Miracle-dz/UniFAR-FTUs huggingface dataset:
Normative anatomy of the anal sphincter detected with 3D-endoanal ultrasonography

Abstract Background: Understanding anal sphincter anatomy is crucial in management of anorectal disorders, including anorectal sepsis and fecal incontinence. Three-dimensional endoanal ultrasound (EAUS) provides better resolution of the tissue layers. Previous normative studies were obtained in Western populations. Objective: We demonstrated the anal sphincter anatomy in normal East Asian subjects. Methods: Forty-six healthy subjects without anorectal symptoms (M:F = 15:31, mean age ± SD = 47 ± 13 years) were enrolled. High-frequency (16 MHz) EAUS was performed with a mechanically rotated probe. Thickness and length of anal sphincter components were measured. Differences between sexes were assessed using a Student t test. Results: We demonstrated 4 differentiable components: the anal sphincter; internal anal sphincter (IAS), subcutaneous external anal sphincter (Sc EAS), superficial external anal sphincter (Sp EAS), and puborectalis muscle (PRm). The mean length of anal sphincter components were obtained in mm (men vs. women), IAS (28.5 vs. 25.3, p = 0.03), Sc EAS (13.2 vs. 11.2, p = 0.005), Sp EAS (24.1 vs. 19.6, p = 0.0001), and PRm (12.4 vs. 12.2, p = 0.84). The anal canal was significantly longer in men (38.6 vs. 34.0, p = 0.007). The mean thickness for IAS (1.7 vs. 1.8, p = 0.095), Sc EAS (7.5 vs. 7.6, p = 0.587), Sp EAS (8.1 vs. 6.9, p = 0.001), and PRm (8.7 vs. 9.0, p = 0.605) were measured. The PRm was the thickest and the Sp EAS was the longest voluntary sphincter. Conclusion: Normative details of anal sphincter components in an East Asian population are described. This data can be used for future consideration of diseased states.
Benefits for specific subpopulations in TRITON-TIMI 38

Dual-antiplatelet therapy with aspirin and thienopyridines can prevent ischaemic events associated with acute coronary syndromes and percutaneous coronary intervention. The Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel–Thrombolysis in Myocardial Infarction (TRITON-TIMI) 38 trial demonstrated that prasugrel, a novel and potent thienopyridine, can reduce ischaemic events compared with clopidogrel therapy, but at the cost of increased bleeding events in some high-risk patients. This review aims to highlight the driving force behind the reductions in ischaemic events in the overall TRITON-TIMI 38 population, and present the efficacy and safety profiles of prasugrel in important TRITON-TIMI 38 sub-populations [patients with ST-elevation myocardial infarction (STEMI) at inclusion, diabetes, and stent placement], compared with clopidogrel. In the overall TRITON-TIMI 38 population, the reduction in the combined primary efficacy endpoint of cardiovascular death, non-fatal myocardial infarction (MI), or non-fatal stroke with prasugrel, compared with clopidogrel, was driven by a reduction in the rate of MI. In the sub-population analyses, prasugrel significantly reduced the rate of the primary endpoint compared with clopidogrel, again primarily through a reduction in MI. Of note, prasugrel did not increase TIMI major non-coronary artery bypass graft bleeding in patients with STEMI or diabetes, relative to clopidogrel. These data suggest that in high-risk patients, the safety of prasugrel is comparable to that of clopidogrel.
Localizing the Global

Tests for hereditary predispositions to breast and ovarian cancer have figured among the first medical applications of the new knowledge gleaned from the Human Genome Project. These applications have set off heated debates on general issues such as intellectual property rights. The genetic diagnosis of breast cancer risks, and the management of women “at risk” has nevertheless developed following highly localized paths. There are major differences in the organization of testing, uses of genetic tests, and the follow up of patients. This article studies testing practices and ways of managing breast cancer risk in France and compares them with those in the United States and United Kingdom. It shows how the complex interaction between global and local factors shapes the multiple meanings assumed by the phrase cancer risk.
MAPK signaling pathways and HDAC3 activity are disrupted during differentiation of emerin-null myogenic progenitor cells

ABSTRACT Mutations in the gene encoding emerin cause Emery–Dreifuss muscular dystrophy (EDMD). Emerin is an integral inner nuclear membrane protein and a component of the nuclear lamina. EDMD is characterized by skeletal muscle wasting, cardiac conduction defects and tendon contractures. The failure to regenerate skeletal muscle is predicted to contribute to the skeletal muscle pathology of EDMD. We hypothesize that muscle regeneration defects are caused by impaired muscle stem cell differentiation. Myogenic progenitors derived from emerin-null mice were used to confirm their impaired differentiation and analyze selected myogenic molecular pathways. Emerin-null progenitors were delayed in their cell cycle exit, had decreased myosin heavy chain (MyHC) expression and formed fewer myotubes. Emerin binds to and activates histone deacetylase 3 (HDAC3). Here, we show that theophylline, an HDAC3-specific activator, improved myotube formation in emerin-null cells. Addition of the HDAC3-specific inhibitor RGFP966 blocked myotube formation and MyHC expression in wild-type and emerin-null myogenic progenitors, but did not affect cell cycle exit. Downregulation of emerin was previously shown to affect the p38 MAPK and ERK/MAPK pathways in C2C12 myoblast differentiation. Using a pure population of myogenic progenitors completely lacking emerin expression, we show that these pathways are also disrupted. ERK inhibition improved MyHC expression in emerin-null cells, but failed to rescue myotube formation or cell cycle exit. Inhibition of p38 MAPK prevented differentiation in both wild-type and emerin-null progenitors. These results show that each of these molecular pathways specifically regulates a particular stage of myogenic differentiation in an emerin-dependent manner. Thus, pharmacological targeting of multiple pathways acting at specific differentiation stages may be a better therapeutic approach in the future to rescue muscle regeneration in vivo. Editors' choice: HDAC3, p38 MAPK and ERK signaling are altered during differentiation of myogenic progenitors lacking emerin; pharmacological activation or inhibition of these signaling proteins rescues specific stages of myogenic differentiation.
Cost effectiveness analyses of influenza A (H1N1) vaccination programs: How accurate were they?

Three economic evaluations of pandemic influenza A (H1N1) vaccination campaigns in North America concluded that the mass vaccination campaigns would be, or were, highly cost-effective, if not cost-saving. This paper re-assesses each study's analysis and presents three arguments: 1) prediction of vaccine program cost-effectiveness is unrealistic, if not impossible, unless quality surveillance data is available; 2) even when surveillance data is available, vaccine cost-effectiveness calculations can still vary dramatically and need to undergo wider-ranging sensitivity analysis; 3) H1N1 vaccination campaigns in North America were likely not as cost-effective as previously thought. Several recommendations are then made for improving transparency, accuracy, portability, and sensitivity analysis in pharmacoeconomic studies more generally. Key words: Pandemic, influenza, vaccination, immunization, cost-effectiveness, health economics, pharmaco-economics.
TPL2-mediated activation of ERK1 and ERK2 regulates the processing of pre-TNFα in LPS-stimulated macrophages

Activation of the TPL2-MKK1/2-ERK1/2 signalling pathway is essential for lipopolysaccharide (LPS)-stimulated production of TNFα in macrophages. Here, we demonstrate that, unexpectedly, TPL2-deficient or MKK1-inhibited macrophages produce near normal levels of pre-TNFα when TLR2, TLR4 and TLR6 are activated by their respective agonists, but fail to secrete TNFα. We show that LPS stimulates the appearance of pre-TNFα at the cell surface and that this is prevented by inhibition of MAPK kinases 1 and 2 (MKK1/2) or in TPL2-deficient macrophages. However, the transport of pre-TNFα from the Golgi to the plasma membrane is unaffected by inhibition of the TPL2-MKK1/2-ERK1/2 pathway. Finally, we show that TACE, the protease that cleaves pre-TNFα to secreted TNFα, is phosphorylated by ERK1 and ERK2 (ERK1/2) at Thr735 in LPS-stimulated macrophages. Therefore, although TACE activity per se is not required for the LPS-stimulated cell surface expression of pre-TNFα, the phosphorylation of this protease might contribute to, or be required for, the cell surface expression of the pre-TNFα–TACE complex.
Weight Loss Behavior in High School Wrestling: Wrestler and Parent Perceptions

Self-reports of weight loss knowledge, attitudes, and methods in a sample of 125 high school wrestlers are described. These responses are compared to perceptions of 88 wrestlers’ parents regarding their son’s weight loss behaviors. Responses to survey questionnaires indicated that wrestlers were highly likely to deliberately lose weight for wrestling and that they most commonly used increased exercise, caloric restriction, and fluid restriction as weight loss techniques. Wrestlers reported use of extreme weight loss techniques (fasting, vomiting, diuretics) in higher proportions than the general adolescent male population, despite their reports of detrimental effects of such methods. Compared to their sons, parents significantly underestimated the use of extreme methods and were more realistic about the potential harmful effects of severe weight loss. Wrestlers and parents alike felt that weight loss is overemphasized in wrestling competition. These findings indicate a need for improved adult monitoring o.
Humoral β‐cell autoimmunity is rare in patients with the congenital rubella syndrome

The congenital rubella syndrome (CRS) is associated with increased risk for diabetes and thyroid disease. However, the mechanisms by which the rubella virus may cause these diseases are poorly characterized. Previous studies were carried out before modern immunological methods were available. The present study aimed at evaluating whether autoimmune mechanisms are involved in the pathogenesis by analysing antibodies to biochemically characterized autoantigens. The incidence of clinical diabetes, thyroid disease, coeliac disease and related antibodies (islet cell antibodies, ICA; insulin autoantibodies, IAA; antibodies to the tyrosine phosphatase related IA‐2 molecule, IA‐2 A and glutamic acid decarboxylase, GADA; thyroid peroxidase, TPO; tissue transglutaminase, TTGA; and gliadin, AGA) and HLA risk genotypes were analysed in 37 subjects affected by or exposed to rubella during fetal life (mean age 22·5 years). One patient had diabetes and four patients had clinical hypothyroidism at the time of the examination. ICA, IAA, GADA or IA‐2 A were not detected in any of the patients, while five patients tested positive for TPO antibodies. Coeliac disease or TTGA were not observed. Eight patients carried the HLA‐DR3–associated HLA‐DQB1*02‐DQA1*05 haplotype. These results provide no evidence of an increased frequency of markers for humoral β‐cell autoimmunity in patients with CRS suggesting that diabetes in CRS may be caused by other than autoimmune mechanisms.
OLSRv2 implementation and performance evaluation with link layer feedback

OLSRv2 is being standardized in the IETF MANET (Mobile Ad hoc Network) working group. OLSRv2 uses the common packet format, that is also being standardized in the MANET WG. It is necessary to validate the OLSRv2 protocol specification by implementing OLSRv2. In addition, OLSRv2 has a great capability to reduce message size compared to OLSR. This is due to address compression. The change of control message size directly affects the total network performance, but how much it affects the various parameters are dependent on the network scale, number of nodes, and address compression implementation. In this context, we have implemented the OLSRv2 protocol, which can run as a real-time protocol or in the QualNet simulator. In addition, we added link disconnection feedback function from MAC layer to OLSRv2 modifying wireless LAN device driver. In this paper our OLSRv2 implementation detail is introduced, and OLSRv2 performance is compared with OLSR by using both a 50 node testbed built in Niigata university and also in the Qualnet simulator. In addition, IP address compression effect is analyzed in the simulator, and the performance of OLSRv2 with link layer disconnection feedback is evaluated in the testbed.
PKCγ mutations in spinocerebellar ataxia type 14 affect C1 domain accessibility and kinase activity leading to aberrant MAPK signaling

Spinocerebellar ataxia type 14 (SCA14) is a neurodegenerative disorder caused by mutations in the neuronal-specific protein kinase C gamma (PKCγ) gene. Since most mutations causing SCA14 are located in the PKCγ C1B regulatory subdomain, we investigated the impact of three C1B mutations on the intracellular kinetics, protein conformation and kinase activity of PKCγ in living cells. SCA14 mutant PKCγ proteins showed enhanced phorbol-ester-induced kinetics when compared with wild-type PKCγ. The mutations led to a decrease in intramolecular FRET of PKCγ, suggesting that they `open' PKCγ protein conformation leading to unmasking of the phorbol ester binding site in the C1 domain. Surprisingly, SCA14 mutant PKCγ showed reduced kinase activity as measured by phosphorylation of PKC reporter MyrPalm-CKAR, as well as downstream components of the MAPK signaling pathway. Together, these results show that SCA14 mutations located in the C1B subdomain `open' PKCγ protein conformation leading to increased C1 domain accessibility, but inefficient activation of downstream signaling pathways.
Effet de 4 semaines d'entraînement sur le temps limite à max

The purpose of this study was to examine the effect of 4 weeks training in running on the time spent at max (tlim max). Eight athletes carried out, before and after an aerobic training, an incremental and five exhaustive tests at 90, 95, 100, 115% v max and at the critical power at max (CV'; slope of the linear relation between the tlim max and the distance limit at max). This training did not significantly improve max (p = 0.17) or tlim max (p = 0.72). However, the "tlim max-intensity" curve was shifted toward the right, meaning that the athlete had to run at a higher intensity after training to obtain the same tlim max. Tlim max at CV' before training was significantly higher than tlim max at 90, 95, 100, and 115%vmax(p < 0.05). This training increased CV' in absolute value (13.9 ± 1.3 vs. 14.9 ± 1.2 km h−1, p < 0.05; n = 6) but not in relative value (86 ± 4 vs. 86 ± 5% v max; p = 0.9). In conclusion, in spite of the shift of the "tlim max-intensity" curve, tlim max was not significantly increased by th.
An AR-Skp2 pathway for proliferation of androgen-dependent prostate-cancer cells

Androgen–androgen-receptor (androgen-AR) signaling in normal prostate epithelium promotes terminal luminal epithelial cell differentiation. In androgen-dependent prostate-cancer cells, androgen-AR signaling gains the ability to promote both differentiation and proliferation. How this signaling promotes proliferation of androgen-dependent prostate-cancer cells and its relationship with the differentiation-promoting functions of the AR are important issues regarding the biology of androgen-dependent prostate-cancer cells. Herein, we report the identification of an AR-Skp2 pathway in prostate-cancer cells that depend on the AR for proliferation; in this pathway, AR is a robust upstream regulator of Skp2 through blocking the D-box-dependent degradation of this protein, and Skp2, in turn, serves as an essential downstream effector of AR in promoting proliferation independently of the differentiation-promoting function of AR. These results provide new knowledge on how AR functions in androgen-dependent prostate-cancer cells and identify strategies to specifically target the proliferation-promoting function of AR without compromising cancer-cell differentiation.
Quantification of 1,3-β-d-Glucan Levels in Children: Preliminary Data for Diagnostic Use of the β-Glucan Assay in a Pediatric Setting

ABSTRACT 1,3-β-d-Glucan serum levels have demonstrated good diagnostic sensitivity and specificity for the diagnosis of candidiasis in adult patients, but normal levels for children have not been established. We found higher 1,3-β-d-glucan levels in children than those previously reported in adults.
Cerebrotendinous xanthomatosis: a critical update

Cerebrotendinous xanthomatosis (CTX) also known as van Bogaert–Scherer–Epstein syndrome, Thiebaut’s syndrome and cerebrotendinous cholesterosis, is an autosomal-recessive lipid-storage disease characterized by the triad of juvenile cataracts, tendon xanthomas and progressive neurodegeneration. Excess cholesterol and cholestanol are deposited in multiple organs, including the cerebrum, cerebellum, lens and tendons. Approximately 300 cases are reported worldwide, but it is suspected that the incidence of CTX is underestimated. The disease is attributed to approximately 50 mutations in the CYP27A1 gene coding for the enzyme sterol 27-hydoxylase, which is responsible for initial oxidation of the side chain of the cholesterol molecule in bile acid biosynthesis. CTX has varied clinical presentations, but no genotype–phenotype relationship has been documented. In some intrafamilial cases, clinical presentations may vary considerably. MRI for CTX is sensitive for diagnosis and classically demonstrates cerebral an.
Importance of the Media in Scaling-Up HIV Testing in Kenya

The main objective of this study was to examine the association between media exposure and voluntary counseling and testing (VCT), and factors that influenced VCT among Kenyan women and men. Retrospective cross-sectional data from Kenya Demographic and Health Survey 2003 were used, adjusting for weights and strata to account for survey complex design. The study sample comprised women aged 15 to 49 (n = 8,050) and men aged 15 to 54 (n = 3,539). Among those who read newspapers/magazines almost every day, fewer women (15%) had been tested for HIV than men (31%), p < . 001. Among women, those who read newspapers/magazines at least once a week (adjusted odds ratio [AOR] = 1.29, p < .001) and almost every day (AOR = 1.3, p < .001) were more likely to be tested than those who did not read at all. Among men, this was nonsignificant. However, those who read newspapers/magazines almost every day (AOR = 1.14, p < .05) were more likely to be tested than those who did not read at all. Significant odds of being tested for HIV were observed among men who watched television almost every day (AOR = 1.21, p < .001) versus women (AOR = 1.07, p < .05) compared with those who did not watch television at all. Results suggest a need to increase HIV messages in all media to scaling-up HIV testing in Kenya.
Lactato sérico como marcador prognóstico em crianças gravemente doentes

Objective: To assess the use of lactate as a marker of tissue hypoperfusion and as a prognostic index in critically ill patients. Methods: Prospective, longitudinal, observational study of 75 patients admitted to the pediatric ICU of Hospital de Clinicas of Universidade Federal do Parana, between November 1998 and May 1999. According to the lactate level on admission, patients were divided into group A (lactate > 18 mg/dl) and group B (lactate 18 mg/dl showed clinical signs of hypoperfusion on admission. The normalization or reduction of lactate levels at and after 24 hours of admission was significantly related with higher chances of survival
Sleep Disorders in Children: A National Assessment of Primary Care Pediatrician Practices and Perceptions

OBJECTIVES: To assess general pediatricians' screening practices for sleep-related issues and assess their knowledge on common sleep complaints in children, their perceived barriers to screening for sleep issues, and whether they have received training regarding sleep issues. METHODS: A national random sample (n = 700) of general pediatricians who were members of the American Academy of Pediatrics were sent a valid and reliable questionnaire on sleep problems in youth. RESULTS: A total of 346 pediatricians (49%) responded. The vast majority (96%) indicated that they believed it was their job to counsel patients/guardians regarding sleep hygiene, yet few pediatricians (18%) had ever received formal training on sleep disorders. Those who did not screen for sleep problems spent significantly less time with each patient and perceived significantly more barriers to screening. Pediatricians who had received training about sleep disorders had significantly higher knowledge scores on sleep problems, perceived significantly fewer barriers to screening, and reported significantly higher confidence scores regarding counseling patients/guardians on sleep problems. CONCLUSION: These findings support the need for formal education on sleep disorders for all pediatricians.
Nasal Continuous Positive Airway Pressure With Heliox in Preterm Infants With Respiratory Distress Syndrome

OBJECTIVE: To assess the therapeutic effects of breathing a low-density helium and oxygen mixture (heliox, 80% helium and 20% oxygen) in premature infants with respiratory distress syndrome (RDS) treated with nasal continuous positive airway pressure (NCPAP). METHODS: Infants born between 28 and 32 weeks of gestational age with radiologic findings and clinical symptoms of RDS and requiring respiratory support with NCPAP within the first hour of life were included. These infants were randomly assigned to receive either standard medical air (control group) or a 4:1 helium and oxygen mixture (heliox group) during the first 12 hours of enrollment, followed by medical air until NCPAP was no longer needed. RESULTS: From February 2008 to September 2010, 51 newborn infants were randomly assigned to two groups, 24 in the control group and 27 in the heliox group. NCPAP with heliox significantly decreased the risk of mechanical ventilation in comparison with NCPAP with medical air (14.8% vs 45.8%). CONCLUSIONS: Heliox increases the effectiveness of NCPAP in the treatment of RDS in premature infants.
Drug Use and HIV Risk Among Middle-Class Young People in Guatemala City

This qualitative study explored the relationship between drug use and risk for HIV transmission among middle-class young people in Guatemala City. It used the PEER methodology, whereby the interviewers were themselves drug users, and each recruited three friends as informants. The 21 peer interviewers recruited a total of 62 informants who participated in three interviews each. The informants viewed drug use favorably: as the social lubricant that facilitates interactions with friends and provides new, pleasurable experiences, free from the conventions of a conservative society. Drug use was limited almost exclusively to noninjection drugs: cocaine, marijuana, ecstasy, lysergic acid diethylamide, and mushrooms. Informants feared pregnancy, detection of their drug use, overdosing, and becoming addicted but did not perceive any risk of HIV. With the recent escalation of drug trafficking in Guatemala, it is important to build the evidence base on drug use in this population and its potential implications for HIV transmission.