text
stringlengths 11
9.77k
| label
stringlengths 2
104
|
|---|---|
This review summarizes data on the distribution of certain glycosylation steps in the Golgi apparatus as revealed by immunolabeling and lectin techniques. The methodical basis for such investigations was provided by the introduction of the colloidal gold marker system for immunolabeling and the development of new means of tissue processing such as the low-temperature embedding technique using Lowicryl K4M. The application of these techniques together with highly specific antibodies has provided much of the basis for our current understanding of the Golgi apparatus in functional terms. Thus, in many cell types, three Golgi apparatus compartments can be distinguished, whereas in others no such functional subdivision is evident. Investigations on sialyltransferase distribution have also provided direct evidence that GERL is structurally and functionally part of the Golgi apparatus. | Golgi Apparatus |
BACKGROUND: The majority of liver fibrosis and liver cirrhosis cases in the Western World is caused by alcohol and hepatotoxic viruses. Colchicine is an anti-inflammatory and anti-fibrotic medication. Several randomised clinical trials have addressed the question whether colchicine has any efficacy in patients with alcoholic as well as non-alcoholic fibrosis and cirrhosis. OBJECTIVES: The objectives were to assess the efficacy of colchicine on mortality, clinical symptoms and complications, liver biochemistry, liver fibrosis markers, liver histology, alcohol consumption, quality of life, and health economics in patients with alcoholic and non-alcoholic fibrosis or cirrhosis, excluding primary biliary cirrhosis and other rarer forms of fibrosis/cirrhosis. Also adverse events were assessed. SEARCH STRATEGY: The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Library, MEDLINE, and full text searches were combined. SELECTION CRITERIA: Only randomised clinical trials were included studying patients with alcoholic fibrosis, alcoholic hepatitis and/or alcoholic cirrhosis as well as patients with viral induced or cryptogenic fibrosis and/or cirrhosis according to the diagnostic work-up of the individual trial. Interventions encompassed peroral colchicine at any dose versus placebo or no intervention. The trials could be double-blind, single-blind or unblinded. The trials could be unpublished or published and no language limitations were applied. DATA COLLECTION AND ANALYSIS: All analyses were performed according to the intention-to-treat method. The statistical package (RevMan and MetaView) provided by the Cochrane Collaboration was used. The methodological quality of the randomised clinical trials was evaluated by the Jadad-scale. MAIN RESULTS: Combining the results of 14 randomised clinical trials including 1150 patients demonstrated no significant effects of colchicine on mortality (Peto odds ratio (OR) 0.90, 95% confidence interval (CI) 0.63 to 1.29), liver related mortality (OR 1.05, 95% CI 0.61 to 1.80), complications (OR 1.01, 95% CI 0.63 to 1.62), liver biochemistry, liver histology, and alcohol consumption (OR 1.02, 95% CI 0.58 to 1.79). Colchicine was associated with a significantly increased risk of adverse events (OR 4.92, 95% CI 2.66 to 9.10; P< 0.001). REVIEWER'S CONCLUSIONS: Colchicine should not be used for alcoholic, viral, or cryptogenic liver fibrosis or liver cirrhosis outside randomised trials. | Liver Cirrhosis, Alcoholic |
Human Mac-2-binding protein (Mac-2-BP) is a secreted glycoprotein that is widely expressed. It binds to the human macrophage-associated lectin Mac-2 and has been suggested to have a role in host defence. Mouse cyclophilin C-associated protein (mCyCAP) is also a secreted glycoprotein that binds with high affinity to cyclophilin C in the absence of the immunosuppressive drug cyclosporin A. The two proteins share a similar domain structure and considerable sequence identity, including a highly conserved scavenger receptor cysteine-rich domain, and both of them exert their function within the immune system. To elucidate whether these molecules are also functional homologues, we compared their ligand binding properties using cell lines which express Mac-2-BP or mCyCAP as well as transfected cell lines stably expressing mCyCAP or a mutant version lacking the scavenger domain. These experiments show that Mac-2-BP is unable to bind to either human or mouse cyclophilin C and thatmCyCAP cannot bind to Mac-2. The scavenger domain is not required for the interaction between mCyCAP and cyclophilin C. We conclude that these proteins may be part of a larger family of proteins of immunological importance in which closer functional homologues might exists. | Cyclophilin C |
There is increasing awareness of the significant and varied actions of endogenous androgens in women, and acknowledgement that women might experience symptoms secondary to androgen deficiency. There is also substantial evidence that prudent testosterone replacement is effective in relieving both the physical and psychological symptoms of androgen insufficiency in clinically affected women. However, our understanding of the actions of testosterone in women is incomplete, with no consensus as to what constitutes either biochemical or clinical testosterone deficiency. The focus of the limited research into testosterone replacement has been on sexuality, primarily sexual desire. However, the influence of testosterone on mood and well being also requires further exploration. | Testosterone |
BACKGROUND: We previously reported our short-term experience of foreskin preputioplasty as an alternative to circumcision for the treatment of foreskin balanitis xerotica obliterans (BXO). In this study, we aimed to compare this technique with circumcision over a longer period. METHODS: Between 2002 and 2007, boys requiring surgery for BXO were offered either foreskin preputioplasty or primary circumcision. The preputioplasty technique involved triradiate preputial incisions and injection of triamcinolone intralesionally. Retrospective case-note analysis was performed to identify patient demographics, symptoms, and outcomes. RESULTS: One hundred thirty-six boys underwent primary surgery for histologically confirmed BXO. One hundred four boys opted for foreskin preputioplasty, and 32, for circumcision. At a median follow-up of 14 months (interquartile range, 2.5-17.8), 84 (81%) of 104 in the preputioplasty group had a fully retractile and no macroscopic evidence of BXO. Of 104, 14 (13%) developed recurrent symptoms/BXO requiring circumcision or repeat foreskin preputioplasty. In the circumcision group, 23 (72%) of 32 had no macroscopic evidence of BXO. The incidence of meatal stenosis was significantly less in the foreskin preputioplasty group, 6 (6%) of 104 vs 6 (19%) of 32 (P = .034). CONCLUSION: Our results show a good outcome for most boys undergoing foreskin preputioplasty and intralesional triamcinolone for BXO. There is a small risk of recurrent BXO, but rates of meatal stenosis may be reduced. | Balanitis Xerotica Obliterans |
The purpose of this study was to compare detection of increments and decrements occurring over limited regions of time and frequency within a 500-ms broadband (0-6000 Hz) noise. Three listeners tracked detection thresholds adaptively in a two-interval, two-alternative forced-choice task. Thresholds were measured for both increments and decrements in level [delta L = 10 log10(1 + delta N0/N0) dB, where N0 is the spectral power density of the noise] as a function of signal duration (T = 30-500 ms) for a range of signal bandwidths (W = 62-6000 Hz) that were logarithmically centered around 2500 Hz. Listeners were forced to rely on temporal- and spectral-profile cues for detection due to randomization of overall presentation level from interval to interval, which rendered overall energy an inconsistent cue. Increments were detectable for all combinations of W and T, whereas decrements were not consistently detectable for W < 500 Hz. Narrow-band decrements were not detectable due to spread of excitation from the spectral edges of the noise into the decrements. Increment and decrement thresholds were similar for W > or = 1000 Hz. Temporal- and spectral-integration effects were observed for both increments and decrements. The exceptions were for random-level conditions in which the signal matched the bandwidth or duration of the standard. A multicue decision process is described qualitatively to explain how the combination of temporal- and spectral-profile cues can produce temporal- and spectral-integration effects in the absence of overall-energy cues." | Recruitment Detection, Audiologic |
Cognitive impairment is a prominent clinical manifestation of vascular depression (VaDep). The current study aimed to assess the efficacy of tandospirone citrate in VaDep cases with mild cognitive impairment (VaDep-MCI) as well as the role of plasma monoamine neurotransmitters during the treatment. In this single-blind, randomized controlled study, 116 participants were randomly assigned to the tandospirone (tandospirone citrate-escitalopram) and control (escitalopram) groups. The primary endpoints were changes in cognitive test scores from baseline to Week 8, including the Rey Auditory Verbal Learning Test (RAVLT), Semantic Verbal Fluency (SVF) test, Trail Making Test (TMT), Digital Span Test (DST) and Clock Drawing Test (CDT) scores. Generalized estimating equation models were used to examine repeated measures. The results showed that compared with the changes in the control group from baseline to Week 8, the tandospirone group showed more significant changes in SVF score at Weeks 4 (p < 0.05) and 8 (p < 0.001), and TMT (B-A) score at Week 8 (p < 0.05). RAVLT, DST and DCT scores were relatively stable in both groups during the study period. Moreover, mediation analysis showed that these results were not mediated by the alleviation of depression symptoms. Partial Spearman correlation analysis showed that only plasma 5-hydroxytryptamine (5-HT) was positively correlated with Hamilton Depression Rating Scale score after Bonferroni correction (r = 0.347, p < 0.001). Augmentation therapy with tandospirone citrate improved the executive and language functions of VaDep-MCI patients. Additionally, plasma 5-HT levels may serve as a potential biomarker of VaDep severity. These findings may provide clinical insights into the treatment of vascular depression. | Vascular Depression |
Zinner's syndrome is a rare congenital abnormality of the Wolffian ducts in male patients. It consists of the triad of renal agenesis, ipsilateral seminal vesicle dilatation, and obstruction of the ejaculatory duct. Symptoms often occur after puberty and can include hematospermia, painful ejaculation, dysuria, and local discomfort. We present the case of a 15-year-old patient with this rare condition who was treated surgically after the diagnosis was confirmed. | Hemospermia |
Patients with chronic lung diseases, particularly interstitial lung disease and chronic obstructive pulmonary disease, frequently develop pulmonary hypertension, which results in clinical deterioration, worsening of oxygen uptake, and an increased mortality risk. Pulmonary hypertension can develop and progress independently from the underlying lung disease. The pulmonary vasculopathy is distinct from that of other forms of pulmonary hypertension, with vascular ablation due to loss of small pulmonary vessels being a key feature. Long-term tobacco exposure might contribute to this type of pulmonary vascular remodelling. The distinct pathomechanisms together with the underlying lung disease might explain why treatment options for this condition remain scarce. Most drugs approved for pulmonary arterial hypertension have shown no or sometimes harmful effects in pulmonary hypertension associated with lung disease. An exception is inhaled treprostinil, which improves exercise capacity in patients with interstitial lung disease and pulmonary hypertension. There is a pressing need for safe, effective treatment options and for reliable, non-invasive diagnostic tools to detect and characterise pulmonary hypertension in patients with chronic lung disease. | Hypertension, Pulmonary |
Steroids have aroused global concern due to their potent endocrine-disrupting effects. Androgens and glucocorticoids are the most abundant species in sewage; however, our understanding of their fate and risks from the source to environmental sinks remains elusive. This study compared the sorption-desorption characteristics of epiandrosterone (EADR) and cortisol (CRL) in sewage sludge and aquatic sediment, and the surface and molecular interactions were tentatively investigated through infrared spectroscopy and the fluorescence excitation-emission matrix. The results showed that the sorption capacities of EADR and CRL in the sludge were 4015 L/kg and 81.17 L/kg, respectively, which are much larger than those in the sediment (EADR: 78.77 L/kg, CRL: 6.39 L/kg); 0.02%-1.2% of EADR and 0.2%-14.5% of CRL could be desorbed from sludge, while the desorption ratios were even lower in the sediment. The high organic content in the sludge might contribute to the larger sorption capacities, while the weak interaction between steroids and organic matter could lead to larger desorption potential. The sediment contained more mineral content and featured a larger specific surface area, which could be responsible for the greater desorption hysteresis for EADR and CRL. These results will help to better understand the potential risk of sewage sludge-associated steroids and their distribution in sediment-water systems. | Androsterone |
The mechanisms underlying tumor dormancy in human primary lesions and bone marrow metastases of nasopharyngeal carcinoma (NPC) are still not completely understood. The aim of this study was to determine differences in the fates of cultured primary NPC (P-NPC) cells, interferon-gamma-transduced primary NPC (IFN-gamma-P-NPC) cells, bone marrow metastatic NPC (BM-NPC), and IFN-gamma-transduced BM-NPC (IFN-gamma-BM-NPC) cells following xenotransplantation into these four groups of SCID mice through subcutaneous injection of 5x10(6) cells/site/animal (4 animals/group). The injected mice were monitored for tumor development at the sites of injection. In only the group injected with IFN-gamma-P-NPC cells, the resulting nodules remained small throughout the 60-day observation period after injection, but gradually became palpably prickly. Histopathological examination revealed that these lesions invariably consisted of mostly structures of horny pearls and keratin bridges with occasional apoptotic and degenerative cells. In contrast, animals injected with nontransduced-P-NPC cells developed tumors progressively with occasional central necroses. In the two groups injected with IFN-gamma-NPC-BM and NPC-BM cells, progressive growths of tumors were noted, with the latter being at slightly faster rates, whereas the xenografts of both groups showed a poorly differentiated phenotype with abundant vascularity. The study results highlight the high susceptibility of P-NPC but not BM-NPC following IFN-gamma gene transfer to the induction of tumor dormancy, which is mediated via induced cell differentiation. Thus, induced cell differentiation could provide a new mechanism by which tumor dormancy is induced." | Interleukin-6 Receptor alpha Subunit |
An increasing number of disorders of metabolism are becoming amenable to the treatment, and GAMT deficiency is one of them. The symptoms and signs are reviewed, emphasising that delayed language development is a particular feature. Other symptoms include learning disorders, autistic behaviour, epileptic seizures, and movement disorders. The condition is inherited in an autosomal recessive manner, and mutations in the GAMT gene severely affect the activity of guanidinoacetate. The MRI scan shows an increased signal in the globus pallidus, and the diagnosis is confirmed by finding increased guanidinoacetate in the urine and a low plasma creatine. Other methods of diagnosis are discussed. Treatment is based on giving creatine supplementation orally and a low-protein diet with restricted arginine and increased ornithine. This results in improvement of many of the symptoms, especially of the epileptic seizures and the abnormal movements. It is justifiable to consider this condition in any patient with unexplained learning disorders." | Guanidinoacetate N-Methyltransferase |
Effects of elevated pCO(2) on Emiliania huxleyi genetic diversity and the viruses that infect E. huxleyi (EhVs) have been investigated in large volume enclosures in a Norwegian fjord. Triplicate enclosures were bubbled with air enriched with CO(2) to 760 ppmv whilst the other three enclosures were bubbled with air at ambient pCO(2); phytoplankton growth was initiated by the addition of nitrate and phosphate. E. huxleyi was the dominant coccolithophore in all enclosures, but no difference in genetic diversity, based on DGGE analysis using primers specific to the calcium binding protein gene (gpa) were detected in any of the treatments. Chlorophyll concentrations and primary production were lower in the three elevated pCO(2) treatments than in the ambient treatments. However, although coccolithophores numbers were reduced in two of the high-pCO(2) treatments; in the third, there was no suppression of coccolithophores numbers, which were very similar to the three ambient treatments. In contrast, there was considerable variation in genetic diversity in the EhVs, as determined by analysis of the major capsid protein (mcp) gene. EhV diversity was much lower in the high-pCO(2) treatment enclosure that did not show inhibition of E. huxleyi growth. Since virus infection is generally implicated as a major factor in terminating phytoplankton blooms, it is suggested that no study of the effect of ocean acidification in phytoplankton can be complete if it does not include an assessment of viruses. | Phycodnaviridae |
Using cross-sectional and longitudinal data, our study looks at the effectiveness of the Emotionally Focused Therapy (EFT) Externship and Core Skills trainings. It is the first study to evaluate EFT Core Skills trainings and the first to evaluate change longitudinally throughout the standardized EFT training program. We used the Hungarian EFT Knowledge and Competency Scale (Hungarian EFT-KACS) to examine self-perceived knowledge, competency, and alliance over three 4-day training blocks (Externship, Core Skills Modules 1&2, Core Skills Modules 3&4). Results indicate that each training block significantly increased self-perceived knowledge, competency, and alliance. During the Externship, participants' knowledge increased the most and remained at this level after each training block. Competency showed a more modest but significant increase during the Externship. However, by the end of the Core Skills training, competency showed a significant increase compared to post-Externship results, demonstrating the unique role of Core Skills training in developing competency in EFT. | Emotion-Focused Therapy |
Bone accretion is a two-stage process, with the osteoblasts laying down osteoid, which is then mineralized. Mineralization of osteoid requires vitamin D to be available in its active form (1,25(OH) 2 D); in addition, mineralization also requires normal levels of serum calcium, phosphorus, and alkaline phosphate. Deficiencies of any of these will result in defective mineralization of bone, in which the mineral-osteoid ratio is reduced (a qualitative abnormality). In the juvenile skeleton deficiencies particularly affect enchondral ossification at the growth plates, giving the characteristic clinical and radiological features of rickets. The bone may be soft, leading to deformity. In this article the causes of rickets in childhood are reviewed, together with the clinical and radiological features and strategies for prevention and treatment. | Hypophosphatemia, Familial |
OBJECTIVE: To determine if the '(Imminent) miscarriage' standard issued by the Dutch College of General Practitioners corresponds to the management by obstetricians. DESIGN: Postal questionnaire. SETTING: Research Centre Primary/Secondary Health Care, Free University Hospital Amsterdam. METHOD: A postal questionnaire was sent in 1994 to all partnerships of obstetricians (n = 122) in the Netherlands about their management in case of an imminent miscarriage. RESULTS: The response rate was 86% (n = 105). Nearly all partnerships (94%) had an agreement about their management in case of an imminent miscarriage, but the individual protocols varied. In case of a miscarriage or an imminent miscarriage 10% and 28% respectively of all partnerships said they would refer the woman to the GP or midwife. Furthermore, 21% of all partnerships said that the GP or midwife could not have an ultrasound scan made themselves, i.e. without referring to the obstetrician. Many respondent knowing the GP standard (64%) did not agree with the guidelines restricting ultrasound scans (39%) or advising expectative management (24%). They thought that an ultrasound scan was essential to diagnosis and that an expectative management would increase the risk of severe blood loss. On the other hand 15% agreed to all the guidelines. CONCLUSION: The management of obstetricians with respect to (imminent) miscarriage is diverse and does not correspond to the guidelines of the '(Imminent) miscarriage' GP standard, notably with respect to the advised expectative management. | Abortion, Threatened |
Taphrina fungi are biotrophic plant pathogens that cause plant deformity diseases. We sequenced the genomes of four Taphrina species-Taphrina wiesneri, T. deformans, T. flavorubra, and T. populina-which parasitize Prunus, Cerasus, and Populus hosts with varying severity of disease symptoms. High levels of gene synteny within Taphrina species were observed, and our comparative analysis further revealed that these fungi may utilize multiple strategies in coping with the host environment that are also found in some specialized dimorphic species. These include species-specific aneuploidy and clusters of highly diverged secreted proteins located at subtelomeres. We also identified species differences in plant hormone biosynthesis pathways, which may contribute to varying degree of disease symptoms. The genomes provide a rich resource for investigation into Taphrina biology and evolutionary studies across the basal ascomycetes clade. | Genes, Fungal |
BACKGROUND: This study is a continuation of a previously published report on the outcome of orthodontic treatment provided in offices representing different modes of practice. METHODS: The sample consisted of duplicate pretreatment (T1) and posttreatment (T2) dental casts of 348 patients from traditional private orthodontic practices (5 offices, 134 patients), company-owned practices (5 offices, 107 patients), offices associated with practice-management organizations (2 offices, 60 patients), and general dental practices (2 offices, 47 patients). Methods were used to obtain random, representative samples from each office, starting with lists of patients who were treated consecutively with full fixed orthodontic appliances. The dental casts were measured by 2 independent judges who used the unweighted PAR score. RESULTS: Good interjudge agreement was shown on the initial casts, but the agreement was not as strong on the final casts. CONCLUSIONS: The measurements showed that treatment outcomes were generally satisfactory, although some significant differences between offices and management modes were shown." | Provider-Sponsored Organizations |
PURPOSE: To investigate stereopsis and other visual functions in patients with unilateral epiretinal membrane (ERM) and to identify vision-related parameters affecting stereopsis. METHODS: This prospective study included 63 consecutive patients who were scheduled to undergo vitrectomy for unilateral idiopathic ERM. We examined stereopsis (Titmus Stereo Test, TST; TNO stereotest, TNO), best-corrected visual acuity (BCVA), letter contrast sensitivity, severity of metamorphopsia, and degree of aniseikonia preoperatively and 6 months postoperatively. RESULTS: Preoperatively, we observed significant correlation between TST scores and other vision-related parameters except severity of metamorphopsia and between TNO score and all the vision-related parameters. Multiple regression analysis showed that preoperative TST and TNO scores were significantly associated with the degree of aniseikonia (both P < 0.01). ERM surgery significantly improved stereopsis, BCVA, contrast sensitivity, and metamorphopsia, but not aniseikonia. Postoperatively, TST was significantly associated with BCVA, and TNO showed association with BCVA and aniseikonia. Postoperative TST and TNO scores showed significant correlation with preoperative aniseikonia (P < 0.005 and P < 0.001, respectively). CONCLUSIONS: Impairment of stereopsis in patients with unilateral ERM was considered to be due to retinally induced aniseikonia. Aniseikonia did not improve by surgery, and preoperative aniseikonia can be a prognostic factor for postoperative stereopsis. | Aniseikonia |
Second generation angioplasty devices remove rather than displace atherosclerotic plaque. For such devices to be useful they must be capable of addressing the major problems not solved by balloon catheters: difficult anatomy, abrupt reclosure, and restenosis. Laser angioplasty systems have proven difficult to adapt to treatment of coronary artery disease, because of heat generation, problems with perforation, and inflexibility of optical fibers. The AIS excimer laser coronary angioplasty system couples a 308 nm pulsed excimer laser to multifiber over-the-wire catheters of 1.3 mm, 1.6 mm, and 2.0 mm diameters. The laser's uniquely long pulse width (250 ns) allows delivery of higher energies through smaller fibers. Because the catheter system is front firing, risk of perforation is reduced. The Excimer Laser Coronary Angioplasty Registry involves six institutions investigating the AIS excimer system. This report deals with 255 lesions in the first 210 patients in the registry. The study cohort resembles a standard angioplasty population in terms of demographics, symptomatology, vessels dilated, and complications. Unlike a standard PTCA cohort, the ELCA patients had a higher prevalence of chronic total occlusions, calcified lesions, long lesions and diffuse disease. Both very distal lesions and those that had previously failed PTCA were successfully treated with ELCA. The laser was successful in 85% of cases, but adjunctive balloon angioplasty was required in the majority. There were no instances of perforation. | Angioplasty, Laser |
The Na+-translocating NADH:ubiquinone oxidoreductase (Na+-NQR) is a component of the respiratory chain of various bacteria. This enzyme is an analogous but not homologous counterpart of mitochondrial Complex I. Na+-NQR drives the same chemistry and also uses released energy to translocate ions across the membrane, but it pumps Na+ instead of H+. Most likely the mechanism of sodium pumping is quite different from that of proton pumping (for example, it could not accommodate the Grotthuss mechanism of ion movement); this is why the enzyme structure, subunits and prosthetic groups are completely special. This review summarizes modern knowledge on the structural and catalytic properties of bacterial Na+-translocating NADH:quinone oxidoreductases. The sequence of electron transfer through the enzyme cofactors and thermodynamic properties of those cofactors is discussed. The resolution of the intermediates of the catalytic cycle and localization of sodium-dependent steps are combined in a possible molecular mechanism of sodium transfer by the enzyme. | Ion Pumps |
Amoeboma is an inflammatory mass of the colon. It is uncommon with most cases occurring in Latin America and South Africa. When amoeboma is the presenting symptom of amoebiasis, it poses the problem of differential diagnosis of colon cancer. This report describes the case of a 60-year-old patient who presented a painful mass in the left hypochondrium. Radiologic and endoscopic examinations depicted a ring-like stenosis of the transverse colon in association with a mesenteric reaction. The presumptive diagnosis was colon cancer and the patient was referred to the National Oncology Institute for surgical treatment. Histological examination of the surgical specimen after segmental colectomy confirmed diagnosis of intestinal amoeboma. The patient was treated medically using metronidazole. Since intestinal amoebiasis is common in our country, amoeboma must be considered as a rare but potential diagnosis in patients presenting masses of the colon. Differential diagnosis of carcinoma is necessary to avoid the risks associated with unnecessary surgery. | Colonic Diseases |
Personal powers of decision and individuality must be respected, grounded on autonomy expressed through informed consent. This paper examines data on the actual use of informed consent in public hospitals in Brazil's Federal District. A questionnaire was completed by dentists in public hospitals, and its findings show that verbal informed consent is obtained at the start of treatment in most of the hospitals. Errors were noted in the use and conceptualization of informed consent. Failing to distinguish between image rights authorization and informed consent, the documents provide little information and do not explain important aspects of the treatment. Dentists practicing in the public hospital network thus need more detailed knowledge of basic bio-ethics in order to merge the long-consolidated and regulated principle of welfare with the principle of autonomy. | Dental Service, Hospital |
Human mutations in PQBP1, a molecule involved in transcription and splicing, result in a reduced but architecturally normal brain. Examination of a conditional Pqbp1-knockout (cKO) mouse with microcephaly failed to reveal either abnormal centrosomes or mitotic spindles, increased neurogenesis from the neural stem progenitor cell (NSPC) pool or increased cell death in vivo. Instead, we observed an increase in the length of the cell cycle, particularly for the M phase in NSPCs. Corresponding to the developmental expression of Pqbp1, the stem cell pool in vivo was decreased at E10 and remained at a low level during neurogenesis (E15) in Pqbp1-cKO mice. The expression profiles of NSPCs derived from the cKO mouse revealed significant changes in gene groups that control the M phase, including anaphase-promoting complex genes, via aberrant transcription and RNA splicing. Exogenous Apc4, a hub protein in the network of affected genes, recovered the cell cycle, proliferation, and cell phenotypes of NSPCs caused by Pqbp1-cKO. These data reveal a mechanism of brain size control based on the simple reduction of the NSPC pool by cell cycle time elongation. Finally, we demonstrated that in utero gene therapy for Pqbp1-cKO mice by intraperitoneal injection of the PQBP1-AAV vector at E10 successfully rescued microcephaly with preserved cortical structures and improved behavioral abnormalities in Pqbp1-cKO mice, opening a new strategy for treating this intractable developmental disorder." | Apc4 Subunit, Anaphase-Promoting Complex-Cyclosome |
A one-month crossover trial comparing Piloplex 3.4% b.i.d. with pilocarpine 2.0% q.i.d. was conducted to compare the effectiveness of the 2 drugs in reducing the intraocular pressure of ocular hypertensive and open-angle glaucoma in subjects previously controlled with pilocarpine 2.0%. For both groups the mean IOP increased slightly from baseline with pilocarpine and decreased significantly from baseline with Piloplex. The side effects of both treatments were minor. Piloplex and pilocarpine treatment were both associated with eye dryness; Piloplex was associated with lacrimation in 2 subjects. This controlled study showed that Piloplex 3.4% b.i.d. was more effective than pilocarpine 2% q.i.d. in lowering intraocular pressure. | Pilocarpine |
Defence mechanisms are mental operations that are involuntary and unconscious and contribute to reduce internal and external stresses. The concept of defensive organisation or style, defined as a set of defence mechanisms relatively stable and characteristic of personality appears to be a major dimension of personality, from normal to pathology. Studies on defence mechanisms have gained the interest of clinicians, largely outside the psychoanalytical field. However, the lack of reliability and validity of the assessment instruments still limits the empirical studies of the relation between defence mechanisms and psychological health as well as of their therapeutic implications." | Passive-Aggressive Personality Disorder |
Lectin-like ox-LDL receptors (LOX-1) play a crucial role in the ox-LDL-induced pathological transformation of vessel-wall components, a crucial early step in atherogenesis. LOX-1 dynamics is quantitatively investigated in human endothelial cells (HUVECs) exposed to environmental nanotopographies. We demonstrate distinct nanotopography-induced cell phenotypes, characterized by different morphology, LOX-1 diffusivity and oligomerization state: HUVECs on flat surfaces exhibit the behavior found in pro-atherogenic conditions, while growth on nanogratings can interfere with LOX-1 dynamics and lead to a behavior characteristic of normal, non-pathological conditions. | Scavenger Receptors, Class E |
This study reports on our experience with whole herpes simplex vaccines in Bulgaria for a period of 17 years. More than 1,500 immunized patients with herpes ophtalmicus showed a reduction of the recovery period, reduced number of the recurrences and reduced risk of visual damage. More than 14,000 patients suffering from other forms of herpes diseases for a longer period showed reduced recovery period and recurrence frequency in over 95% of the cases. Whole vaccines were well tolerable with no side effects. This report emphasizes the usefulness of whole herpes vaccines. | Herpes Labialis |
Abstract We have examined the expression of Eph receptors and their ephrin ligands in adult rat spinal cord before and after lesion. Neurons in adult motor cortex express EphA4 mRNA, but the protein is undetectable in uninjured corticospinal tract. In contrast, after dorsal column hemisection EphA4 protein accumulates in proximal axon stumps. One of the ligands for EphA4, ephrinB2, is normally present in the grey matter flanking the corticospinal tract but after injury is markedly up-regulated in astrocytes in the glial scar. The result is that, after a lesion, corticospinal tract axons bear high levels of EphA4 and are surrounded to front and sides by a continuous basket of cognate inhibitory ephrin ligand. We suggest that a combination of EphA4 accumulation in the injured axons and up-regulation of ephrinB2 in the surrounding astrocytes leads to retraction of corticospinal axons and inhibition of their regeneration in the weeks after a spinal lesion. | Ephrin-B3 |
It has long been speculated that there are discrete patterns of responsiveness to hypnotic suggestions, perhaps paralleling the factor structure of hypnotizability. An earlier study by Brenneman and Kihlstrom (1986), employing cluster analysis, found evidence for 12 such profiles. A new study by Terhune (2015), employing latent profile analysis, found evidence for three such patterns among highly hypnotizable subjects, and a fourth comprising subjects of medium hypnotizability. Some differences between the two studies are described. Convincing identification of discrete types" of high hypnotizability, such as dissociative and nondissociative, may require a larger dataset than is currently available, but also data pertaining directly to divisions in conscious awareness and experienced involuntariness." | Awareness |
Organization of neuronal connections into topographic maps is essential for processing information. Yet, our understanding of topographic mapping has remained limited by our inability to observe maps forming and refining directly in vivo. Here, we used Cre-mediated recombination of a new colorswitch reporter in zebrafish to generate the first transgenic model allowing the dynamic analysis of retinotectal mapping in vivo. We found that the antero-posterior retinotopic map forms early but remains dynamic, with nasal and temporal retinal axons expanding their projection domains over time. Nasal projections initially arborize in the anterior tectum but progressively refine their projection domain to the posterior tectum, leading to the sharpening of the retinotopic map along the antero-posterior axis. Finally, using a CRISPR-mediated mutagenesis approach, we demonstrate that the refinement of nasal retinal projections requires the adhesion molecule Contactin 2. Altogether, our study provides the first analysis of a topographic map maturing in real time in a live animal and opens new strategies for dissecting the molecular mechanisms underlying precise topographic mapping in vertebrates. | Contactin 2 |
INTRODUCTION: The widespread use of artificial intelligence (AI) programs during the COVID-19 pandemic to assess the exact volume of lung tissue damage has allowed them to train a large number of radiologists. The simplicity of the program for determining the volume of the affected lung tissue in acute interstitial pneumonia, which has density indicators in the range from -200 HU to -730 HU, which includes the density indicators of ground glass" and reticulation (the main radiation patterns in COVID-19) allows you to accurately determine the degree of prevalence process. The characteristics of chronic interstitial pneumonia, which are progressive in nature, fit into the same density framework. capital A, Cyrillicim. To small a, Cyrillicssess AI's ability to assess the progression of fibrosing lung disease using lung volume counting programs used for COVID-19 and chronic obstructive pulmonary disease. RESULTS: Retrospective analysis of computed tomography data during follow-up of 75 patients with progressive fibrosing lung disease made it possible to assess the prevalence and growth of interstitial lesions. CONCLUSION: Using the experience of using AI programs to assess acute interstitial pneumonia in COVID-19 can be applied to chronic interstitial pneumonia." | Hamman-Rich Syndrome |
Patients with elevated serum cholesterol concentrations, particularly men, should be treated to lessen their chance of subsequent morbidity from coronary heart disease. Reduction of elevated triglyceride levels is more contentious, but is justified in severely affected individuals. The levels requiring treatment can only be judged by consideration of the overall clinical setting, including patient age and sex, the presence of other risk factors and the particular lipoprotein abnormality. In general, relative youth, male sex, a low level of high density lipoprotein (HDL) cholesterol and a strong family history of coronary heart disease will favour vigorous therapy. The possibility that hyperlipoproteinaemia is secondary to some other metabolic disorder should be considered, particularly in regard to elevated triglyceride levels. | Lipid Metabolism Disorders |
High-degree myopia (HM) is defined as a refractive error above -6 D (-8 diopters). An axial eyeball length above 26 mm and is also connected with excessive myopisation. Mechanical stretching and thinning of the choroids may lead to the development of irreversible degenerative changes in the eyeball and visual impairment. HM prevalence varies significantly by geographical area, ranging from 1.7-3.3%, while in highly urban regions of South-East Asia it affects up to 24% of university students. HM is not a homogenous disease. It is considered to be inherited in different patterns: dominant, autosomal recessive, and X-linked. Many genetic mutations linked to HM development have been described and the different patterns of inheritance may reflect different types of HM. Moreover, the clinical state of the HM eyeball may result from both genetic and environmental risk factors influencing the progression of the refractive error. The development and progression of HM is connected with sustained prolonged near work involving accommodation-convergence imbalance leading to retinal blur, the years spent at school, the amount of near work, especially writing and reading, which is related to slight chronic under-accommodation, and improper light stimuli in early childhood. Contemporary definitions of HM, views on etiopathogenesis, excessive axial elongation, and pathological changes within the eyeball in the course of HM leading to visual impairment are presented here. Genetic and environmental risk factors influencing the progression of HM, its significantly different prevalence in various geographical areas, and therapeutic options for the refractive error are also presented.<br /> | Myopia |
OBJECTIVE: Fibrous dysplasia (FD) is a rare bone disorder that can involve any part of the skeleton, leading to bone pain, deformities, and fractures. Treatment with intravenous bisphosphonates has been used with variable results. Therefore, we aimed to evaluate the effects of zoledronic acid (ZA) therapy in patients with monostotic or polyostotic FD. METHODS: The medical records of thirteen patients with FD evaluated between 2015 and 2020 were retrospectively analyzed. In the subgroup of patients treated with ZA (n = 7), data on pain relief, changes in bone turnover markers (BTMs), and adverse events following ZA infusions were retrieved. Moreover, radiological changes in response to treatment were recorded in patients who underwent radiological follow-up. RESULTS: Of the patients, 5 (38%) presented with monostotic whereas 8 (62%) had polyostotic FD. Bone pain was a common finding (69%), and most patients (62%) exhibited elevated baseline BTMs. Partial or complete pain relief was reported in 6 of 7 patients treated with ZA. BTMs, especially C-telopeptide of type I collagen (CTX), significantly decreased after therapy (change rate: -61.8% [IQR -71, -60%]), and median CTX levels were significantly lower than at baseline (0.296 ng/mL [0.216, 0.298] vs. 0.742 ng/mL [0.549, 0.907], respectively; P = 0.04). No radiological improvement was observed in cases with radiological follow-up (n = 3). No serious adverse effects of ZA were reported. CONCLUSION: ZA treatment was well tolerated and provided beneficial effects in relieving bone pain and reducing BTMs, especially CTX. Our data reinforce the role of ZA in the treatment of FD-related bone pain. | Zoledronic Acid |
BACKGROUND: There is very little information for today's clinician on olecranon spurs. In addition, there is some ambiguity in the literature, with the terms olecranon spur" and "olecranon osteophyte" sometimes being used interchangeably. This review presents the current knowledge about olecranon spur anatomy, pathophysiology, clinical presentation, diagnosis, treatment options and their outcomes, as well as clarification of the terms "spur" and "osteophyte". METHODS: The PubMed and Google Scholar databases were searched using the terms "olecranon spur," "olecranon traction spur," and "olecranon osteophyte." The resulting articles were used to find other manuscripts pertaining to the subject. RESULTS: Very few articles were found as a result of these search criteria and were limited to a few case reports and a study investigating the postoperative outcomes of spur removal. Confusion of the terms "olecranon spur" and "olecranon osteophyte" was noted in 6 of the manuscripts. CONCLUSIONS: The mechanism of olecranon spur formation has not been confirmed but seems to be similar to that of spurs at other entheses. In addition, the current literature represents a small number of patients and selects only those who required surgical intervention. Three methods of spur resection have been published, and all have good outcomes with small patient numbers and limited follow-up." | Osteophyte |
Public awareness of the occurrence and effects of workplace harassment continues to grow. However, despite increasing awareness, ambiguity remains about how harassment is defined and, consequently, how to determine whether a questionable situation should be judged as harassment. For this research we reviewed definitions of workplace harassment and identified four elements that were frequently included as criteria for making judgments of whether harassment had occurred (i.e., repetition, intent, perceived intent, consequences). In two separate studies, fictional scenarios were used to evaluate the extent to which participants' judgments about harassment were affected by the presence or absence of the four elements. Ratings of the scenarios provided by student participants (study one; N=160) and a convenience sample of community participants (study two; N=292) with varying levels of work experience and diverse professional backgrounds were analysed. According to our results the four elements significantly influenced participants' judgments of harassment. The intent of the harasser had the strongest and most consistent effect on harassment judgements and whether the behaviour was repeated had the weakest and least consistent effect. In addition to the unique effects of the individual elements, significant interactions between the elements emerged and suggest that harassment judgements depend on the interplay of a variety of factors. Though the results of these studies add to the growing body of research that focuses on defining workplace harassment, they also highlight the need for additional research in the area. | Workplace |
In Sanders' classification of calcaneus fractures, the medial fracture line (subtype C) is close to the tarsal canal, which contains an artery for the talus and calcaneus. We hypothesized that because of this brittle vascular localization, patients with C line fracture patterns might describe radiologic subtalar arthritis more often and have more complaints. The purpose of the present study was to compare the results of C line fracture patterns with other types of calcaneus fractures. A total of 25 surgically treated feet were involved. Regarding Sanders' classification, group 1 included fractures involving the C line (11 feet), and group 2 included fractures not involving the C line (14 feet). Patient age at admission, trauma date, and interval until surgery were obtained from the patients' medical records. The Bohler angles were determined from the radiographs. At the last follow-up visit, the radiologist graded subtalar arthritis using computed tomography. For clinical follow-up, the American Orthopaedic Foot and Ankle Society and Maryland scores were assessed. No significant differences were found in mean age, follow-up period, delay to surgery, or postoperative Bohler angle between the 2 groups. The mean preoperative Bohler angle was significantly low for group 1. Although not significantly different, the mean American Orthopaedic Foot and Ankle Society and Maryland scores were lower for group 1 (81.9 and 84.3) than group 2 (87.8 and 92.0), and the median subtalar arthritis grade was greater for group 1 (score 2) than for group 2 (score 1.5). The worse results with C line fracture patterns despite satisfactory reduction might result from sinus tarsi artery damage. Angiographic investigations could clarify this theory in the future. Consequently, surgeons must inform and should hesitate to operate on patients with these highly comminuted C line calcaneus fractures. | Fractures, Comminuted |
An analysis of various financial ratios sampled from open and closed hospitals shows that certain leverage, liquidity, capital efficiency, and resource availability ratios can predict hospital closure up to two years in advance of the closure with an accuracy of nearly 75 percent. | Health Facility Closure |
BACKGROUND: Type 1 diabetes mellitus (T1DM) largely affects children, occurring therefore at the same period of deciduous and permanent teeth development. The aim of this work was to investigate birefringence and morphology of the secretory stage enamel organic extracellular matrix (EOECM), and structural and mechanical features of mature enamel from T1DM rats. METHODS: Adult Wistar rats were maintained alive for a period of 56 days after the induction of experimental T1DM with a single dose of streptozotocin (60 mg/kg). After proper euthanasia of the animals, fixed upper incisors were accurately processed, and secretory stage EOECM and mature enamel were analyzed by transmitted polarizing and bright field light microscopies (TPLM and BFLM), energy-dispersive x-ray (EDX) analysis, scanning electron microscopy (SEM), and microhardness testing. RESULTS: Bright field light microscopies and transmitted polarizing light microscopies showed slight morphological changes in the secretory stage EOECM from diabetic rats, which also did not exhibit statistically significant alterations in birefringence brightness when compared to control animals (P > .05). EDX analysis showed that T1DM induced statistically significant little increases in the amount of calcium and phosphorus in outer mature enamel (P < .01) with preservation of calcium/phosphorus ratio in that structure (P > .05). T1DM also caused important ultrastructural alterations in mature enamel as revealed by SEM and induced a statistically significant reduction of about 13.67% in its microhardness at 80 mum from dentin-enamel junction (P < .01). CONCLUSIONS: This study shows that T1DM may disturb enamel development, leading to alterations in mature enamel ultrastructure and in its mechanical features. | Nuclear Microscopy |
BACKGROUND AND METHODS: Metachromatic leukodystrophy (MLD) is a rare, autosomal recessive lysosomal storage disease caused by deficient activity of arylsulfatase A. Neurological involvement results in severe disability and premature death, but understanding of the natural history of the disease remains limited. In this study, 32 caregivers of patients with MLD in the USA (16 with late-infantile MLD; 16 with juvenile MLD) were interviewed about their experiences of the disease. Qualitative analysis of the interview transcripts was performed to gain insights into symptom onset, the diagnostic process and disease progression, with a focus on the differences between late-infantile and juvenile MLD. RESULTS: The mean ages of patients at interview were 7.6 years and 20.7 years for individuals with late-infantile and juvenile MLD, respectively. Patients with late-infantile MLD had a mean age of 1.5 years at symptom onset and 2.6 years at diagnosis. The most common initial symptoms in this group related to problems with gross motor function (12/16 patients); 11 patients never learned to walk independently. For patients with juvenile MLD, the mean ages at symptom onset and diagnosis were 8.7 years and 11.6 years, respectively. Cognitive or social/behavioural problems were the most common first reported symptoms in this group (9/16 and 7/16 patients, respectively); these were generally followed by deterioration in motor function. The rate of functional decline was more rapid in patients with late-infantile MLD than those with juvenile MLD; the mean time from first symptom to first functional loss was 1 year versus 6.1 years, respectively. Nine patients with juvenile MLD and three with late-infantile MLD had undergone a haematopoietic stem cell transplant; outcomes following transplant were variable. CONCLUSIONS: Our data highlight clear overall differences in symptom profiles and disease progression between late-infantile and juvenile MLD, but also indicate some degree of interindividual variability within each subtype. These findings are broadly consistent with previously published descriptions of MLD and enhance our knowledge of the natural history of the disease, which ultimately should help to improve patient care and aid assessments of the effectiveness of disease-related interventions in the future. | Leukodystrophy, Metachromatic |
Aminoacylation of RNA minihelices is speculated to be a key step in the transition from the putative RNA world to the theater of proteins. This reaction affords the opportunity to make chiral selection of an l- or d-amino acid and thus determine the ultimate chirality that is incorporated into proteins. Previous work showed chiral preference of aminoacylation with a nonprotein, nonribozyme, RNA-directed aminoacylation system. This preference was, in turn, determined by the preexisting chirality of the RNA. The alpha-amino group attached to the asymmetric alpha-carbon of the amino acid was an obvious candidate to play a role in chiral selectivity through interactions with the RNA. Also not clear was whether a simple manipulation could change the chiral selectivity, thereby giving insight into the basis of chiral selection in the first place. Here we show, surprisingly, no role for the free alpha-amino group in chiral selection. However, by a sequence manipulation, chiral preference was suppressed and partly reversed. This result and those with further RNA constructs support the idea that the chiral preference for an l-amino acid in these constructs depends on avoiding a sugar-pucker-sensitive steric clash between a pendant group of a base with the amino acid side chain. | Transfer RNA Aminoacylation |
Beyond a doubt organocatalysis belongs to the most exciting and innovative chapters of organic chemistry today. Organocatalysis has emerged not only as a complement to metal-catalyzed reactions and to biocatalysis over the last decade, but also provides new asymmetric organocatalyzed reactions that cannot be accomplished by metal- or biocatalyzed reactions so far. A large number of organocatalytic processes are already well established in organic synthesis. Nevertheless, the number of publications in this field is still on the increase; new important results are produced constantly. This review gives a detailed overview of the latest developments and main streams in organocatalyzed asymmetric CC bond formation processes of the last three years. It is intended to outline the most important current findings focused on especially new synthetic methodologies. | Benzoin |
Classic features of thyrotoxicosis developed in three patients with no prior history of thyroid disease shortly after the discontinuation of therapy with or decrease in doseage of propranolol hydrochloride. Graves' disease probably developed fortuitously after propranolol therapy was instituted, but the beta-adrenergic blockade masked the clinical features of hyperthyroidism. On discontinuation of propranolol therapy or decrease in propranolol dosage, previously latent thyrotoxicosis became manifest. If hyperthyroidism masked by beta-blockade is not recognized before withdrawal of propranolol therapy in patients with ischemic heart disease, the sudden appearance of thyrotoxicosis may lead to symptoms of increased myocardial ischemia. | Propranolol |
Advances in the field of medical oncology were spurred by the development of cytostatic drugs, and cancer is today one of the most treatable (and most curable) of the chronic diseases. Because of the diversity of neoplastic diseases, classification, staging and the important individual patient discriminants must be taken into account more than ever before because of the availability of drugs that can cure or palliate many forms of cancer. The results obtained in advanced disease acted as an impetus to start chemotherapy at an earlier stage. In highly malignant neoplasms and especially in children with cancer, drug treatment has become of increasing importance, and when given appropriately complements surgery and radiotherapy. | Neoplasms |
The effects of recombinant human growth hormone (GH, 0.1 U.kg body wt-1.12 h-1) on systemic and renal acid-base homeostasis were investigated in six normal subjects with preexisting sustained chronic metabolic acidosis, induced by NH4Cl administration (4.2 mmol.kg body wt-1.day-1). GH administration increased and maintained plasma bicarbonate concentration from 14.1 +/- 1.4 to 18.6 +/- 1.1 mmol/l (P < 0.001). The GH-induced increase in plasma bicarbonate concentration was the consequence of a significant increase in net acid excretion that was accounted for largely by an increase in renal NH+4 excretion sufficient in magnitude to override a decrease in urinary titratable acid excretion. During GH administration, urinary pH increased and correlated directly and significantly with urinary NH4+ concentration. Urinary net acid excretion rates were not different during the steady-state periods of acidosis and acidosis with GH administration. Glucocorticoid and mineralocorticoid activities increased significantly in response to acidosis and were suppressed (glucocorticoid) or decreased to control levels (mineralocorticoid) by GH. The partial correction of metabolic acidosis occurred despite GH-induced renal sodium retention (180 mmol; gain in weight of 1.8 +/- 0.2 kg, P < 0.005) and decreased glucocorticoid and mineralocorticoid activities. Thus GH (and/or insulin-like growth factor I) increased plasma bicarbonate concentration and partially corrected metabolic acidosis. This effect was generated in large part by and maintained fully by a renal mechanism (i.e., increased renal NH3 production and NH+4/net acid excretion). | Tetrahydrocortisol |
omega-Agatoxin IVA-sensitive Ca(2+) channels have been thought to be involved in physiological excitatory amino acid glutamate release and these channels may also contribute to the development of ischemic brain injury. Recently, we demonstrated that alpha-eudesmol from Juniperus virginiana Linn. (Cupressaceae) inhibits potently the presynaptic omega-agatoxin IVA-sensitive Ca(2+) channels. In the present study, we investigated the effects of alpha-eudesmol on brain edema formation and infarct size determined after 24 h of reperfusion following 1 h of middle cerebral artery occlusion in rats. We first found that alpha-eudesmol concentration-dependently inhibited glutamate release from rat brain synaptosomes and that its inhibitory effect was Ca(2+)-dependent. In the middle cerebral artery occlusion study, intracerebroventricular (i.c.v.) treatment with alpha-eudesmol significantly attenuated the post-ischemic increase in brain water content. alpha-Eudesmol also significantly reduced the size of the infarct area determined by triphenyltetrazolium chloride staining after 24 h of reperfusion. Using a microdialysis technique, we further demonstrated that alpha-eudesmol inhibits the elevation of the extracellular concentration of glutamate during ischemia. From these results, we suggest that alpha-eudesmol displays an ability to inhibit exocytotic glutamate release and to attenuate post-ischemic brain injury. | omega-Agatoxin IVA |
In this paper we investigate further properties of fuzzy ideals of a BL-algebra. The notions of fuzzy prime ideals, fuzzy irreducible ideals, and fuzzy Godel ideals of a BL-algebra are introduced and their several properties are investigated. We give a procedure to generate a fuzzy ideal by a fuzzy set. We prove that every fuzzy irreducible ideal is a fuzzy prime ideal but a fuzzy prime ideal may not be a fuzzy irreducible ideal and prove that a fuzzy prime ideal omega is a fuzzy irreducible ideal if and only if omega(0) = 1 and |Im(omega)| = 2. We give the Krull-Stone representation theorem of fuzzy ideals in BL-algebras. Furthermore, we prove that the lattice of all fuzzy ideals of a BL-algebra is a complete distributive lattice. Finally, it is proved that every fuzzy Boolean ideal is a fuzzy Godel ideal, but the converse implication is not true. | Fuzzy Logic |
PURPOSE: Although fairly uncommon and sometimes difficult to diagnose, laryngeal clefts have been well-defined in the literature. The submucosal cleft variant has been described anatomically, but not clinically. We describe a series of patients with a submucosal cricoid cleft variant and its clinical relevance. METHODS: This is a case series of patients presenting with submucosal cricoid. A submucosal cricoid cleft is defined as a dehiscent posterior cricoid plate with an intact mucosal bridge. RESULTS: Eight patients presented during a 4 year period from October 2002 to September 2006. Patient ages ranged from 6 days to 15 years, with a mean age of 40 months. Four patients (50%) had a submucosal cricoid cleft only while four children presented with a laryngotracheal cleft in addition to the submucosal cricoid cleft. Six patients were diagnosed with subglottic stenosis and had tracheotomies. Four patients (50%) failed laryngotracheal reconstruction (LTR) prior to submucosal cricoid cleft diagnosis. Two patients had their submucosal cricoid cleft diagnosed during initial airway reconstruction surgery. Two patients were diagnosed after feeding difficulties. The submucosal cricoid cleft was felt to be an important factor contributing to the failure of previous laryngotracheal reconstruction. Almost all of the patients (7/8) had co-morbidities. Two patients needed revision airway surgery, both successful. Four of the six patients with a tracheostomy have been decannulated. CONCLUSION: Because of the subtle nature of its clinical presentation, submucosal cricoid cleft can be a challenging diagnostic entity, and the results of surgical reconstruction may be compromised if the cleft is undiagnosed. | Cricoid Cartilage |
Muscle stem cell (satellite cell) activation post muscle injury is a transient and critical step in muscle regeneration. It is regulated by physiological cues, signaling molecules, and epigenetic regulatory factors. The mechanisms that coherently turn on the complex activation process shortly after trauma are just beginning to be illuminated. In this review, we will discuss the current knowledge of satellite cell activation regulation. | Myoblasts, Skeletal |
The case of a 14-month-old Latin American girl with the diagnosis of Type IV glycogen-storage disease is reported. The diagnosis was reached on the basis of the typical clinical manifestations, the light- and electron-microscopic findings, and the demonstration of absence of the branching enzyme alpha-1,4-glucan:alpha-1,4-glucan 6-glucosyl transferase in the liver and in the cultured skin fibroblasts." | Glycogen Storage Disease Type IV |
Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disease characterized by high plasma levels of low-density lipoprotein cholesterol (LDL-C) and massive risk of premature atheromasia and cardiovascular events. HoFH is caused by mutations in several genes, such as LDLR, APOB, PCSK9 and LDLRAP1. If untreated, the average age of death is 18 years old, but fatalities within the first 5 years of age have been recorded. Therefore, early diagnosis and treatment are crucial, in order to prevent and/or delay the cardiovascular complications of LDL-C exposure. Because HoFH is a rare disorder, it is not frequently encountered in daily clinical practice at the primary/secondary unspecialized cardiological centers. Then the availability of practical indications helping to identify HoFH patients or to arise a suspect of HoFH is particularly strategic to promptly start the appropriate lipid-lowering therapy. For such a purpose, a group of Italian experts suggests three useful algorithms to identify cases requiring accurate and specialized clinical evaluation as potential HoFH patients. These cases with suspected HoFH should be addressed to specialized centres for the optimal management of these patients." | Homozygous Familial Hypercholesterolemia |
The Physalis genus of the Solanaceae family is home to many edible food crops including tomatillo, goldenberry, and groundcherry. These Physalis members have garnered more attention as consumer interest in novel fruits and vegetables has increased because of increasing awareness of the health benefits of eating a diverse diet. As a result of this interest, several preliminary studies were conducted of these Physalis to evaluate their nutritional and chemical profiles associated with health benefits. Results showed these crops contain many essential minerals and vitamins, notably potassium and immune system supporting Vitamin C, also known for its antioxidant activity. Beyond nutritional properties, these crops also contain a class of steroidal lactones called withanolides, which have been recognized for their antitumor, and antinflammatory properties. In some studies, withanolide extract from Physalis species have exhibited cytotoxicity towards cancers cells. Overall, this review focuses on the nutritional and physiochemical properties of tomatillo, goldenberry, and groundcherry and how they relate to human health. | Withanolides |
The effect of substance P (SP) and the SP antagonist [D-Pro2,D-Trp7,9]-SP on basal ventilation was investigated in halothane-anesthetized rats. Microinjections of SP (0.4-1.5 nmol) into the ventrolateral medulla oblongata (VLM), (nuclei gigantocellularis, facialis, ambiguus, and reticularis lateralis) or into the dorsomedial medulla oblongata (DM, nucleus tractus solitarius) and its ventral surroundings dose dependently increased tidal volume (VT) and/or minute ventilation. In sensitive areas, the ventilatory stimulation was initiated within minutes, peaked around 8-10 min, and slowly returned to normal over 30-45 min after the injection. In the VLM sites, the increase in VT was generally accompanied by a decrease in respiratory frequency (f), whereas in the DM, f increased in parallel with VT. Furthermore, within the VLM, the respiratory response patterns differed with the definite location of the SP injection. A shortening of inspiratory time was observed in the ventromedial part, the ventrolateral portion of the nucleus paragigantocellularis and ventral to the nucleus facialis. In contrast, a lengthening of expiratory time was seen when SP was injected or applied more laterally along the ventral portion of nucleus facialis and near or directly on the ventral medullary surface. Application of [D-Pro2, D-Trp7,9]SP before or after SP completely antagonized the excitatory effects of SP on ventilation. The SP antagonist administered into the VLM decreased the ventilatory response to hypoxic breathing but caused no change during hyperoxic conditions. | Substance P |
Interstitial cells of Cajal (ICCs) have recently been identified as the pacemaker cells for contractile activity of the gastrointestinal tract. These cells generate the electrical 'slow-wave' activity that determines the characteristic frequency of phasic contractions of the stomach, intestine and colon. Slow waves also determine the direction and velocity of propagation of peristaltic activity, in concert with the enteric nervous system. Characterization of receptors and ion channels in the ICC membrane is under way, and manipulation of slow-wave activity markedly alters movement of contents through the gut organs. Here Jan Huizinga, Lars Thuneberg, Jean-Marie Vanderwinden and Juri Rumessen, suggest that, as ICCs are unique to the gut, they might be ideal targets for pharmacological intervention in gastrointestinal motility disorders, which are very common and costly. | Gastrointestinal Agents |
BACKGROUND: Changes in work and working conditions continuously give rise to new work-related health risks. Without sufficient knowledge of these, opportunities for prevention and intervention may be missed. AIMS: To develop, implement and evaluate an online tool called SIGNAAL for reporting and assessment of new work-related health risks by occupational health physicians and experts in the Netherlands and Belgium. METHODS: Development and implementation of SIGNAAL to allow both easy and sufficient detailed reporting by occupational health physicians and structured and transparent assessment by occupational health experts. A new work-related health risk is defined as a work-related disease due to specific exposure in a specific work setting not described in the literature before. RESULTS: The online reporting and assessment tool proved to be a feasible means of reporting possible new combinations of health problems and exposures in the work situation. Eleven of the 15 cases reported until October 2014 were fully assessed: one was an entirely new work-related disease, four were known but uncommon work-related diseases, five were known but new in the reported work situation and one was a well-known work-related disease. CONCLUSIONS: An online reporting system used in an occupational health setting can provide insight into new work-related health risks by creating a structured way to gather, report and assess new combinations of health problems and exposure in the workplace." | Occupational Health Physicians |
BACKGROUND: Endoscopic sinus surgery (ESS) and septoplasty are commonly performed procedures without standardized postoperative pain regimens. There is reluctance to prescribe opioids for postoperative pain given their potential for abuse. Nonsteroidal anti-inflammatory drugs (NSAIDs) have been demonstrated to reduce or even obviate the need for opioid pain medications after otolaryngologic surgeries, but prospective validation is lacking. METHODS: A randomized, controlled study comparing the efficacy of diclofenac sodium to hydrocodone/acetaminophen (APAP) after ESS with or without septoplasty was performed. Participants were given a 100-mm visual analog pain scale (VAS) at postoperative days (PODs) 1, 2, 3, and 5 after ESS. Two-sample t tests were used to compare pain scores between groups. RESULTS: One hundred patients enrolled, and 74 patients provided pain scores to the survey. Pain was greatest for both groups on POD 1. Treatment with diclofenac sodium vs hydrocodone/APAP did not statistically impact pain scores at PODs 1, 2, 3, or 5. No cases of epistaxis requiring an emergency room visit or return to the operating room were noted during the study period. CONCLUSION: Diclofenac sodium may be non-inferior to hydrocodone/APAP in treating pain after ESS with or without septoplasty in opioid naive patients without pre-existing pain conditions. Further studies with larger samples are warranted to investigate the potential superiority of diclofenac to hydrocodone/APAP in certain patients after ESS and septoplasty. | Hydrocodone |
The classification of molecules with respect to their inhibiting, activating, or toxicological potential constitutes a central aspect in the field of cheminformatics. Often, a discriminative feature is needed to distinguish two different molecule sets. Besides physicochemical properties, substructures and chemical patterns belong to the descriptors most frequently applied for this purpose. As a commonly used example of this descriptor class, SMARTS strings represent a powerful concept for the representation and processing of abstract chemical patterns. While their usage facilitates a convenient way to apply previously derived classification rules on new molecule sets, the manual generation of useful SMARTS patterns remains a complex and time-consuming process. Here, we introduce SMARTSminer, a new algorithm for the automatic derivation of discriminative SMARTS patterns from preclassified molecule sets. Based on a specially adapted subgraph mining algorithm, SMARTSminer identifies structural features that are frequent in only one of the given molecule classes. In comparison to elemental substructures, it also supports the consideration of general and specific SMARTS features. Furthermore, SMARTSminer is integrated into an interactive pattern editor named SMARTSeditor. This allows for an intuitive visualization on the basis of the SMARTSviewer concept as well as interactive adaption and further improvement of the generated patterns. Additionally, a new molecular matching feature provides an immediate feedback on a pattern's matching behavior across the molecule sets. We demonstrate the utility of the SMARTSminer functionality and its integration into the SMARTSeditor software in several different classification scenarios. | Cyclooxygenase 1 |
The repressive compartment of the nucleus is comprised primarily of telomeric and centromeric regions, the silent portion of ribosomal RNA genes, the majority of transposable element repeats, and facultatively repressed genes specific to different cell types. This compartment localizes into three main regions: the peripheral heterochromatin, perinucleolar heterochromatin, and pericentromeric heterochromatin. Both chromatin remodeling proteins and transcription of noncoding RNAs are involved in maintenance of repression in these compartments. Global reorganization of the repressive compartment occurs at each cell division, during early development, and during terminal differentiation. Differential action of chromatin remodeling complexes and boundary element looping activities are involved in mediating these organizational changes. We discuss the evidence that heterochromatin formation and compartmentalization may drive nuclear organization. | Heterochromatin |
Perivascular epithelioid cells (PEC) in angiomyolipoma (AML) were recently proposed to be its most common progenitor cells. Histologically, triphasic components were present in various proportions, but were overwhelmingly myogenic in epithelioid variants of AML. Despite histological discrimination, the immunophenotypic profiles between triphasic and epithelioid AML have never been compared. The aim of the present study was to clarify the identity of PEC by using immunoreactivity to estrogen receptor (ER), progesterone receptor (PR), bcl-2 and placenta alkaline phosphatase (PLAP), and to use this information to compare triphasic and epithelioid AML. A total of 33 out of 67 cases of renal angiomyolipoma that underwent surgery were reviewed over the period 1998-2003. Two cases were associated with tuberous sclerosis. Ten patients had other malignant tumors, and three patients had a nodal extension. Immunohistochemistry showed that bcl-2 (59.4%), PLAP (46.9%), HMB-45 (100%) was predominantly localized around vessels. The stem cell markers were absolutely negative in all AML types. The estrogen receptors were positive in 14 cases (42.4%) and the progesterone receptors were positive in five cases. Bcl-2 and both female sex hormone receptors were significantly more frequent in the epithelioid variant of AML than in the triphasic type. Perivascular epithelioid cells express bcl-2, ER, PR and PLAP, and ER could be partly associated with myogenic proliferation. | Epithelioid Cells |
BACKGROUND: Acute pancreatitis (AP) is an acute inflammatory condition of the pancreas. The symptoms, treatment, and prognosis of mild and severe AP are different, and severe AP is a potentially life-threatening disease with a high incidence of complications and high mortality rate. Thus, it is urgent to develop an effective approach to reliably discriminate between mild and severe AP. METHODS: We have developed novel gadolinium-diethylenetriaminepentaacetic (Gd-DTPA)-loaded mannosylated liposomes (named thereafter M-Gd-NL) that preferably target macrophages in AP. The targeting ability of M-Gd-NL toward macrophages in AP and its ability to discriminate between mild and severe AP were evaluated. RESULTS: The liposomes were of desired particle size (~100 nm), Gd-DTPA encapsulation efficiency (~85%), and stability. M-Gd-NL and non-targeted Gd-DTPA-loaded liposomes (Gd-NL) exhibited increased relaxivity compared with Gd-DTPA. Compared with Gd-NL and Gd-DTPA, M-Gd-NL showed increased uptake in macrophages, resulting in increased T(1) imaging ability both in vitro (macrophage cell line) and in vivo (severe AP model). Importantly, M-Gd-NL had the ability to discriminate between mild and severe AP, as reflected by a significantly higher T(1) magnetic resonance imaging signal in severe AP than in mild AP. M-Gd-NL did not show severe organ toxicity in rats. CONCLUSION: Our data suggest that M-Gd-NL had enhanced magnetic resonance imaging ability by targeting macrophages in AP and good ability to discriminate between mild and severe AP. We believe that M-Gd-NL could shed new light on the diagnosis of AP in the near future. | Gadolinium DTPA |
BACKGROUND: The traditional focus of residency training programs has been on the development of clinical and surgical skills. The expectation has been that nonclinical skills, including professional development, will be learned in an informal manner rather than through formal teaching. METHODS: After recognizing the absence of formal teaching on professional development in the residency curriculum, we developed a symposium to specifically address this omission. Topics included applying for fellowships, military promotions, overseas assignments, moonlighting, board certification, time management, lifelong orthopaedic learning, and finding a job after the military. Residents were surveyed before and after the symposium to determine the overall usefulness and value of the individual topics. RESULTS: All participating residents reported that they would recommend the symposium to other residents. The course received a mean overall rating of 4.64 (range, 4-5) on a on a scale from 1 (poor) to 5 points (excellent). High ratings were received for course usefulness, content, and relevance to future practice. CONCLUSIONS: A formal professional development program to address topics that are relevant to practice and learning should be integrated into an orthopaedic surgery residency curriculum. | Staff Development |
Burkholderia species are ubiquitous in soil environments. Many Burkholderia species isolated from various environments have the potential to biodegrade man-made chemicals. Burkholderia sp. strain YI23 was isolated from a golf course soil and identified as a fenitrothion-degrading bacterium. In this study, we report the complete genome sequence of Burkholderia sp. strain YI23. | Fenitrothion |
Deregulation of the TH17 subset of helper T cells is closely linked with immunological disorders and inflammatory diseases. However, the mechanism by which TH17 cells are regulated remains elusive. Here we found that the phosphatase DUSP2 (PAC1) negatively regulated the development of TH17 cells. DUSP2 was directly associated with the signal transducer and transcription activator STAT3 and attenuated its activity through dephosphorylation of STAT3 at Tyr705 and Ser727. DUSP2-deficient mice exhibited severe susceptibility to experimental colitis, with enhanced differentiation of TH17 cells and secretion of proinflammatory cytokines. In clinical patients with ulcerative colitis, DUSP2 was downregulated by DNA methylation and was not induced during T cell activation. Our data demonstrate that DUSP2 is a true STAT3 phosphatase that modulates the development of TH17 cells in the autoimmune response and inflammation." | Dual Specificity Phosphatase 2 |
Trafficking of newly synthesized cargo through the early secretory pathway defines and maintains the intracellular organization of eukaryotic cells as well as the organization of tissues and organs. The importance of this pathway is underlined by the increasing number of mutations in key components of the ER export machinery that are causative of a diversity of human diseases. Here we discuss the molecular mechanisms that dictate cargo selection during vesicle budding. While, in vitro reconstitution assays, unicellular organisms such as budding yeast, and mammalian cell culture still have much to offer in terms of gaining a full understanding of the molecular basis for secretory cargo export, such assays have to date been limited to analysis of smaller, freely diffusible cargoes. The export of large macromolecular complexes from the ER such as collagens (up to 300 nm) or lipoproteins (~500 nm) presents a clear problem in terms of maintaining both selectivity and efficiency of export. It has also become clear that in order to translate our knowledge of the molecular basis for ER export to a full understanding of the implications for normal development and disease progression, the use of metazoan models is essential. Combined, these approaches are now starting to shed light not only on the mechanisms of macromolecular cargo export from the ER but also reveal the implications of failure of this process to human development and disease. | Secretory Pathway |
PURPOSE: OK-432 is known to be a potent sclerosant of cystic lesions. The purpose of this study was to evaluate both its safety and pathologic effects after the infusion of OK-432 into the peritoneal cavity of rats. MATERIALS AND METHODS: Twenty male rats were used in this study. Twelve rats were infused intraperitoneally with 0.2 Klinishe Einheit of OK-432 melted in 2 mL of normal saline (group 1: the treated group); four rats each were infused intraperitoneally with 0.5 mL of 99% ethanol (group 2) and normal saline (group 3), and served as the control groups. An abdominal ultrasonographic examination was performed both before and after the infusions in all rats. Three rats in group 1 and one rat in each of groups 2 and 3 were sacrificed each week following the infusion. Gross and microscopic evaluations of the peritoneum and abdominal cavity were performed on each rat. RESULTS: In group 1, the abdomen was clear on gross inspection and the peritoneum was unremarkable on microscopic examination. In group 2, mild-to-moderate peritoneal adhesions were revealed grossly, and inflammation and fibrosis of the peritoneum were demonstrated microscopically. In group 3, no specific abnormalities were noted on gross or microscopic examinations. CONCLUSION: Leakage or abnormal infusion of OK-432 solution into the peritoneal cavity during sclerotherapy of intra-abdominal or retroperitoneal cystic lesions does not result in any significant complications. | Picibanil |
Aggression Replacement Training (ART) is widely used to reduce aggression and is considered to be effective although there are also inconsistent results. Studies investigating the effectiveness of ART do not focus on neurocognitive characteristics. Focusing on these aspects would result in enhanced understanding of underlying mechanisms of ART. The current open uncontrolled treatment study assessed whether neurocognitive characteristics were associated with change in aggression during the social skills and anger control modules of ART among forensic psychiatric outpatients. Furthermore, differences between treatment dropouts and completers and change in these characteristics during ART were examined. A reduction of trait aggression, cognitive distortions, and social anxiety was observed. Neurocognitive characteristics were not associated with change in aggression, could not distinguish treatment completers from dropouts, and did not change after ART. It is suggested that new paradigms should be developed which take into account the social context in which these impairments appear. | Anger Management Therapy |
Three rabies vaccines were compared: 1. the Fermi type vaccine, a phenol-treated suspension of brain tissue from infected sheep; 2. a virus grown in sheep brain, purified from the contaminating material to 85-90% and inactivated with beta-propiolactone; 3. and the MNIIP-74 strain cultured in Japanese quail embryo cells and inactivated with beta-propiolactone. A single immunization of mice with any of the preparations resulted in about 50% inhibition of splenocyte migration after 2 days; by day 15 the inhibition was 95-98%. By day 45 the migration index returned to the initial level. Increased ability to blast transformation in splenocytes was found by day 15, reached the maximum (160 to 212% of the control level taken for 100%) by day 30, and then began to decrease. The most marked change in blast transformation was brought about by the purified cerebral vaccine, while the less marked one by the tissue culture vaccine. The titre of virus-neutralizing antibodies reached a maximum after 15-30 days, 60 days after immunization it dropped twice. The resistance of mice to intracerebral infection with the rabies virus shortly after immunization might be due to cellular protective factors, while at later intervals it correlated with the level of virus-neutralizing antibodies. | Adaptive Immunity |
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease with increasing prevalence worldwide. Angiopoietin-like protein 8 (ANGPTL8), a member of the angiopoietin-like protein family, is involved in glucose metabolism, lipid metabolism, and energy homeostasis and believed to be associated with T2DM. Expression levels of ANGPTL8 are often significantly altered in metabolic diseases, such as non-alcoholic fatty liver disease (NAFLD) and diabetes mellitus. Studies have shown that ANGPTL8, together with other members of this protein family, such as angiopoietin-like protein 3 (ANGPTL3) and angiopoietin-like protein 4 (ANGPTL4), regulates the activity of lipoprotein lipase (LPL), thereby participating in the regulation of triglyceride related lipoproteins (TRLs). In addition, members of the angiopoietin-like protein family are varyingly expressed among different tissues and respond differently under diverse nutritional and metabolic status. These findings may provide new options for the diagnosis and treatment of diabetes, metabolic syndromes and other diseases. In this review, the interaction between ANGPTL8 and ANGPTL3 or ANGPTL4, and the differential expression of ANGPTL8 responding to different nutritional and metabolic status during the regulation of LPL activity were reviewed. | Angiopoietin-like Proteins |
The surface membrane molecule CD5 is expressed on mature T cells and on the B-1a subpopulation of B cells. These CD5 positive B cells express an antibody repertoire with a relatively high frequency of self-reactivity. There is uncertainty about the origins of CD5 B cells and the reasons for this are reviewed. Recent reports which relate to the lineage/selection debate are discussed. For instance, an increase in the frequency of CD5 B cells is a feature of several genetically determined polysystem autoimmune syndromes. In the case of motheaten (me, mev) the pathogenesis of this increase in CD5 B cells is not yet understood, even though the mutation has been mapped to the Hematopoietic cell protein-tyrosine phosphatase (Hcph) gene. Another mutation which affects B cell development, X-linked immunodeficiency (xid), encodes a point mutation in a B cell cytoplasmic tyrosine kinase. Expression of xid in otherwise normal mice causes a lack of CD5 B cells and a shift in the antibody repertoire. Interestingly, expression of both xid and motheaten results in an amelioration of autoantibody production. Evidence is presented that in B cells regulation of expression of CD5 can occur at the level of mRNA and that cross-linking of sIgM can induce the accumulation of CD5 mRNA. The overall concept advanced is that cells expressing natural autoantibodies are triggered via sIgM ligation to become CD5 B cells. | Immunologic Capping |
Transcytosis is a widespread pathway for apical targeting in epithelial cells. MAL2, an essential protein of the machinery for apical transcytosis, functions by shuttling in vesicular carriers between the apical zone and the cell periphery. We have identified INF2, an atypical formin with actin polymerization and depolymerization activities, which is a binding partner of MAL2. MAL2-positive vesicular carriers associate with short actin filaments during transcytosis in a process requiring INF2. INF2 binds Cdc42 in a GTP-loaded-dependent manner. Cdc42 and INF2 regulate MAL2 dynamics and are necessary for apical transcytosis and the formation of lateral lumens in hepatoma HepG2 cells. INF2 and MAL2 are also essential for the formation of the central lumen in organotypic cultures of epithelial MDCK cells. Our results reveal a functional mechanism whereby Cdc42, INF2, and MAL2 are sequentially ordered in a pathway dedicated to the regulation of transcytosis and lumen formation." | Myelin and Lymphocyte-Associated Proteolipid Proteins |
BACKGROUND: Inborn errors of metabolism (IEMs) have been anecdotally reported in the literature as presenting with features of cerebral palsy (CP) or misdiagnosed as 'atypical CP'. A significant proportion is amenable to treatment either directly targeting the underlying pathophysiology (often with improvement of symptoms) or with the potential to halt disease progression and prevent/minimize further damage. METHODS: We performed a systematic literature review to identify all reports of IEMs presenting with CP-like symptoms before 5 years of age, and selected those for which evidence for effective treatment exists. RESULTS: We identified 54 treatable IEMs reported to mimic CP, belonging to 13 different biochemical categories. A further 13 treatable IEMs were included, which can present with CP-like symptoms according to expert opinion, but for which no reports in the literature were identified. For 26 of these IEMs, a treatment is available that targets the primary underlying pathophysiology (e.g. neurotransmitter supplements), and for the remainder (n = 41) treatment exerts stabilizing/preventative effects (e.g. emergency regimen). The total number of treatments is 50, and evidence varies for the various treatments from Level 1b, c (n = 2); Level 2a, b, c (n = 16); Level 4 (n = 35); to Level 4-5 (n = 6); Level 5 (n = 8). Thirty-eight (57%) of the treatable IEMs mimicking CP can be identified by ready available metabolic screening tests in blood or urine, while the remaining IEMs require more specific and sometimes invasive tests. CONCLUSIONS: Limited by the rare nature of IEMs and incomplete information in the literature, we conclude that (1) A surprisingly large number of IEMs can present with CP symptoms, as 'CP mimics', (2) although individually rare, a large proportion of these diseases are treatable such that neurological damage can either be reversed or prevented, (3) clinician awareness of treatable CP mimics is important for appropriate screening, diagnosis, and early intervention, and (4) systematic studies are required to elucidate the collective frequency of treatable IEMs in CP. | Cerebral Palsy |
Advancement in high throughput DNA sequencing technologies has supported a rapid proliferation of microbial genome sequencing projects, providing the genetic blueprint for in-depth studies. Oftentimes, difficult to sequence regions in microbial genomes are ruled intractable" resulting in a growing number of genomes with sequence gaps deposited in databases. A procedure was developed to sequence such problematic regions in the "non-contiguous finished" Desulfovibrio desulfuricans ND132 genome (6 intractable gaps) and the Desulfovibrio africanus genome (1 intractable gap). The polynucleotides surrounding each gap formed GC rich secondary structures making the regions refractory to amplification and sequencing. Strand-displacing DNA polymerases used in concert with a novel ramped PCR extension cycle supported amplification and closure of all gap regions in both genomes. The developed procedures support accurate gene annotation, and provide a step-wise method that reduces the effort required for genome finishing." | Desulfovibrio africanus |
BACKGROUND: Some patients started on nasal intermittent positive pressure ventilation (NIPPV) with the Monnal D ventilator deteriorate after a period. The effects of changing them to the Nippy ventilator were investigated. METHODS: The records of such patients were examined retrospectively. Comparisons were made between blood gas tensions and overnight oximetry records before NIPPV, 12 weeks after the initiation of NIPPV with the Monnal D, at the time of deterioration, and 12 weeks after initiation of treatment with the Nippy ventilator. RESULTS: Ten patients (seven women) were identified. Prior to starting NIPPV their mean (SD) age was 59.6 (8.39) years and their mean arterial oxygen and carbon dioxide tensions (PaO2 and PaCO2) while breathing air were 6.1 (1.79) and 9.6 (3.28) kPa, respectively. All were started on NIPPV with the Monnal D with improvements in symptoms, PaO2, PaCO2, and overnight oximetry after 12 weeks of treatment. After a mean interval of 118 (69.0) weeks all measures of ventilation had deteriorated and the patients were converted to the Nippy ventilator. Twelve weeks after initiation of treatment with the Nippy ventilator symptoms and overnight oximetry were improved again and the mean PaO2 and PaCO2 were 8.9 (1.27) and 6.9 (0.45) kPa, respectively. After a total mean period of 59 (26.9) weeks on the Nippy all but one of the patients have maintained this improvement. CONCLUSIONS: Support with NIPPV using the Monnal D ventilator may fail after an interval and changing to the Nippy ventilator can reverse this deterioration, probably because of its superior responsiveness to leaks and patient effort. The regular follow up of patients on long term NIPPV is necessary if secondary treatment failure is to be identified and effectively treated." | Intermittent Positive-Pressure Ventilation |
We previously demonstrated that GABA and muscimol administered either into the cisterna magna or the fourth ventricle to chloralose-anesthetized cats cause respiratory depression, hypotension, and bradycardia. Injection of these substances into the lateral and third ventricles had no effect. In order to localize the site of action, muscimol and GABA were applied by Perspex rings to the ventral surface of the medulla. Application of muscimol (0.25-2.66 micrograms) to Schlaefke's area in 6 cats reduced minute ventilation from 443 +/- 38 to 291 +/- 52 ml/min by reducing tidal volume from 31.8 +/- 2.3 to 17.6 +/- 1.4 ml, without changing respiratory rate and duration of inspiration. Hypotension and bradycardia were also observed. Application of GABA (0.14-4.86 mg) produced similar effects on respiratory activity and arterial blood pressure. No significant effects occurred when high doses of these agents were applied to Loeschcke's and Mitchell's areas. Application of bicuculline (5-25 micrograms) to Schlaefke's area had the opposite effect of muscimol and GABA on respiratory activity and blood pressure, and reversed the respiratory and cardiovascular depressant effects of both agents. We conclude that GABA receptors are present at Schlaefke's area, and that activation of these receptors results in respiratory depression, hypotension, and bradycardia. Our results suggest that GABA may be an important inhibitory neurotransmitter in the modulation of respiratory and cardiovascular control. | Muscimol |
Pituitary adenoma (PA) rarely coexists with Rathke's cleft cyst (RCC). Previously, only 13 cases of patients with growth hormone (GH)-producing PA and concomitant RCC have been reported. Here, the authors report a 54-year-old female patient with a GH-secreting PA coexisting with an RCC. Acromegaly was diagnosed according to the physical examination and endocrine data. Preoperatively, the coronal magnetic resonance imaging (MRI) contained 2 different signal intensities, these unusually MRI findings for the intrasellar mass were rarely. According to our clinical experience for diagnosis of PA and RCC, besides GH-producing PA in this case, but the possibility of concomitant RCC should be considered. One-and-a-half nostril endoscopic transsphenoidal approach was performed. Intraoperatively, the adenoma was successfully removed and a large amount of grayish fluid from the cyst was released. The endocrine testing was normal soon after the operation and the patient remained well for a follow-up period of 3 months. The postoperative MRI (obtained 3 months after surgery) showed no intrasellar and suprasellar mass. The authors retrospectively analyzed the all 14 cases of concomitant GH-secreting PAs and RCCs and summarized MRI characteristics. When preoperative MRI contained 2 different signal intensities, one mass lesion showed low or isointense signal on the T1-weighted and T2-weighted images, whereas the other lesion showed low signal on the T1-weighted images and hyperintense on the T2-weighted images, the collision MRI features may be helpful for the preoperative diagnosis of concomitant PAs and RCCs." | Growth Hormone-Secreting Pituitary Adenoma |
This study compared the fill density of mineral trioxide aggregate (MTA) produced by hand condensation with that produced by hand condensation with indirect ultrasonic (US) activation. Sixty acrylic blocks with straight or curved canals were instrumented to an apical size 45, and weighed with a digital electronic balance. In 30 randomly chosen specimens, the canal was filled with MTA by hand condensation and weighed. The MTA was removed; the canal was rinsed and dried, and refilled using hand condensation with indirect US activation. In the other 30 specimens, the procedure was carried out identically but in reverse order. The blocks were then reweighed. The weight of the MTA fill produced by the two placement methods in the two canal configurations was analyzed by a two-way ANOVA. Hand condensation with indirect US activation resulted in an MTA fill that was statistically significantly heavier, and thus denser, than that accomplished by hand condensation alone in both curved and straight canals (p < 0.0001). | Root Canal Obturation |
BACKGROUND: Airway epithelial cells (AECs) with impaired barrier function contribute to airway remodeling through the activation of epithelial-mesenchymal trophic units (EMTUs). Although the decreased expression of ITGB4 in AECs is implicated in the pathogenesis of asthma, how ITGB4 deficiency impacts airway remodeling remains obscure. OBJECTIVE: This study aims to determine the effect of epithelial ITGB4 deficiency on the barrier function of AECs, asthma susceptibility, airway remodeling, and EMTU activation. METHODS: AEC-specific ITGB4 conditional knockout mice (ITGB4(-/-)) were generated and an asthma model was employed by the sensitization and challenge of house dust mite (HDM). EMTU activation-related growth factors were examined in ITGB4-silenced primary human bronchial epithelial cells of healthy subjects after HDM stimulation. Dexamethasone, the inhibitors of JNK phosphorylation or FGF2 were administered for the identification of the molecular mechanisms of airway remodeling in HDM-exposed ITGB4(-/-) mice. RESULTS: ITGB4 deficiency in AECs enhanced asthma susceptibility and airway remodeling by disrupting airway epithelial barrier function. Aggravated airway remodeling in HDM-exposed ITGB4(-/-) mice was induced through the enhanced activation of EMTU mediated by Src homology domain 2-containing protein tyrosine phosphatase 2/c-Jun N-terminal kinase/Jun N-terminal kinase-dependent transcription factor/FGF2 (SHP2/JNK/c-Jun/FGF2) signaling pathway, which was partially independent of airway inflammation. Both JNK and FGF2 inhibitors significantly inhibited the aggravated airway remodeling and EMTU activation in HDM-exposed ITGB4(-/-) mice. CONCLUSIONS: Airway epithelial ITGB4 deficiency induces airway remodeling in a mouse model of asthma through enhanced EMTU activation that is regulated by the SHP2/JNK/c-Jun/FGF2 pathway. | Integrin beta4 |
PURPOSE OF REVIEW: Myelodysplastic syndrome (MDS) is a clinically and molecularly heterogeneous disease, which primarily occurs in older adults. Although hypomethylating agents have survival benefit and are the current standard of care, many MDS patients will not garner a response from therapy. For those who do respond, most responses are not durable, and the only hope for a cure is allogeneic stem cell transplant. New therapies to improve outcomes are urgently needed. RECENT FINDINGS: Clinical trials combining standard hypomethylating agents with novel experimental agents are underway in an effort to improve clinical outcomes in MDS patients. Several of these small molecules have demonstrated the ability to augment the response rates of hypomethylating agents alone, including complete remission rates, in both the front line and refractory settings. Combination approaches utilizing hypomethylating agents and novel-targeted therapies have demonstrated the ability to improve response rates in MDS patients in both the front line and salvage settings, and thus may change the standard of care." | Antimetabolites, Antineoplastic |
INTRODUCTION: Inflammation may critically affect mechanisms of liver injury in acetaminophen (APAP) hepatotoxicity. Kupffer cells (KC) play important roles in inflammation, and KC depletion confers protection at early time points after APAP treatment but can lead to more severe injury at a later time point. It is possible that some inflammatory factors might contribute to liver damage at an early injurious phase but facilitate liver regeneration at a late time point. Therefore, we tested this hypothesis by using ethyl pyruvate (EP), an anti-inflammatory agent, to treat APAP overdose for 24-48 hours. METHODS: C57BL/6 male mice were intraperitoneally injected with a single dose of APAP (350 mg/kg dissolved in 1 mL sterile saline). Following 2 hours of APAP challenge, the mice were given 0.5 mL EP (40 mg/kg) or saline treatment every 8 hours for a total of 24 or 48 hours. RESULTS: Twenty-four hours after APAP challenge, compared to the saline-treated group, EP treatment significantly lowered serum transaminases (ALT/AST) and reduced liver injury seen in histopathology; however, at the 48-hour time point, compared to the saline therapy, EP therapy impaired hepatocyte regeneration and increased serum AST; this late detrimental effect was associated with reduced serum TNF-alpha concentration and decreased expression of cell cycle protein cyclin D1, two important factors in liver regeneration. CONCLUSIONS: Inflammation likely contributes to liver damage at an early injurious phase but improves hepatocyte regeneration at a late time point, and prolonged anti-inflammation therapy at a late phase is not beneficial. | Liver Regeneration |
Harmful algal blooms (HABs) are diverse phenomena involving multiple. species and classes of algae that occupy a broad range of habitats from lakes to oceans and produce a multiplicity of toxins or bioactive compounds that impact many different resources. Here, a review of the status of this complex array of marine HAB problems in the U.S. is presented, providing historical information and trends as well as future perspectives. The study relies on thirty years (1990-2019) of data in HAEDAT - the IOC-ICES-PICES Harmful Algal Event database, but also includes many other reports. At a qualitative level, the U.S. national HAB problem is far more extensive than was the case decades ago, with more toxic species and toxins to monitor, as well as a larger range of impacted resources and areas affected. Quantitatively, no significant trend is seen for paralytic shellfish toxin (PST) events over the study interval, though there is clear evidence of the expansion of the problem into new regions and the emergence of a species that produces PSTs in Florida - Pyrodinium bahamense. Amnesic shellfish toxin (AST) events have significantly increased in the U.S., with an overall pattern of frequent outbreaks on the West Coast, emerging, recurring outbreaks on the East Coast, and sporadic incidents in the Gulf of Mexico. Despite the long historical record of neurotoxic shellfish toxin (NST) events, no significant trend is observed over the past 30 years. The recent emergence of diarrhetic shellfish toxins (DSTs) in the U.S. began along the Gulf Coast in 2008 and expanded to the West and East Coasts, though no significant trend through time is seen since then. Ciguatoxin (CTX) events caused by Gambierdiscus dinoflagellates have long impacted tropical and subtropical locations in the U.S., but due to a lack of monitoring programs as well as under-reporting of illnesses, data on these events are not available for time series analysis. Geographic expansion of Gambierdiscus into temperate and non-endemic areas (e.g., northern Gulf of Mexico) is apparent, and fostered by ocean warming. HAB-related marine wildlife morbidity and mortality events appear to be increasing, with statistically significant increasing trends observed in marine mammal poisonings caused by ASTs along the coast of California and NSTs in Florida. Since their first occurrence in 1985 in New York, brown tides resulting from high-density blooms of Aureococcus have spread south to Delaware, Maryland, and Virginia, while those caused by Aureoumbra have spread from the Gulf Coast to the east coast of Florida. Blooms of Margalefidinium polykrikoides occurred in four locations in the U.S. from 1921-2001 but have appeared in more than 15 â¯U.S. estuaries since then, with ocean warming implicated as a causative factor. Numerous blooms of toxic cyanobacteria have been documented in all 50 â¯U.S. states and the transport of cyanotoxins from freshwater systems into marine coastal waters is a recently identified and potentially significant threat to public and ecosystem health. Taken together, there is a significant increasing trend in all HAB events in HAEDAT over the 30-year study interval. Part of this observed HAB expansion simply reflects a better realization of the true or historic scale of the problem, long obscured by inadequate monitoring. Other contributing factors include the dispersion of species to new areas, the discovery of new HAB poisoning syndromes or impacts, and the stimulatory effects of human activities like nutrient pollution, aquaculture expansion, and ocean warming, among others. One result of this multifaceted expansion is that many regions of the U.S. now face a daunting diversity of species and toxins, representing a significant and growing challenge to resource managers and public health officials in terms of toxins, regions, and time intervals to monitor, and necessitating new approaches to monitoring and management. Mobilization of funding and resources for research, monitoring and management of HABs requires accurate information on the scale and nature of the national problem. HAEDAT and other databases can be of great value in this regard but efforts are needed to expand and sustain the collection of data regionally and nationally. | Oceans and Seas |
BACKGROUND: The use of donor human milk is rising. Maternal awareness of donor human milk use, milk donation, and milk banks has not been well described in the United States. RESEARCH AIMS: To explore maternal experience, knowledge, and attitudes regarding donor human milk use and milk donation. We also assessed counseling by medical providers about donor human milk use and donation. METHODS: A cross-sectional prospective survey design was used in this study. We anonymously surveyed mothers (N = 73) attending the 1 to 2-week well newborn appointment. Analyses were completed using one-way ANOVA and logistic regression. RESULTS: Participants' infants primarily received their own mother's milk (87%, n = 61). No infants received donor human milk, but 4% (n = 3) of participants donated milk. The majority of participants had positive responses to attitudinal statements about donor milk. When presented with a hypothetical scenario, participants chose formula (89%, n = 59) over donor human milk (11%, n = 7) for their infant. Moreover, if donor human milk was the only option available, they chose donor human milk from a relative or friend (60%, n = 40) over a milk bank (40%, n = 26). Medical providers had discussed donor human milk use or donation with 4% (n = 3) of participants. CONCLUSIONS: The majority of participants previously had minimal experience using donor human milk and limited knowledge regarding donor human milk and milk banks. According to participants, medical providers did not routinely discuss milk donation and the role of donor human milk with families. | Milk Banks |
Orthodontic retention is the final important stage of orthodontic treatment, the aim of which is to consolidate the functional and aesthetic position of teeth. Among adults, fixed retainers made of different types of wires are the most common. The aim of this study was to analyse the mechanical properties of a new generation of fixed orthodontic retainers-printed by 3D printers. MATERIALS AND METHODS: The study was conducted using samples made of Nextdent MFH C&B N1 resin in the form of cuboid bars with nominal dimensions of width b = 3 mm, thickness d = 0.8 mm; 1 mm; 1.2 mm, length l = 30 mm for each type. The influence of the thickness of the retainers on their strength under loaded conditions was evaluated. Flexural strength, elastic properties, deflection, and creep were compared. The samples were aged in an artificial saliva bath at 37 +/- 1 degrees C during the strength tests. RESULTS: It was shown that differences in the thickness of the samples affected their elastic and strength properties. The highest average flexural modulus, the highest deflection, creep, and strength was characteristic of the samples with the highest thickness (1.2 mm). Samples with an average thickness of 1 mm had the lowest modulus of elasticity. CONCLUSIONS: The mechanical properties of 3D printed retainers show that they can be an alternative to metal retainers and the procedure of making new retainers, especially when patients have aesthetic requirements or allergies to metals. | Orthodontic Retainers |
The calcite grains forming the wall plates of the giant barnacle Austramegabalanus psittacus have a distinctive surface roughness made of variously sized crystalline nanoprotrusions covered by extremely thin amorphous pellicles. This biphase (crystalline-amorphous) structure also penetrates through the crystal's interiors, forming a web-like structure. Nanoprotrusions very frequently elongate following directions related to the crystallographic structure of calcite, in particular, the <- 441> directions, which are the strongest periodic bond chains (PBCs) in calcite. We propose that the formation of elongated nanoprotrusions happens during the crystallization of calcite from a precursor amorphous calcium carbonate (ACC). This is because biomolecules integrated within the ACC are expelled from such PBCs due to the force of crystallization, with the consequent formation of uninterrupted crystalline nanorods. Expelled biomolecules accumulate in adjacent regions, thereby stabilizing small pellicle-like volumes of ACC. With growth, such pellicles become occluded within the crystal. In summary, the surface roughness of the biomineral surface reflects the complex shape of the crystallization front, and the biphase structure provides evidence for crystallization from an amorphous precursor. The surface roughness is generally explained as resulting from the attachment of ACC particles to the crystal surface, which later crystallised in concordance with the crystal lattice. If this was the case, the nanoprotrusions do not reflect the size and shape of any precursor particle. Accordingly, the particle attachment model for biomineral formation should seek new evidence. | Calcium Carbonate |
Lipodystrophy includes a heterogeneous group of rare diseases characterized by different amounts of adipose tissue loss and several metabolic complications, including hypertriglyceridemia, steatohepatitis and particularly insulin resistance, that may lead to severe morbidity and, sometimes, mortality. Therefore, therapy for lipodystrophy primarily consists of a conventional approach that involves standard treatments of metabolic abnormalities. Given the evidence of leptin deficiency in lipodystrophy syndromes, leptin replacement therapy has been considered as a treatment option. Long-term studies on the use of therapy with a methionylated analog of human leptin, metreleptin, first on animals and subsequently on human patients, demonstrated enormous improvements of patients' clinical features and metabolic conditions. Recently, metreleptin was approved by Food and Drug Administration (FDA) for the treatment of generalized lipodystrophy and by European Medicines Agency (EMA) for the treatment of both generalized and partial lipodystrophy. However, further research is being conducted for new and different therapeutic agents, especially helpful for the treatment of patients with partial lipodystrophy, as some of them do not have access to metreleptin therapy or show poor response." | Lipodystrophy, Congenital Generalized |
OBJECTIVE: Marijuana use is relatively common among youth and increases during the transition to adulthood. Yet a substantial number of adolescents and young adults do not use marijuana. The purpose of this study was to examine how high school seniors' reasons for intending not to use marijuana within the next 12 months were prospectively associated with marijuana use reported 1 year later. METHOD: Data were drawn from national longitudinal samples of U.S. high school seniors from the Monitoring the Future study (n = 3,044; 50% female; 65% White). Bivariate and multivariable logistic regression analyses were conducted to examine associations between reasons seniors indicated for intending not to use marijuana within the next 12 months and marijuana use reported 1 year later in the follow-up survey, controlling for sociodemographic characteristics and high school risk factors. Analyses were conducted separately among youth with and without lifetime marijuana use in high school. RESULTS: In multivariable models, reasons associated with marijuana abstinence 1 year later among prior marijuana use abstainers were concerns about becoming addicted, use being against ones' beliefs, not liking marijuana users, and not having friends who use marijuana. Among prior marijuana users, not enjoying marijuana was a significant predictor of marijuana abstinence 1 year later. CONCLUSIONS: Reasons for abstaining from marijuana have predictive utility in relation to later use, but these associations differ between those with and without prior marijuana use. Understanding the underlying reasons for stopping marijuana use or maintaining abstinence may inform youth substance use prevention and intervention programs. | Marijuana Smoking |
In this paper we report that suspensions of human fetal thymocytes contain cells that express high levels of CD34 and Thy-1. These cells were characterized with regard to location within the thymus, phenotype, and function. Confocal laser scan analysis of frozen sections of fetal thymus with anti-CD34 and Thy-1 antibodies revealed that the double-labeled cells were located in the pericortical area. In addition, it was found that the CD34+Thy-1+ cells lacked CD45 and CD50, indicating that these cells are not of hematopoietic origin; this was confirmed by the finding that these cells could be cultured as adherent cells in a medium with cholera toxin and dexamethasone, but failed to grow in mixtures of hematopoietic growth factors. Further analysis indicated that most cultured CD34+Thy-1+ cells expressed cytokeratin (CK) 14 but lacked CK 13, suggesting that these cells are immature epithelial cells. Cultured CD34+Thy-1+ cells were able to induce differentiation of CD1-CD34+CD3-CD4-CD8- thymic precursors into CD4+CD8+ cells in a reaggregate culture in the absence of exogenous cytokines. The CD4+CD8+ cells that developed in these cultures did not express CD3, indicating that CD34+Thy-1+ thymic stromal cells are not capable of completing full T cell differentiation of thymic hematopoietic progenitor cells. | Thymus Gland |
Somatostatin is a peptide able to stop breathing, acting in the neural network that generates and control the respiratory rhythm. In this chapter, we present data on the early postnatal development of somatostatinergic systems in the mouse brainstem and summarize evidence for their influence on the generation and control of the respiratory rhythm. | Brain Stem |
Chronic pain, along with comorbid psychiatric disorders, is a common problem worldwide. A growing number of studies have focused on non-opioid-based medicines, and billions of funds have been put into digging new analgesic mechanisms. Peripheral inflammation is one of the critical causes of chronic pain, and drugs with anti-inflammatory effects usually alleviate pain hypersensitivity. Sophoridine (SRI), one of the most abundant alkaloids in Chinese herbs, has been proved to exert antitumor, antivirus and anti-inflammation effects. Here, we evaluated the analgesic effect of SRI in an inflammatory pain mouse model induced by complete Freund's adjuvant (CFA) injection. SRI treatment significantly decreased pro-inflammatory factors release after LPS stimuli in microglia. Three days of SRI treatment relieved CFA-induced mechanical hypersensitivity and anxiety-like behavior, and recovered abnormal neuroplasticity in the anterior cingulate cortex of mice. Therefore, SRI may be a candidate compound for the treatment of chronic inflammatory pain and may serve as a structural basis for the development of new drugs. | Hyperalgesia |
Lumbar degenerative spondylolisthesis (DS) is a common cause of low back pain, radiculopathy, and/or neurogenic claudication. Treatment begins with a trial of nonsurgical methods, including physical therapy, NSAIDs, and epidural corticosteroid injections. Surgical treatment with decompression and fusion is recommended for patients who do not respond to this initial regimen. Although much has been published in the past two decades on the surgical management of DS, the optimal method remains controversial. Interbody fusion may improve arthrodesis rates and can be performed via numerous surgical approaches. Minimally invasive techniques continue to be developed. Particular attention to surgical management of DS in the elderly is warranted given the increasing numbers of elderly persons. Healthcare utilization in the future must take into account evidence-based medicine that establishes clinically effective practices while simultaneously being cost effective. | Spondylolisthesis |
Methylene blue (MB), as the first fully man-made medicine, has a wide range of clinical applications. Apart from its well-known applications in surgical staining, malaria, and methemoglobinemia, the anti-oxidative properties of MB recently brought new attention to this century-old drug. Mitochondrial dysfunction has been observed in systematic aging that affects many different tissues, including the brain and skin. This leads to increaseding oxidative stress and results in downstream phenotypes under age-related conditions. MB can bypass Complex I/III activity in mitochondria and diminish oxidative stress to some degree. This review summarizes the recent studies on the applications of MB in treating age-related conditions, including neurodegeneration, memory loss, skin aging, and a premature aging disease, progeria. | Methylene Blue |
Studies in recent years have uncovered a diverse set of eukaryotic receptors that recognize lipopolysaccharide (LPS), the major outer-membrane component of Gram-negative bacteria. Indeed, Toll-like receptors, G-protein-coupled receptors, integrins, receptor-like kinases, and caspases have emerged as important LPS-interacting proteins. In this review, the mammalian receptors that detect LPS are described. I highlight how no host protein is involved in all LPS responses, but a single lipid (phosphatidylinositol-4,5-bisphosphate) regulates many LPS responses, including endocytosis, phagocytosis, inflammation, and pyroptosis. I further describe LPS response systems that operate specifically in plants, and discuss potentially new LPS response systems that await discovery. This diversity of receptors for a single microbial product underscores the importance of host-microbe interactions in multiple kingdoms of life. | Activin Receptors |
Delftia lacustris is reported for the first time as a selenate and selenite reducing bacterium, capable of tolerating and growing in the presence of >/= 100 mM selenate and 25 mM selenite. The selenate reduction profiles of D. lacustris were investigated by varying selenate concentration, inoculum size, concentration and source of organic electron donor in minimal salt medium. Interestingly, the bacterium was able to reduce both selenate and selenite under aerobic conditions. Although considerable removal of selenate was observed at all concentrations investigated, D. lacustris was able to completely reduce 0.1 mM selenate within 96 h using lactate as the carbon source. Around 62.2% unaccounted selenium (unidentified organo-selenium compounds), 10.9% elemental selenium and 26.9% selenite were determined in the medium after complete reduction of selenate. Studies of the enzymatic activity of the cell fractions show that the selenite/selenate reducing enzymes were intracellular and independent of NADPH availability. D. lacustris shows an unique metabolism of selenium oxyanions to form elemental selenium and possibly also selenium ester compounds, thus a potential candidate for the remediation of selenium-contaminated wastewaters in aerobic environments. This novel finding will advance the field of bioremediation of selenium-contaminated sites and selenium bio-recovery and the production of potentially beneficial organic and inorganic reactive selenium species. | Selenic Acid |
Locking of metacarpophalangeal (MCP) joints of the thumb may be a consequence of dorsal subluxation from hyperextension injury. The joint is locked in mild hyperextension and cannot flex actively or passively. We report four patients with locked MCP joint of the thumb due to radial sesamoid entrapment after hyperextension or forced flexion injury. All patients had a prominent radial condyle of the metacarpal bone. Three patients had a deformity of the longitudinal groove on which the sesamoid was overlaid. The radial sesamoid was entrapped proximal to the radial condyle which could result in limited extension and hinged flexion of the joint. Excision of the radial sesamoid could release the locked joint. The radial sesamoid should be assessed if the motion of the thumb MCP joint is limited after flexion or extension injury. Level of Evidence: Level V (Therapeutic). | Metacarpophalangeal Joint |
Secondary metabolites, DIBOA, HBOA, 7-OH-HBOA and BOA, were isolated and quantified from S. dulce (Nees), a native species in Chile belonging to the Acanthaceae family. The highest DIBOA and HBOA contents were determined in leaves (9.25 mmol kg(-1) fr. wt) and root (6.81 mmol kg(-1) fr. wt), respectively. Aglycones, 7-OH-HBOA and HBOA, were isolated together from root extracts of Acanthaceae species. Both, HBOA and 7-OH-HBOA should be direct precursors in the biosynthesis of DIBOA and DIMBOA, respectively. | Oxazines |
Twelve normal male subjects received single oral doses of atenolol 100 mg (AT), bendrofluazide 5 mg (BFZ), combined atenolol 100 mg and bendrofluazide 5 mg (AT/BFZ), diazepam 5 mg (Dz), or one of two matching placebos, on each of 6 study days. Tests of psychomotor performance [digit symbol substitution (DSST), letter cancellation (LCT), continuous attention, choice reaction time (CRT), finger tapping, short-term memory, body sway], physiological measurements [critical flicker fusion (CFF), two-flash fusion (2FF)] and subjective assessments using visual analogue scales (VAS), were performed at 2 and 4 hours post-ingestion. Dz (active control) significantly worsened VAS scores at 2 h (+0.68) and reduced DSST scores at both 2 h (-15.0) and 4 h (-11.0). AT and BFZ given alone, each produced significant worsening of VAS at 2 h [AT +1.0; BFZ +1.38], but had no significant effects on performance. In combination however, AT/BFZ at 4 h produced significant impairment of DSST scores (-10.4), reduced finger tapping (-16.5) and increased involuntary rest pauses (+16.5). Despite these effects, no change in VAS scores occurred. In summary, we have demonstrated significant impairment of psychomotor performance in normal subjects with the AT/BFZ combination, which was not evident with the single agents and which occurred in the absence of a change in subjective awareness. These central effects may have important clinical implications for patients taking combined antihypertensive medication. | Bendroflumethiazide |
The interaction of dopamine and glutamate in limbic brain regions mediates behaviors associated with psychostimulants, which act in part to increase dopamine signaling at both D1 receptors (D1Rs) and D2 receptors. Many addictive behaviors are a result of learned associations, and NMDA receptor activation has been shown to be important for these behaviors. We hypothesized that if NMDA receptor activation in dopamine receptor-containing cells is required for the addictive properties of psychostimulants, then mice with reduced NMDA receptor activity in D1R-containing cells would have attenuated long-term behavioral changes to these drugs. We generated a mouse line in which D1R-containing cells express an NR1 NMDA receptor subunit containing a mutation in the pore that reduces calcium flux. Mice expressing the mutant NMDA receptors in D1R-containing cells have normal basal activity and display similar increases in locomotor activity when treated with acute amphetamine or cocaine. However, the mutant mice fail to display locomotor sensitization to repeated cocaine administration. In addition, these mice also have a decreased ability to form a conditioned place preference to cocaine. These data suggest that intact NMDA receptor signaling in D1R-containing cells is required for the manifestation of behaviors associated with repeated drug exposure." | Chromosomes, Artificial, P1 Bacteriophage |
Bacterial meningitis is still a serious disease with a high risk of mortality and sequels. The progress in antibiotic treatment has not improved the prognosis. Thus, optimizing the initial care and the treatment of the most severe cases should improve the outcome. No study has compared the outcome according to the level of care at the admission site. There is evidence that the most severe cases should be managed by critical care units. It seems reasonable to recommend initial admission of common cases to units able to provide intensive care. Most people now agree that fluid restriction has not demonstrated its efficiency, furthermore it might have deleterious effects. However, a fluid overload should be avoided. Maintaining cerebral perfusion is a key issue in the treatment of bacterial meningitis and requires monitoring both arterial blood pressure and intracranial pressure. Intracranial pressure monitoring is probably useful to optimize the treatment of the most severe cases. The aggressive treatments of cerebral edema have not been evaluated but seem, in some limited series, able to improve some life threatening situations. The benefit of systematic glycerol administration needs confirmation. Seizures should be treated with the usual medications. However, drugs with potentially deleterious effects on hemodynamics should be avoided. There is no sufficient evidence to support the administration of a systematic prophylactic treatment. Fever should be treated when above 39.5 degrees C/40 degrees C and in the case of intracranial hypertension. There is no clinical study to explore the modifications of fever on bacterial growth or on inflammation as observed in some experimental studies. | Hypodermoclysis |
BACKGROUND: Recent studies have suggested that genetic predisposition to suicidal behavior may be independent of the risk of suicide associated to mental disorders, such as affective disorders, schizophrenia or alcohol dependence. Given the suicidal behavior heterogeneity and its hereditary complexity, the need to find demonstrable intermediate phenotypes that may make it possible to establish links between genes and suicide behaviors (endophenotypes) seems to be necessary. The main objective is to review which are the candidate endophenotypes of suicidal behaviors. METHODS: We carried out a non-systematic review of all published literature in English, French and Spanish in MEDLINE. The search terms were endophenotypes and suicide behaviors. CONCLUSIONS: The main candidate endophenotypes of suicidal behaviors are neuropsychological (decision-making, executive functions), personality traits (impulsivity, aggressiveness, and neuroticism), neurochemistry (5-HIAA in CNS) and neuroimaging (fMRI of cerebral amygdala or PET of prefrontal cortex metabolism). | Endophenotypes |
OBJECTIVE: Panton-Valentine leukocidin-producing Staphylococcus aureus necrotizing pneumonia is an unusual cause of community-acquired pneumonia, although associated with a high case fatality. This infection mainly affects young individuals, without any history, and is most often preceded by flu-like symptoms. METHOD: We focused on patients presenting with Staphylococcus aureus necrotizing pneumonia in Reunion (Indian Ocean) admitted to the emergency department. We performed a retrospective study based on data collected from laboratory registers and medical files of patients presenting with Staphylococcus aureus necrotizing pneumonia in Reunion between December 2014 and December 2017. RESULTS: A total of 16 patients were recruited for this study, with a median age of 40.5 years. More than half of patients had previously been admitted to the emergency department for acute respiratory distress syndrome or severe sepsis. Fourteen patients were admitted to the intensive care unit and six patients died (five premature deaths). CONCLUSION: Physicians should be aware of this infection during the flu season and quickly adapt the specific antibiotic treatment, including a drug inhibiting toxin production. As methicillin-resistant Staphylococcus aureus is very rarely observed in Reunion, physicians can still adapt the empirical treatment, without glycopeptides. | Pneumonia, Necrotizing |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.