Miracle-dz/UniFAR-FTUs huggingface dataset:
Cost effectiveness of adding leflunomide to a 5-year strategy of conventional disease-modifying antirheumatic drugs in patients with rheumatoid arthritis.

OBJECTIVE To estimate, from a public payer's perspective, the 5-year cost effectiveness of adding leflunomide (LEF) to a sequence of disease-modifying antirheumatic drugs (DMARDs) representative of a typical rheumatoid arthritis (RA) management approach adopted by Canadian rheumatologists. METHODS A DMARD sequence including LEF was compared with one excluding it, using a 5-year simulation model where patients with RA cycle through different treatment regimens. Data were obtained through a systematic literature search (drug withdrawal rates, number and type of adverse events, American College of Rheumatology 20% responder status) and separately conducted surveys (choice of DMARD sequence, management of adverse events). Costs for adverse event management were calculated using the Ontario Schedule of Benefits, and monitoring costs were calculated according to official Canadian product monograph recommendations. Wholesale prices of all drugs were adjusted by the allowable markup and prescription fees. Utilities (as measured by the standard gamble [SG] and rating scale [RS] techniques) were obtained from 482 patients who participated in a 1-year randomized controlled trial that compared LEF, methotrexate, and placebo. Costs and utilities were discounted by 3%. Probabilistic sensitivity analysis was performed. RESULTS Adding LEF to a conventional strategy of DMARDs increased the 5-year management costs by $1,231 compared with the strategy without LEF, which results in a cost-effectiveness ratio of $13,096 per additional year of response to treatment, and cost-utility ratios of $54,229 (RS) and $71,988 (SG) per quality-adjusted life-year gained. CONCLUSION Adding LEF as a new option to a conventional sequence of DMARDs extends the time patients may benefit from DMARD therapy at a reasonable cost effectiveness and cost utility. LEF data are limited to clinical trials; data from observational studies would be needed to corroborate these findings.
Unprenylated RhoA Contributes to IL-1β Hypersecretion in Mevalonate Kinase Deficiency Model through Stimulation of Rac1 Activity

Background: Shortage of isoprenoids causes aberrant activity of prenylated small GTPases. Results: Inactivation of RhoA due to lack of prenylation leads to Rac1 activation and subsequent priming for IL-1β secretion. Conclusion: RhoA inactivation contributes to the pathology of isoprenoid deficiency. Significance: Insight into the multiple networks involving RhoA will benefit new intervention strategies in prenylation-related pathologies. Protein prenylation is a post-translational modification whereby non-sterol isoprenoid lipid chains are added, thereby modifying the molecular partners with which proteins interact. The autoinflammatory disease mevalonate kinase deficiency (MKD) is characterized by a severe reduction in protein prenylation. A major class of proteins that are affected are small GTPases, including Rac1 and RhoA. It is not clear how protein prenylation of small GTPases relates to GTP hydrolysis activity and downstream signaling. Here, we investigated the contribution of RhoA prenylation to the biochemical pathways that underlie MKD-associated IL-1β hypersecretion using human cell cultures, Rac1 and RhoA protein variants, and pharmacological inhibitors. We found that when unprenylated, the GTP-bound levels of RhoA decrease, causing a reduction in GTPase activity and increased protein kinase B (PKB) phosphorylation. Cells expressing unprenylated RhoA produce increased levels of interleukin 1β mRNA. Of other phenotypic cellular changes seen in MKD, increased mitochondrial potential and mitochondrial elongation, only mitochondrial elongation was observed. Finally, we show that pharmacological inactivation of RhoA boosts Rac1 activity, a small GTPase whose activity was earlier implied in MKD pathogenesis. Together, our data show that RhoA plays a pivotal role in MKD pathogenesis through Rac1/PKB signaling toward interleukin 1β production and elucidate the effects of protein prenylation in monocytes.
AdipoQ T45 G and G276 T Polymorphisms and Susceptibility to Nonalcoholic Fatty Liver Disease Among Asian Populations: A Meta‐Analysis and Meta‐Regression

Adiponectin (AdipoQ) is an adipose‐derived plasma protein that plays an important role in hepatic lipoprotein–lipid metabolism. Emerging evidence have shown that two common polymorphisms (T45 G and G276 T) in the AdipoQ gene may contribute to increasing susceptibility to nonalcoholic fatty liver disease (NAFLD); however individually published studies show inconclusive results. This meta‐analysis aimed to derive a more precise estimation of the association of AdipoQ T45 G (rs2241766 T>G) and G276 T (rs1501299 G>T) polymorphisms with NAFLD risk.
Assessing basketball ability in players with mental retardation

Background: Although athletes with mental retardation (MR) have achieved an important role, literature concerning the evaluation tests in basketball is still poor. Objective: To assess basketball ability before and after a 4-month training performed before championship for athletes with MR and to correlate ability variations with MR levels. Methods: 15 trained basketball players with MR (11 men and 4 women; age range 21–43 years; MR: 3 mild, 8 moderate, 8 severe and 1 profound). Athletes were tested before (pre) and after (post) 4 month training preceding the championship. The tests assessed 4 levels of ability, each one characterised by 4 fundamental areas of this game: ball handling, reception, passing and shooting. Each area was divided into 5 specific components. Results: The team average score, based on the score of each athlete’s 4 levels, improved by 6.6 points (41.6 (SD 11.9) vs 48.2 (14.7)). The comparison between pre and post scores in each level showed increases (p<0.01), especially in level II (14.4 (3.5) vs 16.5 (3.3)) and in level III (7.1 (5.7) vs 9.2 (6.6)). Within level II, ball handling (3.67 (1.2) vs 4.37 (0.5); p<0.05) and passing (3.20 (1.2) vs 3.97 (1.3); p<0.01) improved; in level III reception (3.21 (1.1) vs 3.73 (1.1); p = 0.01) and shooting (1.82 (1.1) vs 2.45 (1.3); p<0.05) increased. Conclusions: A 4 month training caused a general improvement, especially evident in levels II and III. Total score reached in level II was negatively correlated with MR level (r = −0.56; p<0.05), indicating that athletes with lower MR obtained higher scores.
Relationship between Psychosocial Impairment, Food Choice Motives, and Orthorexic Behaviors among Polish Adults

Orthorexic behaviors correlate not only with health motives when choosing food but may also coexist with psychosocial impairment. The aim of this study was to assess the motives of food choice and psychosocial impairment among adults with orthorexic behaviors through the use of ORTO-15 and ORTO-7. The data for the study were collected from a sample of 1007 Polish adults through a cross-sectional quantitative survey conducted in 2019. The respondents were asked to complete the ORTO-15 questionnaire, the Food Choice Questionnaire (FCQ), and the Clinical Impairment Assessment (CIA). Orthorexic behaviors were measured using both the 15-item and the shorter 7-item version of the ORTO questionnaire. To determine the factors coexisting with the orthorexic behaviors, linear regression models were developed. The scores of both ORTO-15 and ORTO-7 correlated positively with the global CIA scores and the scores of personal, cognitive, and social impairments, but compared to the ORTO-7 scores, the ORTO-15 scores showed weaker correlations with the global CIA score and individual CIA scales. Orthorexic behaviors measured with ORTO-15 correlated positively with such food choice motives as health, natural content, and weight control; whereas orthorexic behaviors measured with ORTO-7 showed positive bivariate correlations only with two food choice motives: health and weight control. In regression models, sensory appeal, age, and education lower than secondary were associated inversely with orthorexic behaviors measured by both the ORTO-15 and the ORTO-7. In conclusion, the obtained results confirm that orthorexic behaviors are associated with a higher score regarding health motivation and cause an increase in psychosocial impairment. In addition, orthorexic behaviors are associated with greater importance of body weight control, which confirms the relationship between orthorexic behaviors and other eating disorders (ED), such as anorexia nervosa (AN) and bulimia nervosa (BN). However, similar motives for food choice displayed by the groups with higher scores of the ORTO-15 and the ORTO-7 and strong correlation between results obtained from both tools confirmed the similarity between these two questionnaires, thus revealing the weak psychometric properties also of the shorter seven-item version of the ORTO. Future studies on food motives, psychosocial impairment, and orthorexic behaviors should consider using other tools for measuring orthorexic behaviors.
Maternal smoking and the risk of polyhydramnios.

BACKGROUND Washington State birth certificates were used to conduct a population-based case-control study to assess the possible association of maternal smoking with polyhydramnios. METHODS All singleton births complicated by polyhydramnios (n = 557) were identified from the vital records for the years 1984 to 1987. For comparison, 1671 records were randomly selected for the same years from singleton births uncomplicated by polyhydramnios. RESULTS Women who reportedly smoked prenatally were found to be at increased risk for polyhydramnios (relative risk [RR] = 1.7, 95% confidence interval [CI] = 1.5-2.1, adjusted for marital status, maternal age, and parity). When women with conditions known to be associated with polyhydramnios were excluded, the risk for those who smoked prenatally remained elevated (RR = 1.8, 95% CI = 1.1-2.3). CONCLUSION Overdistention of the uterus from polyhydramnios may cause a variety of pregnancy complications. The observed association of smoking with polyhydramnios may be a further indication for public health interventions aimed at preventing smoking during pregnancy.
Intimate Partner Violence: The Lived Experience of Single Women

ABSTRACT Research in intimate partner violence has focused on married, cohabiting, adolescents, or college aged women. The experience of intimate partner violence by single women has not been studied separately from other groups of women. An interpretive phenomenological approach was used with feminist inquiry to gain insight into the experience of intimate partner violence by single women. The overarching theme was control and manipulation by the abuser. Subthemes included not feeling safe, poor communication skills, and caretaking. Nurses need to be aware of the occurrence of intimate partner violence in male and female partnered relationships to provide comprehensive and nonjudgmental care.
Activation of Ca2+ release by caffeine and voltage in frog skeletal muscle.

1. Using a fast flow, computer‐controlled, two‐Vaseline‐gap chamber, single muscle fibres were subjected to ‘pulses’ of caffeine at Ca2+ releasing concentrations, combined with voltage‐clamp depolarizations, while monitoring intracellular [Ca2+]. 2. Ca2+ release flux elicited by caffeine reached 2.5 mM s‐1, or less, after 3 s of exposure, then decayed to zero. The caffeine‐releasable pool of sarcoplasmic reticulum (SR) Ca2+ was 2.9 +/‐ 0.4 mM (mean +/‐ S.E.M., n = 10). 3. In parallel with release induced by caffeine, release induced by voltage pulses applied during a caffeine exposure increased in the first second of exposure, then decreased, to abolition after 5 s. 4. The amount of Ca2+ releasable by depolarizing pulses was always equal to the amount of Ca2+ in the caffeine‐releasable pool. Therefore, there is a single releasable Ca2+ pool. This pool is well stirred‐it takes much more time to lose its Ca2+ by release than to diffusionally homogenize its [Ca2+]. Its depletion explains quantitatively the decay of release induced by caffeine or voltage during an exposure to caffeine. 5. A 1.5 s pulse to 10 mV, applied during exposure to caffeine, resulted in large Ca2+ release and, upon repolarization, termination of the caffeine‐induced release. This is similar to repolarization‐induced stop of caffeine contracture (RISC) in embryonic murine myoballs. The permeability elicited by caffeine (ratio of flux to calcium in the releasable pool) was not affected by depolarizing pulses. Therefore, the mechanism of the RISC‐like effect was Ca2+ depletion. 6. Caffeine‐induced release did not depend on the holding potential. 7. Whether caffeine was present or not, release activated by voltage remained always under voltage control, ending rapidly upon repolarization. A depolarizing pulse induced a release permeability with an early peak, followed by decay to a steady level. Caffeine (10 mM) shifted the mid‐activation voltage of both peak and steady components by ‐15 mV and increased the steepness of their voltage dependence by 15%. The maximum permeability increased by 30% for the peak and 25% for the steady component (n = 5). These results neither support nor disprove the hypothesis that the peak of Ca2+ release is activated by Ca2+. 8. The similar potentiation by caffeine of both components of release, the continued ability of voltage to control release in the presence of caffeine, and its failure to alter caffeine‐induced permeability indicate that caffeine and the voltage sensor enhance independently the channel's tendency to open.
Vertical Visual Features Have a Strong Influence on Cuttlefish Camouflage

Cuttlefish and other cephalopods use visual cues from their surroundings to adaptively change their body pattern for camouflage. Numerous previous experiments have demonstrated the influence of two-dimensional (2D) substrates (e.g., sand and gravel habitats) on camouflage, yet many marine habitats have varied three-dimensional (3D) structures among which cuttlefish camouflage from predators, including benthic predators that view cuttlefish horizontally against such 3D backgrounds. We conducted laboratory experiments, using Sepia officinalis, to test the relative influence of horizontal versus vertical visual cues on cuttlefish camouflage: 2D patterns on benthic substrates were tested versus 2D wall patterns and 3D objects with patterns. Specifically, we investigated the influence of (i) quantity and (ii) placement of high-contrast elements on a 3D object or a 2D wall, as well as (iii) the diameter and (iv) number of 3D objects with high-contrast elements on cuttlefish body pattern expression. Additionally, we tested the influence of high-contrast visual stimuli covering the entire 2D benthic substrate versus the entire 2D wall. In all experiments, visual cues presented in the vertical plane evoked the strongest body pattern response in cuttlefish. These experiments support field observations that, in some marine habitats, cuttlefish will respond to vertically oriented background features even when the preponderance of visual information in their field of view seems to be from the 2D surrounding substrate. Such choices highlight the selective decision-making that occurs in cephalopods with their adaptive camouflage capability.
Do the risks of khat-induced dependence and psychosis warrant the 2014 UK ban?

Khat leaves originate in East Africa and the Arabian Peninsula and are chewed socially for their psychoactive properties. The main constituents of khat, cathinone and cathine, are illegal substances in most of Europe, including the UK, which reclassified khat as a Class C drug in June 2014. Case reports of khat-induced psychosis and dependence are not supported with robust scientific studies, and evidence for a causal relationship is lacking. Cross-sectional population studies reveal that khat abuse is affected by a range of susceptibility factors, such as psychological trauma; this has been experienced by many khat users, due to civil war and/or migration. Most studies on animal models of khat-induced dependence or psychosis use its psychoactive ingredient, cathinone, rather than khat extract. However, the unique chewing method of khat diminishes its addictive potential due to slow and prolonged absorption. Furthermore, the effects of the other constituents present in khat leaves are not well understood. While there are multiple criteria for banning a drug, this review considers the scientific evidence regarding two frequently mentioned criteria: dependence potential and psychosis. It concludes that further investigation, which takes into account susceptibility factors, is required to justify such intervention.
Regionally selective elimination of cutaneous thermal nociception in rats by neonatal capsaicin

We have studied thermal and mechanical nociception in anesthetized adult rats that had received subcutaneous injections of capsaicin as neonates. This treatment appeared not to have impaired mechanonociception in any of the body regions that were examined. In contrast, thermal nociception was present in some locations and absent in others. Its total disappearance from back skin correlated with the loss of C fiber responsiveness in the dorsal cutaneous nerves (DCNs); electrical excitation of these nerves now failed to evoke the delayed component of the cutaneus trunci muscle reflex, although the early reflex response, elicited by excitation of the mechanosensitive Aδ axons, was unaffected. Heat nociception was similarly eliminated from the nonpad glabrous skin of the paws. When the stimulus was applied selectively to the pads, however, a normal foot‐withdrawal response was evoked. The probable basis of this differential heat responsiveness in the paws was revealed by the use of the Evans Blue technique in untreated animals; antidromic activation of the paw nerves to excite their C fiber population led to dye extravasation in the glabrous skin around the pads but to almost none in the pads themselves, indicating a relative absence in the pads of a nociceptive C fiber innervation. In capsaicin‐treated animals, the tail‐flick test revealed a significantly reduced responsiveness to noxious heat in the tail. These results may explain some of the anomalies among the reports of the effects of neonatal capsaicin. It appears that in strategically exposed locations exemplified by the paw pads and tail, capsaicin‐resistant axons that could be the relatively fast‐conducting Aδ ones are involved in the signalling of noxious heat. The heat‐nociceptive C fibers that seem to be solely responsible for such signalling from back skin and nonpad glabrous skin of the paws probably contribute to heat nociception in the tail but not to that in the paw pads.
Youth Perceptions of Parental Involvement and Monitoring, Discrepancies With Parental Perceptions, and Their Associations With First Cigarette Use in Black and White Girls.

OBJECTIVE Low parental involvement and monitoring are risk factors for adolescent cigarette use. Assessments of parental involvement and monitoring by youth and parents may capture an additional source of risk: differences in perceptions of these parenting behaviors. This study tested for unique contributions of youth-reported parental involvement and monitoring and youth-parent discrepancies in reporting to first cigarette use in girls. METHOD Data were drawn from interviews at ages 8-17 with 1,869 girls (57.3% Black, 42.7% White) and their primary caregivers (94% mothers) in the Pittsburgh Girls Study. Cox proportional hazards regression analyses were conducted to predict first cigarette use as a function of girls' reports of parental involvement and monitoring, magnitude and direction of youth-parent reporting discrepancies, and the interaction between them, adjusting for neighborhood, socioeconomic, and individual level factors. RESULTS High magnitude of discrepancy in parental involvement reports (hazard ratio [HR] = 1.14, 95% confidence interval [CI] [1.03, 1.26]) and lower perceived parental involvement by girls (HR = 1.14, CI [1.03, 1.27]) were associated with an elevated risk for first cigarette use. Girls' reports of low parental monitoring also predicted first cigarette use (HR = 1.14, CI [1.06, 1.21]). CONCLUSIONS Girls whose parents have limited awareness of their whereabouts and friends (i.e., low monitoring) are at an elevated risk for trying cigarettes, but parent-daughter differences in perceived awareness do not affect risk. By contrast, girls who perceive a lower degree of parental involvement than their parents do are at increased risk. Monitoring is one component of parenting that may reduce smoking risk; shared perspectives on the parent's level of involvement are similarly important.
Reactivity of Reduced [2Fe-2S] Ferredoxins Parallels Host Susceptibility to Nitroimidazoles

ABSTRACT The kinetics of the electron transfer reaction between reduced [2Fe-2S] ferredoxins and select nitroimidazole antimicrobial agents is reported. The ferredoxins from the protozoan Trichomonas vaginalis and the cyanobacterium Anabaena sp. strain 7120 were studied because they are the proximal electron donors to nitroimidazoles in these two organisms with significantly different nitroimidazole susceptibilities. The rates of electron transfer from Anabaena ferredoxin to all nitroimidazoles were 1 to 2 orders of magnitude lower than for T. vaginalis ferredoxin. Quantitative structure-activity analysis of the kinetic data showed that the size of the alkyl substituent on the N-1 position of the imidazole ring strongly influenced the magnitude of the electron transfer rate constant. This implies that the distance between the iron-sulfur cluster and the nitro group of the imidazole is the critical variable in determining the rate of electron transfer. A correlation between the magnitude of the one-electron transfer rate constant with the susceptibility of the host organism to the cytotoxic effects of nitroimidazoles was also discovered. These results demonstrate that reductive activation is the most crucial step in determining the toxicity of nitroimidazoles.
Efficacy of cell saver in reducing homologous blood transfusions during OPCAB surgery: a prospective randomized trial

summary Despite the refinements in surgical technique, rates of homologous blood transfusion (HBT) in cardiac surgery remain high. The adverse effects of blood transfusion are well documented. Retransfusion of shed mediastinal blood reduces the requirement for HBTs during conventional coronary artery bypass grafting. However, some studies have found that autotransfusion leads to bleeding diathesis and paradoxical increase in blood transfusions. Through this prospective randomized trial, we have studied the safety and efficacy of this modality in patients undergoing off‐pump coronary artery bypass grafting (OPCAB). Fifty patients enrolled in the study and 49 fulfilled the study criteria. They were randomly divided into group C (cell saver) and group N (non‐cell saver). Whereas the cell saver group received processed shed autologous blood and homologous blood if necessary, the non‐saver group was transfused homologous blood only. The threshold for transfusion was haemoglobin of 9 g dL−1 in both the groups. The cell saver group required significantly less number of HBTs (1·6 ± 1·2 vs. 2·4 ± 1·3 units). The incidence of re‐exploration was zero in both the groups. The mean mediastinal drainage in both the groups was not significantly different (355 ± 196 vs. 316 ± 119·8 mL). The number of patients requiring any blood transfusion however was very high. All the patients in the non‐saver group and 20 (83%) of the patients in the saver group received homologous blood. During OPCAB surgery, the use of cell saver reduced the requirement for HBT. Its use is not associated with any clinically significant bleeding diathesis.