text
stringlengths 11
9.77k
| label
stringlengths 2
104
|
|---|---|
The influenza A M2 ion channel was expressed and activity characterized in Xenopus oocytes. Based on the activation properties of the channels, a high throughput, non-electrophysiological screening assay was developed in order to identify novel inhibitors of the channel. This will facilitate discovery of novel agents to treat influenza viral infections. | Viral Matrix Proteins |
The case is described of a patient who underwent artificial ventilation in an intensive therapy unit and received an infusion of alcuronium 10 mg/hour for more than 4 days, in the presence of significant renal (and later, some degree of hepatic) impairment. Prolonged and profound neuromuscular block persisted despite haemodialysis (5 hours on each of 3 days) followed by 72 hours of continuous haemofiltration; it appeared to resolve only after plasma exchange (4 litres). The total of persistent block, for 9 days after the infusion had been stopped, is thought to be the longest period ever reported after administration of alcuronium. Neuromuscular block was monitored throughout this period using the train-of-four twitch technique. The potentiating effects of concurrent aminoglycoside therapy and hepatic dysfunction on the degree of paralysis are discussed. | Alcuronium |
We report novel neuronal nitric oxide synthase (nNOS) inhibitors based on a symmetric double-headed aminopyridine scaffold. The inhibitors were designed from crystal structures of leads 1 and 2 (Delker, S. L.; Ji, H.; Li, H.; Jamal, J.; Fang, J.; Xue, F.; Silverman, R. B.; Poulos, T. L. Unexpected binding modes of nitric oxide synthase inhibitors effective in the prevention of cerebral palsy . J. Am. Chem. Soc. 2010, 132, 5437-5442) and synthesized using a highly efficient route. The best inhibitor, 3j, showed low nanomolar inhibitory potency and modest isoform selectivity. It also exhibited enhanced membrane permeability. Inhibitor 3j binds to both the substrate site and the pterin site in nNOS but only to the substrate site in eNOS. These compounds provide a basis for further development of novel, potent, isoform selective, and bioavailable inhibitors for nNOS. | Nitric Oxide Synthase Type I |
GATA3 polymorphisms were reported to be significantly associated with susceptibility of pediatric B-lineage acute lymphoblastic leukemia (ALL), by impacting on GATA3 expression. We noticed that ALL-related GATA3 polymorphism located around in the tissue-specific enhancer, and significantly associated with GATA3 expression. Although the regulatory network of GATA3 has been well reported in T cells, the functional status of GATA3 is poorly understood in B-ALL. We thus conducted genome-wide gene expression association analyses to reveal expression associated genes and pathways in nine independent B-ALL patient cohorts. In B-ALL patients, 173 candidates were identified to be significantly associated with GATA3 expression, including some reported GATA3-related genes (e.g., ITM2A) and well-known tumor-related genes (e.g., STAT4). Some of the candidates exhibit tissue-specific and subtype-specific association with GATA3. Through overexpression and down-regulation of GATA3 in leukemia cell lines, several reported and novel GATA3 regulated genes were validated. Moreover, association of GATA3 expression and its targets can be impacted by SNPs (e.g., rs4894953), which locate in the potential GATA3 binding motif. Our findings suggest that GATA3 may be involved in multiple tumor-related pathways (e.g., STAT/JAK pathway) in B-ALL to impact leukemogenesis through epigenetic regulation. | GATA3 Transcription Factor |
Lacunar stroke is generally considered to have a fair outcome. However 20-30% of patients with lacunar stroke worsen neurologically in hours or days after onset, reaching eventually an unexpectedly severe disability status. In the field of acute stroke, progressive lacunar stroke remains an important unresolved practice problem, because as yet no treatment does exist proven to prevent or halt progression. Pathophysiology of progression is yet incompletely understood. Hemodynamic factors, extension of thrombosis, excitotoxicity, and inflammation, have been proposed as possible mechanisms of progression. A few clinical studies also aimed at establishing presentation features that may help identifying patients at risk of deterioration. In this paper, we review hypothesized mechanisms of lacunar stroke progression and possible markers of early deterioration. Moreover, based on putative mechanisms and suggestions from reported evidence, we propose a few treatments that seem worthy to be tested by randomized clinical trials. | Stroke, Lacunar |
BACKGROUND: Low expression of NCALD(neurocalcin delta) in peripheral blood of ovarian cancer patients predicts poor prognosis. However, the molecular mechanism of NCALD in ovarian cancer and its relationship with chemotherapy outcomes is unclear. The aim of this study was to investigate the potential signaling pathways of NCALD and to evaluate its ability to predict chemotherapy outcomes and prognosis. METHODS: High-throughput RNA sequencing data were downloaded from TCGA. GSEA explored the potential signaling pathways of NCALD. The expression of NCALD in chemotherapy sensitive and chemotherapy resistant ovarian cancer patients was detected by TCGA data and clinical samples. ROC analysis confirmed the ability of NCALD to predict chemotherapy outcomes. The association between NCALD expression and prognosis in ovarian cancer patients was assessed using Kaplan-Meier plotter. RESULTS: In patients with NCALD overexpression, genes expression related to ERK1 / 2 signaling pathway, NF-kappaB signaling pathway, TGF-beta signaling pathway and immune response pathway was increased, especially ERK1 / 2 signaling pathway. The expression of NCALD in chemoresistant patients was significantly lower than chemosensitive patients. In TCGA data and immunohistochemical samples, the AUC of NCALD expression predicting chemotherapy outcome was 0.59 and 0.64, respectively. In clinical samples, low expression of NCALD was associated with poor OS and PFS. CONCLUSIONS: NCALD may activate the ERK1 / 2 signaling pathway in ovarian cancer. As a new biomarker of chemotherapy sensitivity, NCALD was significantly down-regulated in chemotherapy resistance ovarian cancer patients. Low expression of NCALD in ovarian cancer is associated with poor OS and PFS. In the future, further research will be needed on the potential mechanism and clinical application value of NCALD in ovarian cancer. | Neurocalcin |
Activation of smooth muscle myosin light-chain kinase (MLCK) causes contraction. Here we have proven that MLCK controls Ca2+ entry (CE) in endothelial cells (ECs): MLCK antisense oligonucleotides strongly prevented bradykinin (BK)- and thapsigargin (TG)-induced endothelial Ca2+ response, while MLCK sense did not. We also show that the relevant mechanism is not phosphorylation of myosin light-chain (MLC): MLC phosphorylation by BK required CE, but MLC phosphorylation caused by the phosphatase inhibitor calyculin A did not trigger Ca2+ response. Most important, we provide for the first time strong evidence that, in contrast to its role in smooth muscle cells, activation of MLCK in ECs stimulates the production of important endothelium-derived vascular relaxing factors: MLCK antisense and MLCK inhibitors abolished BK- and TG-induced nitric oxide production, and MLCK inhibitors substantially inhibited acetylcholine-stimulated hyperpolarization of smooth muscle cell membrane in rat mesenteric artery. These results indicate that MLCK controls endothelial CE, but not through MLC phosphorylation, and unveils a hitherto unknown physiological function of the enzyme: vasodilation through its action in endothelial cells. The study discovers a counter-balancing role of MLCK in the regulation of vascular tone. | Myosin-Light-Chain Kinase |
AIMS/HYPOTHESIS: Irreversible arterial damage due to early effects of hypo- or hyperglycaemia could account for the limited success of glucose-lowering treatments in preventing cardiovascular disease (CVD) events. We hypothesised that even brief hypo- or hyperglycaemia could adversely affect arterial gene expression and that these changes, moreover, might not be fully reversible. METHODS: By controlled activation of a 'switchable' c-Myc transgene in beta cells, adult pIns-c-MycER(TAM) mice were rendered transiently hypo- and then hyperglycaemic, after which they were allowed to recover for up to 3 months. Immediate and sequential changes in aortic global gene expression from normal glycaemia through hypo- and hyperglycaemia to recovery were assessed. RESULTS: Gene expression was compared with that of normoglycaemic transgenic and tamoxifen-treated wild-type controls. Overall, expression of 95 genes was significantly affected by moderate hypoglycaemia (glucose down to 2.5 mmol/l), whereas over 769 genes were affected by hyperglycaemia. Genes and pathways activated included several involved in atherogenic processes, such as inflammation and arterial calcification. Although expression of many genes recovered to initial pre-exposure levels when hyperglycaemia was corrected (74.9%), in one in four genes this did not occur. Quantitative reverse transcriptase PCR and immunohistochemistry verified the gene expression patterns of key molecules, as shown by global gene arrays. CONCLUSIONS/INTERPRETATION: Short-term exposure to hyperglycaemia can cause deleterious and persistent changes in arterial gene expression in vivo. Brief hypoglycaemia also adversely affects gene expression, although less substantially. Together, these results suggest that early correction of hyperglycaemia and avoidance of hypoglycaemia may both be necessary to avoid excess CVD risk in diabetes. | Genes, myc |
The interaction atrazine and ct-DNA was studied using fluorescence probe and UV absorption spectroscopy technique. Ethidium bromide (EB) was used as a probe. The effects of atrazine, phosphate, concentration of ions, and potassium iodide on the fluorescence of ct-DNA-EB system were investigated. The results showed that the fluorescence quenching process of atrazine to ct-DNA-EB system was proved to be the simultaneous dynamic and static quenching model. The phenomena of fluorescence quenching of ct-DNA-atrazine system by KI and hyperchromicity and the red shift of DNA UV-absorption caused by atrazine indicated the existence of intercalation between atrazine and ct-DNA. The experiments of phosphate and ionic strength showed that atrazine could combine with the phosphate group of ct-DNA by non-characteristic static force, and this action could be inhibited by high ionic strength. | Potassium Iodide |
Below is a summary of the main conclusions that came from reports presented at this year's Digestive Disease Week (2014) relating to Helicobacter pylori infection. Despite the undeniable decline of the infection's frequency, in the near future, developed countries--or at least some sub-populations--will continue to have a significant prevalence of the infection. Clarithromycin, metronidazole and quinolone resistance rates are considerably high in most countries and these rates are on the rise. The eradication of H. pylori improves symptoms of functional dyspepsia, although only in a minority of patients; adding antidepressants to eradication therapy could improve long-term response. In patients who were admitted with gastrointestinal bleeding from peptic ulcers, it is necessary to thoroughly study the presence of H. pylori infection and administer eradication therapy as early as possible. Eradication of H. pylori in patients undergoing endoscopic resection of early-stage gastric cancer reduces incidence of metachronous tumors. We have some diagnostic innovations, such as carrying out various techniques--a rapid urease test, culture or PCR--based on gastric samples obtained by scraping the mucosa. The effectiveness of conventional triple therapy is clearly insufficient and continues to decline. The superiority of sequential therapy over conventional triple therapies has not been definitively established. Concomitant therapy is simpler and more effective than sequential therapy. Optimized concomitant therapy (with high doses of proton-pump inhibitors [PPI] and over 14 days) is highly effective, more so than standard concomitant therapy. For patients who are allergic to penicillin, 2 treatment options were essentially described: PPI-clarithromycin-metronidazole (clarithromycin-sensitive strains) and quadruple therapy with bismuth (when the bacterial sensitivity is unknown). If conventional triple therapy fails, second-line therapy with levofloxacin is effective and is also easier and better tolerated than quadruple therapy with bismuth. Triple therapy with levofloxacin is also a promising alternative if sequential or concomitant therapy fails. New-generation quinolones, such as moxifloxacin, could be useful as part of rescue eradication therapy. Even after 3 eradication therapies have failed, a fourth empirical rescue therapy (with rifabutin) could be effective. The eradication of H. pylori can finally be obtained in the vast majority of patients by using a rescue strategy of up to 4 consecutive empirical therapies, without conducting bacterial cultures. | Helicobacter Infections |
Contributions of biotic (cell-mediated) and abiotic (mineral-mediated) reactions to carbon tetrachloride (CT) transformation were studied in a model iron-reducing system that used hydrous ferric oxide (HFO) as the electron acceptor, acetate as the substrate, and Geobacter metallireducens as a representative dissimilative iron-reducing bacteria (DIRB). Over a period of 2-3 weeks, nanoscale magnetite particles, Fe3O4, were consistently formed as a product of iron respiration in this system. CT transformation rates were measured independently in resting cell suspensions of G. metallireducens or in suspensions of washed magnetite particles recovered from spent cultures. Protein and surface area-normalized expressions were derived for the biotic and abiotic reaction rates, respectively. Using the yield of total protein and magnetite surface area formed during growth in the model system as a basis for comparison, the mineral-mediated (abiotic) reaction was estimated to be 60-260-fold faster than the biotic reaction throughout the incubation period. We conclude that G. metallireducens induces CT transformation in this system primarily through the formation of reactive mineral surfaces rather than via co-metabolic mechanisms. The findings indicate that reactive biogenic minerals could play a significant role in the natural attenuation of chlorinated solvents in iron-reducing environments. A novel approach for stimulating reductive transformation of contaminants may be to enhance the formation of reactive biogenic minerals in situ. | Carbon Tetrachloride |
Aims: This study estimated the economic and humanistic burden associated with chronic non-communicable diseases (NCCDs) among adults with comorbid major depressive and/or any anxiety disorders (MDD and/or AAD).Materials and methods: A retrospective analysis was conducted using the Medical Expenditure Panel Survey data (2010-2015). The analytic cohort included adults (>/=18 years) with MDD only (C1), AAD only (C2), or both (C3). The presence of either of 6 NCCDs (cardiovascular diseases [CVD], pulmonary disorders [PD], pain, high cholesterol, diabetes, and obesity) were assessed. Study outcomes included healthcare costs, activity limitations, and quality of life. Multivariate regressions were conducted in each of the 3 cohorts to evaluate the association between the presence of NCCDs and outcomes.Results: The analytic sample included 9,160,465 patients: C1 (4,391,738), C2 (3,648,436), C3 (1,120,292). Pain (59%) was the most common condition, followed by CVD (55%), high cholesterol (50%), obesity (42%), PD (17%), and diabetes (14%). Mean annual healthcare costs were the greatest for C3 ($14,317), followed by C1 ($10,490) and C2 ($7,906). For C1, CVD was associated with the highest increment in annual costs ($3,966) followed by pain ($3,617). For C2, diabetes was associated with the highest incremental annual costs ($4,281) followed by PD ($2,997). For C3, cost trends were similar to those seen in C2. NCCDs resulted in a significant decrease in physical quality of life across all cohorts. Pain was associated with a significantly higher likelihood of self-reported physical, social, cognitive, and activity limitations compared to those without pain.Conclusions: 60% of patients with MDD and/or AAD had at least one additional NCCD, which significantly increased the economic and humanistic burden. These findings are important for payers and clinicians in making treatment decisions. These results underscore the need for development of multi-pronged interventions which aim to improve quality of life and reduce activity limitations among patients with mental health disorders and NCCDs. | Noncommunicable Diseases |
The bark of Rhus verniciflua Stokes (RVS) is used as a food additive and herbal medicine for various inflammatory disorders and cancer in Eastern Asia. RVS has been shown to exert anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated macrophages in vitro, but whether oral administration of RVS affects the inflammatory response of macrophage needs to be verified. RVS was given orally to mice for ten days. For isolation of macrophages, intraperitoneal injection of thioglycollate was performed. For determination of serum inflammatory response, intraperitoneal injection of LPS was applied. RVS stimulated monocyte differentiation in thioglycollate-induced peritonitis by increasing the population of cells expressing CD11b and class A scavenger receptors. These monocyte-derived macrophages showed an increased uptake of acetylated low-density lipoprotein. When peritoneal macrophages from the RVS group were stimulated with LPS, the levels of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 in the supernatant decreased, but the level of IL-12 increased. The surface expression of CD86 was reduced, but surface expression of class II major histocompatibility complex molecules was increased. RVS suppressed the serum levels of LPS-induced TNF-alpha and IL-6. Collectively, RVS promoted monocyte differentiation upon inflammatory insults and conferred selective anti-inflammatory activity without causing overall inhibitory effects on immune cells. | Rhus |
Four military recruits with complete distraction-type stress fractures of the femoral neck were treated conservatively. The radiographic diagnosis was made within two weeks of the onset of symptoms and the activities of the patients were matched to the clinical and radiographic progress of fracture healing. None of the fractures displaced and union occurred uneventfully. Our experience suggests that prophylactic internal fixation of these fractures is not necessary. | Crutches |
It is rare for rehabilitation researchers to report substantial relationships between functional capacity and vocational rehabilitation achievements. The reason for this is that there are many other factors that also impact on the return-to-work outcomes people achieve. A solution to the problem of having to take into consideration the effects of multiple factors when evaluating intervention effectiveness is to focus more directly on cognitions and behaviors that have been theoretically and empirically linked with a satisfactory return to work. The aim of this paper is to explore and describe a measure of rehabilitation effectiveness based in cognitive-behavioral theory. Rather than the measurement of employment per se, the described measure is focused on the efforts individuals make in relation to achieving their desired outcome. To test the effectiveness, acceptability, and utility of the approach, the measure was trialed with 170 people with a spinal cord injury. This preliminary work has revealed that participants found the measure acceptable and gave detailed responses in regards to: their satisfaction with their vocational status; what it is they would prefer to be doing; and what it is that they are doing to achieve their aims. Study findings suggest that while the approach is likely to require further development, focusing on process variables holds promise as an evaluation approach when assessing the success of vocational rehabilitation intervention effectiveness. | Rehabilitation, Vocational |
Skeletal muscle shows high plasticity in response to external demand. Moreover, adult skeletal muscle is capable of complete regeneration after injury, due to the properties of muscle stem cells (MuSCs), the satellite cells, which follow a tightly regulated myogenic program to generate both new myofibers and new MuSCs for further needs. Although reactive oxygen species (ROS) and reactive nitrogen species (RNS) have long been associated with skeletal muscle physiology, their implication in the cell and molecular processes at work during muscle regeneration is more recent. This review focuses on redox regulation during skeletal muscle regeneration. An overview of the basics of ROS/RNS and antioxidant chemistry and biology occurring in skeletal muscle is first provided. Then, the comprehensive knowledge on redox regulation of MuSCs and their surrounding cell partners (macrophages, endothelial cells) during skeletal muscle regeneration is presented in normal muscle and in specific physiological (exercise-induced muscle damage, aging) and pathological (muscular dystrophies) contexts. Recent advances in the comprehension of these processes has led to the development of therapeutic assays using antioxidant supplementation, which result in inconsistent efficiency, underlying the need for new tools that are aimed at precisely deciphering and targeting ROS networks. This review should provide an overall insight of the redox regulation of skeletal muscle regeneration while highlighting the limits of the use of nonspecific antioxidants to improve muscle function. Antioxid. Redox Signal. 27, 276-310. | Regeneration |
BACKGROUND: Left ventricular mechanical dyssynchrony (LVMD) is closely associated with left ventricular dysfunction and poor prognosis in patients with acute myocardial infarction (AMI). However, whether mechanical dyssynchrony is present in the noninfarcted areas remains controversial. This research aimed to quantitatively evaluate the global and regional mechanical dyssynchrony early after AMI by phase analysis of single-photon emission computed tomography (SPECT) gated myocardial perfusion imaging (GMPI) and to further explore the related influencing factors. MATERIALS AND METHODS: Of 11 Bama suckling pigs, eight animals were successfully subjected to left anterior descending artery occlusion by balloon to generate porcine AMI models and completed the study. SPECT GMPI was performed before AMI and at 1 day, 1 week, and 4 weeks after AMI. The global bandwidth (BW), SD, entropy, total perfusion deficit, summed rest score, regional BW, regional summed motion score, and regional summed thickening score were measured by SPECT GMPI. RESULTS: The global BW, SD, and entropy values significantly increased after AMI and showed no significant change among the three time points after AMI. The BW in the infarcted area (left anterior descending artery-dominated area) at 1 day, 1 week, and 4 weeks after AMI was significantly higher than that before AMI, as was the BW in the noninfarcted areas (left circumflex artery-dominated and right coronary artery-dominated areas), which revealed that there was less dyssynchrony in the noninfarcted areas than in the infarcted area at the three time points after AMI. The global BW was positively correlated with the scar burden measured by summed rest score (r=0.709-0.832, all P<0.05), whereas the regional BW in the noninfarcted areas after AMI showed moderate to good correlation with regional summed motion score (r=0.733-0.875, all P<0.05) and regional summed thickening score (r=0.713-0.889, all P<0.05). CONCLUSION: LVMD occurs early on the first day after AMI, with no significant worsening over the next 4 weeks. Mechanical dyssynchrony was present in both the infarcted and noninfarcted areas. The global LVMD is mainly influenced by the scar burden, and the regional mechanical dyssynchrony in the noninfarcted areas is closely associated with the abnormal regional wall thickening and motion, which are indicative of reduced myocardial contractility." | Cardiac-Gated Single-Photon Emission Computer-Assisted Tomography |
The use of sensory neurons and assessment of neurite outgrowth in vitro is an important part of understanding neuronal development and plasticity. Cultures of rat dorsal root ganglion (DRG) neurons provide quantitative results very quickly and, when grown on growth promoting or inhibitory substrates, can be utilized to study axonal growth, neurotrophic dependence, and structure and function of growth cones. Since we are interested in axon regeneration and targeting, we have sought to promote neurite outgrowth by refining the techniques of growing DRG neurons in culture. This chapter describes detailed methods for the dissection and purification of DRG neurons and quantitative assessment of neurite on promoting or inhibitory substrates. | Ganglia, Spinal |
The intent of this article is to discuss the evolving role of the myofascial trigger point (MTrP) in myofascial pain syndrome (MPS) from both a historical and scientific perspective. MTrPs are hard, discrete, palpable nodules in a taut band of skeletal muscle that may be spontaneously painful (i.e., active) or painful only on compression (i.e., latent). MPS is a term used to describe a pain condition that can be acute or, more commonly, chronic and involves the muscle and its surrounding connective tissue (e.g. fascia). According to Travell and Simons, MTrPs are central to the syndrome-but are they necessary? Although the clinical study of muscle pain and MTrPs has proliferated over the past two centuries, the scientific literature often seems disjointed and confusing. Unfortunately, much of the terminology, theories, concepts, and diagnostic criteria are inconsistent, incomplete, or controversial. To address these deficiencies, investigators have recently applied clinical, imaging (of skeletal muscle and brain), and biochemical analyses to systematically and objectively study the MTrP and its role in MPS. Data suggest that the soft tissue milieu around the MTrP, neurogenic inflammation, sensitization, and limbic system dysfunction may all play a role in the initiation, amplification, and perpetuation of MPS. The authors chronicle the advances that have led to the current understanding of MTrP pathophysiology and its relationship to MPS, and review the contributions of clinicians and researchers who have influenced and expanded our contemporary level of clinical knowledge and practice. | Myofascial Pain Syndromes |
BACKGROUND: Anterior chamber miotic solutions are widely used during anterior chamber surgery. We examined the effects of solutions containing miotic agents such as carbachol and/or acetylcholine on corneal endothelial pumping activity. METHODS: We monitored, in vitro, the transendothelial electrical potential difference of isolated rabbit corneal endothelial preparations. As controls, we used solutions without miotics. RESULTS: We found that a solution containing 55 mM acetylcholine and minimal amounts of salts (Miochol E) maintains transendothelial electrical potential difference some 30% above control levels for up to 4 h. Two other solutions, one including balanced salts and 0.55 mM carbachol (Miostat), the other a mixture of 0.19 mM carbachol and 55 mM acetylcholine plus minimal salts, are adequate to maintain the potential difference at control levels. Lastly, a solution with acetylcholine but without any salts (Miochol) greatly decreases the potential difference, to 30% of the control level, in 100 min. CONCLUSION: Our results indicate that: (1) 55 mM (1%) acetylcholine stimulates the endothelial electrical potential difference; (2) addition of 0.19 mM (0.003%) carbachol negates the stimulatory effect of acetylcholine; and (3) absence of electrolytes severely depresses the endothelial electrical activity. | Miotics |
Desmoid tumors (DT) are rare, locally aggressive, fibroblastic soft-tissue tumors that are characterized by infiltrative growth and can affect organs and adjacent structures, resulting in substantial clinical burden impacting patients' health-related quality of life. Searches of PubMed, Embase, Cochrane, and key conferences were conducted in November 2021 and updated periodically through March 2023 to identify articles describing the burden of DT. Of 651 publications identified, 96 relevant ones were retained. Diagnosis of DT is challenging because of its morphologic heterogeneity and variable clinical presentation. Patients visit multiple healthcare providers, often facing delays in correct diagnosis. The low incidence of DT (estimated 3-5 cases per million person-years) limits disease awareness. Patients with DT experience a high symptom burden: up to 63% of patients experience chronic pain, which leads to sleep disturbance (73% of cases), irritability (46% of cases), and anxiety/depression (15% of cases). Frequently mentioned symptoms are pain, limited function and mobility, fatigue, muscle weakness, and swelling around the tumor. Overall, quality of life in patients with DT is lower than in healthy controls. There is no treatment approved by the US Food and Drug Administration for DT; however, treatment guidelines reference available options, such as active surveillance, surgery, systemic therapy, and locoregional therapy. Choice of active treatment may depend on tumor location, symptoms, and risk of morbidity. The substantial burden of illness of DT is related to difficulties in timely and accurate diagnosis, high symptom burden (pain and functional limitations), and decreased quality of life. There is a high unmet need for treatments that specifically target DT and improve quality of life. | Fibromatosis, Aggressive |
Findings from a major study of chiropractic in British Columbia are used to illustrate the nature of limitations that should be considered in planning chiropractics future direction. Fifty chiropractors, 60 new clients of chiropractors and selected leaders of the chiropractic profession were interviewed on a variety of issues. Results indicate that sociopolitical factors limiting chiropractic include lack of access to public facilities, absence of representation in government services, lack of public funds for research and education, limits to reimbursement for services and low social valuation. Nine findings are identified as critical to future organizational plans. We suggest that a specific planning approach, such as the critical success factor (CSF) approach, be considered as a planning framework for organizational success in complex sociopolitical environments. | Chiropractic |
BACKGROUND: BAHD acyltransferases are involved in the synthesis and elaboration of a wide variety of secondary metabolites. Previous research has shown that characterized proteins from this family fall broadly into five major clades and contain two conserved protein motifs. Here, we aimed to expand the understanding of BAHD acyltransferase diversity in plants through genome-wide analysis across five angiosperm taxa. We focus particularly on Populus, a woody perennial known to produce an abundance of secondary metabolites. RESULTS: Phylogenetic analysis of putative BAHD acyltransferase sequences from Arabidopsis, Medicago, Oryza, Populus, and Vitis, along with previously characterized proteins, supported a refined grouping of eight major clades for this family. Taxon-specific clustering of many BAHD family members appears pervasive in angiosperms. We identified two new multi-clade motifs and numerous clade-specific motifs, several of which have been implicated in BAHD function by previous structural and mutagenesis research. Gene duplication and expression data for Populus-dominated subclades revealed that several paralogous BAHD members in this genus might have already undergone functional divergence. CONCLUSIONS: Differential, taxon-specific BAHD family expansion via gene duplication could be an evolutionary process contributing to metabolic diversity across plant taxa. Gene expression divergence among some Populus paralogues highlights possible distinctions between their biochemical and physiological functions. The newly discovered motifs, especially the clade-specific motifs, should facilitate future functional study of substrate and donor specificity among BAHD enzymes. | Acyltransferases |
Methylation of the mRNA 5' guanosine cap is essential for efficient gene expression. The 5' methyl cap binds to eIF4E, which is the first step in the recruitment of mRNA to the 40S ribosomal subunit. To investigate whether mRNA cap methylation is regulated in a gene-specific manner, we established a method to detect the relative level of cap methylation on specific mRNAs. We found that two transcription factors, c-Myc and E2F1, induce cap methylation of their transcriptional target genes, and therefore, c-Myc and E2F1 upregulate gene expression by simultaneously inducing transcription and promoting translation. c-Myc-induced cap methylation is greater than transcriptional induction for the majority of its target genes, indicating that this is a major mechanism by which Myc regulates gene expression. | E2F1 Transcription Factor |
Arboviruses are maintained and transmitted through an alternating biological cycle in arthropods and vertebrates, with largely incidental disease in humans and animals. As such, they provide excellent examples of One Health, as their health impact is inextricably linked to their vertebrate hosts, their arthropod vectors and the environment. Prevention and control requires a comprehensive understanding of these interactions, and how they may be effectively and safely modified. This review concentrates on human disease due to Ross River and Murray Valley encephalitis viruses, the two major arboviral pathogens in Australia. It describes how their pattern of infection and disease is influenced by natural climatic and weather patterns, and by anthropogenic activities. The latter includes human-mediated environmental manipulations, such as water impoundment infrastructures, human movements and migration, and community and social changes, such as urban spread into mosquito larval habitats. Effective interventions need to be directed at the environmental precursors of risk. This can best be achieved using One Health approaches to improve collaboration and coordination between different disciplines and cross-sectoral jurisdictions in order to develop more holistic mitigation and control procedures, and to address poorly understood ecological issues through multidisciplinary research. | Encephalitis, Arbovirus |
PURPOSE OF REVIEW: This review offers a comprehensive summary of the recent publications on the treatment of vesicovaginal fistula. Most reports are related to obstetric fistula in the developing world but in the developed world fistula treatment remains a challenge. RECENT FINDINGS: The quality of the research in this field is improving. Efforts are being made to improve the classification of fistula as a prognostic tool. Surgical innovations are few in this field. Laparoscopic approaches are reported but only on a very limited amount of patients. SUMMARY: The surgical management of fistula remains a two-track item: the gigantic experience on obstetric fistula of fistula surgeons in Africa and Asia and the limited experience of some Western centres with mostly a small series of iatrogenic fistula. Advances are made in both worlds. The previously isolated fistula surgeons are now better organized and they stimulate scientific research in countries with very limited resources. The centres in the developed world explore new surgical approaches such as laparoscopy and minimally invasive treatments. | Urinary Fistula |
Understanding the impact of irrigation and fertilizer on rabbiteye blueberry (Vaccinium virgatum) physiology is necessary for its precision planting. Here, we applied varied irrigation and fertilizer under completely randomized experimental design to see its impact on the physiological characteristics and bush growth of rabbiteye blueberries. A comprehensive evaluation of the membership function was used to establish the best water-fertilizer coupling regimes. Rabbiteye blueberry enhanced the net photosynthetic rate, stomatal conductance and transpiration rate of leaf and improved its photosynthetic capacity at maximum level of irrigation water and fertilizer application (F3W4). The high fertilizer-medium water treatment (F3W3) increased leaf-soluble protein contents. The medium fertilizer-medium water treatment (F2W3, F2W2) increased leaf- soluble sugar, superoxide dismutase, and chlorophyll contents; decreased the malondialdehyde content; and enhanced leaf resistance and metabolism. It also promoted the growth of flower buds and new shoots. Combined membership function and cluster analyses revealed that the optimal water and fertilizer conditions for promoting rabbiteye blueberry plant growth were the medium fertilizer-medium water [(NH4)2SO4:Ca(H2PO4)2:K2SO4 at 59:10:20 g plant-1; 2.5 L water plant-1], medium fertilizer-medium-high water [(NH4)2SO4:Ca(H2PO4)2:K2SO4 at 59:10:20 g plant-1; 3.75 L water plant-1], and high fertilizer-medium-high water [(NH4)2SO4:Ca(H2PO4)2:K2SO4 at 118:20:40 g plant-1; 3.75 L water plant-1] treatments. The findings of this study could be used in improving the precision and efficacy of rabbiteye blueberry planting in Guizhou, China. Such an approach can increase the productivity and profitability for local fruit farmers. | Ericaceae |
The synthesis of complex, coordinated movements from simple actions is an important aspect of motor control. Lesion studies have revealed specific brain areas, particularly the cerebellum, to be essential for a variety of coordinated movements, and lend support to the view that the cerebellum is engaged in the integration of simple movements into compound ones. A PET study was therefore conducted to show which brain areas were active specifically during the coordinated execution of an arm and finger movement to visual targets. A two-by-two factorial design was employed, in which subjects either made arm or finger movements alone, made coordinated arm-finger movements, or made no movements. Voxels were identified where activity was significantly greater during the execution of coordinated movements than when movements were made alone and in which this increased activity could not be accounted for simply by the additive effects of the activations for each movement in isolation. The behavioral results showed that subjects coordinated arm and finger movements well during coordination scans. Coordination-specific activations were found in left anterior lobe and bilaterally in the paramedian lobules of the cerebellum. These are known to receive forelimb-specific spinocerebellar proprioceptive inputs that may be related to multijoint movements. The same areas also receive corticocerebellar afference from motor areas that may convey efference copy information to the cerebellum. Coordination-specific activations were also seen in areas of the posterior parietal cortex. The results provide direct evidence in healthy human subjects of specific cerebellar engagement during the coordination of movement, over and above the control of constituent movements. | Spinocerebellar Tracts |
BACKGROUND: This was the first study to investigate the reactogenicity and immunogenicity of heterologous or fractional second dose COVID-19 vaccine regimens in adolescents. METHODS: A phase II, single-blind, multi-centre, randomised-controlled trial recruited across seven UK sites from September to November 2021, with follow-up visits to August 2022. Healthy 12-to-16 years olds were randomised (1:1:1) to either 30 microg BNT162b2 (BNT-30), 10 microg BNT162b2 (BNT-10), or NVX-CoV2373 (NVX), 8 weeks after a first 30 microg dose of BNT162b2. The primary outcome was solicited systemic reactions in the week following vaccination. Secondary outcomes included immunogenicity and safety. 'Breakthrough infection' analyses were exploratory. FINDINGS: 148 participants were recruited (median age 14 years old, 62% female, 26% anti-nucleocapsid IgG seropositive pre-second dose); 132 participants received a second dose. Reactions were mostly mild-to-moderate, with lower rates in BNT-10 recipients. No vaccine-related serious adverse events occurred. Compared to BNT-30, at 28 days post-second dose anti-spike antibody responses were similar for NVX (adjusted geometric mean ratio [aGMR]) 1.09 95% confidence interval (CI): 0.84, 1.42] and lower for BNT-10 (aGMR 0.78 [95% CI: 0.61, 0.99]). For Omicron BA.1 and BA.2, the neutralising antibody titres for BNT-30 at day 28 were similar for BNT-10 (aGMR 1.0 [95% CI: 0.65, 1.54] and 1.02 [95% CI: 0.71, 1.48], respectively), but higher for NVX (aGMR 1.7 [95% CI: 1.07, 2.69] and 1.43 [95% CI: 0.96, 2.12], respectively). Compared to BNT-30, cellular immune responses were greatest for NVX (aGMR 1.73 [95% CI: 0.94, 3.18]), and lowest for BNT-10 (aGMR 0.65 [95% CI: 0.37, 1.15]) at 14 days post-second dose. Cellular responses were similar across the study arms by day 236 post-second dose. Amongst SARS-CoV-2 infection naive participants, NVX participants had an 89% reduction in risk of self-reported 'breakthrough infection' compared to BNT-30 (adjusted hazard ratio [aHR] 0.11 [95% CI: 0.01, 0.86]) up until day 132 after second dose. BNT-10 recipients were more likely to have a 'breakthrough infection' compared to BNT-30 (aHR 2.14 [95% CI: 1.02, 4.51]) up to day 132 and day 236 post-second dose. Antibody responses at 132 and 236 days after second dose were similar for all vaccine schedules. INTERPRETATION: Heterologous and fractional dose COVID-19 vaccine schedules in adolescents are safe, well-tolerated and immunogenic. The enhanced performance of the heterologous schedule using NVX-CoV2373 against the Omicron SARS-CoV-2 variant suggests this mRNA prime and protein-subunit boost schedule may provide a greater breadth of protection than the licensed homologous schedule. FUNDING: National Institute for Health Research and Vaccine Task Force. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number registry: 12348322. | Breakthrough Infections |
Cleft lip and/or palate (CL/P) is phenotypically diverse, making classification difficult. This article explores the evolution of ideas regarding CL/P classification and includes the schemes described by Davis and Ritchie (1922) , Brophy (1923) , Veau (1931) , Fogh-Andersen (1943), Kernahan and Stark (1958) , Harkins et al. (1962) , Broadbent et al. (1968), Spina (1973) , and others. Based on these systems, a longhand structured form is proposed for describing CL/P in a way that is clear, comprehensive, and consistent. A complementary shorthand notation is also described to improve the utility and convenience of this structured form. | Cleft Palate |
Recent progress in the Nerve Growth Factor (NGF) research has shown that this factor acts not only outside its classical domain of the peripheral and central nervous system, but also on non-neuronal and cancer cells. This latter observation has led to divergent hypothesis about the role of NGF, its specific distribution pattern within the tissues and its implication in induction as well as progression of carcinogenesis. Moreover, other recent studies have shown that NGF has direct clinical relevance in certain human brain neuron degeneration and a number of human ocular disorders. These studies, by suggesting that NGF is involved in a plethora of physiological function in health and disease, warrant further investigation regarding the true role of NGF in carcinogenesis. Based on our long-lasting experience in the physiopathology of NGF, we aimed to review previous and recent in vivo and in vitro NGF studies on tumor cell induction, progression and arrest. Overall, these studies indicate that the only presence of NGF is unable to generate cell carcinogenesis, both in normal neuronal and non-neuronal cells/tissues. However, it cannot be excluded the possibility that the co-expression of NGF and pro-carcinogenic molecules might open to different consequence. Whether NGF plays a direct or an indirect role in cell proliferation during carcinogenesis remains to demonstrate. | Nerve Growth Factor |
Acetylation of prothrombin fragment 1 in acetate-borate buffer at pH 8.5 resulted in the appearance of increased light absorbance at about 250 nm. Protease digestions resulted in isolation of a single peptide (residues 94-99) with intense absorbance at about 250 nm (estimated extinction coefficient of 5000 M-1 cm-1). Amino acid analysis showed the expected composition except for the absence of His-96. Instead, an unidentified amino acid which had a ninhydrin product with absorption properties similar to those of proline eluted near aspartate. When sequenced, this peptide (YP?KPE containing epsilon-amino-acetyllysine) lacked histidine at the third position but gave a high yield of a PTH derivative that eluted near PTH-Gly from the HPLC column. Fast atom bombardment mass spectrometry of the derivatized 94-99 peptide showed a mass that was 74 units higher than expected. The histidine degradation product was identified as a di-N-acetylated side chain with an opened imidazole ring and loss of C2 of the ring. While a similar degradation pattern has previously been reported during acylation of histidine, the high chemical reactivity exhibited by His-96 was unusual. For example, under conditions sufficient for quantitative derivatization of His-96, His-105 of fragment 1 was not derivatized to a detectable level. Furthermore, His-96 in fragment 1 was at least an order of magnitude more susceptible to degradation than His-96 in the isolated 94-99 peptide. His-96 is therefore one of several neighboring amino acids of the kringle portion of fragment 1 that displays highly unusual chemistry (see also Asn-101 [Welsch, D.J., & Nelsestuen, G. L. (1988) Biochemistry 27 4946-4952] and Lys-97 [Pollock, J.S., Zapata, G.A., Weber, D.J., Berkowitz, P., Deerfield, D.W., II, Olson, D.L., Koehler, K.A., Pedersen, L.G., & Hiskey, R.G. (1988) in Current Advances in Vitamin K Research (Suttie, J.W., Ed.) pp 325-334, Elsevier Science, New York]).(ABSTRACT TRUNCATED AT 250 WORDS) | Acetic Anhydrides |
A recent investigation into the myxozoan fauna of common gobies, Pomatoschistus microps, from the Forth Estuary in Scotland, revealed numerous myxosporean cysts within the gill cartilage. They were composed of polysporous plasmodia containing myxobolid spores that were morphologically different from the other known species of Myxobolus and from the myxosporeans previously recorded from this host (i.e. the ceratomyxid Ellipsomyxa gobii, infecting the gall bladder, and the kudoid Kudoa camarguensis, infecting the muscle tissues). Spores were ovoid, 9.4 x 9.1 microm with a thickness of 6.6 microm, with two pyriform polar capsules, the polar filaments of which had four to five turns. Molecular analysis of the parasite's small subunit rDNA region, based upon a contiguous sequence of 1,558 base pairs, discriminated it from other myxosporean species that have been characterized so far. A comparison of the spore morphology and the molecular sequences determined for this new isolate with other myxozoans described to date, confirmed its identity as a previously unknown myxobolid supporting the proposal that this isolate be elevated to the species level as a new species within the genus Myxobolus. A phylogenetic analysis places this new myxobolid, Myxobolus albi n. sp., in a basal position of a clade containing the majority of Henneguya spp. sequenced to date and various Myxobolus spp. | Myxobolus |
BACKGROUND: Parasites excrete and secrete a wide range of molecules that act as the primary interface with their hosts and play critical roles in establishing parasitism during different stages of infection. Strongyloides venezuelensis is a gastrointestinal parasite of rats that is widely used as a laboratory model and is known to produce both soluble and insoluble (adhesive) secretions during its parasitic stages. However, little is known about the constituents of these secretions. RESULTS: Using mass spectrometry, we identified 436 proteins from the infective third-stage larvae (iL3s) and 196 proteins from the parasitic females of S. venezuelensis. The proteins that were secreted by the iL3s were enriched with peptidase activity, embryo development and the oxidation-reduction process, while those of the parasitic females were associated with glycolysis, DNA binding (histones) and other unknown functions. Trypsin inhibitor-like domain-containing proteins were identified as the main component of the adhesive secretion from parasitic females. An absence of secretion signals in many of the proteins indicated that they are secreted via non-classical secretion pathways. CONCLUSIONS: We found that S. venezuelensis secretes a wide range of proteins to establish parasitism. This includes proteins that have previously been identified as being involved in parasitism in other helminths as well as proteins that are unique to this species. These findings provide insights into the molecular mechanisms underlying Strongyloides parasitism. | Helminth Proteins |
In the whole animal kingdom, fear learning is an essential process that allows living beings to survive. Therefore, revealing the neurophysiological processes that govern the expression of emotional fear memory and exploring its neurobiological underpinnings are the imperatives of affective neuroscience. Learned fear memories activate defensive behaviors in anticipation of harm, thus minimizing the impact of the threat. However, despite a century of research, the neural circuitry underlying fear learning in humans is still a matter of debate. This editorial will discuss recent evidence of the neural and behavioral correlates of fear learning in humans, with an emphasis on the role of the human prefrontal cortex (PFC). | Fear |
The role of phosphodiesterase type 5 (PDE5) in the mechanism of male erection has been well understood, and several drugs inhibiting this enzyme are being used for the treatment of erectile dysfunction (ED). Discovery of inhibitors with improved selectivity versus other PDE isozymes could lead to drugs with improved safety profile. Achievement of selectivity versus PDE6, co-inhibition of which results in disturbances of color perception, remains the most challenging aspect of current drug discovery programs. The present review describes several case studies, where significant (>100 fold) selectivity versus PDE6 has been attained via investigation of structure-activity relationships (SAR). Special attention is given to the chemical routes leading to novel chemotypes and allowing efficient exploration of their SAR's. Strategies for attaining inhibitor selectivity discussed below may be applicable for other drug discovery programs. | Phosphoric Diester Hydrolases |
OBJECTIVE: To compare prenatal and perinatal outcomes of twin pregnancies in which one twin the nuchal translucency (NT) was above the 95th percentile in dichorionic twins (DCT) and monochorionic twins (MCT). METHOD: In this retrospective study, 93 twin pregnancies (186 fetuses) in which one twin the NT was above the 95th percentile and the co-twin had normal NT were analyzed. Results of of G-banding and Chromosomal microarray (CMA), ultrasound findings and pregnancy outcomes were reviewed. RESULTS: Totally, 57 pregnancies (114 fetuses) were DCT and 36 pregnancies (72 fetuses) were MCT. Karyotyping and CMA results shown that clinically significant chromosomal abnormalities were found in 16 fetuses, including 13 aneuploidies, 2 chromosomal mosaic and 1 pathological Copy number variations (CNVs) (14 were DCT and 2 were MCT). Overall, the incidence of fetal chromosomal abnormalities was 12.3% (14/114) in DCT and 2.8%(2/72) in MCT (chi(2) = 3.932, p = 0.047). Among the cases with normal prenatal diagnosis result, structural abnormalities were found in four fetuses (4.0%, 4/100) in DCT and two fetuses (2.9%, 2/70) in MCT (p > 0.999). There were one intrauterine fetal demises (IUFD) and two miscarry in DCT. One IUFD, three subsequently developed Twin-to-Twin Transfusion Syndrome (TTTS) and four developed selective intrauterine growth restriction (sIUGR) in MCT. Totally, the overall fetal survival rate was 85.1% (97/114) in DCT and 80.6% (58/72) in MCT (chi(2) = 0.653, p = 0.419). CONCLUSION: Compared to MCT, the incidence of chromosomal abnormalities in DCT discordant for one fetus with NT above the 95th percentile was higher. The risk of structural abnormalities and the rate of fetal survival for both MCT and DCT was similar." | Nuchal Translucency Measurement |
Repetitive and stereotyped behavior is a prominent element of both animal and human behavior. Similar behavior is seen across species, in diverse neuropsychiatric disorders and in key phases of typical development. This raises the question whether these similar classes of behavior are caused by similar neurobiological mechanisms or whether they are neurobiologically unique? In this paper we discuss fundamental animal research and translational models. Imbalances in corticostriatal function often result in repetitive behavior, where different classes of behavior appear to be supported by similar neural mechanisms. Although the exact nature of these imbalances are not yet fully understood, synthesizing the literature in this area provides a framework for studying the neurobiological systems involved in repetitive behavior. | Stereotyped Behavior |
The functional form W = (W0Kc + Wf t(c)) /(Kc + t(c)), where W is body size at age t, W0 and Wf are the zero- and infinite-time values of W, respectively, and K and c are constants, is derived. This new generalized Michaelis-Menten-type equation provides a flexible model for animal growth capable of describing sigmoidal and diminishing returns behavior. The parameters of the nonlinear model are open to biological interpretation and can be used to calculate reliable estimates of growth traits, such as maximum or average postnatal growth rates. To evaluate the new model, the derived equation and standard growth functions such as the Gompertz and Richards were used to fit 83 growth data sets of different animal species (fish, mice, hamsters, rats, guinea pigs, rabbits, cats, dogs, broilers, turkeys, sheep, goats, pigs, horses, and cattle) with a large range in body size. A comparative study was carried out based on mathematical, statistical, and biological characteristics of the models. The statistical goodness-of-fit achieved with the new model was similar to that of Richards, and both were slightly superior to the Gompertz. The new model differed from the others with respect to some of the estimated growth traits, but there were highly significant correlation coefficients between estimates obtained with the different models, and the ranking of animals based on growth parameters computed with the new function agreed with the rankings computed by the other models. Therefore, the new model, with its variable inflection point, was able to adequately describe growth in a wide variety of animals, to fit a range of data showing sigmoidal growth patterns, and to provide satisfactory estimates of traits for quantifying the growth characteristics of each type of animal. | Mammals |
Mass spectrometers that use different types of analyzers for the first and second stages of mass analysis in tandem mass spectrometry (MS/MS) experiments are often referred to as hybrid" mass spectrometers. The general goal in the design of a hybrid instrument is to combine different performance characteristics offered by various types of analyzers into one mass spectrometer. These performance characteristics may include mass resolving power, the ion kinetic energy for collision-induced dissociation, and speed of analysis. This paper provides a review of the development of hybrid instruments over the last 30 years for analytical applications." | Tandem Mass Spectrometry |
As the foremost journal in spiritual care and counseling (SCC), Journal of Pastoral Care & Counseling (JPCC) functions as a barometer for the discipline's research and interests. This article presents the findings of a review of the research literature in JPCC between 2010 and 2014. It examines research articles by asking the following questions: What are the quantity and types of research published? What are the dominant themes in this research? What are the quantity and methodologies of qualitative research? Findings are presented, discussed and recommendations are made in an effort to assess and further build the research base of the discipline. | Religion and Psychology |
Zebrafish (Danio rerio) is a well-established vertebrate animal model. A comprehensive collection of reverse genetics tools has been developed for studying gene function in this useful organism. Morpholino is the most widely used reagent to knock down target gene expression post-transcriptionally. For a long time, targeted genome modification has been heavily relied on large-scale traditional forward genetic screens, such as ENU (N-ethyl-N-nitrosourea) mutagenesis derived TILLING (Targeting Induced Local Lesions IN Genomes) strategy and pseudo-typed retrovirus mediated insertional mutagenesis. Recently, engineered endonucleases, including ZFNs (zinc finger nucleases) and TALENs (transcription activator-like effector nucleases), provide new and efficient strategies to directly generate site-specific indel mutations by inducing double strand breaks in target genes. Here we summarize the major reverse genetic approaches for loss-of-function studies used and emerging in zebrafish, including strategies based on genome-wide mutagenesis and methods for site-specific gene targeting. Future directions and expectations will also be discussed. | INDEL Mutation |
OBJECTIVE: To assess the effectiveness and safety of fast-track cardiac anesthesia using the short-acting opioid sufentanil in children undergoing intraoperative device closure of ventricular septal defect (VSD). METHODS: This retrospective clinical study included 65 children who underwent intraoperative device closure of VSD between January 2017 and June 2017. Patients were diagnosed with isolated perimembranous VSD by transthoracic echocardiography. Then, they were divided into two groups, group F (n=30), whose patients were given sufentanil-based fast-track cardiac anesthesia, and group C (n=35), whose patients were given conventional cardiac anesthesia. Perioperative clinical data were analyzed. RESULTS: No significant differences were found between the preoperative clinical parameters and intraoperative hemodynamic indices between the two groups. In group C, compared with group F, the postoperative duration of mechanical ventilation, the length of stay in the intensive care unit, the length of hospital stay, and the hospital costs were significantly increased. CONCLUSION: In this retrospective study at a single center, sufentanil-based fast-track cardiac anesthesia was shown to be a safe and effective technique for minimally-invasive intraoperative device closure of VSD in children, which was performed with reduced in-hospital costs." | Anesthesia, Cardiac Procedures |
In parasitic protozoan Leishmania enriettii, the role of a multidrug resistance (mdr) gene LeMDR1 (L. enriettii multidrug resistance 1) in mediating vinblastine resistance has been previously demonstrated by association, transfection and gene knockout" studies. LeMDR1 has been shown to be located intracellularly and it was proposed to mediate drug resistance by sequestering drugs into intracellular organelles rather than by active efflux. Here we compared LeMDR1 overexpressed cell lines (Vint3 and V160), wild type (Le) and LeMDR1 "double knockout" mutant (LeMDR1-/-) and demonstrated that LeMDR1 gene copy number was associated with (1) higher level of intracellular iron, (2) increased sensitivity to an iron-dependent antibiotic, streptonigrin and (3) increased enzyme activity of an iron-sulfur-containing mitochondrial enzyme, aconitase. This result suggests that the normal function of LeMDR1 is related to mitochondrial iron homeostasis. To test such hypothesis, we have used the LeMDR1-overexpressing mutant V160 and LeMDR1-/- mutant to determine how iron level can affect its resistance level to drugs targeting either cytosol (vinblastine) or mitochondria (rhodamine 123 and pentamidine). It was found that the resistance level of V160 to vinblastine can be increased by iron whereas resistance to both rhodamine 123 and pentamidine can be increased by iron depletion and vice versa. Iron treatment can potentiate rhodamine 123 and pentamidine accumulation whereas iron deprivation can cause the reduction of rhodamine 123 accumulation. Our result highly suggests that LeMDR1's function in mediating drug resistance is iron-dependent." | Leishmania enriettii |
In March 2016, the UK government announced the Soft Drinks Industry Levy (SDIL) which came into effect in April 2018. In common with the reaction to sugar-sweetened beverage (SSB) taxes in other countries, the SDIL announcement was met with strong industry opposition, with claims that it would harm their profits. The SDIL was designed to incentivise reformulation of SSBs by providing a 2-year delay between the announcement and the enforcement of the levy, and adopting a two-tiered rate based on the sugar content of the drinks. Using interrupted time series analysis, this paper examines how the domestic turnover of UK soft drinks manufacturers changed after the announcement and the implementation of the SDIL. Our results show some evidence of a short-term negative impact of the SDIL announcement on the domestic turnover of the UK soft drinks manufacturers. This effect, however, did not continue post-implementation. These findings suggest that manufacturers were, to a large extent, able to mitigate the effects of levy before it came into effect. | Carbonated Beverages |
Secondary metabolites from bracken fern (Pteridium aquilinum (L.) Kuhn) are suspected of causing cancer in humans. The main carcinogen is the highly water-soluble norsesquiterpene glucoside ptaquiloside, which may be ingested by humans through food, e.g. via contaminated water, meat or milk. It has been postulated that carcinogens could also be ingested through breathing air containing bracken spores. Ptaquiloside has not previously been identified in bracken spores. The aim of the study was to determine whether ptaquiloside is present in bracken spores, and if so, to estimate its content in a collection of spores from Britain. Ptaquiloside was present in all samples, with a maximum of 29 mug g(-1), which is very low compared to other parts of the fern. Considering the low abundance of spores in breathing air under normal conditions, this exposure route is likely to be secondary to milk or drinking water. | Pteridium |
REV-ERBalpha (NR1D1) is a circadian clock component that functions as a transcriptional repressor. Due to its role in direct modulation of metabolic genes, REV-ERBalpha is regarded as an integrator of cell metabolism with circadian clock. Accordingly, REV-ERBalpha is first proposed as a drug target for treating sleep disorders and metabolic syndromes (e.g., dyslipidaemia, hyperglycaemia and obesity). Recent years of studies uncover a rather broad role of REV-ERBalpha in pathological conditions including local inflammatory diseases, heart failure and cancers. Moreover, REV-ERBalpha is involved in regulation of circadian drug metabolism that has implications in chronopharmacology. In the meantime, recent years have witnessed discovery of an array of new REV-ERBalpha ligands most of which have pharmacological activities in vivo. In this article, we review the regulatory role of REV-ERBalpha in various types of diseases and discuss the underlying mechanisms. We also describe the newly discovered ligands and the old ones together with their targeting potential. Despite well-established pharmacological effects of REV-ERBalpha ligands in animals (preclinical studies), no progress has been made regarding their translation to clinical trials. This implies certain challenges associated with drug development of REV-ERBalpha ligands. In particular, we discuss the potential challenges related to drug safety (or adverse effects) and bioavailability. For new drug development, it is advocated that REV-ERBalpha should be targeted to treat local diseases and a targeting drug should be locally distributed, avoiding the adverse effects on other tissues." | Nuclear Receptor Subfamily 1, Group D, Member 1 |
The safety, tolerance, and pharmacokinetics of transnasal butorphanol were evaluated in a double-blind, multiple-dose phase I study. A total of 18 subjects received either placebo (n = 6) or a single transnasal dose of 2 mg butorphanol tartrate on the first day and 1, 2, and 4 mg doses of butorphanol tartrate every 6 hours on days 2 through 6, 7 through 11, and 12 through 16, respectively. Safety assessment was performed on days 7, 12, and 17. Serial blood samples were collected on days 1, 6, 11, and 16, and the plasma was analyzed for unchanged butorphanol by a validated and specific radioimmunoassay. Butorphanol was rapidly absorbed and peak levels in plasma were generally attained within 1 hour after the nasal administration. The values of maximum concentration, minimum concentration, and area under the concentration versus time curve from time zero to the dosing interval [AUC(0-tau)] increased as the administered dose increased in a dose-proportional manner. The values of AUC from time zero to infinity after a single dose of 2 mg butorphanol tartrate, 10.9 ng.hr/ml, were identical to the values of AUC(0-tau) after a multiple administration of 2 mg dose, 10.4 ng.hr/ml. Mean elimination half-life value was 5.45 hours. Steady state was reached in fewer than eight doses when given every 6 hours. Transnasal butorphanol was well tolerated by all subjects. After repeated administration of transnasal butorphanol, no significant changes were observed in the nasal examination, which included evaluation of color, wetness, and thickness of nostril membrane, air flow, airway patency, and general nasal conditions.(ABSTRACT TRUNCATED AT 250 WORDS) | Butorphanol |
The AAA(+) ATPase p97 regulates ubiquitin-dependent protein homeostasis and has been pursued as a cancer drug target. The ATP-competitive inhibitor CB-5083 and allosteric inhibitor NMS-873 are the most advanced p97 inhibitors described to date. Previous studies have reported that their cytotoxicity can be readily overcome and involves single p97 mutations in the linker between the D1 and D2 ATPase domains and within D2. We report here that the proline 472 to leucine (P472L) mutation, in the D1-D2 linker and identified in CB-5083-resistant cells, desensitizes p97 to both inhibitor classes. This mutation does not disrupt the distinct D2-binding sites of the inhibitors. Instead, P472L changes ATPase domain communication within the p97 hexamer. P472L enhances cooperative D2 ATP binding and hydrolysis. This mechanism alters the function of the D1-D2 linker in the control of D2 activity involving the ATP-bound state of D1. Although increased D2 activity is sufficient to desensitize the P472L mutant to NMS-873, the mutant's desensitization to CB-5083 also requires D1 ATPase domain function. Our study highlights the remarkable adaptability of p97 ATPase domain communication that enables escape from mechanistically distinct classes of cytotoxic p97 inhibitors. | Adenosine Triphosphatases |
Nanozymes are a class of nanomaterials with intrinsic enzyme-like characteristics which overcome the limitations of natural enzymes such as high cost, low stability and difficulty to large scale preparation. Nanozymes combine the advantages of chemical catalysts and natural enzymes together, and have exhibited great potential in biomedical applications. However, the size controllable synthesis and targeting modifications of nanozymes are still challenging. Here, we introduce ferritin nanozymes to solve these problems. Ferritins are natural nanozymes which exhibit intrinsic enzyme-like activities (e.g. ferroxidase, peroxidase). In addition, by biomimetically synthesizing nanozymes inside the ferritin protein shells, artificial ferritin nanozymes are introduced, which possess the advantages of versatile self-assembly ferritin nanocage and enzymatic activity of nanozymes. Ferritin nanozymes provide a new horizon for the development of nanozyme in disease targeted theranostics research. The emergence of ferritin nanozyme also inspires us to learn from the natural nanostructures to optimize or rationally design nanozymes. In this review, the intrinsic enzyme-like activities of ferritin and bioengineered synthesis of ferritin nanozyme were summarized. After that, the applications of ferritin nanozymes were covered. Finally, the advantages, challenges and future research directions of advanced ferritin nanozymes for biomedical research were discussed. | Theranostic Nanomedicine |
Using endoscopic ultrasonography (EUS), it is practicable to diagnose subepithelial lesions (SEL) with originating layer, echo level, and internal echo pattern etc. Lipoma, lymphangioma, and cyst have characteristic features; therefore, there is no need for endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Ectopic pancreas and glomus tumors, which originate from the third and fourth layers, are frequently seen in the antrum. However, ectopic pancreas located in the fundus or body is large and originates from the third and fourth layers (thickening of fourth layer). Each subepithelial lesion has characteristic findings. However, imaging differentiation of tumors originating from the fourth layer is very difficult, even if contrast echo is used. Therefore, EUS-FNA should be done in these tumors, but the diagnostic yield for small lesions is not sufficient for clinical demands. Generally, those tumors, including small ones, should be first followed up in 6 months, then yearly follow up in cases of no significant change in size and features. When those tumors become larger than 1-2 cm, EUS-FNA is recommended. Furthermore, unusual SEL and SEL with malignant findings such as nodular, heterogeneous, anechoic area, and ulceration indicate EUS-FNA. Cap-attached forward-viewing echoendoscope is very helpful for EUS-FNA of small SEL. | Epithelium |
BACKGROUND: Subclavian vein and brachiocephalic vein occlusions are challenging problems in dialysis patients with ipsilateral upper extremity (UE) vascular access or in need of one. HeRO grafts (Hemodialysis Reliable Outflow, Merit Medical Systems, Inc, South Jordan, UT) have been used to manage such occlusions but patients with chronic hypotension treated with HeRO graft may have threatened patency. We describe an alternative technique using a supraclavicular stent graft to reconstruct the venous outflow, evaluate outcomes of this procedure, and discuss its role in complex hemodialysis patients. METHODS: From January 2019 to January 2020, we performed open surgical and endovascular dialysis access procedures in 297 patients. Eight patients (2.7%) with failing or failed access and subclavian and or brachiocephalic vein occlusion were treated with supraclavicular stent graft placement. Mean age was 52 years, ranging from 32 to 70. Five patients had failed access and were dialyzed using catheters (two femoral). Three patients with failing fistulas had severe arm edema. Two patients had recurrent HeRO graft thrombosis. We performed a retrospective review of these 8 patients and evaluated access patency and complications. RESULTS: Technical success and access function were 100% in all patients. One patient developed ischemic neuropathy and underwent proximalization of the arterial inflow with improvement. Already-existing fistulas were used for dialysis the day after the procedure and new grafts within 2-4 weeks. Arm edema resolved within one week after the procedure. Median follow-up was 254.5 days, range 24-408 days, with primary patency rate of 87.5% and secondary patency rate of 100%. Only one patient has required reintervention. Postoperative evaluation with ultrasound has revealed patent stent graft in the area of the subcutaneous cervical tunnel over the clavicle. CONCLUSIONS: Supraclavicular stent graft placement to a central vein can be used successfully to reconstruct venous outflow in hemodialysis patients with complex central vein occlusions. A supraclavicular extra-anatomic path can be used safely and effectively to place new UE vascular access or salvage threatened access in this challenging patient population. | Brachiocephalic Veins |
In our efforts to determine the components participating in the electron transport to nitrogenase in Rhodospirillum rubrum, we have identified a gene encoding a new ferredoxin. We have generated mutants in both the new ferredoxin and ferredoxin I and demonstrate that the new ferredoxin, FdN and not the previously identified FdI is the main donor of electrons to nitrogenase. | Rhodospirillum rubrum |
Autologous peripheral blood stem cell transplantation (PBSCT) has been demonstrated to result in rapid. stable long-term engraftment. However, there has been considerable debate concerning the cells responsible for early and late hematopoietic reconstitution after PBSCT. Recently, CD34+ hematopoietic stem and progenitor cells have been clearly divided into two subpopulations by flow cytometry; namely undifferentiated pluripotent stem cells and differentiated committed progenitor cells. However, only a few studies have defined which subset contained in graft products might be the most predictive for late hematopoietic reconstitution after PBSCT. In this review, we present updated information regarding the relationships between the number of infused CD34+ cells or their immature subsets such as CD34+ CD90+ cells and the late hematopoietic reconstitution after PBSCT, and discuss the threshold dose of CD34 + CD90+ cells required for sustained long-term engraftment. | Thy-1 Antigens |
Five adult patients were admitted to the neurological department in a state of status epilepticus. All were treated unsuccessfully with IV diazepam and diphenylhydantoin. Administration of sodium valporate or phenobarbital also was ineffective. However, after treatment with intrarectal chloral hydrate, all seizures ceased. The excellent effect of this drug was proved both clinically and electrodiagnostically. Discussed is the possibility of using chloral hydrate to treat patients with status epilepticus in whom conventional treatment has failed. | Chloral Hydrate |
BACKGROUND: Sodium glucose cotransporter-2 (SGLT-2) inhibitors have been widely used in the clinic to reduce blood glucose levels by enhancing glucose excretion. However, whether such agents might also reduce glucose absorption via the peritoneal function of human peritoneal mesothelial cells (HPMCs) that also express SGLT-2 is not clear. METHODS: An acute peritoneal dialysis (PD) model in nonuremic rats was established. Ratios of peritoneal glucose uptake at D4/D0 of Sprague-Dawley rats treated with the SGLT-2 inhibitor, empagliflozin were tested to evaluate the effect of this inhibitor on peritoneal glucose absorption. An in vitro model of HPMCs obtained from peritoneal dialysate effluent in patients undergoing PD was used. HPMCs were exposed to high glucose (60 mM) in the presence and absence of empagliflozin. Glucose uptake and glucose consumption, which were used to estimate the activity of SGLT-2 in HPMCs, were measured by flow cytometry and hexokinase respectively. The expression of SGLT-2 in both peritoneum and HPMCs was also observed by real-time polymerase chain reaction (PCR), western blot, and immunofluorescence staining. RESULTS: Both ratios of peritoneal glucose uptake at D4/D0 and ultrafiltration of rats treated with 3 mg kg(-1) of empagliflozin for 3 days increased significantly compared to those of the control group (0.32 +/- 0.40 vs. 0.11 +/- 0.11 mM, P = 0.001ï¼Â17.00 +/- 3.58 vs. -13.67 +/- 17.25 ml, P = 0.002). Compared to the control group, the expression of mRNA and protein in SGLT-2 increased significantly in the rats treated with 3 mg kg(-1) of empagliflozin for 3 days. Both glucose consumption and uptake of HPMCs incubated with 1 muM of empagliflozin for 24 h decreased significantly compared to control values (8.69 +/- 1.77 vs. 11.48 +/- 1.00 mM, P = 0.004; 31.97 +/- 4.81 vs. 43.98 +/- 1.38, P = 0.002). CONCLUSION: An SGLT-2 inhibitor was able to exert a glucose-lowering effect in peritoneum exposed to PD solution by inhibiting the activity of SGLT-2. | Sodium-Glucose Transporter 2 |
Using delivery system innovations to advance health care reform continues to be of widespread interest. However, it is difficult to generalize about the success of specific types of innovations, since they have been examined in only a few studies. To gain a broader perspective, we analyzed the results of forty-three ambulatory care programs funded by the first round of the Center for Medicare and Medicaid Innovation's Health Care Innovations Awards. The innovations' impacts on total cost of care were estimated by independent evaluators using multivariable difference-in-differences models. Through the first two years, most of the innovations did not show a significant effect on total cost of care. Using meta-regression, we assessed the effects on costs of five common components of these innovations. Innovations that used health information technology or community health workers achieved the greatest cost savings. Savings were also relatively large in programs that targeted clinically fragile patients-clinically complex populations at risk for disease progression. While the magnitude of these effects was often substantial, none achieved conventional levels of significance in our analyses. Meta-analyses of a larger number of delivery system innovations are needed to more clearly establish their potential for patient care cost savings. | Ambulatory Care |
Pro-inflammatory mediators hold important functions in human body in response to infection, trauma and vascular disease. However, their action is down regulated by the release of anti-inflammatory cytokines, thus restoring a balance which reflects the immune status of a given individual. Recent studies have stressed out the importance of circulating levels of cytokines for forensic purposes even if there is a lack of studies regarding the role of post-mortem mucosa-associated lymphoid tissue. In this respect, Peyer's patches (PP), represent one of the most important immunological site of the body and the major component of the gut -associated lymphoid tissue. The aim of this study was to evaluate post-mortem PP immune response in 40 serial autopsy cases of people who died from natural and traumatic death. The study examined spontaneous release of the following cytokines by fresh isolated PP cells: interleukin (IL)-12, tumor necrosis factor (TNF)-alpha, IL-10, IL-6, IL-1 beta, and IL-8. Results will show that higher levels of TNF-alpha, IL-6, IL-1 beta, and IL-8 are statistically correlated with the traumatic death group. From a forensic point of view these data demonstrate that fundamental lymphoid organs, such as PP, may have a potential in diagnosing the cause of death. | Peyer's Patches |
An ion-transporting human epithelial cell line, NCL-SG3, has been established by simian virus 40 (SV40) infection of primary cultures from eccrine sweat glands. The line has been passaged 38 times (over 100 population doublings), has an aneuploid karyotype but has not undergone any 'crisis'. The cells have retained epithelial morphology and expression of cytokeratin, the intermediate filament characteristic of epithelial cells. Approximately 85% of the population shows at least weak co-expression of vimentin, an intermediate filament associated with mesenchymal and some other non-epithelial cell types in vivo. In addition, SV40 large T-antigen is present, in a predominantly nuclear localization. Electrically resistant cell sheets are formed on dialysis tubing and cellulose-ester permeable supports. Electrogenic ion transport can be stimulated by the beta-adrenergic agonist isoproterenol (10(-6) M) and by lysylbradykinin (10(-7) M) but not by the cholinergic agonist carbachol at 10(-6) M). | Sweat Glands |
Chromosomal aberrations associated with schizophrenic disorders may suggest regions in which to focus a search for genes predisposing to schizophrenia by a linkage strategy. As for other genetic illnesses, chromosomal abnormalities may also provide useful tools for subsequent physical mapping, fine localisation, and isolation of important susceptibility genes. Identification of several chromosomal aberrations may be especially important, given the unknown pathophysiology, the paucity of known brain genes, and the probable genetic heterogeneity of schizophrenia and manic-depression. However, because psychiatric disorders are common and inherited in a complex manner, researchers must use caution when drawing inferences about associations with chromosomal aberrations. Reported abnormalities involving autosomes (chromosomes 1-22) associated with psychotic disorders are reviewed. Their relevance to linkage studies localising genes for schizophrenia was estimated by standardised criteria for specificity, diagnosis, family history, and overall weight of evidence. Four 'possibly relevant' chromosomal regions were identified: 5q, 11q, 18q, and 19p. This paper outlines strategies for future studies to detect new chromosomal aberrations associated with major psychotic disorders that may be relevant to isolating the genes for schizophrenia. | Chromosomes |
Reverse shoulder arthroplasty (RSA) was designed for the treatment of elderly patients with cuff tear arthropathy. Because of its success, the indications for RSA have expanded beyond cuff tear arthropathy to include acute fractures, fracture sequelae, massive rotator cuff tears, inflammatory arthritis, and revision shoulder arthroplasty. Consequently, the number of RSAs performed has increased steadily. Glenoid bone loss is not uncommon in patients undergoing primary or revision RSA. Failure to appreciate and address glenoid bone loss during RSA can lead to improper baseplate positioning and early failure or complications such as dislocation or scapular notching. The authors present a review of the current literature as well as recommended strategies for characterization of glenoid bone loss and preferred surgical techniques for addressing bone loss during RSA. | Arthroplasty, Replacement |
Recent studies have highlighted the importance of an accurate individual head model for reliably using high-density electroencephalography (hdEEG) as a brain imaging technique. Correct identification of sensor positions is fundamental for accurately estimating neural activity from hdEEG recordings. We previously introduced a method of automated localization and labelling of hdEEG sensors using an infrared colour-enhanced 3D scanner. Here, we describe an extension of this method, the spatial positioning toolbox for head markers using 3D scans (SPOT3D), which integrates a graphical user interface (GUI). This enables the correction of imprecisions in EEG sensor positioning and the inclusion of additional head markers. The toolbox was validated using 3D scan data collected in four participants wearing a 256-channel hdEEG cap. We quantified the misalignment between the 3D scan and the head shape, and errors in EEG sensor locations. We assessed these parameters after using the automated approach and after manually adjusting its results by means of the GUI. The GUI overcomes the main limitations of the automated method, yielding enhanced precision and reliability of head marker positioning. | Head |
INTRODUCTION: Acromegaly is a rare disease that severely impacts patients' health all the while, being a slowly progressing illness. In the past decades, advancements in treatment modalities, especially development of new drugs, as well as focused guidelines has improved management of acromegaly. Still, many patients are considered not sufficiently treated and there remains an ongoing need for further development. AREAS COVERED: This article reviews new medical treatments currently under clinical investigation (such as pasireotide, oral octreotide and somatoprim) and under experimental development (such as octreotide implants, CAM2029 and ATL-1103). EXPERT OPINION: As it seems unlikely that one single agent may achieve cure in 100% of cases, there is an urgent need for new agents that help patients where current medication fails. Imperatively, this means we have to improve our understanding of the underlying pathogenetic and molecular mechanisms. | Somatostatin |
A new inducer of the monooxygenase system zixoryn (oral dose--100 mg/kg, for 4 days) increased the excretion and maximum tubular transport of cardiotrast (diodrast) in rats. Zixoryn had no effect on daily and water diuresis and renal excretion of sodium, potassium and creatinine. | Iodopyridones |
AIM: From betulinic acid (1a), we synthesized 30-oxobetulinic acid (2a) that is highly cytotoxic against many cancer cell lines; however, its generic toxicity is the main obstacle in further development as cytostatic. Methodology & results: From 2a, we prepared a new class of compounds - nonsymmetrical azines and tested their in vitro cytotoxicity. All new azines with a free 28-COOH group (4a-4e) were highly and selectively cytotoxic against the T-lymphoblastic leukemia cell line CCRF-CEM and exhibited dose-dependent inhibition of RNA and DNA synthesis and other cell-cycle alterations, including the M-phase block. CONCLUSION: The potential use of azines (4a-4e) in drug development focused on hematological cancers is significantly higher than that of previously studied acids 1a and 2a. | Hydrazines |
Little has been written about the pathogenesis of pes cavus in Charcot-Marie-Tooth disease (CMT). In 12 of 22 patients in a family with known autosomal dominant CMT, a predictable pattern of progression was related to a centrifugal pattern of innervation of the extremity. The gait pattern had greater complexity than the steppage gait. Pelvic shift and elevation on the swing side were used to clear the drop foot" from the floor. Lateral flexion of the trunk to the opposite direction was used for balance. Previous descriptions of the etiology of pes cavus did not apply to this family. The mode of development of pes cavus in CMT is not known and requires further investigation." | Charcot-Marie-Tooth Disease |
Inhalation injuries comprise three distinct clinical entities that may be classified according to the time of onset of symptoms, etiologic agents, and the anatomic location of injury. These entities are carbon monoxide toxicity, upper airway obstruction, and smoke inhalation or chemical injury. Each has a distinct pathophysiology, clinical manifestations, treatment, and prognosis. The emergency management of inhalation injury is frequently based on the health professional's degree of suspicion despite the availability of sophisticated diagnostic tests. Early aggressive treatment, including maintaining a patent airway, administering humidified oxygen and bronchodilators, and providing pulmonary toilet, is necessary to ensure the best possible outcome. Understanding the pathophysiology, clinical manifestations, diagnosis, medical management, and nursing implications of inhalation injuries can improve patient survival. | Airway Obstruction |
The Korea Research Institute of Standards and Science has developed a new concrete reference material (RM) for measuring gamma-emitting radionuclides, such as (134)Cs, (137)Cs, (65)Zn, (241)Am, and (60)Co, to improve and maintain the quality assurance and quality control of the radioactivity measurement in radioactive waste generated during the decommissioning of nuclear power plants. In this study, cement, SiO(2), and bentonite, which are the main components of concrete, were mixed in an appropriate ratio with radionuclides. For certification and homogeneity assessment, 10 bottles were randomly selected, two sub-samples were collected from each bottle, and radionuclides were measured via HPGe gamma spectrometry. The results of the homogeneity tests using a one-way analysis of variance on (241)Am, (134)Cs, (137)Cs, (65)Zn, and (60)Co in the concrete RM fulfilled the requirements of ISO Guide 35. Coincidence summing and self-absorption correction were performed on measurement results by introducing the Monte Carlo efficiency transfer code and Monte Carlo N-Particle transport code. The reference values for five radionuclides ((60)Co, (65)Zn, (241)Am, (134)Cs, and (137)Cs) in the RM were in the range of 15-40 Bq/kg, and the expanded uncertainty was within 10% (k = 2). To the best of our knowledge, this was the first study to develop concrete RM for measuring gamma-emitting radionuclides. | Nuclear Power Plants |
The linalool dehydratase-isomerase from Castellaniella defragrans strain 65Phen catalyzes in the thermodynamically unfavourable direction the hydration of betamyrcene to linalool and further the isomerization to geraniol, the initial steps in anaerobic beta-myrcene biodegradation. We have now investigated the stereochemistry of this reaction. (S)-(+)-Linalool is formed with an enantiomeric excess of at least 95.4%. (R)-(-)-Linalool was not detected. This indicates an introduction of the hydroxy group on the si-face of beta-myrcene. | Hydro-Lyases |
A mixture of behaviorally active volatiles was identified from the fruit of snowberry, Symphoricarpos albus laevigatus, for Rhagoletis zephyria flies reared from snowberry fruit. A nine-component blend containing 3-methylbutan-1-ol (3%), dimethyl trisulfide (1%), 1-octen-3-ol (40%), myrcene (8%), nonanal (9%), linalool (13%), (3E)-4,8-dimethyl-1,3,7-nonatriene (DMNT, 6%), decanal (15%), and beta-caryophyllene (5%) was identified that gave consistent electroantennogram activity and was behaviorally active in flight tunnel tests. In other flight tunnel assays, snowberry flies from two sites in Washington state, USA, displayed significantly greater levels of upwind oriented flight to sources with the snowberry volatile blend compared with previously identified volatile blends from domestic apple (Malus domestica) and downy hawthorn (Crataegus mollis) fruit from the eastern USA, and domestic apple, black hawthorn (C. douglasii) and ornamental hawthorn (C. monogyna) from Washington state. Selected subtraction assays showed that whereas removal of DMNT or 1-octen-3-ol significantly reduced the level of upwind flight, removal of myrcene and beta-caryophyllene, or dimethyl trisulfide alone did not significantly affect the proportion of upwind flights. Our findings add to previous studies showing that populations of Rhagoletis flies infesting different host fruit are attracted to unique mixtures of volatile compounds specific to their respective host plants. Taken together, the results support the hypothesis that differences among flies in their behavioral responses to host fruit odors represent key adaptations involved in sympatric host plant shifts, contributing to host specific mating and generating prezygotic reproductive isolation among members of the R. pomonella sibling species complex. | Symphoricarpos |
Primary bone tumors, osteosarcomas and chondrosarcomas, derive from mesenchymal stem cells committed into osteoblasts and chondrocytes; in Ewing sarcomas (ESs), the oncogenic fusion protein EWS-FLI1 prevents mesenchymal differentiation and induces neuroectodermic features. Oncostatin M (OSM) is a cytokine from the IL-6 family that modulates proliferation and differentiation in numerous cells. The basis for inhibition versus induction of proliferation by this cytokine is obscure, although MYC was described as a potent molecular switch in OSM signaling. We show herein that, in contrast to osteosarcomas and chondrosarcomas, for which OSM was cytostatic, OSM induced proliferation of ES cell lines. Knockdown experiments demonstrated that growth induction by OSM depends on both types I [leukemia inhibitory factor receptor (LIFR)] and II [OSM receptor (OSMR)] receptors, high STAT3 activation, and induction of MYC to a high expression level. Indeed, ES cell lines, mice xenografts, and patient biopsy specimens poorly expressed LIF, precluding LIFR lysosomal degradation and OSMR transcriptional induction, thus leading to a high LIFR/OSMR ratio. Because other neuroectodermic tumors (ie, glioma, medulloblastoma, and neuroblastoma) had a similar expression profile, the main role of EWS-FLI1 could be through maintenance of stemness and neuroectodermic features, characterized by a low LIF, a high LIFR/OSMR ratio, and high MYC expression. Thus, this study on rare bone malignancies gives valuable insights on more common cancer regulatory mechanisms and could provide new therapeutic opportunities. | Receptors, Oncostatin M |
BACKGROUND: Nematodirus spp. are among the most common nematodes of ruminants worldwide. N. oiratianus and N. spathiger are distributed worldwide as highly prevalent gastrointestinal nematodes, which cause emerging health problems and economic losses. Accurate identification of Nematodirus species is essential to develop effective control strategies for Nematodirus infection in ruminants. Mitochondrial DNA (mtDNA) could provide powerful genetic markers for identifying these closely related species and resolving phylogenetic relationships at different taxonomic levels. METHODS: In the present study, the complete mitochondrial (mt) genomes of N. oiratianus and N. spathiger from small ruminants in China were obtained using Long-range PCR and sequencing. RESULTS: The complete mt genomes of N. oiratianus and N. spathiger were 13,765 bp and 13,519 bp in length, respectively. Both mt genomes were circular and consisted of 36 genes, including 12 genes encoding proteins, 2 genes encoding rRNA, and 22 genes encoding tRNA. Phylogenetic analyses based on the concatenated amino acid sequence data of all 12 protein-coding genes by Bayesian inference (BI), Maximum likelihood (ML) and Maximum parsimony (MP) showed that the two Nematodirus species (Molineidae) were closely related to Dictyocaulidae. CONCLUSIONS: The availability of the complete mtDNA sequences of N. oiratianus and N. spathiger not only provides new mtDNA sources for a better understanding of nematode mt genomics and phylogeny, but also provides novel and useful genetic markers for studying diagnosis, population genetics and molecular epidemiology of Nematodirus spp. in small ruminants. | Nematodirus |
Age-related changes in human T-cell populations are important contributors to immunosenescence. In particular, terminally differentiated CD8(+) effector memory CD45RA(+) TEMRA cells and their subsets have characteristics of cellular senescence, accumulate in older individuals, and are increased in age-related chronic inflammatory diseases. In a detailed T-cell profiling among individuals over 65 years of age, we found a high interindividual variation among CD8(+) TEMRA populations. CD8(+) TEMRA proportions correlated positively with cytomegalovirus (CMV) antibody levels, however, not with the chronological age. In the analysis of over 90 inflammation proteins, we identified plasma TRANCE/RANKL levels to associate with several differentiated T-cell populations, including CD8(+) TEMRA and its CD28(-) subsets. Given the strong potential of CD8(+) TEMRA cells as a biomarker for immunosenescence, we used deep-amplicon bisulfite sequencing to match their frequencies in flow cytometry with CpG site methylation levels and developed a computational model to predict CD8(+) TEMRA cell proportions from whole blood genomic DNA. Our findings confirm the association of CD8(+) TEMRA and its subsets with CMV infection and provide a novel tool for their high throughput epigenetic quantification as a biomarker of immunosenescence. | Immunosenescence |
Thymic carcinomas are rare malignant neoplasms. We present a case of adenoid cystic carcinoma of thymus in a 65-year-old woman that was initially misdiagnosed and was treated as non-small cell carcinoma of the lung. We describe the clinical and pathologic features of this extremely rare thymic epithelial tumor, with survival at 2 years and 6 months of follow-up. | Carcinoma, Adenoid Cystic |
Herpetic gingivo-stomatitis is a common, often painful affliction of young children. Recently, aciclovir treatment has been found to be effective in hospital-referred cases, an approach limited in general practice where laboratory diagnosis is invariably impractical. This study demonstrated that 49 out of 63 clinical diagnoses of herpetic gingivo-stomatitis [PPV = 78%] made by 27 GPs were subsequently validated by laboratory virus culture. This suggests that herpetic gingivo-stomatitis might be treated with aciclovir in general practice on the basis of a clinical diagnosis alone. | Stomatitis, Herpetic |
Safety climate represents the meaningfulness of safety and how safety is valued in an organization. The contributions of safety climate to organizational safety have been well documented. There is a dearth of empirical research, however, on specific safety climate interventions and their effectiveness. The present study aims at examining the trend of safety climate interventions and offering compiled information for designing and implementing evidence-based safety climate interventions. Our literature search yielded 384 titles that were inspected by three examiners. Using a stepwise process that allowed for assessment of interobserver agreement, 19 full articles were selected and reviewed. Results showed that 10 out of the 19 articles (52.6%) were based on a quasi-experimental pre- and postintervention design, whereas 42.1% (n = 8) studies were based on a mixed-design approach (including both between- and within-subject design). All interventions in these 19 studies involved either safety-/health-related communication or education/training. Improvement of safety leadership was also a common component of safety climate interventions. According to the socio-technical systems classification of intervention strategies, all studies were categorized as interventions focusing on improving organizational and managerial structure as well as the personnel subsystem; four of them also aimed at improving technological aspects of work, and five of them aimed at improving the physical work subsystem. In general, a vast majority of the studies (89.5%, n = 17) showed a statistically significant improvement in safety climate across their organizations postintervention. (PsycINFO Database Record (c) 2019 APA, all rights reserved). | Safety Management |
Polymers play a central role in controlling the crystallization of pharmaceuticals with effects as divergent as amorphous form stabilization and the acceleration of crystallization. Here, using pyrazinamide and hydrochlorothiazide as model pharmaceuticals, it is demonstrated that the same functional group interactions are responsible for these opposing behaviors and that whether a polymer speeds or slows a crystallization can be controlled by polymer solubility. This concept is applied for the discovery of polymers to maintain drug supersaturation in solution: the strength of functional group interactions between drug and polymer is assessed through polymer-induced heteronucleation, and soluble polymers containing the strongest-interacting functional groups with drug are shown to succeed as precipitation inhibitors. | Hydrochlorothiazide |
The possibility of using different criteria for estimation of the productivity of the vegetative inoculum of the oleandomycin-producing organism was studied with a purpose of providing maximum levels of the biosynthetic process. The use of the criteria of the culture respiration intensity and accumulation of the physiologically active mycelium as the main ones was shown to be advisable. The quantity and distribution of the mycelium in samples and the time course of changes in active acidity of the medium during the inoculum growth may be used as auxiliary criteria. | Oleandomycin |
While many would debate the very reality of Post Abortion Syndrome, the author of this article has experienced Post Abortion Syndrome first hand. Excerpted from a speech she gave before a Florida meeting of the National Organization of Episcopalians for Life (NOEL), the article outlines the various stages and symptoms of Post Abortion Syndrome: denial, repression, guilt, anxiety, depression. She then describes the process for healing and recovery, and presents a model for a Post Abortion support group which is patterned after Alcoholics Anonymous. | Abortion, Induced |
A C-N bond-forming cross-dehydrogenative coupling of a collection of Tyr-containing peptides and estrogens with heteroarenes is described. This oxidative coupling is distinguished by its scalability, operational simplicity, and air tolerance and enables the appendance of phenothiazines and phenoxazines in phenol-like compounds. When incorporated into a Tb(III) metallopeptide, the Tyr-phenothiazine moiety acts as a sensitizer for the Tb(III) ion, providing a new tool for the design of luminescent probes. | Oxidative Coupling |
Gastrulation is a fundamental process during embryonic development, conserved across all multicellular animals [1]. In the majority of metazoans, gastrulation is characterised by large scale morphogenetic remodeling, leading to the conversion of an early pluripotent embryonic cell layer into the three primary 'germ layers': an outer ectoderm, inner endoderm and intervening mesoderm layer. The morphogenesis of these three layers of cells is closely coordinated with cellular diversification, laying the foundation for the generation of the hundreds of distinct specialized cell types in the animal body. The process of gastrulation has for a long time attracted tremendous attention in a broad range of experimental systems ranging from sponges to mice. In humans the process of gastrulation starts approximately 14 days after fertilization and continues for slightly over a week. However our understanding of this important process, as it pertains to human, is limited. Donations of human fetal material at these early stages are exceptionally rare, making it nearly impossible to study human gastrulation directly. Therefore, our understanding of human gastrulation is predominantly derived from animal models such as the mouse [2,3] and from studies of limited collections of fixed whole samples and histological sections of human gastrulae [4-7], some of which date back to over a century ago. More recently we have been gaining valuable molecular insights into human gastrulation using in vitro models of hESCs [8-12] and increasingly, in vitro cultured human and non-human primate embryos [13-16]. However, while methods have been developed to culture human embryos into this stage (and probably beyond), current ethical standards prohibit the culture of human embryos past 14 days again limiting our ability to experimentally probe human gastrulation. This review discusses recent molecular insights from the study of a rare CS 7 human gastrula obtained as a live sample and raises several questions arising from this recent study that it will be interesting to address in the future using emerging models of human gastrulation. | Gastrulation |
BACKGROUND: Peace Corps Volunteers (PCVs) are a unique expatriate population at risk for dengue. Previous studies examined travelers or lacked demographic information about expatriates. We examined dengue incidence among PCVs before and after deployment of an electronic medical record (EMR) to assess temporal and demographic factors. METHODS: Dengue cases within Peace Corps' Epidemiologic Surveillance System from 2000 to 2019 were identified using a standard case definition, and two timeframes were compared: pre-EMR 2000-2015 and post-EMR 2016-2019. RESULTS: Annual infections occurred in a roughly 3-year cyclic pattern from 2007 to 2019. Incidence rate decreased from 1.35 cases per 100 dengue Volunteer-years (95% CI 1.28-1.41) in 2000-2015 to 1.25 cases (95% CI 1.10-1.41) in 2016-2019. Among PCVs who served from 2016 to 2019, the majority of infections occurred in females and 20-29 year olds, and 7% were medically evacuated. Among PCVs who served from 2015 to 2019, 21% were hospitalized in-country. CONCLUSIONS: Among PCVs, a non-significant decrease in dengue incidence occurred from 2000-2015 to 2016-2019. Annual infection rates peaked every three years, offering opportunities for targeted prevention efforts. Dengue infection in PCVs appears to mimic the overall demographic of Peace Corps. Expatriates like PCVs are at an increased risk for dengue infection compared to short-term travelers. | Peace Corps |
Besides the mechanical loading-dependent paradigm, skeletal muscle also serves as an endocrine organ capable of secreting cytokines to modulate bone metabolism. In this review, we focused on reviewing the myokines involved in communication from skeletal muscle to bone, i.e. (1) myostatin and myostatin-binding proteins including follistatin and decorin, (2) interleukins including interleukin-6 (IL-6), interleukin-7 (IL-7) and interleukin-15 (IL-15), (3) insulin-like growth factor 1 (IGF-1) and its binding proteins, (4) other myokines including PGC-1alpha-irisin system and osteoglycin (OGN). To better understand the molecular communication from skeletal muscle to bone, we have summarized the recent advances in muscle-derived cytokines regulating bone metabolism in this review. | Paracrine Communication |
The performed studies covered 1100 subjects being 18 years old (both girls and boys) representing large and small towns as well as villages situated in 13 provinces. The material and methods were based on the instruction provided by WHO Basic Methods 1986". Answers given to questionnaire inquiries in the area of nutrition and oral cavity hygiene furnished an image of health consciousness and behaviours of 18-agers in Poland. Dental state and stomatologic treatment requirement jointly with the effects of stomatologic care were evaluated on the basis of the results established by epidemiological studies. The accomplished analysis encompassed the influence of sex, living environment, type of schools and variable content of fluoride in water, exerted on the pattern of the investigated epidemiological parameters. No correlation was recorded between health consciousness and behaviours in 18-year-old youth on the one hand, and the dental state as well as the therapeutic requirements on the other. The questionnaire responses and the epidemiologic studies made it possible to disclose some drawbacks in transmitting and introducing the education-health principles, which was reflected by not the best results concerning the health consciousness and behaviours particularly in male youth and in rural inhabitants. The dental condition is unsatisfactory in the studied population, despite being provided, in most instances, with permanent stomatological care. This indicates that optimization of adequate stomatological service is indispensable. A low percentage of youth with dentition does not predict good prognosis for them to achieve 3-rd health objective set up by WHO for the year 2000. The studies have confirmed the influence of big urban environment, with complete profile of stomatological care and water fluoridation, being exerted on the state of dental therapeutic requirements in 18-year-old youth. Difficult as it appeared was the detection of the sugars consumption role and that of oral cavity hygiene, in the course of one-stage investigation." | School Dentistry |
Abuse and addiction of histaminergic agonists and antagonists were investigated. The withdrawal signs may become after using drugs such as L-histidine, histamine-N-methyl, promethazine, pheniramine, astemizole, etc. Some medicines which include these active metabolites could lead to dependence cause different side effects. This case suggests that pheniramine abuse also could to dependence. We should pay attention to trend of pheniramine and other histaminergic drugs dependence and need to regulate the market by law more severely. | Pheniramine |
Mitochondrial trifunctional protein (MTP) is a complex protein that catalyzes the last three steps of long chain fatty acid oxidation. MTP defects have emerged recently as important inborn errors of metabolism because of their clinical implications. These disorders are recessively inherited and display a spectrum of clinical phenotypes in affected children including hepatic dysfunction, cardiomyopathy, neuro-myopathy, and may cause sudden unexpected infant death if undiagnosed and untreated. Interestingly, mothers who carry fetuses with MTP defects develop life-threatening complications during pregnancy. Recently, we delineated disease-causing mutations in MTP and reported the molecular basis for the pediatric and fetal-maternal genotype-phenotype correlations. Current management of patients with MTP defects include long-term dietary therapy of fasting avoidance, low fat diet with the restriction of long chain fatty acid intake and substitution with medium chain fatty acids. The long-term outcome of patients treated by dietary modifications remains unknown. Thus, treatment that aims at correcting the metabolic defect remains the therapy of choice for this disorder. Currently, we are exploring the potential use of protein transfection domains (PTD) for treatment of these disorders. We have shown that the transactivator of transcription (TAT) peptide from the human immunodeficiency virus can deliver proteins to mitochondria. We have further developed methods to localize these proteins to mitochondria by including a mitochondrial targeting in the fusion protein construct. Finally, we have shown that the fusion protein can cross the placenta and was detectable in the fetus and newborn pups. The practical therapeutic implications of this novel approach will be discussed." | Mitochondrial Trifunctional Protein |
The aim of this laboratory-based study was to determine the shaping ability of NT Engine and McXim nickel-titanium rotary instruments in simulated root canals. A total of 40 canals with four different shapes in terms of angle and position of curve were prepared with NT Engine and McXim instruments, using the technique recommended by the manufacturer. Part 2 of this report describes the efficacy of the instruments in terms of prevalence of canal aberrations, the amount and direction of canal transportation and overall postoperative shape. Pre- and postoperative images of the canals were taken using a video camera attached to a computer with image analysis software. The pre- and postoperative views were superimposed to highlight the amount and position of material removed during preparation. No zips, elbows, perforations or danger zones were created during preparation. Forty-two per cent of canals had ledges on the outer aspect of the curve, the majority of which (16 out of 17) occurred in canals with short acute curves. There were significant differences (P < 0.001) between canal shapes in terms of the incidence of ledges. There were highly significant differences (P < 0.001) between the canal shapes in total canal width at specific points along the canal length and in the amount or resin removed from the inner and outer aspects of the curve. The direction of canal transportation at the end-point of preparation was most frequently towards the outer aspect of the curve, especially in canals with 40 degrees curves. At the beginning of the curve, transportation in the majority of canals was towards the inner aspect of the curve. Mean absolute transportation was less than 0.03 mm throughout the curve and towards the end-point, with significant differences between canal shapes occurring at the apex (P < 0.05) and at the beginning of the curve (P < 0.001). Under the conditions of this study, NT Engine and McXim rotary nickel-titanium instruments created no aberrations other than ledges and produced only minimal transportation. The overall shape of canals was good. | Tooth Preparation |
Unlike physical training, skill acquisition does not currently utilise periodisation to plan, monitor and evaluate programs. Development of a skill acquisition periodisation framework would allow for systematic investigation into the acute and longitudinal effectiveness of such interventions. Using the physical training literature as a reference point, a skill-training periodisation framework was developed for use in high-performance sport. Previous research undertaken in skill acquisition was used to provide support for the framework. The specificity, progression, overload, reversibility and tedium (SPORT) acronym was adopted. Each principle was then re-conceptualised so that it related to relevant skill acquisition principles. Methods for the measurement and analysis of each principle are provided and future directions for the longitudinal assessment of skill acquisition are discussed. The skill acquisition periodisation framework proposed in this study represents an opportunity for the principles relating to skill acquisition training to be measured in a systematic and holistic manner. This can also allow for a more sophisticated evaluation of the efficacy of longitudinal training programmes and interventions designed for sustained skill enhancement. | Motor Skills |
We have studied the low temperature phase diagram and water activities of the ammonium sulfate/maleic acid/water system using differential scanning calorimetry and infrared spectroscopy of thin films. Using the results from our experiments, we have mapped the solid/liquid ternary phase diagram, determined the water activities based on the freezing point depression, and determined the ice/maleic acid phase boundary as well as the ternary eutectic composition and temperature. We also compare our results to the predictions of the extended AIM aerosol thermodynamics model and find good agreement for the ice melting points in the ice primary phase field of this system; however significant differences were found with respect to phase boundaries, maleic acid dissolution, and ammonium sulfate dissolution. | Ammonium Sulfate |
Outer membrane vesicles (OMVs) are spherical, bilayered, and nanosized membrane vesicles that are secreted from gram-negative bacteria. OMVs play a pivotal role in delivering lipopolysaccharide, proteins and other virulence factors to target cells. Multiple studies have found that OMVs participate in various inflammatory diseases, including periodontal disease, gastrointestinal inflammation, pulmonary inflammation and sepsis, by triggering pattern recognition receptors, activating inflammasomes and inducing mitochondrial dysfunction. OMVs also affect inflammation in distant organs or tissues via long-distance cargo transport in various diseases, including atherosclerosis and Alzheimer's disease. In this review, we primarily summarize the role of OMVs in inflammatory diseases, describe the mechanism through which OMVs participate in inflammatory signal cascades, and discuss the effects of OMVs on pathogenic processes in distant organs or tissues with the aim of providing novel insights into the role and mechanism of OMVs in inflammatory diseases and the prevention and treatment of OMV-mediated inflammatory diseases. | Bacterial Outer Membrane |
Intracellular recordings were made from a selection of identified neurons in the sub-oesophageal ganglia of Helix aspersa, and their responses to the molluscan neuropeptides FMRF-amide and pQDPFLRF-amide compared. While FMRF-amide excited certain neurons and inhibited others, pQDPFLRF-amide did not produce excitation in any of the cells tested. A few cells were unresponsive to pQDPFLRF-amide, but most were inhibited with varying potency. FMRF-amide was generally 10-100 times more potent than pQDPFLRF-amide, but one cell, E13 in the visceral ganglion, showed equal sensitivity to the two peptides. On most cells there was no clear evidence for cross desensitization between the two peptides, although it is possible that in some cases where both peptides are inhibitory they may be acting on a single receptor. | Helix, Snails |
BACKGROUND: Olipudase alfa is a recombinant human acid sphingomyelinase (ASM) enzyme replacement therapy (ERT) for non-central-nervous-system manifestations of acid sphingomyelinase deficiency (ASMD). We report 2-year cumulative safety and efficacy data after olipudase alfa treatment in 20 children (four adolescents [12-17 year], nine children [6-11 year], and seven infants/early child [1-5 year]) with baseline splenomegaly and growth deficits who completed the 1-year ASCEND-Peds clinical trial (NCT02292654) and who continue to receive olipudase alfa in a long-term study (NCT02004704). Efficacy endpoints include spleen and liver volumes, diffusing capacity of the lung for carbon monoxide (DL(CO)), high-resolution computed tomography (HRCT) lung imaging, lipid profiles, liver function tests, and height Z-scores. RESULTS: All 20 former ASCEND-Peds patients completed at least 2 years of olipudase alfa treatment. No patient discontinued and no new safety issue arose during the second year of treatment; 99% of adverse events were mild or moderate. During year 2, one patient had two treatment-related serious events of hypersensitivity that resolved. Mean reductions from baseline in spleen and liver volumes were 61% and 49%, respectively (p < 0.0001) and mean percent-predicted-DL(CO) increased by 46.6% (p < 0.0001) in nine patients who performed the test at baseline. Lipid profiles and elevated liver transaminase levels that improved or normalized by 1 year remained stable. Mean height Z-scores improved in all age groups (mean change from baseline 1.17, P < 0.0001). CONCLUSION: Olipudase alfa was generally well-tolerated during 2 years of treatment. Improvements in clinically relevant disease endpoints observed during the first year of treatment were maintained or augmented in the second year. Trial registration NCT02004704 registered 26 Nov 2013, https://clinicaltrials.gov/ct2/show/record/NCT02004704 . | Niemann-Pick Disease, Type A |
One hundred eighty-one adult cats, with body weight greater than 1.8 kg, were obtained from animal shelters, then were administered a sodium pentobarbital-lidocaine euthanasia agent by either the intraperitoneal (IP; n = 77) or intrahepatic (IH; n = 85) route. A preliminary study (n = 19 cats) indicated that most cats gave no indication of perception of injection (responding) if restraint was minimal and injection was rapid. During IP injection, 3 of the 77 cats (4%) responded (turned the head backward or vocalized). Of the 85 cats given IH injection, 8 (9%) responded; however, no response approached the magnitude of that observed after IM injection of ketamine hydrochloride. After either injection route, cats were observed for excitement (any exaggerated activities of stage-I and -II anesthesia (eg, vocalizing, flopping, sneezing, licking, running, paddling), and after cardiac standstill, cats were necropsied to identify exact location (final site) of the injection. Of 53 initial IP injections, final site for 22 (42%) was in the peritoneal cavity (PC). Use of a sideport needle (n = 24) did not significantly increase accuracy of IP injection. The small and large intestines were penetrated by 27% (15/55) of the IP injections from the right side, and the spleen was penetrated by 32% (7/22) of the left-side injections. Intrahepatic injection was significantly (P less than 0.05) more accurate, with 70 of 85 (82%) of the final sites being the liver only, the liver/PC, or the PC only. Twenty-five percent (13/53) of IP injections resulted in excitement (all stage-I and -II anesthesia-exaggerated activities cumulative to 30 seconds).(ABSTRACT TRUNCATED AT 250 WORDS) | Injections, Intraperitoneal |
Noma is an orofacial gangrene affecting primarily children living in extreme poverty in remote parts of subtropical and tropical countries. Mortality and disability are high, and survivors often have physical and functional deformities resulting in stigma and isolation. Many healthcare professionals and primary healthcare workers where noma risk factors exist have no knowledge about noma and its implications. Public health measures to improve nutrition, immunizations, sanitation, and access to healthcare and measures to eliminate extreme poverty can lead to the eradication of noma. Research allocation has been insufficient to study the epidemiology, treatment, and prevention of noma. In a recent editorial by Hotez and colleagues in PLOS Neglected Tropical Diseases (NTDs), What constitutes an NTD?" Noma is not included. The exclusion of noma from NTDs constitutes this preventable childhood disease as a neglected neglected disease. The purpose of this article is the inclusion of noma with the PLOS NTDs. Increased awareness and attention to noma can lead to the eradication of this disease affecting the world's most vulnerable." | Noma |
Regular monitoring of left ventricular ejection fraction (LVEF) for thalassemia major is widely practiced, but its informativeness for iron chelation treatment is unclear. Eighty-one patients with thalassemia major but no history of cardiac disease underwent quantitative annual LVEF monitoring by radionuclide ventriculography for a median of 6.0 years (interquartile range, 2-12 years). Intraobserver and interobserver reproducibility for LVEF determination were both less than 3%. LVEF values before and after transfusion did not differ, and exercise stress testing did not reliably expose underlying cardiomyopathy. An absolute LVEF of less than 45% or a decrease of more than 10 percentage units was significantly associated with subsequent development of symptomatic cardiac disease (P <.001) and death (P =.001), with a median interval between the first abnormal LVEF findings and the development of symptomatic heart disease of 3.5 years, allowing time for intervention. In 34 patients in whom LVEF was less than 45% or decreased by more than 10 percentage units, intensified chelation therapy was recommended (21 with subcutaneous and 13 with intravenous deferoxamine). All 27 patients who complied with intensification survived, whereas the 7 who did not comply died (P <.0001). The Kaplan-Meier estimate of survival beyond 40 years of age for all 81 patients is 83%. Sequential quantitative monitoring of LVEF is valuable for assessing cardiac risk and for identifying patients with thalassemia major who require intensified chelation therapy. | Chelation Therapy |
In recent years, foot-and-mouth disease virus (FMDV) serotype O, topotype Middle East-South Asia (ME-SA), lineage Ind-2001d has spread from the Indian subcontinent to the Middle East, North Africa, and Southeast Asia. In the current report, we describe the first detection of this lineage in Vietnam in May, 2015 in Dak Nong province. Three subsequent outbreaks caused by genetically related viruses occurred between May-October, 2015 after which the virus was not detected in clinical outbreaks for at least 15 subsequent months. The observed outbreaks affected (in chronological order): cattle in Dak Nong province, pigs in Dak Lak province and Dak Nong province, and cattle in Ninh Thuan province. The clinical syndromes associated with these outbreaks were consistent with typical FMD in the affected species. Overall attack rate on affected premises was 0.85 in pigs and 0.93 in cattle over the course of the outbreak. Amongst 378 pigs at risk on affected premises, 85 pigs died during the outbreaks; there were no deaths among cattle. The manner in which FMDV/O/ME-SA/Ind-2001d was introduced into Vietnam remains undetermined; however, movement of live cattle is the suspected route. This incursion has substantial implications for epidemiology and control of FMD in Southeast Asia. | Foot-and-Mouth Disease Virus |
In this retrospective study of breed differences in susceptibility to disease caused by ovine progressive pneumonia (OPP) virus, 29 Border Leicester sheep were compared with 46 Columbia sheep. As judged by frequency and severity of clinical signs and lesions attributable to the infection, Border Leicester sheep were markedly more susceptible than Columbia sheep and experimentally infected sheep were slightly more susceptible than naturally infected sheep. Differences in susceptibility to infection by the virus were not determined." | Pneumonia, Progressive Interstitial, of Sheep |
Polycythemia vera shares basic features of pathogenesis with other subtypes of the group of chronic myeloproliferative disorders. All myelopoietic cells are derived from one transformed hemopoietic stem cell. Genetic instability of mitotic clonal cells explains the risk of leukemic transformation, which may be enhanced by cytoreductive treatment. Recent data show that erythroid hyperplasia is not due to erythropoietin hypersensitivity, but rather to abnormal stimulation by other cytokine growth factors. Treatment as established by clinical trials has almost normalized life expectancy in older patients, but the optimal strategy for subgroups of patients is still unknown. For younger patients, new and potentially curative approaches should be investigated. | Polycythemia Vera |
Previous literature suggests a relationship between individual characteristics of motion perception and the peak frequency of motion sickness sensitivity. Here, we used well-established paradigms to relate motion perception and motion sickness on an individual level. We recruited 23 participants to complete a two-part experiment. In the first part, we determined individual velocity storage time constants from perceived rotation in response to Earth Vertical Axis Rotation (EVAR) and subjective vertical time constants from perceived tilt in response to centrifugation. The cross-over frequency for resolution of the gravito-inertial ambiguity was derived from our data using the Multi Sensory Observer Model (MSOM). In the second part of the experiment, we determined individual motion sickness frequency responses. Participants were exposed to 30-minute sinusoidal fore-aft motions at frequencies of 0.15, 0.2, 0.3, 0.4 and 0.5 Hz, with a peak amplitude of 2 m/s(2) in five separate sessions, approximately 1 week apart. Sickness responses were recorded using both the MIsery SCale (MISC) with 30 s intervals, and the Motion Sickness Assessment Questionnaire (MSAQ) at the end of the motion exposure. The average velocity storage and subjective vertical time constants were 17.2 s (STD = 6.8 s) and 9.2 s (STD = 7.17 s). The average cross-over frequency was 0.21 Hz (STD = 0.10 Hz). At the group level, there was no significant effect of frequency on motion sickness. However, considerable individual variability was observed in frequency sensitivities, with some participants being particularly sensitive to the lowest frequencies, whereas others were most sensitive to intermediate or higher frequencies. The frequency of peak sensitivity did not correlate with the velocity storage time constant (r = 0.32, p = 0.26) or the subjective vertical time constant (r = - 0.37, p = 0.29). Our prediction of a significant correlation between cross-over frequency and frequency sensitivity was not confirmed (r = 0.26, p = 0.44). However, we did observe a strong positive correlation between the subjective vertical time constant and general motion sickness sensitivity (r = 0.74, p = 0.0006). We conclude that frequency sensitivity is best considered a property unique to the individual. This has important consequences for existing models of motion sickness, which were fitted to group averaged sensitivities. The correlation between the subjective vertical time constant and motion sickness sensitivity supports the importance of verticality perception during exposure to translational sickness stimuli. | Motion |
OBJECTIVE: To investigate the prevalence of diagnosed Eustachian tube dysfunction and related otologic diagnoses among children with achondroplasia as compared to a control population. METHODS: The TriNetX Analytics Network, a federated health research network that aggregates the de-identified electronic health record data of over 78 million patients across the United States, was queried for patients 18 years old or younger with achondroplasia. Patients in this group with any occurrence of diagnosed Eustachian tube dysfunction or specified otologic diagnoses were recorded and reported. RESULTS: Out of 2,195 patients 18 years old or younger with diagnosed achondroplasia, 379 (17.27%, 95% CI: 15.71-18.91) had a diagnosis of Eustachian tube dysfunction with an 8.65 (95% CI: 7.89-9.48) times higher risk than children without achondroplasia (n = 12,818,655). Children with achondroplasia also had higher risks for diagnosed otitis media (RR: 2.21), tympanic membrane retraction (RR: 7.29), middle ear cholesteatoma (RR: 6.35), cleft palate (RR: 12.24), conductive hearing loss (RR: 12.15), and tympanostomy tube placement (RR: 9.71). Each increased risk was maintained when cleft palate patients were removed from the achondroplasia group. CONCLUSION: Children with achondroplasia are at a significantly higher risk for diagnosed Eustachian tube dysfunction and related middle ear diagnoses. Atypical craniofacial anatomy among children with achondroplasia may play a role in the dysfunction of the Eustachian tube and thus the observed epidemiology of otologic conditions. Children with achondroplasia should be monitored closely for middle ear conditions and the constellation of symptoms related to a dysfunctional Eustachian tube. | Achondroplasia |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.