Miracle-dz/UniFAR-FTUs huggingface dataset:
Loss-of-function mutations in co-chaperone BAG3 destabilize small HSPs and cause cardiomyopathy

Defective protein quality control (PQC) systems are implicated in multiple diseases. Molecular chaperones and co-chaperones play a central role in functioning PQC. Constant mechanical and metabolic stress in cardiomyocytes places great demand on the PQC system. Mutation and downregulation of the co-chaperone protein BCL-2–associated athanogene 3 (BAG3) are associated with cardiac myopathy and heart failure, and a BAG3 E455K mutation leads to dilated cardiomyopathy (DCM). However, the role of BAG3 in the heart and the mechanisms by which the E455K mutation leads to DCM remain obscure. Here, we found that cardiac-specific Bag3-KO and E455K-knockin mice developed DCM. Comparable phenotypes in the 2 mutants demonstrated that the E455K mutation resulted in loss of function. Further experiments revealed that the E455K mutation disrupted the interaction between BAG3 and HSP70. In both mutants, decreased levels of small heat shock proteins (sHSPs) were observed, and a subset of proteins required for cardiomyocyte function was enriched in the insoluble fraction. Together, these observations suggest that interaction between BAG3 and HSP70 is essential for BAG3 to stabilize sHSPs and maintain cardiomyocyte protein homeostasis. Our results provide insight into heart failure caused by defects in BAG3 pathways and suggest that increasing BAG3 protein levels may be of therapeutic benefit in heart failure.
Cooperation contrasted with intra-group and inter-group competition.

One hundred fifty-seven undergraduate students participated as members of four-person laboratory groups under one of three experimental conditions of cooperation or competition. Conditions were created by differential instructions to students as to how their laboratory exercises were to be graded. Measures included an assessment of both the quantity and quality of group performance, participant and observer ratings of group process, and participant post-session reactions. The prediction was confirmed that both individual and group competition produce higher motivation and quantity of performance. However, contrary to hypothesis, the quality of performance was also higher for the competitive conditions. The purely cooperative condition yielded the lowest level of group performance, but induced the most favorable interpersonal relations among group members. Results suggested the need for qualification of the usual generalizations drawn from previous studies of cooperation and competition.
Troy+ brain stem cells cycle through quiescence and regulate their number by sensing niche occupancy

Significance Adult mammalian tissues contain stem cells that contribute to tissue homeostasis and regeneration, with potential therapeutic applications. Specialized niches regulate their fate. Here we evaluated quantitatively how the subependymal zone niche regulates neural stem cell (NSC) number in the adult mouse brain. Using knock-in reporter alleles and single-cell RNA sequencing, we show that the Wnt target Tnfrsf19/Troy identifies both active and quiescent NSCs. Using the Ki67-iresCreER mouse model, we found that dividing stem cells have long-term self-renewal potential. We propose a model where the fate of NSCs is coupled to their density within a closed niche. Our results suggest a new mechanism for regulating adult stem cell number, which might be deregulated in brain malignancies and in aging. The adult mouse subependymal zone provides a niche for mammalian neural stem cells (NSCs). However, the molecular signature, self-renewal potential, and fate behavior of NSCs remain poorly defined. Here we propose a model in which the fate of active NSCs is coupled to the total number of neighboring NSCs in a shared niche. Using knock-in reporter alleles and single-cell RNA sequencing, we show that the Wnt target Tnfrsf19/Troy identifies both active and quiescent NSCs. Quantitative analysis of genetic lineage tracing of individual NSCs under homeostasis or in response to injury reveals rapid expansion of stem-cell number before some return to quiescence. This behavior is best explained by stochastic fate decisions, where stem-cell number within a shared niche fluctuates over time. Fate mapping proliferating cells using a Ki67iresCreER allele confirms that active NSCs reversibly return to quiescence, achieving long-term self-renewal. Our findings suggest a niche-based mechanism for the regulation of NSC fate and number.
Inferring loneliness levels in older adults from smartphones

The number of older adult has increased significantly in most current societies. One problem that is accentuated in the stage of old age is loneliness which is a serious health risk. Therefore, new methods for early detection of this condition that make use of new non-intrusive technologies are required. Loneliness includes four main factors (family, spousal, social and existential crisis). In this paper, four predictive models to determine the level of loneliness of each factor are proposed, focusing on the activities that can be monitored using a Smartphone. Predictive models have been evaluated on basis of their accuracy, sensitivity, specificity, predictive values, type I and type II error rates. This paper also presents the results of the experimentation of the proposed approach in practice and with real users through a mobile application called “! 'Vive! ” that implements the predictive models.
Interlocking Nailing Versus Interlocking Plating in Intra-articular Calcaneal Fractures

Background: Open reduction and internal fixation with a plate is deemed to represent the gold standard of surgical treatment for displaced intra-articular calcaneal fractures. Standard plate fixation is usually placed through an extended lateral approach with high risk for wound complications. Minimally invasive techniques might avoid wound complications but provide limited construct stability. Therefore, 2 different types of locking nails were developed to allow for minimally invasive technique with sufficient stability. The aim of this study was to quantify primary stability of minimally invasive calcaneal interlocking nail systems in comparison to a variable-angle interlocking plate. Material and Methods: After quantitative CT analysis, a standardized Sanders type IIB fracture model was created in 21 fresh-frozen cadavers. For osteosynthesis, 2 different interlocking nail systems (C-Nail; Medin, Nov. Město n. Moravě, Czech Republic; Calcanail; FH Orthopedics SAS; Heimsbrunn, France) as well as a polyaxial interlocking plate (Rimbus; Intercus GmbH; Rudolstadt, Germany) were used. Biomechanical testing consisted of a dynamic load sequence (preload 20 N, 1000 N up to 2500 N, stepwise increase of 100 N every 100 cycles, 0.5 mm/s) and a load to failure sequence (max. load 5000 N, 0.5 mm/s). Interfragmentary movement was detected via a 3-D optical measurement system. Boehler angle was measured after osteosynthesis and after failure occurred. Results: No significant difference regarding load to failure, stiffness, Boehler angle, or interfragmentary motion was found between the different fixation systems. A significant difference was found with the dynamic failure testing sequence where 87.5% of the Calcanail implants failed in contrast to 14% of the C-Nail group (P < .01) and 66% of the Rimbus plate. The highest load to failure was observed for the C-Nail. Boehler angle showed physiologic range with all implants before and after the biomechanical tests. Conclusion: Both minimally invasive interlocking nail systems displayed a high primary stability that was not inferior to an interlocking plate. Clinical relevance: Based on our results, both interlocking nails appear to represent a viable option for treating displaced intra-articular calcaneal fractures.
Long‐term follow‐up of bone mineral density and bone metabolism in transsexuals treated with cross‐sex hormones

It is unknown whether long term cross‐sex hormone treatment affects the human skeleton. We monitored bone mineral density and biochemical markers of bone turnover for 28–63 months in 20 male‐to‐female transsexuals (M → F) treated with anti‐androgens and oestrogens, and 19 female‐to‐male transsexuals (F → M) treated with androgens. They underwent gonadectomy 13–35 months after the start of cross‐sex hormone administration.
Lack of allelic polymorphism for the major outer membrane protein gene of the agent of guinea pig inclusion conjunctivitis (Chlamydia psittaci)

The major outer membrane protein gene (omp1) was sequenced for each of six Chlamydia psittaci (guinea pig inclusion conjunctivitis [GPIC]) strains isolated from guinea pigs. Five of the isolates were obtained in the United States during the 1960s and 1970s, including the prototype strain isolated by Murray in 1962. The other isolate was obtained from a guinea pig in England. The nucleotide sequence of the omp1 gene for each strain was identical. The lack of omp1 allelic polymorphism among GPIC isolates suggests that, unlike C. trachomatis, the GPIC agent lacks antigenic variation in the major outer membrane protein.
High-Sensitive Fiber-Optic Refractometer Based on a Core-Diameter-Mismatch Mach–Zehnder Interferometer

An in-fiber Mach-Zehnder interferometer (MZI) for high-sensitive refractive index (RI) measurement is proposed and experimentally demonstrated. The sensing head is formed by a single-mode fiber (SMF) sandwiched between two short sections of thin-core fibers (TCFs), i.e., TCF-SMF-TCF MZI configuration with a length of 9 mm. A well-defined interference pattern is obtained as the result of fiber-core mismatch and core-cladding modes interference. The selected interference dip is extremely sensitive to ambient RI, providing a stable RI response with sensitivity up to 159 nm/RIU for water-based solutions close to the RI of 1.33, making it a good candidate for bio-chemical measurements.
Stereochemical analysis of 3,4-methylenedioxymethamphetamine and its main metabolites by gas chromatography/mass spectrometry.

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is consumed as the racemate but some metabolic steps are enantioselective. In addition, chiral properties are preserved during MDMA biotransformation. A quantitative analytical methodology using gas chromatography/mass spectrometry (GC/MS) to determine enantioselective disposition in the body of MDMA and its main metabolites including 3,4-methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxymethamphetamine (HMMA), and 4-hydroxy-3-methoxyamphetamine (HMA) was developed. Plasma and urine samples were collected from a male volunteer. The analysis of MDMA, MDA, and 4-hydroxy-3-methoxy metabolites by GC/MS required a two-step derivatization procedure. The first step consisted of derivatization of the amine with enantiomerically pure Mosher's reagent ((R)-MTPCl). Triethylamine was used as a base to neutralize hydrochloric acid formed during the reaction allowing quantitative derivatization, which resulted in a substantial improvement in the sensitivity of the method compared with other previously described techniques. Further treatment with ammonium hydroxide was required since both amine and hydroxyl groups underwent derivatization in the reaction. Ammonium hydroxide breaks bonds formed with hydroxyl groups without affecting amine derivatives. The second derivatization step using hexamethyldisilazane was needed for metabolites containing phenol residues. This derivatization method permitted the stereochemically specific study of MDMA and its main monohydroxylated metabolites by GC/MS. A detailed study of the chemical reactions involved in the derivatization steps was indispensable to develop a straightforward, sensitive, and reproducible method for the analysis of the parent drug compound and its metabolites.
Low-grade inflammation, thrombogenicity, and atherogenic lipid profile in cigarette smokers.

BACKGROUND Cigarette smoking is one of the major risk factors for atherosclerotic coronary disease, but the precise mechanism(s) by which cigarette smoking promotes atherosclerosis remains unknown. As there is now increasing evidence that atherosclerosis is an inflammatory condition, the present study investigated whether inflammation exists in smokers. METHODS AND RESULTS The inflammatory markers and lipid profiles were compared among a current-smoker group (210 patients, mean age 61.8 +/- 11.0 years), past-smoker group (115 patients, 67.1 +/- 9.0 years) and never-smoked group (113 patients, 68.2 +/- 10.7 years), all of whom had no apparent signs of inflammation. The respective levels of blood leukocytes, platelets, C-reactive protein and fibrinogen were significantly higher in current-smokers than in the never-smoked group (6,600 +/- 1,723 /microl vs 5,638 +/- 1,313 /microl p<0.01; 22.7 +/- 6.8 x 10(4) /microl vs 18.7 +/- 7.4 x 10(4) /microl, p<0.01; 3.50+/-4.91 mg/L vs 1.92+/-3.02 mg/L, p<0.01; 334.2 +/- 90.9 mg/dl vs 314.7 +/- 80.2 mg/dl, p<0.05). The respective levels of plasma triglycerides, remnant-like particle cholesterol and apolipoprotein-B were significantly higher and that of high-density lipoprotein cholesterol significantly lower in the current-smokers than in the never-smoked group (152.4 +/- 96.2 mg/dl vs 120.5 +/- 58.1 mg/dl, p<0.01; 5.4+/-6.3 mg/dl vs 3.8 +/- 2.0 mg/dl, p<0.05; 101.6 +/- 23.7 mg/dl vs 95.0 +/- 21.2 mg/dl, p<0.05; 45.2 +/- 12.3 mg/dl vs 50.6 +/- 15.6 mg/dl, p<0.01). Past smokers had intermediate values between those of current-smokers and never-smoked. CONCLUSIONS Low-grade inflammation, atherogenic dyslipidemia, and hypercoagulability are present in smokers compared with those who have never smoked among subjects without apparent inflammation who underwent coronary angiography on suspicion of coronary artery disease.
Renal transplantation for Type II diabetic patients compared with Type I diabetic patients and patients over 50 years old: a single‐center experience

Introduction. Transplantation of renal allografts for Type II diabetic patients has become increasingly common. Like Type I diabetics and patients over age 50, Type II diabetics are in a high‐risk category for renal transplantation. Some investigators argue that the scarce resources of the valuable donor pool should not be allocated to these high‐risk, older individuals with end‐stage renal disease (ESRD) who often have significant comorbidity. We studied the outcome of renal transplantation for 90 Type II diabetics and compared it with the outcome for Type I diabetics and patients over age 50 with other primary diseases. Methods. We conducted a retrospective review of data on all renal transplants performed at the University of Minnesota since September 1984 for Type II diabetics. We analyzed both patient and graft survival rates and compared them with the outcome for Type I diabetics and separately for all nondiabetics over age 50. We grouped recipients by donor source (living vs. cadaver) and age at transplant (<50 vs.> 50). We studied reasons for graft loss, patient death, pre‐operative morbidity, and post‐operative complications. Results. We found that recipient age and donor source did not affect outcome. Overall 5‐yr patient survival for Type II diabetics was 61%; graft survival, 53%. Type II diabetics had significantly worse patient and graft survival than Type I diabetics and than nondiabetics over age 50. However, death‐censored graft survival was not different between these groups, suggesting little difference in immunologic graft loss. Conclusions. Renal transplantation is a relatively safe, viable option for Type II diabetics with ESRD and significant comorbidity. Although their overall graft survival is less than for Type I diabetics and nondiabetics over age 50, the immunologic graft failure rate is the same in all three groups.
Reproducibility of bacterial and copepod density assessment in bathing and artisanal fishing water of the Eastern Mediterranean

Faecal bacteriological indicators and copepod density assessment are used to predict the environmental health of seawater for recreational bathing and artisanal fishing, respectively. The reproducibility of bacterial culture-count and copepod-microscopic density assessment after respective capturing of the sampled seawater on 0.22 μm Millipore filter and 150 μm mesh sieve copepod net, is determined. The paired t-test was performed to evaluate the reproducibility of each obtained parameter-mean in first and second simultaneous water samplings of a total of 10 sites selected along a 200 km distance, at about 500 – 1000 m offshore. The means of each bacterial indicator in colony forming units/100 ml of sea water in first versus (vs.) second sampling of the 10 sites, followed by the P values were: total bacterial count (6.3 × 102 vs. 6.2 × 102, P = 0.958), Coliform count (3.9 × 102 vs. 2.6 × 102, P = 0.212), Staphylococcus aureus (3.0 × 102 vs. 2.4 × 102, P = 0.551), and Clostridium perfringens (1.4 × 10 vs. 0.4 × 10, P = 0.298). However, the average copepod density in five microscopic fields at magnification of 100× in sample 1 vs. sample 2 were: (1.40 vs. 1.60 respectively, P = 0.267). This sampling design along the 200 km coast, the used technique for capturing the indicators, and the quantitative laboratory assessment of the indicator densities resulted in high reproducibility with a non-significant difference between the first and second sampling within the 95% confidence limits (P > 0.05), a data in support of future monitoring protocol of the environmental health of the coastal water of the Mediterranean sea.
Development and preliminary validation of the 'Mind the Gap' scale to assess satisfaction with transitional health care among adolescents with juvenile idiopathic arthritis.

BACKGROUND To develop a scale to assess satisfaction with transitional health care among adolescents with a chronic illness and their parents. METHODS The 'Mind the Gap' scale was developed using evidence from a previous needs assessment, in three stages: (1) definition of the construct; (2) design of the scale items, response options and instructions; (3) full administration of the scale, item analysis and dimensionality analysis. The scale was administered to 308 adolescents with juvenile idiopathic arthritis (JIA) and 303 parents/guardians, prior to and 12 months after the implementation of an evaluation of a structured and co-ordinated programme of transitional care. The patient population involved adolescents with JIA and their parents recruited from 10 major UK rheumatology centres. RESULTS A total of 301 (97.7%) adolescents and 286 (95.0%) parents chose to complete the questionnaire, with median item completion rates of 100.0% (0-100%) for both adolescents and parents thus confirming feasibility. Face and content validity were confirmed. Factor analyses revealed a three-factor structure which explained 49.5% and 56.1% of the variation in adolescent and parent scores respectively. The internal consistency of each subscale ('management of environment', 'provider characteristics' and 'process issues') was indicated by Cronbach's alphas of 0.71, 0.89 and 0.89 for adolescents, respectively, and 0.83, 0.91 and 0.92 for parents respectively. Cronbach's alphas for the entire scales were 0.91 and 0.94 for the adolescent and parent forms respectively. CONCLUSION These preliminary results report the potential of the 'Mind the Gap' scale in evaluating transitional care for adolescents with JIA. In view of the generic nature of transitional care reflected in the scale, this scale has wider potential for use with adolescents with other chronic illness in view of the generic nature of transition. This development is particularly timely in the context of transitional care developments in the UK and further validation of the scale is in progress.
Ectodermal abnormalities associated with methimazole intrauterine exposure.

I've been prescribed methimazole @ 10mg/3x a day in preparation for a thyroidectomy. Meanwhile, it appears I am pregnant and I had no idea. QUESTION I have a 33-year-old patient with hyperthyroidism who is 6 weeks pregnant. Her thyroid function is well controlled with a 5-mg dose of methimazole 3 . Mar 9, 2011. Both methimazole (MMI) and propylthiouracil (PTU) may be used during pregnancy; however, PTU is preferred in the first trimester and should . Propylthiouracil (PTU) is a medication used to treat hyperthyroidism. This includes hyperthyroidism due to Graves' disease and toxic multinodular goiter. In a thyrotoxic crisis it is generally more effective than methimazole. PTU is preferred over methimazole (which is also a class D) only in the first trimester of pregnancy . Nov 4, 2014. In a final report from the team, due in 2015, results will clarify whether cessation of methimazole in early pregnancy, at 4 or 5 gestational weeks, . Mar 15, 2017. Carbimazole (which is converted into methimazole in the body) is. Antithyroid drugs during pregnancy — Propylthiouracil is the drug of choice . Nov 5, 2014. Most recommendations instruct clinicians to stop methimazole during pregnancy because of earlier associations with birth defects. Advice and warnings for the use of Methimazole during pregnancy. FDA Pregnancy Category D Positive evidence of risk. before their pregnancy, and the rest had received mothers treated with MMI during pregnancy had cil (PTU) may be safer than methimazole (MMI) for.
MALE COURTSHIP BEHAVIOR IN CERATITIS CAPITATA (DIPTERA: TEPHRITIDAE) THAT HAVE RECEIVED AROMATHERAPY WITH GINGER ROOT OIL

Abstract The results of previous studies that showed that exposing mass-reared male Mediterranean fruit flies Ceratitis capitata (Wiedemann) to ginger root oil (“aromatherapy”) increases the likelihood of mating with wild females were confirmed. The increased male success could be due to female responses to changes in male behavior or male pheromones. There were no significant differences in the types of courtship movements executed by males with and without aromatherapy. The durations of movements also did not differ when mass-reared males were paired with mass-reared females; however, when they were paired with wild females, there were a few, small differences. Previous studies indicated that the effectiveness of the male long-distance attractant pheromone is not affected by aromatherapy, but these studies did not consider pheromones released at close range during courtship, which behavioral analyses suggest may be different. We propose the following possible explanation for the different effects of aromatherapy with different females. Selection on males under mass rearing may have altered their close-range pheromones in ways that can be remedied by aromatherapy; and only wild females respond because the pheromonal responsiveness of mass-reared females has also changed. We propose observations that could test these ideas.
Methemoglobinemia in aluminium phosphide poisoning in rats.

Aluminium phosphide (AlP) a grain fumigant is the leading cause of intentional poisoning in North India. The mechanisms involved in toxicity are not known and there is no antidote till date. The present study was carried out to investigate the oxygen free radical generation, methemoglobinemia and effect of methylene blue treatment on survival time in rat model of AlP poisoning. AlP (50 mg/kg, intragastric) was administered in one group and the other group received AlP + Methylene Blue (MB) (0.1%, 1 mg/kg/5 min, i.v.). Malonyldialdehyde (MDA) and methemoglobin (MeHb) levels were measured at 10 and 30 min intervals. Blood MDA levels increased at 10 and 30 min after AlP exposure with simultaneous rise in MeHb levels suggesting methemoglobinemia could be due to increased oxygen free radical generation. Methylene blue caused a significant fall in both the parameters with prolongation of survival time. It is concluded that AlP causes methemoglobinemia responding to methylene blue treatment.