName UI="Q000528" MajorTopicYN="Y">radiation effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D021621" MajorTopicYN="N">Imaging, Three-Dimensional</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="N">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008279" MajorTopicYN="N">Magnetic Resonance Imaging</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="N">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009206" MajorTopicYN="N">Myocardium</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D058958" MajorTopicYN="N">Organs at Risk</DescriptorName><QualifierName UI="Q000528" MajorTopicYN="N">radiation effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011667" MajorTopicYN="N">Pulmonary Veins</DescriptorName><QualifierName UI="Q000528" MajorTopicYN="Y">radiation effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016634" MajorTopicYN="N">Radiosurgery</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011879" MajorTopicYN="N">Radiotherapy Dosage</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013552" MajorTopicYN="N">Swine</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2013</Year><Month>12</Month><Day>5</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2014</Year><Month>2</Month><Day>21</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2014</Year><Month>2</Month><Day>24</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2014</Year><Month>4</Month><Day>23</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2014</Year><Month>4</Month><Day>23</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2014</Year><Month>7</Month><Day>31</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">24751407</ArticleId><ArticleId IdType="doi">10.1016/j.ijrobp.2014.02.036</ArticleId><ArticleId IdType="pii">S0360-3016(14)00280-6</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">24749255</PMID><DateCompleted><Year>2014</Year><Month>05</Month><Day>08</Day></DateCompleted><DateRevised><Year>2014</Year><Month>04</Month><Day>22</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0201-7563</ISSN><JournalIssue CitedMedium="Print"><Issue>6</Issue><PubDate><Year>2013</Year><Season>Nov-Dec</Season></PubDate></JournalIssue><Title>Anesteziologiia i reanimatologiia</Title><ISOAbbreviation>Anesteziol Reanimatol</ISOAbbreviation></Journal>[Correction of hemodynamics and heart rate disorders in paitients with right coronary artery disease].
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To perform a proof-of-principle dose-escalation study to radiosurgically induce scarring in cardiac muscle tissue to block veno-atrial electrical connections at the pulmonary vein antrum, similar to catheter ablation.</AbstractText>Nine mini-pigs underwent pretreatment magnetic resonance imaging (MRI) evaluation of heart function and electrophysiology assessment by catheter measurements in the right superior pulmonary vein (RSPV). Immediately after examination, radiosurgery with randomized single-fraction doses of 0 and 17.5-35 Gy in 2.5-Gy steps were delivered to the RSPV antrum (target volume 5-8 cm(3)). MRI and electrophysiology were repeated 6 months after therapy, followed by histopathologic examination.</AbstractText>Transmural scarring of cardiac muscle tissue was noted with doses ≥32.5 Gy. However, complete circumferential scarring of the RSPV was not achieved. Logistic regressions showed that extent and intensity of fibrosis significantly increased with dose. The 50% effective dose for intense fibrosis was 31.3 Gy (odds ratio 2.47/Gy, P<.01). Heart function was not affected, as verified by MRI and electrocardiogram evaluation. Adjacent critical structures were not damaged, as verified by pathology, demonstrating the short-term safety of small-volume cardiac radiosurgery with doses up to 35 Gy.</AbstractText>Radiosurgery with doses >32.5 Gy in the healthy pig heart can induce circumscribed scars at the RSPV antrum noninvasively, mimicking the effect of catheter ablation. In our study we established a significant dose-response relationship for cardiac radiosurgery. The long-term effects and toxicity of such high radiation doses need further investigation in the pursuit of cardiac radiosurgery for noninvasive treatment of atrial fibrillation.</AbstractText>Copyright © 2014 Elsevier Inc. All rights reserved.</CopyrightInformation>
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2,333,621 |
Fetal effects of combined spinal-epidural vs epidural labour analgesia: a prospective, randomised double-blind study.
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We have compared fetal heart rate patterns, Apgar scores and umbilical cord gas values following initiation of labour analgesia using either combined spinal-epidural or epidural. One hundred and fifteen healthy women requesting neuraxial analgesia in the first stage of labour were randomly assigned to receive either combined spinal-epidural (n = 62) or epidural analgesia (n = 53). Fetal heart rate traces, recorded for 30 min before and 60 min after neuraxial block, were categorised as normal, suspicious or pathological according to national guidelines. Sixty-one fetal heart rate tracings were analysed in the combined spinal-epidural group and 52 in the epidural group. No significant differences were found in fetal heart rate patterns, Apgar scores or umbilical artery and vein acid-base status between groups. However, in both combined spinal-epidural and epidural groups, there was a significant increase in the incidence of abnormal fetal heart rate patterns following neuraxial analgesia (p < 0.0001); two before compared with eight after analgesia in the combined spinal-epidural group and zero before compared with 11 after in the epidural group. These changes comprised increased decelerations (p = 0.0045) (combined spinal-epidural group nine before and 14 after analgesia, epidural group four before and 16 after), increased late decelerations (p < 0.0001) (combined spinal-epidural group zero before and seven after analgesia, epidural group zero before and eight after), and a reduction in acceleration rate (p = 0.034) (combined spinal-epidural group mean (SD) 12.2 (6.7) h(-1) before and 9.9 (6.1) h(-1) after analgesia, epidural group 11.0 (7.3) h(-1) before and 8.4 (5.9) h(-1) after). These fetal heart rate changes did not affect neonatal outcome in this healthy population.
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2,333,622 |
In vitro and in vivo effects of a nutrient mixture on breast cancer progression.
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Long-term survival of patients with breast cancer remains poor, due to metastasis and recurrence. We investigated the effects of a novel nutrient mixture (NM) containing ascorbic acid, lysine, proline and green tea extract in vitro and in vivo on 4T1 murine breast cancer, a representative model for metastatic breast cancer. After one week of isolation, 5-6-week-old female Balb/C mice were inoculated with 5x10⁵ 4T1 cells into the mammary pad and randomly divided into two groups; the control group was fed a regular diet and the NM group a regular diet supplemented with 0.5% NM. After four weeks, the mice were sacrificed and their tumors, lungs, livers, kidneys, hearts and spleens were excised and processed for histology. Dimensions (length and width) of tumors were measured using a digital caliper, and the tumor burden was calculated using the following formula: 0.5 x length x width. We also tested the effect of NM in vitro on 4T1 cells, measuring cell proliferation by MTT assay, MMP secretion by zymography, invasion through Matrigel, migration by scratch test and morphology by H&E staining. NM inhibited tumor weight and burden of 4T1 tumors by 50% (p=0.02) and 53.4% (p≤0.0001), respectively. Lung metastasis was profoundly inhibited by NM supplementation: mean number of colonies was reduced by 87% (p<0.0001) and mean weight of lungs by 60% (p=0.0001) compared to control mice. Metastasis to liver, spleen, kidney and heart was significantly reduced with NM supplementation. In vitro, NM exhibited 50% toxicity over the control at 250 and 500 µg/ml concentrations. Zymography demonstrated MMP-2 and MMP-9 secretion which was inhibited by NM in a dose-dependent manner, with virtual total inhibition of both at 1,000 µg/ml. Migration by scratch test and invasion through Matrigel were inhibited in a dose-dependent manner with total block of invasion at 250 and of migration at 1,000 µg/ml. These results suggest that NM has therapeutic potential in the treatment of breast cancer.
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2,333,623 |
Comparison of regional vs. systemic analgesia for post-thoracotomy care in infants.
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In infants, post-thoracotomy analgesia traditionally consists of systemic opiates, while regional techniques have gained more favor in recent years. We compare the two techniques for thoracotomy in infants.</AbstractText>All consecutive patients below 6 months of age who underwent thoracotomy for congenital pulmonary malformations in the study period were retrospectively divided according to the chosen postoperative analgesia: Group S systemic opiates, Group R continuous regional (epidural or extrapleural paravertebral) block. We studied the following outcomes: need for NICU and mechanical ventilation, pain score, requirement for additional analgesics, heart rate 1 h postsurgery, time to pass first stool and to full feed, complications, and duration of hospitalization.</AbstractText>Forty consecutive patients were included, 19 in Group S and 21 in Group R. Median age at surgery was 89 days (40-110) and 90 days (46-117), respectively. Five of 19 patients in Group S vs none in Group R required postoperative intensive care (P = 0.017). Patients in Group R had significantly lower postoperative heart rate (145 [138-150] vs. 160 [152-169] b·min(-1) , P = 0.007), earlier passage of first stools (24 h [12-24] vs. 36 h [24-48] P = 0.004), and earlier time to full feed (36 h [24-48] vs. 84 h [60-120] P = 0.0001) than those in Group S. The only observed complication was one catheter dislocation.</AbstractText>In infants undergoing thoracotomy, loco-regional analgesia is effective and associated with a reduced intensity of postoperative care and earlier full feeding than systemic analgesia; it should therefore be considered a better option.</AbstractText>© 2014 John Wiley & Sons Ltd.</CopyrightInformation>
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2,333,624 |
Discovery of structure-based small molecular inhibitor of αB-crystallin against basal-like/triple-negative breast cancer development in vitro and in vivo.
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αB-crystallin (CRYAB) is present at a high frequency in poor prognosis basal-like breast tumours, which are largely absent of oestrogen, progesterone receptors and HER2 known as triple-negative breast cancer (TNBC). CRYAB functions as a molecular chaperone to bind to and correct intracellular misfolded/unfolded proteins such as vascular endothelial growth factor (VEGF), preventing non-specific protein aggregations under the influence of the tumour microenvironment stress and/or anti-cancer treatments including bevacizumab therapy. Directly targeting CRYAB can sensitize tumour cells to chemotherapeutic agents and decrease tumour aggressiveness. However, growing evidence shows that CRYAB is a critical adaptive response element after ischemic heart disease and stroke, implying that directly targeting CRYAB might cause serious unwanted side effects. Here, we used structure-based molecular docking of CRYAB and identified a potent small molecular inhibitor, NCI-41356, which can strongly block the interaction between CRYAB and VEGF165 without affecting CRYAB levels. The disruption of the interaction between CRYAB and VEGF165 elicits in vitro anti-tumour cell proliferation and invasive effects through the down-regulation of VEGF signalling in the breast cancer cells. The observed in vitro anti-tumour angiogenesis of endothelial cells might be attributed to the down-regulation of paracrine VEGF signalling in the breast cancer cells after treatment with NCI-41356. Intraperitoneal injection of NCI-41356 greatly inhibits the tumour growth and vasculature development in in vivo human breast cancer xenograft models. Our findings provide 'proof-of-concept' for the development of highly specific structure-based alternative targeted therapy for the prevention and/or treatment of TNBC.
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2,333,625 |
Diagnosis, management and post-mortem findings of a human case of rabies imported into the United Kingdom from India: a case report.
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Human rabies infection continues to be a significant public health burden globally, and is occasionally imported to high income settings where the Milwaukee Protocol for intensive care management has recently been employed, with limited success in improving survival. Access to molecular diagnostics, pre- and post-mortem, and documentation of pathophysiological responses while using the Milwaukee protocol, can add useful insights for the future of rabies management.</AbstractText>A 58-year-old British Asian woman was referred to a regional general hospital in the UK with hydrophobia, anxiety and confusion nine weeks after receiving a dog bite in North West India. Nuchal skin biopsy, saliva, and a skin biopsy from the site of the dog bite wound, taken on the day of admission, all demonstrated the presence of rabies virus RNA. Within 48 hours sequence analysis of viral RNA confirmed the diagnosis and demonstrated that the virus was a strain closely related to canine rabies viruses circulating in South Asia. Her condition deteriorated rapidly with increased agitation and autonomic dysfunction. She was heavily sedated and intubated on the day after admission, treated according to a modified Milwaukee protocol, and remained stable until she developed heart block and profound acidosis and died on the eighth day. Analysis of autopsy samples showed a complete absence of rabies neutralizing antibody in cerebrospinal fluid and serum, and corresponding high levels of virus antigen and nucleic acid in brain and cerebrospinal fluid. Quantitative PCR showed virus was also distributed widely in peripheral tissues despite mild or undetectable histopathological changes. Vagus nerve branches in the heart showed neuritis, a probable Negri body but no demonstrable rabies antigen.</AbstractText>Rapid molecular diagnosis and strain typing is helpful in the management of human rabies infection. Post-mortem findings such as vagal neuritis highlight clinically important effects on the cardiovascular system which are typical for the clinical course of rabies in humans. Management guided by the Milwaukee protocol is feasible within well-resourced intensive care units, but its role in improving outcome for canine-derived rabies remains theoretical.</AbstractText>
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2,333,626 |
Deepwater Horizon crude oil impacts the developing hearts of large predatory pelagic fish.
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The Deepwater Horizon disaster released more than 636 million L of crude oil into the northern Gulf of Mexico. The spill oiled upper surface water spawning habitats for many commercially and ecologically important pelagic fish species. Consequently, the developing spawn (embryos and larvae) of tunas, swordfish, and other large predators were potentially exposed to crude oil-derived polycyclic aromatic hydrocarbons (PAHs). Fish embryos are generally very sensitive to PAH-induced cardiotoxicity, and adverse changes in heart physiology and morphology can cause both acute and delayed mortality. Cardiac function is particularly important for fast-swimming pelagic predators with high aerobic demand. Offspring for these species develop rapidly at relatively high temperatures, and their vulnerability to crude oil toxicity is unknown. We assessed the impacts of field-collected Deepwater Horizon (MC252) oil samples on embryos of three pelagic fish: bluefin tuna, yellowfin tuna, and an amberjack. We show that environmentally realistic exposures (1-15 µg/L total PAH) cause specific dose-dependent defects in cardiac function in all three species, with circulatory disruption culminating in pericardial edema and other secondary malformations. Each species displayed an irregular atrial arrhythmia following oil exposure, indicating a highly conserved response to oil toxicity. A considerable portion of Gulf water samples collected during the spill had PAH concentrations exceeding toxicity thresholds observed here, indicating the potential for losses of pelagic fish larvae. Vulnerability assessments in other ocean habitats, including the Arctic, should focus on the developing heart of resident fish species as an exceptionally sensitive and consistent indicator of crude oil impacts.
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2,333,627 |
Visceral adipose tissue mass in nonlactating dairy cows fed diets differing in energy density(1).
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Our objective was to determine dietary energy effects on feed intake, internal fat deposition, body condition score (BCS), visceral organ mass, and blood analytes in Holstein cows. Eighteen nonpregnant, nonlactating cows (BCS = 3.04 ± 0.25) were blocked based on initial BCS and were randomly assigned within each block to 2 treatments. Treatments were either high energy [HE; net energy for lactation (NEL)=1.62 Mcal/kg] or low energy (LE; NEL = 1.35 Mcal/kg) diets fed as total mixed rations for 8 wk. The LE diet consisted of 81.7% forage, including 40.5% wheat straw and 28.3% corn silage, whereas the HE diet contained 73.8% forage with no straw and 49.9% corn silage (dry matter basis). Cows were fed for ad libitum intake once daily at 0800 h. Feed intake was recorded daily, blood was sampled at wk 1, 4, and 7, and BCS was assigned at wk 1, 4, and 7. Cows were killed following the 8-wk period, and visceral organs, mammary gland, and internal adipose tissues were weighed and sampled. The HE group had greater dry matter intake (15.9 vs. 11.2 ± 0.5 kg/d) and energy intakes than cows fed LE, but neutral detergent fiber intake did not differ (5.8 vs. 5.6 ± 0.25 kg/d for HE and LE). Final body weight was greater for cows fed HE (807 vs. 750 kg), but BCS did not differ between groups (3.52 vs. 3.47 for HE and LE). Omental (26.8 vs. 15.2 ± 1.6 kg/d), mesenteric (21.5 vs. 11.2 ± 1.9 kg), and perirenal (8.9 vs. 5.4 ± 0.9 kg) adipose tissue masses were larger in HE cows than in LE cows. Although subcutaneous adipose mass was not measured, carcass weight (including hide and subcutaneous fat) did not differ between HE (511 kg) and LE (496 kg). Liver weight tended to be greater for cows fed HE, but weights of gastrointestinal tract, heart, and kidney did not differ. Serum insulin tended to be greater and the glucose to insulin ratio was lower for cows fed HE. Serum concentrations of β-hydroxybutyrate and cholesterol were greater for HE cows than for LE cows but concentrations of glucose, nonesterified fatty acids, total protein, and albumin did not differ. Final BCS was correlated with masses of omental (r = 0.57), mesenteric (r = 0.59), and perirenal (r = 0.72) adipose tissue, but mesenteric adipose mass increased more as BCS increased for cows fed HE. The similar final BCS between HE and LE cows demonstrates that BCS may lack sensitivity to detect differences in visceral fat deposition that might increase risk for peripartal diseases and disorders.
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2,333,628 |
Comparison of intrathecal dexmedetomidine with buprenorphine as adjuvant to bupivacaine in spinal asnaesthesia.
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The supplementation of local anaesthetics with adjuvants to improve the efficacy of subarachnoid block has been recognised since long. The most preferred drug has been opioids, but newer drugs like dexmedetomidine has also been introduced and investigated as an effective adjuvant.</AbstractText>This study was conducted to evaluate and compare the characteristics of subarachnoid blockade, hemodynamic stability and adverse effects of intrathecal buprenorphine and intrathecal dexmedetomidine as an adjuvant to 0.5% hyperbaric bupivacaine for lower abdominal surgeries.</AbstractText>The present study included 60 patients aged between 18-60 years classified as American Society of Anesthesiologists (ASA) Physical Status (PS) I/II scheduled for elective lower abdominal surgeries. The patients were randomly allotted to two groups to receive intrathecal 3ml of 0.5% bupivacine with 60µg of buprenorphine (Group B; n=30) or 3ml of 0.5% bupivacaine with 5µg of dexmedetomidine (Group D; n=30). The onset time to peak sensory level, motor block, sedation, Haemodynamic variables, duration of motor block, analgesia and any adverse effects were noted.</AbstractText>There was no significant difference between groups regarding demographic characteristics and type of surgery. The motor, sensory blockade and time of rescue analgesia were significantly prolonged in Group D compared to Group B. The sedation level was higher in Group D compared to Group B. There was no significant difference in haemodynamic variables although Group B had lower Heart Rate (HR) than Group D.</AbstractText>Intrathecal dexmedetomidine when compared to intrathecal buprenorphine causes prolonged anaesthesia and analgesia with reduced need for sedation and rescue analgesics.</AbstractText>
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2,333,629 |
Systematic assessment of dexmedetomidine as an anesthetic agent: a meta-analysis of randomized controlled trials.
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Here we aimed to study the effectiveness of dexmedetomidine as an anesthetic adjunct in surgery.</AbstractText>A systematic evaluation was performed on published clinical trials. Major databases such as Medline database were employed to search and identify relevant studies and then Rev.Man 5 was used for meta-analysis as well as forest plots. Mean difference (MD) was chosen as the effect size for measurement data, while odds ratio (OR) was calculated for enumeration data.</AbstractText>A total of 18 studies met the inclusion criteria. The postoperative heart rate and mean arterial pressure for the dexmedetomidine group were significantly lower than the control group (combined MDs were -14.12 and -9.96). The incidence rates of postoperative nausea and vomiting, chills, and shivering of the dexmedetomidine group were lower than the control group (pooled ORs were 0.41, 0.21 and 0.14, respectively). However, the occurrence rates of bradycardia and hypotension in the dexmedetomidine group were higher than the control group (pooled ORs were 5.14 and 3.00).</AbstractText>Dexmedetomidine can stabilize blood pressure and heart rate, and prevent postoperative adverse reactions. However, patients with original hypovolemia or heart block should be cautious. Besides, the quality of such studies should be improved in methodology to evaluate their efficacy and safety comprehensively.</AbstractText>
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2,333,630 |
Role of ion channels and subcellular Ca2+ signaling in arachidonic acid-induced dilation of pressurized retinal arterioles.
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To investigate the mechanisms responsible for the dilatation of rat retinal arterioles in response to arachidonic acid (AA).</AbstractText>Changes in the diameter of isolated, pressurized rat retinal arterioles were measured in the presence of AA alone and following pre-incubation with pharmacologic agents inhibiting Ca(2+) sparks and oscillations and K(+) channels. Subcellular Ca(2+) signals were recorded in arteriolar myocytes using Fluo-4-based confocal imaging. The effects of AA on membrane currents of retinal arteriolar myocytes were studied using whole-cell perforated patch clamp recording.</AbstractText>Arachidonic acid dilated pressurized retinal arterioles under conditions of myogenic tone. Eicosatetraynoic acid (ETYA) exerted a similar effect, but unlike AA, its effects were rapidly reversible. Arachidonic acid-induced dilation was associated with an inhibition of subcellular Ca(2+) signals. Interventions known to block Ca(2+) sparks and oscillations in retinal arterioles caused dilatation and inhibited AA-induced vasodilator responses. Arachidonic acid accelerated the rate of inactivation of the A-type Kv current and the voltage dependence of inactivation was shifted to more negative membrane potentials. It also enhanced voltage-activated and spontaneous large-conductance calcium-activated K(+) (BK) currents, but only at positive membrane potentials. Pharmacologic inhibition of A-type Kv and BK currents failed to block AA-induced vasodilator responses. Arachidonic acid suppressed L-type Ca(2+) currents.</AbstractText>These results suggest that AA induces retinal arteriolar vasodilation by inhibiting subcellular Ca(2+)-signaling activity in retinal arteriolar myocytes, most likely through a mechanism involving the inhibition of L-type Ca(2+)-channel activity. Arachidonic acid actions on K(+) currents are inconsistent with a model in which K(+) channels contribute to the vasodilator effects of AA.</AbstractText>
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2,333,631 |
Inadvertent temporary pacemaker lead placement in aortic sinus.
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Inadvertent placement of pacing leads into abnormal locations is potentially very dangerous. However, in emergency situations and without fluoroscopic guidance, these complications do occur. We report a case of an elderly male who underwent temporary pacemaker lead implantation without fluoroscopic guidance for cardiac arrest, but later the pacemaker lead was found to be in the non-coronary aortic sinus, but still capturing the myocardium. Interestingly, the post-pacing electrocardiography was mimicking atrial pacing.
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2,333,632 |
Remission of congenital complete heart block without anti-Ro/La antibodies: A case report.
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Anti-Ro/La negative congenital heart block (CHB) is uncommon. We report one such case of CHB, with no associated structural heart disease or maternal autoantibodies. The heart block reverted to sinus rhythm spontaneously at two weeks of age, and the patient remains in sinus rhythm at a one year followup. Whether patients with antibody negative complete heart block have a different clinical course is conjectural.
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2,333,633 |
The molecular biology and pathophysiology of vascular calcification.
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Vascular calcification (VC), commonly encountered in renal failure, diabetes, and aging, is associated with a large increase in the risk for cardiovascular events and mortality. Calcification of the arterial media and of heart valves clearly plays a mediating role in this regard, whereas it is less clear how calcification of plaque influences atherogenesis and risk for plaque rupture. Vascular calcification is an active process in which vascular smooth muscle cells (VSMCs) adopt an osteoblastic phenotype and deposit hydroxyapatite crystals; apoptosis of VSMCs also promotes this deposition. Drivers of this phenotypic transition, which include elevated serum phosphate, advanced glycation end-products, bone morphogenetic proteins, inflammatory cytokines, and leptin, invariably induce oxidative stress in VSMCs, which appears to be a necessary and sufficient condition for induction of the runt-related transcription factor 2 gene (RUNX2) and the shift to osteoblastic behavior. Magnesium antagonizes the impact of phosphate on VSMC osteoblastic transition, both by a direct effect within VSMCs and by suppressing absorption of dietary phosphate. Antioxidants that suppress reduced nicotinamide adenine dinucleotide phosphate oxidase activity may have the potential to block the osteoblastic transition of VSMCs. Minimizing the absorption of dietary phosphate may also be helpful in this regard, particularly in renal failure, and it can be achieved with plant-based dietary choices, avoidance of phosphate additives, and administration of pharmaceutical phosphate binders, supplemental magnesium, and niacin. Good vitamin K status opposes VC by optimizing the γ-carboxylation of matrix Gla protein, a physiological antagonist of VC. Adequate but not excessive vitamin D status also appears to discourage VC. Etidronate, a structural analogue of pyrophosphate, has shown potential for blocking VC.
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2,333,634 |
A prospective randomized observer-blinded study to assess postoperative analgesia provided by an ultrasound-guided bilateral thoracic paravertebral block for children undergoing the Nuss procedure.
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This prospective, randomized, single-blinded study evaluates the effectiveness of the ultrasound-guided bilateral thoracic paravertebral (BTPV) block for providing postoperative pain control in children undergoing the Nuss procedure.</AbstractText>Thirty American Society of Anesthesiologists I-II children with pectus excavatum, scheduled for the Nuss procedure, were enrolled at West China Hospital of Sichuan University. The patients were randomly allocated into the BTPV block group or the control group. In the BTPV group, 0.25% ropivacaine 0.5 mL/kg with 1:200,000 epinephrine was injected under ultrasound guidance on each side at the level of the fifth thoracic vertebra. Postoperative pain was evaluated in both groups for the first 48 hours. Total opioid administered and cumulative attempts on the patient/parent-controlled intravenous analgesia (PCA) pump were recorded. Postoperative negative behavioral changes in the children were evaluated on postoperative days 1, 7, and 30, respectively, using the posthospital behavior questionnaire.</AbstractText>The pain scores were significantly reduced in the postanesthesia care unit and for the first 48 hours postoperatively in the BTPV group compared to the control group (P < 0.01). The sufentanil use in the postanesthesia care unit was significantly greater in the control group [mean (SD), 0.2 (0) mcg/kg] compared to the BTPV group [mean (SD), 0.05 (0.06) mcg/kg] (P < 0.01). The postoperative sufentanil use was significantly higher in the control group during the first 24 hours (P < 0.01). Numbers of attempts on the PCA pump were significantly greater in the control group (P < 0.01). The posthospital behavior questionnaire score was lower in the BTPV group on day 1, day 7, and 1 month, respectively (P < 0.01).</AbstractText>Ultrasound-guided BTPV block provides improved postoperative analgesia for children undergoing the Nuss procedure as compared with intravenous PCA and decreases the incidence of postoperative behavioral disturbance.</AbstractText>
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2,333,635 |
Effects of dual-mode non-invasive brain stimulation on motor function.
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The purpose of this study was to investigate the effects of dual-mode non-invasive brain stimulation (NBS) on motor function and cortical excitability using both repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) over the bilateral primary motor cortices (M1s) of healthy individuals. Fifteen healthy right-handed volunteers (8 women; mean age 23.2 years) participated in this sham-controlled random-ordered crossover study. All of the participants received four randomly arranged dual-mode stimulations with a 24-h washout period: condition 1, preconditioning with cathodal tDCS over the left M1 followed by 10 Hz rTMS over the right M1; condition 2, preconditioning Lt. anodal tDCS followed by Rt. 10 Hz rTMS; condition 3, Lt. sham tDCS followed by Rt. 10 Hz rTMS; and condition 4, Lt. sham tDCS followed by Rt. sham rTMS. Corticomotor excitability and motor function were assessed in the left hand before and after stimulation. The motor evoked potential (MEP) amplitudes significantly increased after dual-mode stimulation in conditions 1 and 3, and significantly decreased in condition 2. The MEP latency became significantly shorter in condition 1. The motor function tests revealed a significant improvement in the Purdue pegboard test in condition 1, and in the box and block tests in conditions 1 and 3. The preconditioning tDCS over the contralateral M1 modulated the effects of subsequent rTMS on cortical excitability and motor function.
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2,333,636 |
Skin sympathetic nerve activity in humans during exposure to emotionally-charged images: sex differences.
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While it is known that anxiety or emotional arousal affects skin sympathetic nerve activity (SSNA), the galvanic skin response (GSR) is the most widely used parameter to infer increases in SSNA during stress or emotional studies. We recently showed that SSNA provides a more sensitive measure of emotional state than effector-organ responses. The aim of the present study was to assess whether there are gender differences in the responses of SSNA and other physiological parameters such as blood pressure, heart rate, skin blood flow and sweat release, while subjects viewed neutral or emotionally-charged images from the International Affective Picture System (IAPS). Changes in SSNA were assessed using microneurography in 20 subjects (10 male and 10 female). Blocks of positively-charged (erotica) or negatively-charge images (mutilation) were presented in a quasi-random fashion, following a block of neutral images, with each block containing 15 images and lasting 2 min. Images of both erotica and mutilation caused significant increases in SSNA, with increases being greater for males viewing erotica and greater for females viewing mutilation. The increases in SSNA were often coupled with sweat release and cutaneous vasoconstriction; however, these markers were not significantly different than those produced by viewing neutral images and were not always consistent with the SSNA increases. We conclude that SSNA increases with both positively-charged and negatively-charged emotional images, yet sex differences are present.
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2,333,637 |
A large conditioned pain modulation response is not related to a large blood pressure response: a study in healthy men.
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Endogenous pain modulation has been studied with the conditioned pain modulation (CPM) paradigm with large differences in the magnitude of the CPM effect. We hypothesized that differences in CPM effects might be associated with differences in blood pressure responses to the conditioning stimulus when comparing the CPM effects using two different conditioning stimuli.</AbstractText>A single-blind repeated-measures design with block-randomization was applied on 25 healthy male subjects. The test stimulus (TS; tonic heat pain for 120 s) was first presented alone, thereafter in parallel with a conditioning stimulus (CS). Conditioning stimuli were either a cold pressor test (CPT) or equally painful ischaemic muscle pain (ISC), both lasting 120 s. Finger blood pressure and heart rate were recorded continuously. Data were analysed in a linear mixed model framework with CS type (CPT or ISC) and conditioning (TS or TS + CS) as independent factors.</AbstractText>An inhibitory CPM effect was found for both types of conditioning (p < 0.001). The CPM effect was larger during CPT conditioning compared with ISC conditioning (p = 0.001). No association with the concomitant cardiovascular response (blood pressure and heart rate) was found (p > 0.34).</AbstractText>Cold pressor pain CS induces larger CPM effects than ischaemic pain CS. The larger CPM effect is, however, not associated with a larger blood pressure response. Other factors related to the CS should be investigated to understand why different CS modalities give different CPM effects.</AbstractText>© 2014 European Pain Federation - EFIC®</CopyrightInformation>
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2,333,638 |
The heart-rate-reducing agent, ivabradine, reduces mechanical allodynia in a rodent model of neuropathic pain.
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Peripheral nerve injury increases the excitability of primary sensory neurons. This triggers the onset of neuropathic pain and maintains its persistence. Because changes in hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels are implicated in this process, we examined the action of the heart-rate-reducing agent, ivabradine, a clinically approved HCN blocker, in the rat chronic constriction injury (CCI) model of neuropathic pain.</AbstractText>The effects of ivabradine on mechanical allodynia were assessed using von Frey filaments, and the effects on cardiovascular parameters were monitored by telemetry. Ivabradine block of HCN channels in dorsal root ganglion neurons was confirmed by whole-cell recording.</AbstractText>In rats subject to CCI, ivabradine (6 mg/kg by gavage twice a day) significantly reduced mechanical allodynia. Cumulative effects were seen with twice daily oral administration over a 4-day period. Allodynia returned 4 days after the final drug dose. Mean arterial pressure was maintained and only a 15% pharmacological reduction in heart rate was observed. There was no cumulative effect of ivabradine on cardiovascular parameters.</AbstractText>Because ivabradine is effective at an oral dose that produces only moderate pharmacological heart rate reduction, and this is known to be well tolerated in a clinical context, these results underline its possible use in neuropathic pain management.</AbstractText>© 2014 European Pain Federation - EFIC®</CopyrightInformation>
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2,333,639 |
Ring block with levobupivacaine 0.25% and paracetamol vs. paracetamol alone in children submitted to three different surgical techniques of circumcision: A prospective randomized study.
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circumcision in children is a painful procedure. We aim compare the intraoperative and postoperative efficacy of three different surgical procedures of the ring block using levobupivacaine 0.25% combined with rectal paracetamol as opposed to rectal paracetamol alone.</AbstractText>the study included 106 boys scheduled to undergo circumcision. The patients were randomly assigned within two groups to receive either ring block with levobupivacaine 0.25% and rectal paracetamol 30 mg/kg, or rectal paracetamol 30 mg/kg alone. The following surgical procedures were performed: sutureless proctoplasty, preputial plasty, and conventional circumcision. The efficacy of intraoperative analgesia was estimated on the basis of increases in heart rate and mean arterial pressure. Postoperatively, children were assessed for pain, pain-free (PF) period, and the total doses of analgesics administered during hospitalization, on the day after discharge, and on the first and second postoperative days.</AbstractText>all children remained stable during anesthesia. Postoperatively, the mean pain score did not show statistical differences between the groups. Children who received combined analgesia had a longer PF period (P < 0.001). However, the total doses of paracetamol administered during the observational period showed no differences. Children undergoing sutureless prepuceplasty received lower doses of paracetamol postoperatively (P < 0.001).</AbstractText>subcutaneous ring block either with levobupivacaine 0.25% plus rectal paracetamol or rectal paracetamol alone provides adequate intraoperative and postoperative analgesia in circumcised children. However, combined analgesia allows a longer PF period. The need for less analgesic administration in children undergoing sutureless prepuceplasty could mean that the circumcision techniques might be a mitigating factor in terms of pain.</AbstractText>
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2,333,640 |
Predictive value of high-sensitivity troponin-I for future adverse cardiovascular outcome in stable patients with type 2 diabetes mellitus.
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High-sensitivity cardiac troponin I(hs-TnI) and T levels(hs-TnT) are sensitive biomarkers of cardiomyocyte turnover or necrosis. Prior studies of the predictive role of hs-TnT in type 2 diabetes mellitus(T2DM) patients have yielded conflicting results. This study aimed to determine whether hs-TnI, which is detectable in a higher proportion of normal subjects than hsTnT, is associated with a major adverse cardiovascular event(MACE) in T2DM patients.</AbstractText>We compared hs-TnI level in stored serum samples from 276 consecutive patients (mean age 65 ± 10 years; 57% male) with T2DM with that of 115 age-and sex-matched controls. All T2DM patients were prospectively followed up for at least 4 years for incidence of MACE including heart failure(HF), myocardial infarction(MI) and cardiovascular mortality. At baseline, 274(99%) patients with T2DM had detectable hs-TnI, and 57(21%) had elevated hs-TnI (male: 8.5 ng/L, female: 7.6 ng/L, above the 99th percentile in healthy controls). A total of 43 MACE occurred: HF(n = 18), MI(n = 11) and cardiovascular mortality(n = 14). Kaplan-Meier analysis showed that an elevated hs-TnI was associated with MACE, HF, MI and cardiovascular mortality. Although multivariate analysis revealed that an elevated hs-TnI independently predicted MACE, it had limited sensitivity(62.7%) and positive predictive value(38.5%). Contrary to this, a normal hs-TnI level had an excellent negative predictive value(92.2%) for future MACE in patients with T2DM.</AbstractText>The present study demonstrates that elevated hs-TnI in patients with T2DM is associated with increased MACE, HF, MI and cardiovascular mortality. Importantly, a normal hs-TnI level has an excellent negative predictive value for future adverse cardiovascular events during long-term follow-up.</AbstractText>
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2,333,641 |
Altered vascular smooth muscle function in the ApoE knockout mouse during the progression of atherosclerosis.
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Relaxation of vascular smooth muscle (VSM) requires re-uptake of cytosolic Ca(2+) into the sarcoplasmic reticulum (SR) via the Sarco/Endoplasmic Reticulum Ca(2+) ATPase (SERCA), or extrusion via the Plasma Membrane Ca(2+) ATPase (PMCA) or sodium Ca(2+) exchanger (NCX). Peroxynitrite, a reactive species formed in vascular inflammatory diseases, upregulates SERCA activity to induce relaxation but, chronically, can contribute to atherogenesis and altered vascular function by escalating endoplasmic reticulum stress. Our objectives were to determine if peroxynitrite-induced relaxation and Ca(2+) handling processes within vascular smooth muscle cells were altered as atherosclerosis develops.</AbstractText>Aortae from control and ApoE(-/-) mice were studied histologically, functionally and for protein expression levels of SERCA and PMCA. Ca(2+) responses were assessed in dissociated aortic smooth muscle cells in the presence and absence of extracellular Ca(2+).</AbstractText>Relaxation to peroxynitrite was concentration-dependent and endothelium-independent. The abilities of the SERCA blocker thapsigargin and the PMCA inhibitor carboxyeosin to block this relaxation were altered during fat feeding and plaque progression. SERCA levels were progressively reduced, while PMCA expression was upregulated. In ApoE(-/-) VSM cells, increases in cytosolic Ca(2+) [Ca(2+)]c in response to SERCA blockade were reduced, while SERCA-independent Ca(2+) clearance was faster compared to control.</AbstractText>As atherosclerosis develops in the ApoE(-/-) mouse, expression and function of Ca(2+) handling proteins are altered. Up-regulation of Ca(2+) removal via PMCA may offer a potential compensatory mechanism to help normalise the dysfunctional relaxation observed during disease progression.</AbstractText>Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.</CopyrightInformation>
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2,333,642 |
End-of-life care in general practice: A cross-sectional, retrospective survey of 'cancer', 'organ failure' and 'old-age/dementia' patients.
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End-of-life care is often provided in primary care settings.</AbstractText>To describe and compare general-practitioner end-of-life care for Dutch patients who died from 'cancer', 'organ failure' and 'old-age or dementia'.</AbstractText>A cross-sectional, retrospective survey was conducted within a sentinel network of general practitioners. General practitioners recorded the end-of-life care of all patients who died (1 January 2009 to 31 December 2011). Differences in care between patient groups were analysed using multivariate logistic regressions performed with generalised linear mixed models.</AbstractText><AbstractText Label="SETTING/PARTICIPANTS" NlmCategory="METHODS">Up to 63 general practitioners, covering 0.8% of the population, recorded the care of 1491 patients.</AbstractText>General practitioners personally provided palliative care for 75% of cancer, 38% of organ failure and 64% of old-age/dementia patients (adjusted odds ratio (confidence interval): cancer (reference category); organ failure: 0.28 (0.17, 0.47); old-age/dementia: 0.31 (0.15, 0.63)). In the week before death, 89% of cancer, 77% of organ failure and 86% of old-age/dementia patients received palliative treatments: (adjusted odds ratio (confidence interval): cancer (reference category); old-age/dementia: 0.54 (0.29, 1.00); organ failure: 0.38 (0.16, 0.92)). Options for palliative care were discussed with 81% of cancer, 44% of organ failure and 39% of old-age/dementia patients (adjusted odds ratio (confidence interval): cancer (reference category); old-age/dementia: 0.34 (0.21, 0.57); organ failure: 0.17 (0.08, 0.36)).</AbstractText>The results highlight the need to integrate palliative care with optimal disease management in primary practice and to initiate advance care planning early in the chronic disease trajectory to enable all patients to live as well as possible with progressive illness and die with dignity and comfort.</AbstractText>© The Author(s) 2014.</CopyrightInformation>
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2,333,643 |
Patient selection in outpatient and short-stay total knee arthroplasty.
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The purpose of the current study is to identify patients who are at high risk for rehospitalization, revision, complications, and mortality after outpatient and short-stay total knee arthroplasty (TKA). The Medicare 5% limited data set sample was used to identify patients with a TKA procedure who were treated in an outpatient setting or who were discharged within 1 or 2 days in the hospital setting. Rehospitalization risk increased with higher Charlson score (i.e., poorer health status), older patients, inpatients (vs. outpatients), patients not receiving a femoral nerve block, earlier (vs. recent) year of surgery, and those with a recent history of heart failure. The findings of this study suggest that existing comorbidities, particularly heart failure, have the greatest effect on event risk after outpatient and short-stay TKA. The information obtained from this study should assist with patient selection for TKA performed on an outpatient basis.
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2,333,644 |
Ropivacaine plasma levels following local infiltration analgesia for primary total hip arthroplasty.
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We measured total and free plasma concentrations of ropivacaine following high-volume, high-dose local infiltration analgesia in 19 patients aged 65 years or over undergoing unilateral total hip arthroplasty. The patients received 180 ml ropivacaine 0.2% (360 mg), which was injected into the deep and peri-capsular tissues, the gluteal muscles and fascia lata, and the subcutaneous tissues and skin. Patients were monitored for clinical symptoms and signs of systemic local anaesthetic toxicity. Total levels of plasma ropivacaine varied from 0.081 to 1.707 μg.ml(-1) (mean (SD) 0.953 (0.323) μg.ml(-1) ). Free levels of plasma ropivacaine varied from 0.000 to 0.053 μg.ml(-1) (mean (SD) 0.024 (0.011) μg.ml(-1) ). No samples reached the toxic threshold for venous ropivacaine concentration, although four patients exhibited mild symptoms consistent with local anaesthetic toxicity. One patient had episodes of complete heart block on ECG monitoring, but plasma ropivacaine levels were below toxic levels. We conclude that plasma levels for ropivacaine associated with toxicity in a volunteer population (total 2.2 μg.ml(-1) , free 0.15 μg.ml(-1) ) are not reached during local infiltration analgesia for hip arthroplasty in elderly patients.
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2,333,645 |
Evaluation of cyclodextrin (sugammadex) for reversal of intense neuromuscular block of rocuronium and vecuronium, experimental and clinical studies.
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This study evaluated and explored time course, efficacy, relation, safety, changes in heart rate, and blood pressure after a bolus dose of sugammadex or neostigmine for reversal of a prolonged rocuronium and vecuronium induced neuromuscular block. A total of 60 patients of both sexes, 'ASA' grade I, II and all were scheduled for elective surgery of 30-45 minutes duration. Informed oral consent was obtained from all patients to participate in this study. The results showed statistically significant progressive decrease of heart rate and blood pressure at 2, 5 and 10 minutes when compared to their basal values before anesthesia, then it starts to gain its normal value at 5 and 10 minutes, regardless the dose of sugammadex (effect of anesthesia). Also, heart rate and blood pressure showed statistically non-significant variance between groups of sugammadex when compared at any time of the study with the neostigmine groups (i.e. no effect of the dose on heart rate).
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2,333,646 |
Cardiovascular risk with and without antihypertensive drug treatment in the Japanese general population: participant-level meta-analysis.
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To evaluate the cardiovascular mortality risk in association with blood pressure level among people with and without antihypertensive treatment, we performed the participant-level meta-analysis that included 39,705 Japanese from 6 cohorts (58.4% women; mean age, 60.1 years; 20.4% treated). Multivariable-adjusted Cox models were used to analyze the risk of cardiovascular mortality and its subtypes among 6 blood pressure levels according to recent guidelines, optimal to Grade 3 hypertension, and the usage of antihypertensive medication at baseline. During median 10.0 years of follow-up, there were 2032 cardiovascular deaths (5.1 per 1000 person-years), of which 410 deaths were coronary heart disease, 371 were heart failure, and 903 deaths were stroke. Treated participants had significantly higher risk for cardiovascular mortality (hazard ratios, 1.50; 95% confidence intervals, 1.36-1.66), coronary heart disease (hazard ratios, 1.53; confidence intervals, 1.23-1.90), heart failure (hazard ratios, 1.39; confidence intervals, 1.09-1.76), and stroke (hazard ratios, 1.48; confidence intervals, 1.28-1.72) compared with untreated people. Among untreated participants, the risks increased linearly with an increment of blood pressure category (P≤0.011). The risk increments per blood pressure category were higher in young participants (<60 years; 22% to 79%) than those in old people (≥60 years; 7% to 15%) with significant interaction for total cardiovascular, heart failure, and stroke mortality (P≤0.026). Among treated participants, the significant linear association was also observed for cardiovascular mortality (P=0.0003), whereas no stepwise increase in stroke death was observed (P=0.19). The risks of cardiovascular mortality were ≈1.5-fold high in participants under antihypertensive medication. More attention should be paid to the residual cardiovascular risks in treated patients.
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2,333,647 |
Generation of differentially modified microtubules using in vitro enzymatic approaches.
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Tubulin, the building block of microtubules, is subject to chemically diverse and evolutionarily conserved post-translational modifications that mark microtubules for specific functions in the cell. Here we describe in vitro methods for generating homogenous acetylated, glutamylated, or tyrosinated tubulin and microtubules using recombinantly expressed and purified modification enzymes. The generation of differentially modified microtubules now enables a mechanistic dissection of the effects of tubulin post-translational modifications on the dynamics and mechanical properties of microtubules as well as the behavior of motors and microtubule-associated proteins.
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2,333,648 |
How to do random allocation (randomization).
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To explain the concept and procedure of random allocation as used in a randomized controlled study.</AbstractText>We explain the general concept of random allocation and demonstrate how to perform the procedure easily and how to report it in a paper.</AbstractText>
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2,333,649 |
Nuclear factor-κB as a link between endoplasmic reticulum stress and inflammation during cardiomyocyte hypoxia/reoxygenation.
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Endoplasmic reticulum stress (ERS) can initiate inflammation, and the coupling of these responses is thought to be fundamental to the pathogenesis of cardiovascular disease. However, the mechanism linking ERS and inflammation in myocardial ischemia/reperfusion needs further investigation. Cultured cardiomyocytes were pretreated with SP600125 or salubrinal, followed by tunicamycin to clarify the involvement of the IRE1α and PERK pathways in ERS inflammation. The cardiomyocytes were given hypoxia/reoxygenation (H/R), and the effects of the NF-κB inhibitor, SN50, were followed. GRP78 protein levels were similar in the tunicamycin (Tm), salubrinal, and SP600125 groups, but were lower in cells treated with SN50. SN50 might effectively block the H/R-induced link between ERS and inflammation in cardiomyocytes by decreasing GRP78. This knowledge will aid in the development of therapies for myocardial ischemia/reperfusion injury.
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2,333,650 |
Effects of sodium-glucose co-transporter 2 inhibitors on blood pressure: a systematic review and meta-analysis.
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Sodium-glucose co-transporter 2 (SGLT2) inhibitors represent a new class of antihyperglycemic agents that block renal sodium and glucose reabsorption and may reduce blood pressure (BP). We assessed the BP lowering ability of these agents using meta-analytic techniques. PubMed, SCOPUS, and Cochrane Central were searched through October 2013. We included fully published randomized controlled trials (RCTs) that evaluated SGLT2 inhibitors in patients with type-2 diabetes mellitus and reported change in systolic and/or diastolic BP. Subgroup analyses were performed for placebo-controlled trials and those with active controls. We also conducted meta-regression to assess for a dose-response effect, and whether baseline BP, changes in body weight, heart rate, and hematocrit were associated with the BP effects. Twenty-seven RCTs (n = 12,960 participants) were included. SGLT2 inhibitors significantly reduced both systolic BP (weighted mean difference, -4.0 mm Hg; 95% confidence interval, -4.4 to -3.5) and diastolic BP (weighted mean difference, -1.6 mm Hg; 95% confidence interval, -1.9 to -1.3) from baseline. Only canagliflozin had a significant dose-response relationship with SBP (P = .008). Significant reductions in body weight and hematocrit were seen with the SGLTs. SGLTs had no significant effect on the incidence of orthostatic hypotension (P > .05). SGLT2 inhibitors significantly reduce BP in patients with type 2 diabetes.
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2,333,651 |
Speech pathologists' experiences with stroke clinical practice guidelines and the barriers and facilitators influencing their use: a national descriptive study.
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Communication and swallowing disorders are a common consequence of stroke. Clinical practice guidelines (CPGs) have been created to assist health professionals to put research evidence into clinical practice and can improve stroke care outcomes. However, CPGs are often not successfully implemented in clinical practice and research is needed to explore the factors that influence speech pathologists' implementation of stroke CPGs. This study aimed to describe speech pathologists' experiences and current use of guidelines, and to identify what factors influence speech pathologists' implementation of stroke CPGs.</AbstractText>Speech pathologists working in stroke rehabilitation who had used a stroke CPG were invited to complete a 39-item online survey. Content analysis and descriptive and inferential statistics were used to analyse the data.</AbstractText>320 participants from all states and territories of Australia were surveyed. Almost all speech pathologists had used a stroke CPG and had found the guideline "somewhat useful" or "very useful". Factors that speech pathologists perceived influenced CPG implementation included the: (a) guideline itself, (b) work environment, (c) aspects related to the speech pathologist themselves, (d) patient characteristics, and (e) types of implementation strategies provided.</AbstractText>There are many different factors that can influence speech pathologists' implementation of CPGs. The factors that influenced the implementation of CPGs can be understood in terms of knowledge creation and implementation frameworks. Speech pathologists should continue to adapt the stroke CPG to their local work environment and evaluate their use. To enhance guideline implementation, they may benefit from a combination of educational meetings and resources, outreach visits, support from senior colleagues, and audit and feedback strategies.</AbstractText>
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2,333,652 |
Peripheral nerve blocks versus general anesthesia for total knee replacement in elderly patients on the postoperative quality of recovery.
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Both peripheral nerve blocks with sedation or general anesthesia can be used for total knee replacement surgery.</AbstractText>We compared these anesthetic techniques on the postoperative quality of recovery early in elderly patients.</AbstractText>In our study, 213 patients who were ≥65 years old and undergoing total knee replacement were randomized to peripheral nerve blocks (PNBs) - lumbar plexus and sciatic - with propofol sedation, or general anesthesia with combined propofol and remifentanil. Blocks were performed using nerve stimulation and 0.35% ropivacaine. All patients received postoperative multimodal analgesia. Postoperative recovery was assessed at 15 minutes, 40 minutes, 1 day, 3 days, and 7 days after surgery, with the Postoperative Quality of Recovery Scale, in physiological, nociceptive, emotive, modified activities of daily living, modified cognitive, and overall patient perspective domains.</AbstractText>Intraoperative blood pressure and heart rate were more stable with PNBs (P<0.001). The recovery was better with PNBs in physiological (P<0.001), emotive (depression and anxiety) (P<0.001), nociceptive (pain and nausea) (P<0.001), modified cognitive (P<0.001), and all domains recovery (P<0.001), but not in activities of daily living (P=0.181). Intraoperative drugs and the postoperative sulfentanil requirement of the PNBs group were lower (all P<0.001). Differences were greatest early after surgery with equivalence by 1 week. Satisfaction was high and not different between groups (P=0.059).</AbstractText>Lumbar plexus and sciatic blocks with sedation facilitates faster postoperative recovery than general anesthesia, but not at 1 week after total knee replacement in patients who were 65 years or older. The trial has been registered at ClinicalTrials.gov. (NCT01871012).</AbstractText>
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2,333,653 |
Netrin-1 promotes adipose tissue macrophage retention and insulin resistance in obesity.
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During obesity, macrophage accumulation in adipose tissue propagates the chronic inflammation and insulin resistance associated with type 2 diabetes. The factors, however, that regulate the accrual of macrophages in adipose tissue are not well understood. Here we show that the neuroimmune guidance cue netrin-1 is highly expressed in obese but not lean adipose tissue of humans and mice, where it directs the retention of macrophages. Netrin-1, whose expression is induced in macrophages by the saturated fatty acid palmitate, acts via its receptor Unc5b to block their migration. In a mouse model of diet-induced obesity, we show that adipose tissue macrophages exhibit reduced migratory capacity, which can be restored by blocking netrin-1. Furthermore, hematopoietic deletion of Ntn1 facilitates adipose tissue macrophage emigration, reduces inflammation and improves insulin sensitivity. Collectively, these findings identify netrin-1 as a macrophage retention signal in adipose tissue during obesity that promotes chronic inflammation and insulin resistance.
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2,333,654 |
Dexmedetomidine prolongs the effect of bupivacaine in supraclavicular brachial plexus block.
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We compared the effects of adding dexmedetomidine to a 30 ml solution of 0.325% bupivacaine in supraclavicular brachial plexus block. Onset and duration of sensory and motor block along with the duration of analgesia were the primary endpoints.</AbstractText>Fifty patients posted for upper limb surgeries were enrolled for a prospective, randomized, double-blind, placebo-controlled trial. Patients were divided into two groups, the control group S and the study group SD. In group S (n = 25), 30 ml of 0.325% bupivacaine + 1 ml normal saline; and in group SD (n = 25), 30 ml of 0.325% bupivacaine + 1 ml (100 μg) dexmedetomidine were given for supraclavicular brachial plexus block using the peripheral nerve stimulator. Onset and duration of sensory and motor blocks were assessed along with the duration of analgesia, sedation, and adverse effects, if any. Hemodynamic parameters, like heart rate (HR), systolic arterial blood pressure (SBP), and diastolic arterial blood pressure (DBP) were also monitored.</AbstractText>Demographic data and surgical characteristics were comparable in both the groups. The onset times for sensory and motor blocks were significantly shorter in SD than S group (P < 0.001), while the duration of blocks was significantly longer (P < 0.001) in SD group. Except for the initial recordings (at 0, 5, 10, and 15 min), heart rate levels in group SD were significantly lower (P < 0.001). SBP and DBP levels in SD group at 15, 30, 45, 60, 90 and 120 min were significantly lower than in S group (P < 0.001). In fact, when the percentage changes in HR/SBP/DBP were compared from 0-5/0-10/0-15/0-30/0-45/0-60/0-90/0-120 min in SD with S group, they came out to be highly significant (P < 0.001) in group SD. The duration of analgesia (DOA) was significantly longer in SD group than S group (P < 0.001). Except that, bradycardia was observed in one patient in the group SD, no other adverse effects were observed in either of the groups.</AbstractText>Dexmedetomidine added as an adjuvant to bupivacaine for supraclavicular brachial plexus block significantly shortens the onset time and prolongs the duration of sensory and motor blocks and duration of analgesia. Patients in group SD were adequately sedated (modified Ramsay Sedation Score, RSS = 2/6 or 3/6) with no adverse effects except bradycardia in one patient of group SD.</AbstractText>
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2,333,655 |
Combined spinal-epidural anesthesia using a reduced-dose of spinal bupivacaine and epidural top up leads to faster motor recovery after lower extremity surgeries.
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The purpose of the present study is to investigate the anesthetic effect of reduced doses of spinal bupivacaine with epidural top ups in comparison with those of spinal bupivacaine and to determine the adequate doses of drugs used during lower extremity surgeries.</AbstractText>SIXTY ADULT PATIENTS WERE RANDOMIZED TO THREE DIFFERENT TECHNIQUE GROUPS: S group (10 mg of spinal bupivacaine), SE1 group (7.5 mg of spinal bupivacaine + epidural 1.5% lidocaine 10 ml) or SE2 group (5 mg of spinal bupivacaine + epidural 1.5% lidocaine 10 ml). The level of sensory block, modified Bromage motor scores (MBS), systolic blood pressure and heart rate were recorded for 30 min following anesthesia. Peak sensory block height and MBS, time for sensory regression to L1 and motor recovery to MBS 1, side effects and operator's satisfaction were noted.</AbstractText>The levels of peak sensory block were similar among the groups (P > 0.05). For the SE2 group, the regression to the L1 dermatome was faster (P = 0.004) and the maximum MBS was lower (P = 0.001) than that of the other two groups. Motor block recovery to MBS 1 was faster for the SE1 and SE2 groups than for the S group (P < 0.001). The operator's satisfaction scores of the SE2 group were lower than those of the other two groups (P = 0.019).</AbstractText>During combined spinal-epidural anesthesia, 7.5 mg of spinal bupivacaine and epidural 1.5% lidocaine 10 ml produced faster motor recovery than did 10 mg of spinal bupivacaine in patients undergoing lower extremity surgeries.</AbstractText>
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2,333,656 |
The effect of levobupivacaine and bupivacaine on QT, corrected QT (Qtc), and P wave dispersions in cesarean section.
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In our study we aimed to investigate the effect of bupivacaine and levobupivacaine on QT, corrected QT (QTc), and P wave dispersion durations during spinal anesthesia in cesarean section.</AbstractText>Sixty parturients scheduled for elective cesarean section in ASA I-II risk groups were included in the study. Baseline electrocardiographic (ECG) records of the patients were obtained in the operation room. Heart rate (HR), non-invasive blood pressure (NIBP), peripheral oxygen saturation (SpO2) and respiration rates (RR) were recorded. Venous cannulation was performed with 18G cannula and fluid preload made with 10 mL.kg(-1). Lactated Ringer solution. After fluid preload, second ECG recordings were taken and the patients were randomly separated into two groups. Group B (n = 30) received 10mg of bupivacaine and Group L (n = 30) received 10mg of levobupivacaine for spinal anesthesia. ECG recordings were repeated at 1, 5 and 10 minutes after spinal block. HR, NIBP, SpO2, RR and sensory block levels were also recorded at the same time intervals. At predetermined time intervals of spinal anesthesia, P wave dispersion (Pwd), QT dispersion (QTd), and QTc dispersion (QTcd) durations were measured from ECG records. QT and QTc durations are calculated with Bazzett formula.</AbstractText>There was no difference between two groups according to block levels, hemodynamic parameters, Pwd, QTd, QTc and QTcd durations.</AbstractText>Bupivacaine and levobupivacaine may be preferred in spinal anesthesia in pregnant patients who have extended Pwd and QTcd preoperatively.</AbstractText>Copyright © 2013 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.</CopyrightInformation>
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2,333,657 |
Compressed sensing MRI exploiting complementary dual decomposition.
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Compressed sensing (CS) MRI exploits the sparsity of an image in a transform domain to reconstruct the image from incoherently under-sampled k-space data. However, it has been shown that CS suffers particularly from loss of low-contrast image features with increasing reduction factors. To retain image details in such degraded experimental conditions, in this work we introduce a novel CS reconstruction method exploiting feature-based complementary dual decomposition with joint estimation of local scale mixture (LSM) model and images. Images are decomposed into dual block sparse components: total variation for piecewise smooth parts and wavelets for residuals. The LSM model parameters of residuals in the wavelet domain are estimated and then employed as a regional constraint in spatially adaptive reconstruction of high frequency subbands to restore image details missing in piecewise smooth parts. Alternating minimization of the dual image components subject to data consistency is performed to extract image details from residuals and add them back to their complementary counterparts while the LSM model parameters and images are jointly estimated in a sequential fashion. Simulations and experiments demonstrate the superior performance of the proposed method in preserving low-contrast image features even at high reduction factors.
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2,333,658 |
Pentamidine exerts in vitro and in vivo anti Trypanosoma cruzi activity and inhibits the polyamine transport in Trypanosoma cruzi.
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Pentamidine is an antiprotozoal and fungicide drug used in the treatment of leishmaniasis and African trypanosomiasis. Despite its extensive use as antiparasitic drug, little evidence exists about the effect of pentamidine in Trypanosoma cruzi, the etiological agent of Chagas' disease. Recent studies have shown that pentamidine blocks a polyamine transporter present in Leishmania major; consequently, its might also block these transporters in T. cruzi. Considering that T. cruzi lacks the ability to synthesize putrescine de novo, the inhibition of polyamine transport can bring a new therapeutic target against the parasite. In this work, we show that pentamidine decreases, not only the viability of T. cruzi trypomastigotes, but also the parasite burden of infected cells. In T. cruzi-infected mice pentamidine decreases the inflammation and parasite burden in hearts from infected mice. The treatment also decreases parasitemia, resulting in an increased survival rate. In addition, pentamidine strongly inhibits the putrescine and spermidine transport in T. cruzi epimastigotes and amastigotes. Thus, this study points to reevaluate the utility of pentamidine and introduce evidence of a potential new action mechanism. In the quest of new therapeutic strategies against Chagas disease, the extensive use of pentamidine in human has led to a well-known clinical profile, which could be an advantage over newly synthesized molecules that require more comprehensive trials prior to their clinical use.
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2,333,659 |
Effects of intrathecal bupivacaine and bupivacaine plus sufentanil in elderly patients undergoing transurethral resection.
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The present study compared the effect of bupivacaine and bupivacaine + sufentanil on hemodynamic parameters and characteristics of spinal anesthesia in elderly patients undergoing transurethral resection of the prostate (TURP) under spinal anesthesia.</AbstractText>The study included 40 American Society of Anesthesiologists (ASA) I-III patients scheduled to undergo TURP. Patients were blindly and randomly divided into two groups. Group B (n = 20) received 10 mg of intrathecal bupivacaine and group BS (n = 20) received 7.5 mg of bupivacaine + 5 μg of sufentanil. Sensory and motor block characteristics, hemodynamic changes, side effects, and time to first analgesic requirement were recorded. No differences in mean arterial pressure or heart rate, time for sensory blockade to reach the T10 level, and maximum sensory level were observed between the two groups. The time to first analgesic request was longer in group BS (P < 0.05). Motor block was significantly higher in group B (P < 0.05). In terms of side effects, no statistically significant differences occurred between the groups.</AbstractText>Similar hemodynamic stability and sufficient level of sensory blockade were provided by bupivacaine and bupivacaine + sufentanil used for spinal anesthesia in patients undergoing TUR. Due to the fact that less motor block was observed and the time to first analgesic request was longer, the combination of bupivacaine + sufentanil might be appropriate for patients undergoing TUR.</AbstractText>
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2,333,660 |
Early identification of palliative care needs by family physicians: A qualitative study of barriers and facilitators from the perspective of family physicians, community nurses, and patients.
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There is a growing recognition that a palliative care approach should be initiated early and not just in the terminal phase for patients with life-limiting diseases. Family physicians then play a central role in identifying and managing palliative care needs, but appear to not identify them accurately or in a timely manner.</AbstractText>To explore the barriers to and facilitators of the early identification by family physicians of the palliative care needs.</AbstractText><AbstractText Label="DESIGN, SETTING, AND PARTICIPANTS" NlmCategory="METHODS">Six focus groups (four with family physicians, n = 20, and two with community nurses, n = 12) and 18 interviews with patients with cancer, chronic obstructive pulmonary disease, heart failure, and dementia were held. Thematic analysis was used to derive themes that covered barriers and facilitators.</AbstractText>Key barriers and facilitators found relate to communication styles, the perceived role of a family physician, and continuity of care. Family physicians do not systematically assess non-acute care needs, and patients do not mention them or try to mask them from the family physician. This is embedded within a predominant perception among patients, nurses, and family physicians of the family physician as the person to appeal to in acute and standard follow-up situations rather than for palliative care needs. Family physicians also seemed to pay more often attention to palliative care needs of patients in a terminal phase.</AbstractText>The current practice of palliative care in Belgium is far from the presently considered ideal palliative care approaches. Facilitators such as proactive communication and communication tools could contribute to the development of guidelines for family physicians and policymakers in primary care.</AbstractText>
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2,333,661 |
Efficacy and safety of aldose reductase inhibitor for the treatment of diabetic cardiovascular autonomic neuropathy: systematic review and meta-analysis.
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Aldose reductase inhibitors (ARIs) can block the metabolism of the polyol pathway, and have been used to slow or reverse the progression of diabetic cardiovascular autonomic neuropathy (DCAN). The purpose of this study was to review the effectiveness and safety of ARIs in the treatment of DCAN as determined by five cardiac autonomic neuropathy function tests.</AbstractText>CENTRAL, MEDLINE, EMBASE, Scopus databases (inception to May 2012) were searched to identify randomized controlled trials (RCTs) and non-randomized controlled trials (non-RCTs) investigating ARIs for the treatment of DCAN with an English-language restriction. The data were analyzed using RevMan 5.0, and the heterogeneity between the trials was evaluated using the Cochrane's Q-test as well as the I² test. The type of model (random or fixed) used for analysis was based on heterogeneity. Weighted mean differences (WMD) with 95% confidence intervals (CI) were computed for the five cardiac automatic neuropathy function tests to evaluate the effects.</AbstractText>Ten articles met the prerequisites for this review. Analysis of the results showed that ARIs significantly improved function in at least three of the five automatic neuropathy tests, including the resting heart rate variation coefficients (WMD = 0.25, 95%CI 0.02 to 0.48, P = 0.040); the 30∶15 ratio (WMD = 0.06, 95%CI 0.01 to 0.10, P = 0.010) and the postural systolic blood pressure change (WMD = -5.94, 95%CI -7.31 to -4.57, P = 0.001). The expiration/inspiration ratio showed a marginally significant benefit (WMD = 0.05, 95%CI 0.00 to 0.09, P = 0.040). Glycaemic control was not significantly affected by ARIs. Adverse effects of ARIs except for Tolerestat were minimal.</AbstractText>Based on these results, we conclude that ARIs could ameliorate cardiac automatic neuropathy especially mild or asymptomatic DCAN but need further investigation.</AbstractText>
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2,333,662 |
The early sociability of toddlers: The origins of teaching.
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Toddlers' person-directed behaviors were recorded longitudinally in a naturalistic preschool setting. An observer (O, the author) recorded children's behaviors with an IC recorder during play sessions. Seventeen children, as a group, were observed once a week in 3 blocks of 7 weeks (21 total hours). Person-directed behaviors toward the observer increased with each block. Toddlers' teaching behaviors were classified precisely. This teaching classification should be the first event of the origins of teaching.
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2,333,663 |
Using caffeine and other adenosine receptor antagonists and agonists as therapeutic tools against neurodegenerative diseases: a review.
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Caffeine is the most consumed pychostimulant in the world, and it is known to affect basic and fundamental human processes such as sleep, arousal, cognition and learning and memory. It works as a nonselective blocker of adenosine receptors (A1, A2a, A2b and A3) and has been related to the regulation of heart rate, the contraction/relaxation of cardiac and smooth muscles, and the neural signaling in the central nervous system (CNS). Since the late 1990s, studies using adenosine receptor antagonists, such as Caffeine, to block the A1 and A2a adenosine receptor subtypes have shown to reduce the physical, cellular and molecular damages caused by a spinal cord injury (SCI) or a stroke (cerebral infarction) and by other neurodegenerative diseases such as Parkinson's and Alzheimer's diseases. Interestingly, other studies using adenosine receptor agonists have also shown to provide a neuroprotective effect on various models of neurodegenerative diseases through the reduction of excitatory neurotransmitter release, apoptosis and inflammatory responses, among others. The seemingly paradoxical use of both adenosine receptor agonists and antagonists as neuroprotective agents has been attributed to differences in dosage levels, drug delivery method, extracellular concentration of excitatory neurotransmitters and stage of disease progression. We discuss and compare recent findings using both antagonists and agonists of adenosine receptors in animal models and patients that have suffered spinal cord injuries, brain strokes, and Parkinson's and Alzheimer's diseases. Additionally, we propose alternative interpretations on the seemingly paradoxical use of these drugs as potential pharmacological tools to treat these various types of neurodegenerative diseases.
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2,333,664 |
Effect of positioning on patient outcomes after coronary angiography: a single-blind randomized controlled trial.
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Restoring patient homeostasis after coronary angiography, the gold standard diagnostic test for coronary heart disease is usually achieved by manual compression of the puncture site using a sandbag and prolonged bed rest. However, this process frequently results in patient complaints of back pain and discomfort.</AbstractText>The aim of study was to assess the effect of positioning on patient outcomes after coronary angiography.</AbstractText>This study used a single-blind randomized control trial approach. The sample consisted of 80 patients who had undergone a nonemergency coronary angiography via the femoral artery. Balanced block randomization was used to allocate participants into intervention and control groups. Routine care for the intervention group (n = 40) was adjusted to include the following: (1) intermittent changes to patient body and head position in bed during first 6 hours after catheterization, (2) reduction of sandbag compression time on the puncture site to 1 hour, and (3) regular examination for bleeding during the first 6 hours after catheterization. Intervention group participants were allowed to ambulate without restriction 6 hours after catheterization. Patients in the control group (n = 40) received routine care, consisting of (1) 6-24 hours of bed rest in the supine position with the affected leg fixed straight and immobilized and (2) sandbag compression on the puncture site for 6 hours. The main outcomes used in this study were level of back pain, discomfort, foot pain, bleeding, and hematoma.</AbstractText>Intervention group patients had significantly less back pain and foot pain and higher comfort than the control group at the second, third, and sixth hour after catheterization (p = .00). There was no significant difference between the two groups in terms of amount of bleeding and hematoma (p > .05).</AbstractText>Findings suggest that changes in patient position may be safer in the early period of postcatheterization bed rest than currently indicated in standard practice protocols. Furthermore, limiting sandbag compression to 1 hour has no measurable effect on the incidence and severity of vascular complications.</AbstractText>
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2,333,665 |
Median arcuate ligament syndrome confirmed with the use of intravascular ultrasound.
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Median arcuate ligament syndrome, a rarely reported condition, is characterized by postprandial abdominal pain, nausea, vomiting, and weight loss. Its cause is unclear. We present the case of a 45-year-old woman who had intermittent chronic positional abdominal pain without weight loss. Magnetic resonance angiograms and computed tomograms revealed stenosis of the celiac artery. Ostial compression was confirmed on catheter angiographic and intravascular ultrasonographic images. Intravascular ultrasound revealed far greater stenosis than did the initial imaging methods and confirmed a diagnosis of median arcuate ligament syndrome. In lieu of surgery, the patient underwent a celiac ganglion block procedure that substantially relieved her symptoms. To our knowledge, this is the first report of the use of intravascular ultrasound in the diagnosis of median arcuate ligament syndrome. We recommend using this imaging method preoperatively in other suspected cases of the syndrome, to better identify patients who might benefit from corrective surgery.
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2,333,666 |
CNS vasculitis and stroke in neonatal lupus erythematosus: a case report and review of literature.
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Neonatal lupus erythematosus refers to the clinical spectrum of cardiac, cutaneous and other systemic abnormalities in neonates born to mothers with autoantibodies against Ro/SSA and La/SSB antigens. Isolated central nervous system involvement is very rare and has been described as transient vasculopathy only. We describe a 2-months-old girl who presented with acute ischemic stroke secondary to central nervous system vasculitis without any cardiac, cutaneous or hematological manifestations. The mother was pauci-symptomatic with raised anti-Ro autoantibody titers; the baby was positive for autoantibodies against Ro-antigen. Angiography confirmed vasculitis in cerebral vasculature. Our case highlights that neonatal lupus erythematosus can present with isolated nervous system manifestations and the vascular damage can be permanent in the form of vasculitis. Early recognition will help pediatricians identify such possible permanent complications in newborns with neonatal lupus erythematosus. A review of previously reported central nervous system manifestations of neonatal lupus is also presented.
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2,333,667 |
[Effect of electric acupoint stimulation on shivering in cesarean section].
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To explore the efficacy of electric acupoint stimulation on shivering in cesarean section.</AbstractText>Eighty cases of parturients, under the America Society of Anesthesiologists (ASA) physical status II , were randomized into a transcutaneous electrical acupoint stimulation (TEAS) assisted anesthesia group (group A) and an anesthesia group (group B). Spinal-epidural anesthesia(CSEA) puncture was applied to both groups and 8 mg of 0. 75% bubivacaine was given by spinal injection, the block level was T4 T8. In group A, TEAS was applied before CSEA at paired acupoints-ipsilateral Hegu (LI 4)-Laogong (PC 8) and Sanyinjiao (SP 6)-Zusanli (ST 36) till ending the surgery. The 4 pair of bilateral acupoints were fixed with self-adhesive electrodes and connected with Han's acupoint and nerve stimulator (HANS, LH402H), the frequency was 2 Hz/ 15 Hz, the intensity was 10- 30 mA and the form was densedisperse wave within the patients' tolarance. The heart rate (HR), mean arterial pressure (MAP), oxyhemoglobin saturation (SPO) and shivering degree were recorded before anesthesia (To), 1 min after anesthesia puncture (Ti), 1 min after the delivery (Tz), during abdomen closure (T3) and at the end of surgery (T4).</AbstractText>The occurrence rate of shivering was 35. 0% (14/40) in group A, which was lower to 67. 5% (27/40, P<0. 05) in group B; the degree of shivering was lighter in group A than that in group B at T2, T3 and T4 (all P<0. 01). In group A, HR was faster at T1 and T2 compared to that at To (all P<0. 05), while at T3 and T4, the HR was the same with that before anesthesia (all P>0. 05). In group B, the HR was faster at T1, T2, T3 and T4 compared to that at T0 (P<0. 05, P<0. 01). In both groups, the MAP was lower at T1, T2 (P<0.05,P<0.01) and resumed to that before anesthesia at T3 and T4 (all P>0.05); there was no statistical significance of SPO2 in both groups (all P>0.05).</AbstractText>TEAS can reduce the occurrence rate of shivering and steady the heart rate in cesarean section.</AbstractText>
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2,333,668 |
Resolution of the three dimensional structure of components of the glomerular filtration barrier.
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The human glomerulus is the primary filtration unit of the kidney, and contains the Glomerular Filtration Barrier (GFB). The GFB had been thought to comprise 3 layers - the endothelium, the basement membrane and the podocyte foot processes. However, recent studies have suggested that at least two additional layers contribute to the function of the GFB, the endothelial glycocalyx on the vascular side, and the sub-podocyte space on the urinary side. To investigate the structure of these additional layers is difficult as it requires three-dimensional reconstruction of delicate sub-microscopic (<1 μm) cellular and extracellular elements.</AbstractText>Here we have combined three different advanced electron microscopic techniques that cover multiple orders of magnitude of volume sampled, with a novel staining methodology (Lanthanum Dysprosium Glycosaminoglycan adhesion, or LaDy GAGa), to determine the structural basis of these two additional layers. Serial Block Face Scanning Electron Microscopy (SBF-SEM) was used to generate a 3-D image stack with a volume of a 5.3 x 105 μm3 volume of a whole kidney glomerulus (13% of glomerular volume). Secondly, Focused Ion Beam milling Scanning Electron Microscopy (FIB-SEM) was used to image a filtration region (48 μm3 volume). Lastly Transmission Electron Tomography (Tom-TEM) was performed on a 0.3 μm3 volume to identify the fine structure of the glycocalyx.</AbstractText>Tom-TEM clearly showed 20 nm fibre spacing in the glycocalyx, within a limited field of view. FIB-SEM demonstrated, in a far greater field of view, how the glycocalyx structure related to fenestrations and the filtration slits, though without the resolution of TomTEM. SBF-SEM was able to determine the extent of the sub-podocyte space and glycocalyx coverage, without additional heavy metal staining. Neither SBF- nor FIB-SEM suffered the anisotropic shrinkage under the electron beam that is seen with Tom-TEM.</AbstractText>These images demonstrate that the three dimensional structure of the GFB can be imaged, and investigated from the whole glomerulus to the fine structure of the glycocalyx using three dimensional electron microscopy techniques. This should allow the identification of structural features regulating physiology, and their disruption in pathological states, aiding the understanding of kidney disease.</AbstractText>
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2,333,669 |
Comparison of Maternal and Neonatal Effects of Combined Spinal Epidural Anaesthesia in Either the Sitting or Lateral Position During Elective Cesarean Section.
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Our goal was to demonstrate which position would be hemodynamically and technically better by comparing the effects of combined spinal epidural (CSE) in the sitting or lateral decubitus position for elective cesarean deliveries on maternal and neonatal parameters and ephedrine requirement.</AbstractText>Sixty parturients were randomly assigned into two groups to perform CSE in the sitting (Group I, n=30) or right lateral decubitus position (Group II, n=30) using hyperbaric 10 mg bupivacaine and 20 μg fentanyl. Mean arterial pressure (MAP), heart rate (HR), and characteristics of sensory and motor block were recorded from intrathecal drug administration until the end of surgery. Ephedrine and 1(st) analgesic requirement, number of attempts to perform CSE, incidence of paresthesia during spinal needle insertion, and Apgar scores were recorded.</AbstractText>Ephedrine requirements and HR changes were similar in both groups. However, MAP values at 45 min in Group II were significantly less than in Group I. Maximum sensory block levels in Group II were significantly higher than in Group I. Despite similar motor block recovery times in both groups, regression times of sensory block and 1st analgesic requirement in Group II were significantly longer than in Group I. Incidence of paresthesia due to spinal needle (3.3% versus 20% in Groups I and II, respectively) and number of attempts to perform CSE (26.7% versus 60% in Groups I and II, respectively) were significantly higher in Group II. Apgar scores were similar in both groups.</AbstractText>Performing CSE in the sitting position would be safer and easier because higher and earlier onset of sensory block, and a greater number attempts at epidural insertion and paresthesia develop to spinal needle insertion in the right lateral position.</AbstractText>
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2,333,670 |
Draining the edema: a new role for aquaretics?
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Investigations into edema formation in nephrotic syndrome have mostly focused on the primary role of sodium. While there is controversy about whether sodium retention is an inherent aspect of nephrotic syndrome (overfill hypothesis) or a secondary consequence (underfill hypothesis), the critical role of sodium in driving fluid retention is generally accepted. Consequently, treatment of edema is based on enhancing renal sodium excretion, using saluretics to block tubular reabsorption of sodium. However, there is also evidence of renal water retention: urine in nephrotic patients is typically highly concentrated (unless urinary concentrating ability is impaired by loop diuretics), and vasopressin levels are commonly elevated. Consequently, aquaretics, i.e., drugs that inhibit renal water reabsorption, may constitute effective treatments for nephrotic edema. In fact, these drugs are already approved for the treatment of non-nephrotic edematous states, such as those encountered in congestive heart or liver failure. In this edition of Pediatric Nephrology, two case reports raise the possibility that aquaretics may also be helpful in the treatment of nephrotic edema. These case reports provide no solid evidence for such treatment, and there clearly are serious concerns about inducing critical hypovolemia with potentially catastrophically consequences, such as thrombosis and shock. Yet these concerns similarly apply to saluretics, which clinicians routinely use in the treatment of edema. In addition, the described powerful effect of aquaretics with respect to the resolution of edema, as well as our understanding of the underlying physiology, argue for a more systematic, yet careful assessment of these drugs in the treatment of nephrotic syndrome.
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2,333,671 |
Role of vacuolar ATPase and Skp1 in Sjögren's syndrome.
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Immune mechanisms alone cannot directly account for exocrine gland dysfunction and extraglandular features such as renal tubular acidosis, neuropathy, hearing loss and fatigue in Sjögren's syndrome (SS). Absence of Vacuolar ATPase (V-ATPase) has been reported in SS related renal tubular acidosis (RTA). We hypothesise how defect in V-ATPase could account for decreased neurotransmitter release leading onto exocrine dysfunction, neuroendocrine manifestations and hearing loss which are well described manifestations in SS. S-phase-kinase-associated protein-1 (Skp1) is a constituent of RAVE which is involved in V-ATPase assembly. It is also a component of SCF ligase which is crucial in NFκB signalling. SKP1 also interacts with TRIM 21/Ro 52 which is an autoantigen in SS. By virtue of these interactions, we postulate how a defective skp1 could fit into the existing pathogenesis of SS and also account for increased risk of lymphoma in SS as well as congenital heart block in fetus of mothers with SS.
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2,333,672 |
The effect of different doses of chloroprocaine on saddle anesthesia in perianal surgery.
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To investigate a saddle anesthesia with different doses of chloroprocaine in perianal surgery.</AbstractText>Total 60 Patients aged 18-75 years (Anesthesiologists grade I or II) scheduled to receive perianal surgery. Patients using saddle anesthesia were randomized to group A, group B and group C with the same concentration (0.5%) chloroprocaine with different doses 1.0 mL, 0.8 mL and 0.6 mL, respectively. Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) and the sensory and motor block were recorded to evaluate the anesthesia effect of chloroprocaine in each group.</AbstractText>The duration of sensory block of group C is shorter than those of group A and B. The maximum degree of motor block is observed (group C: 0 level, group A: III level; and group B: I level) after 15 minutes. Besides, there was a better anesthetic effect in group B than group A and group C, such as walking after saddle anesthesia. However, there is also no significant difference of blood pressure decreasing in these three groups.</AbstractText>It's worth to employ a saddle anesthesia with appropriate doses of chloroprocaine in clinical perianal surgery.</AbstractText>
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2,333,673 |
Assessing hERG pore models as templates for drug docking using published experimental constraints: the inactivated state in the context of drug block.
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Many structurally and therapeutically diverse drugs interact with the human heart K+ channel hERG by binding within the K+ permeation pathway of the open channel, leading to drug-induced 'long QT syndrome'. Drug binding to hERG is often stabilized by inactivation gating. In the absence of a crystal structure, hERG pore homology models have been used to characterize drug interactions. Here we assess potentially inactivated states of the bacterial K+ channel, KcsA, as templates for inactivated state hERG pore models in the context of drug binding using computational docking. Although Flexidock and GOLD docking produced low energy score poses in the models tested, each method selected a MthK K+ channel-based model over models based on the putative inactivated state KcsA structures for each of the 9 drugs tested. The variety of docking poses found indicates that an optimal arrangement for drug binding of aromatic side chains in the hERG pore can be achieved in several different configurations. This plasticity of the drug "binding site" is likely to be a feature of the hERG inactivated state. The results demonstrate that experimental data on specific drug interactions can be used as structural constraints to assess and refine hERG homology models.
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2,333,674 |
Peroral Endoscopic Myotomy (POEM) in a Patient with Complete Heart Block-a Case Report.
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Achalasia cardia is the commonest esophageal motility disorder. Recently, a new endoscopic procedure-peroral endoscopic myotomy (POEM)-has emerged for treating this chronic and debilitating condition. It has shown comparable success rates in prospective studies with conventional Heller's myotomy with lesser rates of postoperative reflux. Literature regarding this procedure from India is scarce due to its limited availability. This case report illustrates the use of POEM in a patient with a permanent cardiac pacemaker and demonstrates its safety and efficacy in such a situation.
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2,333,675 |
Ultrasound and neurophysiological correlation in common fibular nerve conduction block at fibular head.
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Ultrasound (US) and neurophysiological examination are useful tools in the evaluation of common fibular mononeuropathy. There is only a report comparing US and electrophysiological parameters in patients with common fibular nerve (CFN) conduction block at fibular head. We investigated the correlation between US and neurophysiologic findings in this condition.</AbstractText>We retrospectively reviewed patients with CFN assessed in our lab during last 2 years. Each patient underwent to clinical, neurophysiological and ultrasound evaluations. Cross sectional area (CSA) of CFN at fibular head was assessed.</AbstractText>Twenty-four patients were included. Motor nerve conduction study showed a reduction of distal compound muscle action potential (CMAP) amplitude in 10 patients (mean 1.3 mV). US showed an increased CSA in 10 patients. Statistical analysis revealed a strong correlation between the increased CSA and the CMAP reduction of CFN.</AbstractText>Our data suggest that usually US examination is normal in CFN conduction block at fibular head. However the association with axonal damage is frequently accompanied by an increase of CSA.</AbstractText>Ultrasound evaluation may represent a powerful diagnostic/prognostic tool in cases with CPN conduction block at fibular head because it usually shows normal pattern in pure conduction block and increase of CSA in associated axonal damage.</AbstractText>Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.</CopyrightInformation>
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2,333,676 |
Stroke in a case of neonatal lupus: an uncommon complication.
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Stroke is an extremely rare complication of congenital heart block in children. We report a 2-year-old girl with congenital complete heart block who presented with acute-onset right middle cerebral artery territory stroke. The congenital heart block was secondary to maternal lupus.
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2,333,677 |
Brainstem mechanisms controlling cardiovascular reflexes in channel catfish.
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Microinjections of kynurenic acid and kainic acid into the general visceral nucleus (nGV), homologous to the mammalian nucleus tractus solitarius of the medulla, in anesthestized, spontaneously breathing catfish were used to identify central areas and mechanisms controlling resting normoxic heart rate and blood pressure and the cardiovascular responses to hypoxia. Kynurenic acid, an antagonist of ionotropic glutamate receptors, significantly reduced resting normoxic heart rate but did not block the bradycardia associated with aquatic hypoxia. Kainic acid (an excitotoxic glutamatergic receptor agonist) also significantly reduced normoxic heart rate, but blocked the hypoxia-induced bradycardia. Neither kynurenic acid nor kainic acid microinjections affected blood pressure in normoxia or hypoxia. The results of this study indicate that glutamatergic receptors in the nGV are involved in the maintenance of resting heart rate and the destruction of these neurons with kainic acid abolishes the bradycardia associated with aquatic hypoxia.
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2,333,678 |
The comparison of clinically relevant doses of intrathecal ropivacaine and levobupivacaine with fentanyl for labor analgesia.
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Intrathecal labor analgesia using new local anesthetics such as ropivacaine or levobupivacaine becomes more popular by virtues of their safety and decreased motor weakness. However, the analgesic efficacy of the clinically effective intrathecal doses of these new local anesthetics combined with fentanyl has yet to be determined.</AbstractText>Sixty parturients who requested neuraxial analgesia in early active labor were randomly assigned to either ropivacaine (group R, n = 30) or levobupivacaine (group L, n = 30) group. Group R received 3 mg of intrathecal ropivacaine and the group L received 3 mg of intrathecal levobupivacaine mixed with 20 µg of fentanyl as part of a combined spinal-epidural (CSE) technique. The associated block parameters, such as pain scores, duration of analgesia, the highest levels of the sensory block and motor block scores 30 mins after the injection were compared between two groups.</AbstractText>Intrathecal ropivacaine offered shorter analgesia (87 ± 41 min vs. 122 ± 56 min, P < 0.05) with lower sensory height (T8.5 vs. T6, P < 0.05) and led to lower incidence of complete analgesia (73 vs. 97%, P < 0.05) compared with intrathecal levobupivacaine. Although motor weakness was comparable in both groups, significantly weak perineal squeezing was noticed in Group L (7 of 30 parturients vs. 16 of 30, P < 0.05).</AbstractText>Clinically relevant doses of intrathecal levobupivacaine in combination with fentanyl as part of a CSE technique provides more effective analgesia than equivalent doses of intrathecal ropivacaine in early labor, but is accompanied by slight motor weakness.</AbstractText>
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2,333,679 |
Systemic lupus erythematosus and pregnancy outcomes: an update and review of the literature.
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This review synthesizes new data from the studies published between 2011 and 2013, with particular focus on the different information gleaned by various study types.</AbstractText>Population-based cohorts have demonstrated that women with systemic lupus erythematosus (SLE) have fewer live births and more pregnancy complications, but can have successful live births after having a poor outcome. A retrospective study suggests that only 4 months, not the traditional 6 months of disease quiescent SLE prior to pregnancy improves outcomes. Prospective studies identified several novel predictors of poor pregnancy outcomes, including uterine Doppler and laboratory findings. A prospective study found great success in transitioning to azathioprine from mycophenolate mofetil prior to pregnancy in patients with quiet lupus nephritis. Two retrospective analyses suggest that hydroxychloroquine may prevent congenital heart block in pregnancies exposed to SSA/Ro antibodies. Finally, the initial pregnancy data for belimumab suggest a high degree of transplacental transfer, but thus far no definitive link between belimumab and congenital abnormalities.</AbstractText>Recent studies suggest both novel markers of poor pregnancy outcomes and new approaches to the management of lupus during pregnancy.</AbstractText>
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2,333,680 |
Cucurbit[7]uril assisted ultraviolet to visible fluorescence switch of a heart medicine.
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Host-guest interactions between cucurbit[7]uril (CB7) and a cardiotonic drug, milrinone, have been explored using steady state and pico-second time-resolved techniques. A novel fluorescence switch from ultraviolet (UV) to visible (cyan) is observed as a consequence of upward pKa shift of the drug inside the nano-cavity of cucurbit[7]uril.
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2,333,681 |
Combined PKC and MEK inhibition for treating metastatic uveal melanoma.
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Uveal melanoma (UM) is the most common primary intraocular malignancy and the second most common form of melanoma. UM has a strong tendency for metastatic disease, and no effective treatments have yet been identified. Activating oncogenic mutations are commonly found in GNAQ and GNA11 in UM, and inhibiting key downstream effectors of the GNAQ/11 signaling pathway represents a rational therapeutic approach for treating metastatic UM. Chen et al., doi:10.1038/onc.2013.418, now confirm activation of the MAPK and PKC pathways as a result of GNAQ and GNA11 activating mutations in melanocytes, and they demonstrate that MAPK activation occurs downstream of PKC activation. PKC inhibitors disrupt MAPK signaling and block proliferation of GNAQ/11 mutant UM cell lines and slow the in vivo growth of xenografted UM tumors without inducing their shrinkage. However, a combination of PKC and MEK inhibition led to sustained MAPK pathway inhibition and tumor regression in vivo. Hence, the authors concluded that MEK and PKC inhibition is synergistic, with superior efficacy to treatment of GNAQ/GNA11 mutant UMs with either drug alone.
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2,333,682 |
Up-regulation of miR-200b in biliary atresia patients accelerates proliferation and migration of hepatic stallate cells by activating PI3K/Akt signaling.
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An increasing body of evidence suggests that miRNAs are involved in fibrotic process of several organs including heart, lung and kidney. It has been observed recently that aberrant expression of miR-200s are associated with hepatic fibrosis. However, the role and underlying mechanism of miR-200s in hepatic fibrogenesis remains unknown. Here, we investigate the role of miR-200b in the activation of immortalized human hepatic stallate cells (HSCs), LX-2 cells. We firstly found that miR-200b significantly enhanced proliferation and migration of LX-2 cells. Secondly, our findings showed that miR-200b enhanced the phosphorylation of Akt, a downstream effector of phosphatidyl-inositol 3-Kinase (PI3K). FOG2, as the targets of fly miR-8 and human miR-200s, directly binds to p85α and inhibits the activation of the PI3K/Akt pathway. Here, we showed that FOG2 protein levels in LX-2 cells were suppressed significantly by miR-200b mimics. FOG2 knockdown by siRNAs activated the PI3K/Akt signaling, which increased cell growth and migration that mimicked the effect of miR-200b. Conversely, LY294002, a highly selective inhibitor of PI3K, could block phosphorylation of Akt and effect of miR-200b. In addition, we showed that miR-200b enhanced the expression of matrix metalloproteinase-2 (MMP-2), which may increase the migration of LX-2 cells. Finally, our results indicated that the expression of miR-200b was unregulated in the biliary atresia (BA) and associated with liver fibrotic progression. These data suggest a potential mechanism for Akt activation through FOG2 down-regulation by miR-200b that can lead to HSC growth and migration. In view of the putative pathogenic role of miR-200b in HSCs, miR-200b may constitute a potential marker for HSC activation and liver fibrosis progression.
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2,333,683 |
Thiol oxidation is crucial in the desensitization of the mitochondrial F1FO-ATPase to oligomycin and other macrolide antibiotics.
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The macrolide antibiotics oligomycin, venturicidin and bafilomycin, sharing the polyketide ring and differing in the deoxysugar moiety, are known to block the transmembrane ion channel of ion-pumping ATPases; oligomycins are selective inhibitors of mitochondrial ATP synthases.</AbstractText>The inhibition mechanism of macrolides was explored on swine heart mitochondrial F1FO-ATPase by kinetic analyses. The amphiphilic membrane toxicant tributyltin (TBT) and the thiol reducing agent dithioerythritol (DTE) were used to elucidate the nature of the macrolide-enzyme interaction.</AbstractText>When individually tested, the macrolide antibiotics acted as uncompetitive inhibitors of the ATPase activity. Binary mixtures of macrolide inhibitors I1 and I2 pointed out a non-exclusive mechanism, indicating that each macrolide binds to its binding site on the enzyme. When co-present, the two macrolides acted synergistically in the formed quaternary complex (ESI1I2), thus mutually strengthening the enzyme inhibition. The enzyme inhibition by macrolides displaying a shared mechanism was dose-dependently reduced by TBT≥1μM. The TBT-driven enzyme desensitization was reversed by DTE.</AbstractText>The macrolides tested share uncompetitive inhibition mechanism by binding to a specific site in a common macrolide-binding region of FO. The oxidation of highly conserved thiols in the ATP synthase c-ring of FO weakens the interaction between the enzyme and the macrolides. The native macrolide-inhibited enzyme conformation can be restored by reducing crucial thiols oxidized by TBT.</AbstractText>The findings, by elucidating the macrolide inhibitory mechanism on FO, indirectly cast light on the F1FO torque generation involving crucial amino acid residues and may address drug design and antimicrobial therapy.</AbstractText>Copyright © 2014 Elsevier B.V. All rights reserved.</CopyrightInformation>
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Rosuvastatin can block pro-inflammatory actions of transgenic human C-reactive protein without reducing its circulating levels.
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Statins have antiinflammatory effects and are known to decrease risk of cardiovascular events and to reduce serum levels of C-reactive protein (CRP), a widely studied biomarker and potential mediator of inflammation and heart disease. However, it is unclear whether statins can block pro-inflammatory effects of human CRP independent of their ability to reduce serum levels of human CRP. Here, we investigated whether rosuvastatin could block pro-inflammatory effects of human CRP without reducing circulating levels of human CRP.</AbstractText>We studied the antiinflammatory effects of rosuvastatin in spontaneously hypertensive rats (SHR) transgenically expressing human CRP (CRP-transgenic SHR) and in nontransgenic SHR lacking human CRP (nontransgenic SHR). The CRP-transgenic SHR is characterized by increased serum levels of human CRP and inflammation. In the CRP-transgenic strain, we found that rosuvastatin treatment decreased circulating levels of inflammatory response markers IL6 and TNFα without decreasing circulating levels of human CRP. In contrast, in the nontransgenic strain lacking human CRP, rosuvastatin treatment had little or no effect on IL6 and TNFα levels. Rosuvastatin also reduced cardiac inflammation and oxidative tissue damage, reduced epididymal fat mass, and improved adipose tissue lipolysis much more in the CRP-transgenic strain than in the nontransgenic strain.</AbstractText>Rosuvastatin can protect against pro-inflammatory effects of human CRP in a manner that is not dependent on achieving a reduction in circulating levels of human CRP.</AbstractText>© 2014 John Wiley & Sons Ltd.</CopyrightInformation>
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2,333,685 |
The effects of stellate ganglion block on the electroencephalogram in rats.
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It is reported that the sympathetic nervous system may play an important role in the arousal response. The present study evaluated the effect of stellate ganglion block (SGB) on electroencephalogram (EEG) activity in rats.</AbstractText>Adult male Sprague-Dawley rats were divided into two groups: SGB (n = 10) or intramuscular (IM, n = 10) injection was performed with 0.2 ml 0.25 % bupivacaine. The spectral edge frequency 95 % (SEF 95 %), median frequency (MF), beta to theta ratio (BTR), and beta to delta ratio (BDR) were estimated 30 min before bupivacaine injection and 15, 20, 25, 30, 45, 55, and 100 min after SGB or IM injection.</AbstractText>Ipsilateral ptosis occurred in all the rats that underwent SGB but did not occur in the IM group. Significant decrease of the 95 % SEF value, MF, BTR, and BDR was observed from 15 to 45 min after SGB compared with those of the IM group, respectively (p < 0.05).</AbstractText>SGB with 0.2 ml 0.25 % bupivacaine significantly decreased EEG activities in rats. These results suggest that SGB can induce a sedative effect in rats. Further studies are required to investigate the behavioral tests for sedative effects of SGB.</AbstractText>
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2,333,686 |
Changes in PR and QTc intervals after switching from olanzapine to risperidone in patients with stable schizophrenia.
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We examined the difference between the effects of olanzapine (OLZ) and risperidone (RIS) on PR and QT intervals among patients with stable schizophrenia using a cohort analysis.</AbstractText>Twenty-one subjects treated with OLZ were enrolled in the study. Following baseline assessments, which included PR and QT intervals, OLZ was switched to RIS for each subject. The same parameters were evaluated following the switch to RIS.</AbstractText>All patients who had been treated with OLZ were successfully switched to RIS. In all patients, we observed a significant decrease in PR interval (t = 2.397, P = 0.029) and no change in either QTc or RR interval. In female patients, the QTc interval was significantly decreased (t = 3.495, P = 0.008) following the switch, while in male patients, the QTc interval did not change. No patients showed a PR interval of >200 ms or a QTc interval of >500 ms.</AbstractText>OLZ treatment has a greater prolonging effect on PR and QT intervals compared with RIS. Careful attention may need to be paid to the cardiac conduction system in addition to QT prolongation during OLZ treatment.</AbstractText>© 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.</CopyrightInformation>
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2,333,687 |
Ultrasound-guided tranversus abdominis plane block for herniorrhaphy in children: what is the optimal dose of levobupivacaine?
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Regional anaesthesic techniques are commonly used for the management of pain following lower abdominal surgery in children. The transversus abdominis plane (TAP) block has shown promise for perioperative analgesia, but data on the optimal dose regimen are limited.</AbstractText>To evaluate the optimal dose of levobupivacaine for successful ultrasound-guided TAP block in children.</AbstractText>A dose finding prospective study using Dixon's up-and-down sequential method.</AbstractText>University Hospital Paediatric Anaesthesia Unit.</AbstractText>Twenty-seven consecutive children aged 1 to 5 years scheduled for day-case elective herniorrhaphy.</AbstractText>After standardised induction of general anaesthesia, ultrasound-guided TAP block was performed with a fixed volume of 0.2  ml  kg(-1) of levobupivacaine solution. The dose of levobupivacaine was determined by Dixon's up-and-down method starting from 0.5  mg  kg(-1)with an interval of 0.1 mg   kg(-1). Block failure was defined as a 20% increase in heart rate or mean arterial pressure from baseline. Rescue analgesia consisted of intravenous remifentanil infusion during surgery and intravenous nalbuphine in the postanaesthetic care unit (PACU). Patients were assessed using the FLACC (face, legs, activity, cry and consolability) pain scale, the rescue analgesic consumption in the PACU and day-case unit and the postoperative pain measure for parents score at home.</AbstractText>The mean effective dose of levobupivacaine resulting in an effective TAP block in 50% of cases (ED50) obtained by using Dixon's up-and-down sequential method. The ED50 and ED95 were further estimated by bootstrapping.</AbstractText>The ED50 according to the up-and-down staircase method was 0.22  mg   kg(-1) [95% confidence interval (CI) 0.19 to 0.25]. Bootstrap replicates of the original dataset resulted in ED50 and ED95 estimates of 0.16  mg    kg(-1) (95% CI 0.11 to 0.24) and 0.43 mg  kg(-1)(95% CI 0.30 to 0.57), respectively.</AbstractText>As part of a multimodal analgesia strategy, ultrasound-guided TAP block with 0.2  ml  kg(-1)of 0.2% levobupivacaine provides successful peroperative analgesia in 95% of children who underwent herniorrhaphy.</AbstractText>
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2,333,688 |
5-Methoxytryptophan-dependent protection of cardiomyocytes from heart ischemia reperfusion injury.
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5-Methoxytryptophan (5-MTP), a catabolic product of tryptophan, can block Cox-2 overexpression in cancer cells as well as suppress cancer cell growth, migration and invasion. The aim of this study was to in vitro examine whether 5-MTP is able to reduce reactive oxygen species (ROS)-induced heart ischemia reperfusion injury and activate the cardiomyocyte's damage surveillance systems. Accordingly, rattus cardiomyocytes were treated with H2O2 as a heart ischemia reperfusion model prior to incubation with/without 5-MTP and proteomic analysis was performed to investigate the physiologic protection of 5-MTP in H2O2-induced ischemia reperfusion in cardiomyocyte. Our data demonstrated that 5-MTP treatment does protect cardiomyocyte in the ROS-induced ischemia reperfusion model. 5-MTP has also been shown to significantly facilitate cell migration and wound healing via cytoskeletal regulations. Additionally, two-dimensional differential gel electrophoresis (2D-DIGE) combined matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/TOF MS) analysis showed that 5-MTP might modulate growth-associated proteins, cytoskeleton regulation, redox regulation and protein folding to stimulate wound healing as well as prevent these ischemia reperfusion-damaged cardiomyocytes from cell death through maintaining cellular redox-balance and reducing ER-stress. To our knowledge, we report for the first time the cell repair mechanism of 5-MTP against ischemia reperfusion-damage in cardiomyocytes based on cell biology and proteomic analysis.
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2,333,689 |
Cilostazol administered to female mice induces ovulation of immature oocytes: a contraceptive animal model.
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Both Cilostamide and Org 9935 are phosphodiesterase 3A (PDE3A) inhibitors that were evaluated in rodents and monkeys for their non-steroidal contraceptive properties. Although both compounds inhibited oocyte maturation, an adverse effect on heart rate was observed. Cilostazol (CLZ, Pletal) is a safe PDE3A inhibitor that was recently reported to block pregnancy in naturally cycling mice. In this study, the dose, frequency, time of administration, and reversibility effects of CLZ on oocyte maturation were defined using superovulated mice.</AbstractText>Superovulated mice were gavaged once or twice with 0, 7.5, or 15 mg CLZ at various times around the ovulatory stimulus. Ovulated oocytes were then evaluated for maturational stages.</AbstractText>CLZ resulted in mice ovulating significant numbers of immature oocytes when administered anytime between 9h before the ovulatory stimulus and 2 h after the stimulus. This inhibitory effect was greater when CLZ dose was increased, administered twice or closer to the time of the ovulatory stimulus. Conversely, ovulated immature oocytes resumed maturation in oviducts when CLZ dose was reduced, administered once and away from the time of the stimulus.</AbstractText>Controlling CLZ dose, frequency, and time of administration produced mice ovulating immature oocytes at different stages, which may be an advantage over the conventional collection of immature oocytes from ovaries. More importantly, the capability of a clinically approved PDE3A inhibitor, with a reasonable margin of safety, to arrest oocyte maturation over a wide range of administration times and at doses extrapolated from human therapeutic doses demonstrates the contraceptive capacity of CLZ.</AbstractText>Published by Elsevier Inc.</CopyrightInformation>
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2,333,690 |
Electrical and Myocardial Remodeling in Primary Aldosteronism.<Pagination><StartPage>7</StartPage><MedlinePgn>7</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">7</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.3389/fcvm.2014.00007</ELocationID><Abstract><AbstractText Label="OBJECTIVE AND DESIGN" NlmCategory="OBJECTIVE">Primary aldosteronism (PA) represents the most common cause of secondary hypertension. A higher risk of cardiovascular events has been reported in patients with PA than in otherwise similar patients with essential hypertension (EH). So far, only a few studies investigated the electrocardiographic changes in PA patients compared to EH patients.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">To investigate the electrocardiographic changes and heart remodeling in PA, we enrolled 61 consecutive patients, 30 with PA [12 with aldosterone-producing adrenal cortical adenoma (APA) and 18 with bilateral adrenal hyperplasia-idiopathic adrenal hyperplasia] and 30 with EH. In all subjects, electrocardiographic parameters were evaluated from 12-lead electrocardiograms and heart remodeling with echocardiogram.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">No significant differences in age, sex, body mass index, and blood pressure were found in two groups. The P wave and PR interval duration were significantly prolonged in patients with PA respect to EH (p < 0.003 and <0.002, respectively). A first degree atrio-ventricular block was present in 16% of the patients with PA and only in 3.2% of those with EH. In PA patients, the interventricular septum thickness (IVST) correlated with PR duration (r = 0.51; p < 0.03). Left ventricular hypertrophy was present in 53% of the patients with PA and in 26% of the patients with EH (χ(2), p < 0.03).</AbstractText><AbstractText Label="CONCLUSION" NlmCategory="CONCLUSIONS">In this case-control study, patients with PA show more anatomic and electrical heart remodeling than those with EH. We hypothesize that in patients with PA these cardiac changes may play a role for the increased risk of future cardiovascular events.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Curione</LastName><ForeName>Mario</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine and Medical Specialties, Sapienza University of Rome , Rome , Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Petramala</LastName><ForeName>Luigi</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Specialized Center of Secondary Hypertension, Sapienza University of Rome , Rome , Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Savoriti</LastName><ForeName>Claudio</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine and Medical Specialties, Sapienza University of Rome , Rome , Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Verrenti</LastName><ForeName>Marisa</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine and Medical Specialties, Sapienza University of Rome , Rome , Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Baiocco</LastName><ForeName>Erika</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine and Medical Specialties, Sapienza University of Rome , Rome , Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Salvatore</LastName><ForeName>Stephanie</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine and Medical Specialties, Sapienza University of Rome , Rome , Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zinnamosca</LastName><ForeName>Laura</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Specialized Center of Secondary Hypertension, Sapienza University of Rome , Rome , Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Iannucci</LastName><ForeName>Gino</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Specialized Center of Secondary Hypertension, Sapienza University of Rome , Rome , Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sciomer</LastName><ForeName>Susanna</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Specialized Center of Secondary Hypertension, Sapienza University of Rome , Rome , Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Letizia</LastName><ForeName>Claudio</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Specialized Center of Secondary Hypertension, Sapienza University of Rome , Rome , Italy.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2014</Year><Month>11</Month><Day>06</Day></ArticleDate></Article><MedlineJournalInfo><Country>Switzerland</Country><MedlineTA>Front Cardiovasc Med</MedlineTA><NlmUniqueID>101653388</NlmUniqueID><ISSNLinking>2297-055X</ISSNLinking></MedlineJournalInfo><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">conduction disturbance</Keyword><Keyword MajorTopicYN="N">electrocardiography</Keyword><Keyword MajorTopicYN="N">essential hypertension</Keyword><Keyword MajorTopicYN="N">hyperaldosteronism</Keyword><Keyword MajorTopicYN="N">left ventricular hypertrophy</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2014</Year><Month>6</Month><Day>18</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2014</Year><Month>9</Month><Day>28</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2015</Year><Month>12</Month><Day>15</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2014</Year><Month>1</Month><Day>1</Day><Hour>0</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2014</Year><Month>1</Month><Day>1</Day><Hour>0</Hour><Minute>1</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">26664858</ArticleId><ArticleId IdType="pmc">PMC4668839</ArticleId><ArticleId IdType="doi">10.3389/fcvm.2014.00007</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Stowasser M. 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Am J Hypertens (2002) 15:896–902.10.1016/S0895-7061(02)02969-2</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/S0895-7061(02)02969-2</ArticleId><ArticleId IdType="pubmed">12372677</ArticleId></ArticleIdList></Reference><Reference><Citation>Mulatero P, Stowasser M, Loh KC, Fardella CE, Gordon RD, Mosso L, et al. Increased diagnosis of primary aldosteronism, including surgically correctable forms, in centers from five continents. J Clin Endocrinol Metab (2004) 89:1045–50.10.1210/jc.2003-031337</Citation><ArticleIdList><ArticleId IdType="doi">10.1210/jc.2003-031337</ArticleId><ArticleId IdType="pubmed">15001583</ArticleId></ArticleIdList></Reference><Reference><Citation>Rossi GP, Bernini G, Caliumi C, Desideri G, Fabris B, Ferri C, et al. A prospective study of the prevalence of primary aldosteronism in 1,125 hypertensive patients. J Am Coll Cardiol (2006) 48:2293–300.10.1016/j.jacc.2006.07.059</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.jacc.2006.07.059</ArticleId><ArticleId IdType="pubmed">17161262</ArticleId></ArticleIdList></Reference><Reference><Citation>Stowasser M, Gordon RD, Rutherford JC, Nikwan NZ, Daunt N, Slater GJ. Diagnosis and management of primary aldosteronism. J Renin Angiotensin Aldosterone Syst (2001) 2:156–69.10.3317/jraas.2001.022</Citation><ArticleIdList><ArticleId IdType="doi">10.3317/jraas.2001.022</ArticleId><ArticleId IdType="pubmed">11881117</ArticleId></ArticleIdList></Reference><Reference><Citation>Milliez P, Girerd X, Plouin PF, Blacher J, Safar ME, Mourad JJ. Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J Am Coll Cardiol (2005) 45:1243–8.10.1016/j.jacc.2005.01.015</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.jacc.2005.01.015</ArticleId><ArticleId IdType="pubmed">15837256</ArticleId></ArticleIdList></Reference><Reference><Citation>Savard S, Amar L, Plouin PF, Steichen O. Cardiovascular complications associated with primary aldosteronism: a controlled cross-sectional study. Hypertension (2013) 62:331–6.10.1161/HYPERTENSIONAHA.113.01060</Citation><ArticleIdList><ArticleId IdType="doi">10.1161/HYPERTENSIONAHA.113.01060</ArticleId><ArticleId IdType="pubmed">23753408</ArticleId></ArticleIdList></Reference><Reference><Citation>Maule S, Mulatero P, Milan A, Leotta G, Caserta M, Bertello C, et al. QT interval in patients with primary aldosteronism and low-renin essential hypertension. J Hypertens (2006) 24:2459–64.10.1097/01.hjh.0000251908.93298.a0</Citation><ArticleIdList><ArticleId IdType="doi">10.1097/01.hjh.0000251908.93298.a0</ArticleId><ArticleId IdType="pubmed">17082730</ArticleId></ArticleIdList></Reference><Reference><Citation>Iacobellis G, Petramala L, Cotesta D, Pergolini M, Zinnamosca L, Cianci R, et al. Adipokines and cardiometabolic profile in primary hyperaldosteronism. J Clin Endocrinol Metab (2010) 95:2391–8.10.1210/jc.2009-2204</Citation><ArticleIdList><ArticleId IdType="doi">10.1210/jc.2009-2204</ArticleId><ArticleId IdType="pubmed">20194710</ArticleId></ArticleIdList></Reference><Reference><Citation>Rossi GP, Bernini G, Desideri G, Fabris B, Ferri C, Giacchetti G, et al. Renal damage in primary aldosteronism: results of the PAPY study. Hypertension (2006) 48:232–8.10.1161/01.HYP.0000230444.01215.6a</Citation><ArticleIdList><ArticleId IdType="doi">10.1161/01.HYP.0000230444.01215.6a</ArticleId><ArticleId IdType="pubmed">16801482</ArticleId></ArticleIdList></Reference><Reference><Citation>Catena C, Colussi G, Lapenna R, Nadalini E, Chiuch A, Gianfagna P, et al. Long-term cardiac effects of adrenalectomy or mineralocorticoid antagonists in patients with primary aldosteronism. Hypertension (2007) 50:911–8.10.1161/HYPERTENSIONAHA.107.095448</Citation><ArticleIdList><ArticleId IdType="doi">10.1161/HYPERTENSIONAHA.107.095448</ArticleId><ArticleId IdType="pubmed">17893375</ArticleId></ArticleIdList></Reference><Reference><Citation>Brown NJ. Aldosterone and vascular inflammation. Hypertension (2008) 51:161–7.10.1161/HYPERTENSIONAHA.107.095489</Citation><ArticleIdList><ArticleId IdType="doi">10.1161/HYPERTENSIONAHA.107.095489</ArticleId><ArticleId IdType="pubmed">18172061</ArticleId></ArticleIdList></Reference><Reference><Citation>Ahmad N, Romero DG, Gomez-Sanchez EP, Gomez-Sanchez CE. Do human vascular endothelial cells produce aldosterone? Endocrinology (2004) 145:3626–9.10.1210/en.2004-0081</Citation><ArticleIdList><ArticleId IdType="doi">10.1210/en.2004-0081</ArticleId><ArticleId IdType="pubmed">15117882</ArticleId></ArticleIdList></Reference><Reference><Citation>Rossi GP, Di Bello V, Ganzaroli C, Sacchetto A, Cesari M, Bertini A, et al. Excess aldosterone is associated with alterations of myocardial texture in primary aldosteronism. Hypertension (2002) 40:23–7.10.1161/01.HYP.0000023182.68420.EB</Citation><ArticleIdList><ArticleId IdType="doi">10.1161/01.HYP.0000023182.68420.EB</ArticleId><ArticleId IdType="pubmed">12105133</ArticleId></ArticleIdList></Reference><Reference><Citation>de Jong S, van Veen TA, van Rijen HV, de Bakker JM. Fibrosis and cardiac arrhythmias. J Cardiovasc Pharmacol (2011) 57:630–8.10.1097/FJC.0b013e318207a35f</Citation><ArticleIdList><ArticleId IdType="doi">10.1097/FJC.0b013e318207a35f</ArticleId><ArticleId IdType="pubmed">21150449</ArticleId></ArticleIdList></Reference><Reference><Citation>Brilla CG, Janicki JS, Weber KT. Impaired diastolic function and coronary reserve in genetic hypertension. Role of interstitial fibrosis and medial thickening of intramyocardial coronary arteries. 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Int J Cardiol (2002) 84:33–9.10.1016/S0167-5273(02)00115-8</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/S0167-5273(02)00115-8</ArticleId><ArticleId IdType="pubmed">12104061</ArticleId></ArticleIdList></Reference><Reference><Citation>Yang TY, Cheng NJ, Ko YS, Kuo CT. QT interval is prolonged but QT dispersion is maintained in patients with primary aldosteronism. Int J Clin Pract (2007) 61:392–6.10.1111/j.1742-1241.2006.00982.x</Citation><ArticleIdList><ArticleId IdType="doi">10.1111/j.1742-1241.2006.00982.x</ArticleId><ArticleId IdType="pubmed">16749916</ArticleId></ArticleIdList></Reference><Reference><Citation>Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized aldactone evaluation study investigators. N Engl J Med (1999) 341:709–17.10.1056/NEJM199909023411001</Citation><ArticleIdList><ArticleId IdType="doi">10.1056/NEJM199909023411001</ArticleId><ArticleId IdType="pubmed">10471456</ArticleId></ArticleIdList></Reference><Reference><Citation>Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med (2003) 348:1309–21.10.1056/NEJMoa030207</Citation><ArticleIdList><ArticleId IdType="doi">10.1056/NEJMoa030207</ArticleId><ArticleId IdType="pubmed">12668699</ArticleId></ArticleIdList></Reference><Reference><Citation>Yee KM, Pringle SD, Struthers AD. Circadian variation in the effects of aldosterone blockade on heart rate variability and QT dispersion in congestive heart failure. J Am Coll Cardiol (2001) 37:1800–7.10.1016/S0735-1097(01)01243-8</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/S0735-1097(01)01243-8</ArticleId><ArticleId IdType="pubmed">11401114</ArticleId></ArticleIdList></Reference><Reference><Citation>Rossi GP, Sacchetto A, Visentin P, Canali C, Graniero GR, Palatini P, et al. Changes in left ventricular anatomy and function in hypertension and primary aldosteronism. Hypertension (1996) 27:1039–45.10.1161/01.HYP.27.5.1039</Citation><ArticleIdList><ArticleId IdType="doi">10.1161/01.HYP.27.5.1039</ArticleId><ArticleId IdType="pubmed">8621194</ArticleId></ArticleIdList></Reference><Reference><Citation>Tanabe A, Naruse M, Naruse K, Hase M, Yoshimoto T, Tanaka M, et al. Left ventricular hypertrophy is more prominent in patients with primary aldosteronism than in patients with other types of secondary hypertension. 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Ultrasound Med Biol (2013) 39:54–61.10.1016/j.ultrasmedbio.2012.08.023</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.ultrasmedbio.2012.08.023</ArticleId><ArticleId IdType="pubmed">23200178</ArticleId></ArticleIdList></Reference><Reference><Citation>Casale PN, Devereux RB, Milner M, Zullo G, Harshfield GA, Pickering TG, et al. Value of echocardiographic measurement of left ventricular mass in predicting cardiovascular morbid events in hypertensive men. Ann Intern Med (1986) 105:173–8.10.7326/0003-4819-105-2-173</Citation><ArticleIdList><ArticleId IdType="doi">10.7326/0003-4819-105-2-173</ArticleId><ArticleId IdType="pubmed">2942070</ArticleId></ArticleIdList></Reference><Reference><Citation>Muiesan ML, Salvetti M, Paini A, Monteduro C, Galbassini G, Bonzi B, et al. Inappropriate left ventricular mass changes during treatment adversely affects cardiovascular prognosis in hypertensive patients. Hypertension (2007) 49:1077–83.10.1161/HYPERTENSIONAHA.107.087320</Citation><ArticleIdList><ArticleId IdType="doi">10.1161/HYPERTENSIONAHA.107.087320</ArticleId><ArticleId IdType="pubmed">17372030</ArticleId></ArticleIdList></Reference><Reference><Citation>Robert V, Van Thiem N, Cheav SL, Mouas C, Swynghedauw B, Delcayre C. Increased cardiac types I and III collagen mRNAs in aldosterone-salt hypertension. Hypertension (1994) 24:30–6.10.1161/01.HYP.24.1.30</Citation><ArticleIdList><ArticleId IdType="doi">10.1161/01.HYP.24.1.30</ArticleId><ArticleId IdType="pubmed">8021005</ArticleId></ArticleIdList></Reference><Reference><Citation>Yamada M, Kushibiki M, Osanai T, Tomita H, Okumura K. Vasoconstrictor effect of aldosterone via angiotensin II type 1 (AT1) receptor: possible role of AT1 receptor dimerization. Cardiovasc Res (2008) 79:169–78.10.1093/cvr/cvn064</Citation><ArticleIdList><ArticleId IdType="doi">10.1093/cvr/cvn064</ArticleId><ArticleId IdType="pubmed">18326554</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">26281149</PMID><DateCompleted><Year>2015</Year><Month>09</Month><Day>08</Day></DateCompleted><DateRevised><Year>2016</Year><Month>11</Month><Day>25</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0890-9016</ISSN><JournalIssue CitedMedium="Print"><PubDate><Year>2014</Year></PubDate></JournalIssue><Title>Clinical transplants</Title><ISOAbbreviation>Clin Transpl</ISOAbbreviation></Journal>Treatment of Biopsy-Proven Acute Antibody-Mediated Rejection Using Thymoglobulin (ATG) Monotherapy and a Combination of Rituximab, Intravenous Immunoglobulin, and Plasmapheresis: Lesson Learned from Primary Experience.
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Primary aldosteronism (PA) represents the most common cause of secondary hypertension. A higher risk of cardiovascular events has been reported in patients with PA than in otherwise similar patients with essential hypertension (EH). So far, only a few studies investigated the electrocardiographic changes in PA patients compared to EH patients.</AbstractText>To investigate the electrocardiographic changes and heart remodeling in PA, we enrolled 61 consecutive patients, 30 with PA [12 with aldosterone-producing adrenal cortical adenoma (APA) and 18 with bilateral adrenal hyperplasia-idiopathic adrenal hyperplasia] and 30 with EH. In all subjects, electrocardiographic parameters were evaluated from 12-lead electrocardiograms and heart remodeling with echocardiogram.</AbstractText>No significant differences in age, sex, body mass index, and blood pressure were found in two groups. The P wave and PR interval duration were significantly prolonged in patients with PA respect to EH (p < 0.003 and <0.002, respectively). A first degree atrio-ventricular block was present in 16% of the patients with PA and only in 3.2% of those with EH. In PA patients, the interventricular septum thickness (IVST) correlated with PR duration (r = 0.51; p < 0.03). Left ventricular hypertrophy was present in 53% of the patients with PA and in 26% of the patients with EH (χ(2), p < 0.03).</AbstractText>In this case-control study, patients with PA show more anatomic and electrical heart remodeling than those with EH. We hypothesize that in patients with PA these cardiac changes may play a role for the increased risk of future cardiovascular events.</AbstractText>
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2,333,691 |
Clinical Potentials of Cardiomyocytes Derived from Patient-Specific Induced Pluripotent Stem Cells.
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The lack of appropriate human cardiomyocyte-based experimental platform has largely hindered the study of cardiac diseases and the development of therapeutic strategies. To date, somatic cells isolated from human subjects can be reprogramed into induced pluripotent stem cells (iPSCs) and subsequently differentiated into functional cardiomyocytes. This powerful reprogramming technology provides a novel in vitro human cell-based platform for the study of human hereditary cardiac disorders. The clinical potential of using iPSCs derived from patients with inherited cardiac disorders for therapeutic studies have been increasingly highlighted. In this review, the standard procedures for generating patient-specific iPSCs and the latest commonly used cardiac differentiation protocols will be outlined. Furthermore, the progress and limitations of current applications of iPSCs and iPSCs-derived cardiomyocytes in cell replacement therapy, disease modeling, drug-testing and toxicology studies will be discussed in detail.
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2,333,692 |
Clinical risk prediction by exploring high-order feature correlations.
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Clinical risk prediction is one important problem in medical informatics, and logistic regression is one of the most widely used approaches for clinical risk prediction. In many cases, the number of potential risk factors is fairly large and the actual set of factors that contribute to the risk is small. Therefore sparse logistic regression is proposed, which can not only predict the clinical risk but also identify the set of relevant risk factors. The inputs of logistic regression and sparse logistic regression are required to be in vector form. This limits the applicability of these models in the problems when the data cannot be naturally represented vectors (e.g., medical images are two-dimensional matrices). To handle the cases when the data are in the form of multi-dimensional arrays, we propose HOSLR: High-Order Sparse Logistic Regression, which can be viewed as a high order extension of sparse logistic regression. Instead of solving one classification vector as in conventional logistic regression, we solve for K classification vectors in HOSLR (K is the number of modes in the data). A block proximal descent approach is proposed to solve the problem and its convergence is guaranteed. Finally we validate the effectiveness of HOSLR on predicting the onset risk of patients with Alzheimer's disease and heart failure.
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2,333,693 |
Dexmedetomidine: an adjuvant making large inroads into clinical practice.
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The introduction of newer more selective α(-2) adrenergic agonist, dexmedetomidine has made a revolution in the field of anesthesia owing to its varied application. The aim of the current review is to highlight the various clinical and pharmacological aspects of dexmedetomidine in daily routine practice of anesthesiology and intensive care besides its potential role in other clinical specialties. This review of dexmedetomidine was carried out after searching the medical literature in Pubmed, Science direct, Scopus, Google scholar and various text books and journal articles using keywords anesthesia, dexmedetomidine, neurosurgery, pediatric surgery, regional dexmedetomidine, anesthesia, regional, neurosurgery, and pediatric surgery. Dexmedetomidine has made its application from a novel sedating agent in the intensive care unit to its use as an adjuvant in various regional anesthetic techniques because of its "cooperative sedation" without any respiratory depression. It has a favorable pharmacokinetic profile suitable to be used in the perioperative period to reduce the requirements of opioids and anesthetic drugs. There are few side-effects of dexmedetomidine, which should always be kept in mind before choosing the patients for its use. The various side-effects associated with dexmedetomidine include, but are not limited to hypotension, bradycardia, worsening of heart block, dry mouth, and nausea. However, large scale randomized controlled trials are still needed to establish various effects of dexmedetomidine and to clearly define its safety profile.
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2,333,694 |
Analgesic efficacy and outcome of transversus-abdominis plane block versus low thoracic-epidural analgesia after laparotomy in ischemic heart disease patients.
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Tranversus-abdominis plane (TAP) block is a novel technique alternative to central neural blockade in providing analgesia to the anterior abdominal wall. As such, we compared the analgesic efficacy of TAP block with low thoracic-epidural analgesia (TEA) in ischemic heart disease patients after abdominal laparotomy.</AbstractText>Forty-four American Society of Anesthesiologists physical status (ASA) III patients, 59-75 years of age and undergoing elective upper abdominal surgery under general anesthesia, were assigned randomly to receive either continuous low TEA or intermittent administration of local anesthetic in TAP block. Supplemental analgesia was provided with intravenous morphine with patient-controlled-analgesia. Morphine consumption and pain intensity using verbal rating scale (VRS) at rest and coughing over the first 48 h were recorded.</AbstractText>Whereas all patients in the TAP group required morphine, 16 (72.2 %) patients in TEA group received morphine postoperatively (p = 0.021). Morphine consumed on day 1 and day 2 was 11.5 mg (7.5-12.3 mg) and 7 mg (4.5-8 mg) for the TEA group, while in the TAP group, it was 18 mg (16-19 mg) and 11 mg (10-13 mg), respectively (p < 0.001). Time for first request of morphine was 311.2 ± 18.5 min in the TEA group versus 210 ± 22.2 min in the TAP group (p < 0.001). VRS at rest and cough were lower in the TEA group compared with the TAP group at 1, 6, 12, 18, 24, 36 and 48 h (p < 0.001). Incidence of hypotension and ephedrine administration were significantly higher in the TEA group than in the TAP group (p = 0.007).</AbstractText>Low TEA reduced morphine consumption and provided a higher analgesic efficacy compared with TAP block after laparotomy in ischemic heart disease patients.</AbstractText>
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2,333,695 |
β2-Adrenoceptor gene variants affect vasopressor requirements in patients after thoracic epidural anaesthesia.
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While the β2-adrenoceptor pathway is essential for cardiovascular regulation, the impact of ADRB2 gene variations on circulatory responses is unclear, possibly due to neural compensatory mechanisms. We tested the hypotheses that (i) sympathetic block by thoracic epidural anaesthesia (TEA) unmasks the influence on arterial pressure of genetic variations and (ii) vasopressor requirements during TEA depend on ADRB2 gene variation.</AbstractText>Ninety-three elective patients undergoing abdominal surgery were included prospectively. After epidural bupivacaine 0.5% (15 mg test dose+50 mg), arterial pressure, heart rate, and progression of sensory block were measured for 20 min in the supine awake state and for 20 min after standardized anaesthetic induction of general anaesthesia. The primary endpoint was cumulative dose of the α-adrenoreceptor agonist phenylephrine administered to sustain a mean arterial pressure >70 mm Hg. The ADRB2 polymorphisms Arg16Gly and Gln27Glu were genotyped using Slowdown-PCR.</AbstractText>After TEA, 86 (93%) patients required phenylephrine. The mean dosages (sd) were significantly different between the ADRB2 genotypes [Arg16Arg 357 µg (326), Arg16Gly 776 µg (449), Gly16Gly 600 µg (443), P=0.036; Gln27Gln 356 µg (254), Gln27Glu 639 µg (354), Glu27Glu 577 µg (388), P=0.007]. Multiple linear regression analysis revealed that age, male gender, rostral extent of sensory block, lower arterial pressure before TEA, and ADRB2 Glu27 allele together explained 37% of phenylephrine dosage variation, with genetic variants being the second most important predictor (10%; P<0.001).</AbstractText>The ADRB2 Glu27 allele is an independent predictor of arterial hypotension and vasopressor requirements after TEA. Neural block can unmask genetic influences on neurohumoral regulation. Clinical trial registration DRKS00005260.</AbstractText>
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2,333,696 |
Estimating the decline in excess risk of chronic obstructive pulmonary disease following quitting smoking - a systematic review based on the negative exponential model.
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We quantified the decline in COPD risk following quitting using the negative exponential model, as previously carried out for other smoking-related diseases. We identified 14 blocks of RRs (from 11 studies) comparing current smokers, former smokers (by time quit) and never smokers, some studies providing sex-specific blocks. Corresponding pseudo-numbers of cases and controls/at risk formed the data for model-fitting. We estimated the half-life (H, time since quit when the excess risk becomes half that for a continuing smoker) for each block, except for one where no decline with quitting was evident, and H was not estimable. For the remaining 13 blocks, goodness-of-fit to the model was generally adequate, the combined estimate of H being 13.32 (95% CI 11.86-14.96) years. There was no heterogeneity in H, overall or by various studied sources. Sensitivity analyses allowing for reverse causation or different assumed times for the final quitting period little affected the results. The model summarizes quitting data well. The estimate of 13.32years is substantially larger than recent estimates of 4.40years for ischaemic heart disease and 4.78years for stroke, and also larger than the 9.93years for lung cancer. Heterogeneity was unimportant for COPD, unlike for the other three diseases.
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2,333,697 |
Isoflurane modulates cardiac mitochondrial bioenergetics by selectively attenuating respiratory complexes.
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Mitochondrial dysfunction contributes to cardiac ischemia-reperfusion (IR) injury but volatile anesthetics (VA) may alter mitochondrial function to trigger cardioprotection. We hypothesized that the VA isoflurane (ISO) mediates cardioprotection in part by altering the function of several respiratory and transport proteins involved in oxidative phosphorylation (OxPhos). To test this we used fluorescence spectrophotometry to measure the effects of ISO (0, 0.5, 1, 2mM) on the time-course of interlinked mitochondrial bioenergetic variables during states 2, 3 and 4 respiration in the presence of either complex I substrate K(+)-pyruvate/malate (PM) or complex II substrate K(+)-succinate (SUC) at physiological levels of extra-matrix free Ca(2+) (~200nM) and Na(+) (10mM). To mimic ISO effects on mitochondrial functions and to clearly delineate the possible ISO targets, the observed actions of ISO were interpreted by comparing effects of ISO to those elicited by low concentrations of inhibitors that act at each respiratory complex, e.g. rotenone (ROT) at complex I or antimycin A (AA) at complex III. Our conclusions are based primarily on the similar responses of ISO and titrated concentrations of ETC. inhibitors during state 3. We found that with the substrate PM, ISO and ROT similarly decreased the magnitude of state 3 NADH oxidation and increased the duration of state 3 NADH oxidation, ΔΨm depolarization, and respiration in a concentration-dependent manner, whereas with substrate SUC, ISO and ROT decreased the duration of state 3 NADH oxidation, ΔΨm depolarization and respiration. Unlike AA, ISO reduced the magnitude of state 3 NADH oxidation with PM or SUC as substrate. With substrate SUC, after complete block of complex I with ROT, ISO and AA similarly increased the duration of state 3 ΔΨm depolarization and respiration. This study provides a mechanistic understanding in how ISO alters mitochondrial function in a way that may lead to cardioprotection.
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2,333,698 |
The HLA locus contains novel foetal susceptibility alleles for congenital heart block with significant paternal influence.
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The main aim of this study was to identify foetal susceptibility genes on chromosome six for Ro/SSA autoantibody-mediated congenital heart block.</AbstractText>Single nucleotide polymorphism (SNP) genotyping of individuals in the Swedish Congenital Heart Block (CHB) study population was performed. Low-resolution HLA-A, -Cw and -DRB1 allele typing was carried out in 86 families comprising 339 individuals (86 Ro/SSA autoantibody-positive mothers, 71 fathers, 87 CHB index cases and 95 unaffected siblings).</AbstractText>A case-control comparison between index cases and population-based out-of-study controls (n = 1710) revealed association of CHB with 15 SNPs in the 6p21.3 MHC locus at a chromosome-wide significance of P < 2.59 × 10(-6) (OR 2.21-3.12). In a family-based analysis of association of SNP markers as well as distinct MHC class I and II alleles with CHB, HLA-DRB1*04 and HLA-Cw*05 variants were significantly more frequently transmitted to affected individuals (P < 0.03 and P < 0.05, respectively), whilst HLA-DRB1*13 and HLA-Cw*06 variants were significantly less often transmitted to affected children (P < 0.04 and P < 0.03). We further observed marked association of increased paternal (but not maternal) HLA-DRB1*04 transmission to affected offspring (P < 0.02).</AbstractText>HLA-DRB1*04 and HLA-Cw*05 were identified as novel foetal HLA allele variants that confer susceptibility to CHB in response to Ro/SSA autoantibody exposure, whilst DRB1*13 and Cw*06 emerged as protective alleles. Additionally, we demonstrated a paternal contribution to foetal susceptibility to CHB for the first time.</AbstractText>© 2013 The Association for the Publication of the Journal of Internal Medicine.</CopyrightInformation>
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2,333,699 |
Comparison of eutectic mixture of local anesthetics cream with dorsal penile nerve block using lignocaine for circumcision in infants.
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Circumcision is a commonly performed surgical procedure but choice of anesthesia remained an issue of research and debate. This study was conducted to find out the effectiveness of the eutectic mixture of local anesthetic (EMLA) cream with dorsal penile nerve block (DPNB) using lignocaine, for reduction of pain during circumcision.</AbstractText>This was comparative study carried out in Surgical Unit B of National Institute of Child Health Karachi, from May 2008 to October 2008. Patients under six month of age were randomized in to two groups (EMLA and DPNB) of fifty patients each. The effectiveness of pain control was assessed by measuring the baseline heart rate (HR), respiratory rate (RR) and Neonatal infant Pain Scale (NIPS scale) before the start of procedure and measuring of these parameters for each step of circumcision. Independent sample t -test was used to compare means and repeated ANOVA was used to compare means of HR, RR, oxygen (O2) saturations and NIPS.</AbstractText>The mean age in both the groups was 2.3 months. There was no statistically significant difference in baseline parameters in both the groups except the respiratory rate, which was significantly raised in DPNB group (33 breaths/min in EMLA and 38 in DPNB P < 0.04). During circumcision there was significant increase in heart rate in DPNB group, especially in step three and step four (p < 0.04). Oxygen saturation dropped in both the groups (baseline saturation 98% up to 91% in step 4). While assessing NIPS scores in both the groups, statistically significant difference was found between NIPS at step two and step four in two groups (p < 0.04).</AbstractText>The overall pain control was equal in both the groups, although NIPS score was higher in DPNB in step two and four of circumcision. There was difference in application and cost. EMLA was easy to apply but has increased cost; while DPNB required expertise.</AbstractText>
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