Miracle-dz/UniFAR-FTUs huggingface dataset:
Glutathione Levels and Sensitivity to Apoptosis Are Regulated by Changes in Transaldolase Expression*

Transaldolase (TAL) is a key enzyme of the reversible nonoxidative branch of the pentose phosphate pathway (PPP) that is responsible for the generation of NADPH to maintain glutathione at a reduced state (GSH) and, thus, to protect cellular integrity from reactive oxygen intermediates (ROIs). Formation of ROIs have been implicated in certain types of apoptotic cell death. To evaluate the role of TAL in this process, Jurkat human T cells were permanently transfected with TAL expression vectors oriented in the sense or antisense direction. Overexpression of TAL resulted in a decrease in glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities and NADPH and GSH levels and rendered these cells highly susceptible to apoptosis induced by serum deprivation, hydrogen peroxide, nitric oxide, tumor necrosis factor-α, and anti-Fas monoclonal antibody. In addition, reduced levels of TAL resulted in increased glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities and increased GSH levels with inhibition of apoptosis in all five model systems. The effect of TAL expression on susceptibility to apoptosis through regulating the PPP and GSH production is consistent with an involvement of ROIs in each pathway tested. Production of ROIs in Fas-mediated cell death was further substantiated by measurement of intracellular ROI production with oxidation-sensitive fluorescent probes, by the protective effects of GSH precursor, N-acetyl cysteine, free radical spin traps 5,5-dimethyl-1-pyrroline-1-oxide and 3,3,5,5-tetramethyl-1-pyrroline-1-oxide, the antioxidants desferrioxamine, nordihydroguaiaretic acid, and Amytal, and by the enhancing effects of GSH depletion with buthionine sulfoximine. The results provide definitive evidence that TAL has a role in regulating the balance between the two branches of PPP and its overall output as measured by GSH production and thus influences sensitivity to cell death signals.
Painful Functional Bowel Disorders : Psychological Factors

Painful functional bowel syndromes such as irritable bowel syndrome and functional dyspepsia (FD) are characterized by unexplained persistent or recurrent pain in the abdomen. These syndromes are common across the world, affecting up to 15–20% of the population [3,10,12,15]. A number of mechanisms have been suggested to explain this syndrome, with two major themes dominating the clinical literature [10]. First, visceral hypersensitivity to mechanical distension is found in a significant subset of patients and appears to correlate with postprandial pain [14,18,22]. Second, psychological and psychiatric problems are very common and are widely held to have a pathogenic role, given that patients with FD are more anxious and depressed than healthy controls [3,12,15,21]. In a clinical study that included structured psychiatric interviews, the investigators found that 87% of patients with FD, compared to 25% of patients with organic dyspepsia, had a psychiatric diagnosis [15]. Psychological factors related to FD patients included major depressive disorders, anxiety disorders, and somatization [10,12].
In Pursuit of a Killer

OUAGADOUGOU, BURKINA FASO-- Because of its location between rainforest and dry sahel, Burkina Faso has perhaps one of the heaviest mosquito burdens in Africa. Armed with microscopes, tweezers, and modified Shop-Vac wet-dry vacuums, researchers here are hunting malaria mosquitoes in an effort to learn what makes them dangerous--and vulnerable.
Effect of mouth wash extracted from Salvadora persica (Miswak) on dental plaque formation: A clinical trail

Chewing sticks or Miswak are used for teeth cleaning in many parts of the world, these Miswaks are believed to contain chemical substances which inhibit plaque formation and gingivitis. In the present study, Salvadora persica (Miswak) was extracted with 60% ethanol and was examined for its toxic effect, assessed its antibacterial activity and evaluated clinically for its effect on dental plaque formation. A 4 day plaque regrowth, double - blind, crossover design was used in which 10 dental students volunteers were rendered plaque free (0.3), ceased tooth cleaning, then, asked to rinse twice daily for 1.5 min each time with 10 ml of chlorhexidine 0.2% mouth rinse and three times daily for 1.5 min each time with 10 ml of S. persica 10% solution and placebo mouth rinse. On day five, plaque was scored by the plaque index system (PLI). A wash out period of 2 days was allowed in which the volunteers returned to self- performed plaque control, then a new test period was initiated. Statistical analysis showed that the mean PLI score were 1.48 for S. persica mouth rinse, 0.48 for chlorhexidine and 2.07 for placebo mouth rinse. Acute toxicity test revealed no mortality among the experimental animals which is an indication that S. persica crude extract solution is well tolerated, disk diffusion test showed a marked antibacterial effect in vitro and this effect is concentration dependent, had an effect in in vivo, but this effect cannot be considered absolute.
Histomorphometric Evaluation of Ischemia-Reperfusion Injury and the Effect of Preservation Solutions Histidine-Tryptophan-Ketoglutarate and University of Wisconsin in Limb Transplantation

Background The effect of cold ischemia (CI) in vascularized composite allotransplantation is unknown. We herein assess tissue-specific damage, acceptable CI time, and the effect of preservation solutions in a syngenic rat hindlimb transplant model. Methods Lewis rat limbs were flushed and stored for 2, 10, or 30 hr CI in saline, histidine-tryptophan-ketoglutarate or University of Wisconsin preservation solution before transplantation. Morphologic alterations, inflammation, and damage of the individual tissues were analyzed on day 10 using histomorphology, confocal, light, and transmission-electron microscopy. Results Two-hour CI led to mild inflammation of tissues on day 10, whereas 10-hr and 30-hr CI resulted in massive inflammation and tissue damage. Although muscle was mainly affected after prolonged CI (≥10 hr), nerve was affected in all CI groups. A perineural cell infiltrate, hypercellular appearance, pronounced vacuolization, and mucoid degeneration, appearing as Wallerian degeneration, were observed. Staining with propidium iodide and Syto 16 revealed a decrease in viable muscle cell nuclei in the anterior tibial muscle on day 10 in all groups, which was most pronounced in 10-hr and 30-hr CI animals. Transmission-electron microscopy indicated that a large number of mitochondria were degenerated in the 10-hr and 30-hr CI groups. Histidine-tryptophan-ketoglutarate preservation solution slightly decreased inflammation and tissue damage compared to University of Wisconsin-treated and saline-treated animals, especially in skin and muscle when CI times did not exceed 10 hr. Conclusion Severe inflammation and tissue damage are observed after prolonged CI in muscle and nerve. Ischemia times in vascularized composite allotransplantation should be kept as short as possible and certainly below 10 hr.
Understanding Dr. No - a Comprehensive Model Explaining Physicians' Acceptance of Telemedical Systems

Today’s healthcare systems face tremendous challenges: demographic change and an ageing society lead to increasing healthcare needs and costs. Telemedical systems (TMS) might be an answer by improving healthcare systems’ efficiency and effectiveness. However, the diffusion of such systems is still low. A major barrier is the lack of acceptance by the key players in healthcare: physicians. To enhance the understanding of their intention to use TMS, we propose a comprehensive conceptual model and tested it empirically with survey data gathered from 213 medical doctors in Germany. Our statistical analysis confirms a very high explanatory power of the model. We extend the body of knowledge in this field of research by showing significant influences on physicians’ intentions to use TMS. The influencing factors stem from physicians’ technological contexts (data security and data reliability), financial contexts (billability and costs), individual contexts (technology affinity, subjective norms and motivations), and organizational contexts (compatibility of TMS with existing processes). Our findings have important implications for policy-makers, physicians' associations, providers of TMS, and system engineers. We give specific recommendations regarding the design of TMS and the regulatory framework. Furthermore, we identified specialized clinicians as the most promising lead-users.
Association of cytochrome b5 with 16-androstene steroid synthesis in the testis and accumulation in the fat of male pigs.

The 16-androstene steroids, one of the principal causes of boar taint, are synthesized in the testis by the andien-beta synthase enzyme system. This system has been shown in vitro to involve both cytochrome P450c17 and cytochrome b5. The objective of this work was to investigate the relationship between the levels of cytochrome b5 in the testis, in vitro steroidogenesis, and the accumulation of 16-androstene steroids in the fat of pubertal boars. We found that the in vitro rate of 16-androstene steroidogenesis in testis microsomes was correlated with 16-androstene steroid concentrations in fat (r = .66, P < .01). Western blots were used to determine the amounts of cytochrome b5 and cytochrome P450c17 protein in testis, and two immunoreactive cytochrome b5 proteins of approximately 12 and 16 kDa were found. Levels of cytochrome P450c17 or the high molecular weight cytochrome b5 in testis were not significantly correlated to levels of 16-androstene steroids in fat. However, levels of total cytochrome b5 immunoreactive protein and levels of the low molecular weight immunoreactive cytochrome b5 were correlated to fat 16-androstene steroid concentrations (r = .59, P < .001; r = .72, P = .0001, respectively). Levels of the low molecular weight immunoreactive cytochrome b5 were also correlated to 16-androstene steroid synthesis rates in vitro (r = .62, P < .05). These results indicate that increased levels of a low molecular weight immunoreactive cytochrome b5 protein, and not of cytochrome P450c17, are related to increased testicular 16-androstene steroid production and accumulation in fat. These results support the hypothesis that selection for reduced levels of this low molecular weight immunoreactive cytochrome b5 protein in the testis may result in decreased levels of 16-androstene steroids in fat and reduced boar taint in uncastrated male pigs.
Diet and Parkinson's disease: A potential role of dairy products in men

Diet may play a causative role in Parkinson's disease (PD), but potential associations between diet and PD risk rarely have been assessed in prospective studies. We investigated associations between food intakes and PD risk in two large prospective cohorts in which 210 incident PD cases in men and 184 in women were documented. A positive association was found between dairy intake and PD risk in men (relative risk [RR] comparing extreme categories, 1.8; p trend = 0.004), but not in women (RR, 1.1; p trend = 0.9). No other food groups were associated with PD risk in either men or women. Further analyses among men showed significant positive associations with PD risk for intakes of several dairy foods as well as dairy calcium (RR, 1.5; p trend = 0.02), dairy vitamin D (RR, 1.6; p trend = 0.004), dairy protein (RR, 1.6; p trend = 0.01), and lactose (RR, 1.8; p trend = 0.002), but not dairy fat (RR, 1.1; p trend = 0.4). Intakes of calcium, vitamin D, and protein from other dietary or supplemental sources were not related to PD risk in men. Our results suggest that higher intake of dairy products may increase the risk of PD in men; however, this finding needs further evaluation, and the underlying active components need to be identified.
Process planning in mass production

In the practical production of identical products in large quantities, we can reduce production costs with the proper selection of manufacturing technology and machining conditions. Some improvements in producing a real product from a hand tool factory are presented. Significant results were achieved by introducing near-net-shape technology. In addition to that, an analysis was made to confirm the necessity of studying the machining operations in the direction of using modern tools and supporting the process planning with real data-tool base.
Caring for adults with intellectual disabilities: perceived challenges for nurses in accident and emergency units.

AIM This paper reports a study exploring the experiences of nurses in accident and emergency units caring for people with intellectual disabilities. BACKGROUND People with intellectual disabilities are increasingly in contact with healthcare professionals in accident and emergency units. Often this contact occurs within the accident and emergency service, an area in which staff care for a diverse range of people. The experiences of people with intellectual disabilities within acute general hospitals in the United Kingdom and internationally has largely been reported as quite negative. Conversely, little is known about the experiences of nurses working in acute general hospitals, nor the exact nature of any challenges they encounter, in providing care to people with intellectual disabilities. This lack of understanding weakens opportunities for nurses to reduce barriers to providing an equitable service for people with intellectual disabilities. METHOD Five focus groups were conducted with 27 accident and emergency nurses from five hospitals in Northern Ireland in the spring of 2004. The data were then coded and recurring themes identified. FINDINGS This paper focuses on two themes: lack of knowledge of the nature of intellectual disability and dependence on carers. Whilst these themes have been acknowledged in the existing literature, they have received limited attention and exploration. The experience of fear and vulnerability was considered by participants to be a consequence of their lack of knowledge. The experience of these emotions is viewed as a key factor in nurses' over-dependence on patients' informal carers. CONCLUSION Increased awareness is needed among professionals in accident and emergency units of the abilities and needs of people with intellectual disabilities.
Data Envelopment Analysis with Uncertain Inputs and Outputs

Data envelopment analysis (DEA), as a useful management and decision tool, has been widely used since it was first invented by Charnes et al. in 1978. On the one hand, the DEA models need accurate inputs and outputs data. On the other hand, in many situations, inputs and outputs are volatile and complex so that they are difficult to measure in an accurate way. The conflict leads to the researches of uncertain DEA models. This paper will consider DEA in uncertain environment, thus producing a new model based on uncertain measure. Due to the complexity of the new uncertain DEA model, an equivalent deterministic model is presented. Finally, a numerical example is presented to illustrate the effectiveness of the uncertain DEA model.
ORIGINAL RESEARCH—WOMEN'S SEXUAL HEALTH A Periclitoral Mass as a Cause of Persistent Genital Arousal Disorder

Introduction. Persistent genital arousal disorder (PGAD) is an intrusive and unremitting disorder for which several possible etiologies and treatments have been suggested. Aim. To describe a woman who developed PGAD in association with a periclitoral mass, a potential physical cause of the disorder that has not been previously described in the medical literature. Methods. A postmenopausal woman presented with 6 months of persistent, unrelenting genital arousal and clitoral pain that was unrelated to sexual stimuli. Careful examination revealed a tender, firm, mobile, left-sided mass that appeared to compress the dorsal nerve of the clitoris. Results. Complete excision of the mass resulted in full resolution of her symptoms over several weeks. Conclusion. Localized causes of persistent genital arousal, though rare, should be included in the differential diagnosis PGAD as detection and treatment can lead to a complete recovery. Bedell S, Goldstein AT, and Burrows L. A periclitoral mass as a cause of persistent genital arousal disorder. J Sex Med 2014;11:136-139.
Manipulation Checks as Manipulation: Another Look at the Ease-of-Retrieval Heuristic

Previous findings suggest that individuals rely on ease of retrieval primarily under low judgment elaboration. However, in these previous studies the manipulation check (MC) has always been measured before the dependent variable (DV). It is argued that this sequence increases the likelihood that individuals rely on subjective experience particularly under conditions that prevent considering retrieved contents. Four conceptual replications of such previous findings are reported where the manipulation of the MC—DV order was added to the original design. In all four cases (Study 1 on accuracy motivation, Study 2 on cognitive capacity, Study 3 using a misattribution paradigm, and Study 4 on power), ease-of-retrieval effects under low-judgment-elaboration conditions were observed only if the MC measurement preceded the DV, but not with reversed order.
A randomized controlled trial of an appearance-related smoking intervention.

OBJECTIVES To investigate whether exposure to a smoking-related facial age-progression technique impacts on quit smoking cognitions, nicotine dependence, and self-reported and objectively assessed smoking in young women in a randomized controlled trial. METHODS eighteen- to 34-year-old women smokers (n = 70) were allocated at random to either an appearance-related intervention (plus usual care) or control (usual care) group. Women completed questionnaires assessing attitudes, subjective norms, perceived behavioral control and intention to quit smoking immediately before, immediately after, and four weeks after receiving the intervention or usual care. At the first and last time points they also completed measures of nicotine dependence and self-reported and objectively assessed smoking (breath carbon monoxide levels). RESULTS The two groups were well matched at baseline. Using intention to treat analyses and baseline as a covariate, women in the appearance-related intervention group compared to the control group had significantly more positive attitudes, subjective norms, perceived behavioral control, and intentions to quit smoking immediately after exposure. Only the effects on quit smoking attitudes remained significant at four weeks postintervention. Nicotine dependence and self-reported smoking (total cigarettes in last seven days), but not objective smoking, were significantly lower in the intervention compared with control group at four weeks. CONCLUSIONS This study suggests that an appearance-related smoking intervention may be a useful adjunct to traditional cessation programs with young women smokers.
Effectiveness of Pilates over Conventional Physiotherapeutic Treatment in Females with Primary Dysmenorrhea .

Background: Incidence of Primary dysmenorrhea is very high among the females of reproductive age group. It is responsible for the school, college and work absenteeism because of pain and discomfort. Objective: The objective of the present study was to find out the effectiveness of Pilates in reducing the pain and improving Quality of Life in females with primary dysmenorrhea. Methods: The Experimental study consists of 50 subjects between the age of 18 to 30 years randomly selected as per the inclusion and exclusion criteria. The participants were divided equally by alternate sampling method . 25 subjects were in group A (pilates group) and the other 25 in group B (conventional). Group A received pilates and group B received conventional physiotherapy treatment. Outcome measures were pain (VAS) and Quality of Life (Menstrual Distress Questionnaire) which was measured before and after intervention. Results: The result showed that there was highly significant changes pain (group A-Pre-7.44 and post-5.88), (group BPre-7.92 and post 7.16) and Quality of Life ( group Apre-43.72 and post-35.04) (group Bpre41.96 and post-39.06) (p<0.001) after 12 weeks of Pilates than conventional physiotherapy treatment. Conclusion: Pilates reduces the pain as well as improves the Quality of Life in females with Primary Dysmenorrhea.
A Novel Approach for Pathway Analysis of GWAS Data Highlights Role of BMP Signaling and Muscle Cell Differentiation in Colorectal Cancer Susceptibility

Genome-wide association studies (GWAS) have revolutionized the field of gene mapping. As the GWAS field matures, it is becoming clear that for many complex traits, a proportion of the missing heritability is attributable to common variants of individually small effect. Detecting these small effects individually can be difficult, and statistical power would be increased if relevant variants could be grouped together for testing. Here, we propose a VEGAS2Pathway approach that aggregates association strength of individual markers into pre-specified biological pathways. It accounts for gene size and linkage disequilibrium between markers using simulations from the multivariate normal distribution. Pathway size is taken into account via a resampling approach. Importantly, since the approach only requires summary data, the method can easily be applied in all GWASs, including meta-analysis, singleton-based, family-based, and DNA-pooling-based designs. This approach is implemented in a user-friendly web page https://vegas2.qimrberghofer. edu.au and a command line tool. The web implementation uses gene-sets from the gene ontology (GO), curated gene-sets from MSigDB (containing canonical pathways and gene-sets from BIOCARTA, REACTOME, KEGG databases), PANTHER, and pathway commons databases, enabling analysis of a wide range of complex traits. We applied this method on a colorectal cancer GWAS meta-analysis data set (10,934 cases, 12,328 controls) from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). We report statistically significant enrichment of association signal for the ‘BMP signaling’ and ‘muscle cell differentiation’ pathways, suggesting a possible role for these pathways onto the risk of colorectal cancer.
A Novel Leflunomide Analog, UTL-5b (GBL-5b), Suppresses JAK3, MAP3K2, and LITAF Genes

UTL-5b (GBL-5b) is a novel analog of leflunomide with anti-inflammatory and antiarthritic effects. It has been shown to lower serum tumor necrosis factor-alpha (TNF-α) level induced by lipopolysaccharide (LPS) in an animal model. In this study, the effect of UTL-5b on nitric oxide (NO) and dihydroorotate dehydrogenase (DHODH) was investigated. Our in vitro studies showed that (1) UTL-5b is a stronger inhibitor of NO production as compared to leflunomide and its active metabolite, teriflunomide, and (2) Unlike leflunomide, a potent inhibitor of DHODH, UTL-5b does not inhibit DHODH activity. These findings show that UTL-5b acts in a manner different from that of leflunomide. To further investigate the mode of action of UTL-5b, an ex vivo gene array study was performed. C57BL/6 mice were injected subcutaneously with of UTL-5b 24 hr before injection of E. coli LPS. Mice were sacrificed 90 min later and the whole spleen mRNA was isolated for gene microarray analysis. The results showed that UTL-5b significantly suppressed three genes that are relevant to the TNF- pathway: Janus kinase 3 (JAK3), mitogen-activated protein kinase kinase kinase 2 (MAP3K2) and lipopolysaccharide-induced TNF- factor (LITAF). In summary, our results showed that UTL-5b has a stronger inhibitory effect on NO production than leflunomide; yet, unlike leflunomide, UTL-5b does not inhibit DHODH in vitro. In addition, gene array analysis showed that the biological effects of UTL-5b are attributed at least in part to the suppression of JAK3, MAP3K2 and LITAF gene expression.