Miracle-dz/UniFAR-FTUs huggingface dataset:
Fatigue management in patients with IBD: a randomised controlled trial

Objective To assess the effectiveness of solution-focused therapy (SFT) on fatigue and quality of life (QoL) in patients with fatigued inflammatory bowel disease (IBD). Design Randomised controlled trial in two Dutch hospitals. Patients with IBD with quiescent IBD and with a Checklist Individual Strength—Fatigue (CIS—fatigue) score of ≥35 were enrolled. Patients were 1:1 randomised to receive SFT or care as usual (CAU) for 3 months. Patients were followed for a further 6 months after the SFT. Primary endpoint was defined as changes in fatigue and QoL during follow-up. Secondary endpoints included change in anxiety and depression, medication use, side effects to medication, disease activity, laboratory parameters (C-reactive protein, leucocytes and haemoglobin) and sleep quality. Results Ninety-eight patients were included, of whom 63% were women, mean age was 40.1 years. After the SFT course, 17 (39%) patients in the SFT group had a CIS-fatigue score below 35 compared with eight (18%) of patients in the CAU group (p=0.03). The SFT group also showed a greater reduction in fatigue across the first 6 months compared with the CAU group (CIS-fatigue: p=<0.001 and CIS-total: p=0.001). SFT was associated with a significant higher mean IBD questionnaire change at 3 months (p=0.020). At 9 months, no significant differences between the two groups were observed. Conclusions SFT has a significant beneficial effect on the severity of fatigue and QoL in patients with quiescent IBD. However, this effect diminished during follow-up.
HIV protease inhibitors induce senescence and alter osteoblastic potential of human bone marrow mesenchymal stem cells: beneficial effect of pravastatin

HIV‐infected patients receiving antiretroviral therapy present an increased prevalence of age‐related comorbidities, including osteoporosis. HIV protease inhibitors (PIs) have been suspected to participate to bone loss, but the mechanisms involved are unknown. In endothelial cells, some PIs have been shown to induce the accumulation of farnesylated prelamin‐A, a biomarker of cell aging leading to cell senescence. Herein, we hypothesized that these PIs could induce premature aging of osteoblast precursors, human bone marrow mesenchymal stem cells (MSCs), and affect their capacity to differentiate into osteoblasts. Senescence was studied in proliferating human MSCs after a 30‐day exposure to atazanavir and lopinavir with or without ritonavir. When compared to untreated cells, PI‐treated MSCs had a reduced proliferative capacity that worsened with increasing passages. PI treatment led to increased oxidative stress and expression of senescence markers, including prelamin‐A. Pravastatin, which blocks prelamin‐A farnesylation, prevented PI‐induced senescence and oxidative stress, while treatment with antioxidants partly reversed these effects. Moreover, senescent MSCs presented a decreased osteoblastic potential, which was restored by pravastatin treatment. Because age‐related bone loss is associated with increased bone marrow fat, we also evaluated the capacity of PI‐treated MSCs to differentiate into adipocyte. We observed an altered adipocyte differentiation in PI‐treated MSCs that was reverted by pravastatin. We have shown that some PIs alter osteoblast formation by affecting their differentiation potential in association with altered senescence in MSCs, with a beneficial effect of statin. These data corroborate the clinical observations and allow new insight into pathophysiological mechanisms of PI‐induced bone loss in HIV‐infected patients.
Targeting glycogen synthase kinase 3 for therapeutic benefit in lymphoma.

Targeting the B-cell receptor and PI3K/mTOR signaling pathways has shown meaningful but incomplete anti-tumor activity in lymphoma. Glycogen Synthase 3 (GSK3) kinase α and β are two homologous and functionally overlapping serine/threonine kinases that phosphorylate multiple protein substrates in several of key signaling pathways. To date, no agents targeting GSK3 have been approved for lymphoma therapy. We show that lymphoma cells abundantly express GSK3α and GSK3β compared to normal B- and T-lymphocytes at both mRNA and protein levels. By use of a new GSK3 inhibitor 9-ING-41 and by genetic deletion of GSK3α and GSK3β genes using CRISPR/CAS9 knockout, GSK3 was demonstrated to be functionally important to lymphoma cell growth and proliferation. GSK3β binds to centrosomes and microtubules, and lymphoma cells treated with 9-ING-41 become arrested in mitotic prophase, supporting the notion that GSK3β is necessary for the progression of mitosis. By analyzing recently published RNA-Seq data on 234 DLBCL patients, we found higher expression of either GSK3α or GSK3β correlate well with shorter overall survival. These data provide rationale for testing GSK3 inhibitors in lymphoma patient trials.
Leisure, Health and Well-Being

Abstract This paper provides an overview of the scientific evidence available on the impact of leisure directly on individual health and well-being and indirectly on health through its influence on the work, interpersonal relationship and family domains of life. The growth of time pressure, stress, and sedentary lifestyles associated with contemporary changes in work and the dominant role of technology in people's lives are contributing to unhealthy lifestyles and growing demands on health care systems. The potential contributions of leisure to health are being viewed increasingly from a public and population health perspective—a view that health is largely controllable and determined by people's actions. Increasingly, leisure is viewed to be the domain of lifestyle where people have greatest control and consequently it is seen an important resource for health. Evidence suggests that leisure viewed as discretionary behavior outside of work and other obligations can positively influence physical, psychological and spiritual health. Leisure choices and activities also can have neutral or negative impacts and displace behaviors that contribute to health and well-being. The factors that allow leisure opportunities and behavior to positively contribute to health have been the subject of growing research efforts in many western countries and increasingly in other regions of the world.
Sirt2‐BubR1 acetylation pathway mediates the effects of advanced maternal age on oocyte quality

The level of Sirt2 protein is reduced in oocytes from aged mice, while exogenous expression of Sirt2 could ameliorate the maternal age‐associated meiotic defects. To date, the underlying mechanism remains unclear. Here, we confirmed that specific depletion of Sirt2 disrupts maturational progression and spindle/chromosome organization in mouse oocytes, with compromised kinetochore–microtubule attachments. Candidate screening revealed that acetylation state of lysine 243 on BubR1 (BubR1‐K243, an integral part of the spindle assembly checkpoint complex) functions during oocyte meiosis, and acetylation‐mimetic mutant BubR1‐K243Q results in the very similar phenotypes as Sirt2‐knockdown oocytes. Furthermore, we found that nonacetylatable‐mimetic mutant BubR1‐K243R partly prevents the meiotic deficits in oocytes depleted of Sirt2. Importantly, BubR1‐K243R overexpression in oocytes derived from aged mice markedly suppresses spindle/chromosome anomalies and thereupon lowers the incidence of aneuploid eggs. In sum, our data suggest that Sirt2‐dependent BubR1 deacetylation involves in the regulation of meiotic apparatus in normal oocytes and mediates the effects of advanced maternal age on oocyte quality.
Myofibroblastic cells function as progenitors to regenerate murine livers after partial hepatectomy

Objective Smoothened (SMO), a coreceptor of the Hedgehog (Hh) pathway, promotes fibrogenic repair of chronic liver injury. We investigated the roles of SMO+ myofibroblast (MF) in liver regeneration by conditional deletion of SMO in α smooth muscle actin (αSMA)+ cells after partial hepatectomy (PH). Design αSMA-Cre-ERT2×SMO/flox mice were treated with vehicle (VEH) or tamoxifen (TMX), and sacrificed 24–96 h post-PH. Regenerating livers were analysed for proliferation, progenitors and fibrosis by qRT-PCR and quantitative immunohistochemistry (IHC). Results were normalised to liver segments resected at PH. For lineage-tracing studies, αSMA-Cre-ERT2×ROSA-Stop-flox-yellow fluorescent protein (YFP) mice were treated with VEH or TMX; livers were stained for YFP, and hepatocytes isolated 48 and 72 h post-PH were analysed for YFP by flow cytometric analysis (FACS). Results Post-PH, VEH-αSMA-SMO mice increased expression of Hh-genes, transiently accumulated MF, fibrosis and liver progenitors, and ultimately exhibited proliferation of hepatocytes and cholangiocytes. In contrast, TMX-αSMA-SMO mice showed loss of whole liver SMO expression, repression of Hh-genes, enhanced accumulation of quiescent HSC but reduced accumulation of MF, fibrosis and progenitors, as well as inhibition of hepatocyte and cholangiocyte proliferation, and reduced recovery of liver weight. In TMX-αSMA-YFP mice, many progenitors, cholangiocytes and up to 25% of hepatocytes were YFP+ by 48–72 h after PH, indicating that liver epithelial cells were derived from αSMA-YFP+ cells. Conclusions Hh signalling promotes transition of quiescent hepatic stellate cells to fibrogenic MF, some of which become progenitors that regenerate the liver epithelial compartment after PH. Hence, scarring is a component of successful liver regeneration.
Prevalence of hospital-based malaria among children in Jos, North Central Nigeria.

___________________________________________________________________________________________ ABSTRACT Background: In Nigeria, malaria is one of the main causes of morbidity and mortality in children. Nigeria government has put in efforts on malaria control and prevention. This is in consonance with Roll back malaria initiative’s objectives. Thus, with the expiration of RBM 2010 target deadline for malaria, there is a need to assess the prevalence of malaria among the risk group in this malaria endemic area, to ascertain how far we have gone in achieving the initiatives objectives. Objective: The aim of this study was to determine the prevalence of malaria among children. Method: This is a hospital based cross- sectional study of 600 children with or without malaria attending various health care centers in the urban area of Jos, North central Nigeria. Giemsa stained thick and thin blood films were examined for malaria parasite using x 100 (oil immersion) objective. Result: Six hundred children with or without malaria were recruited for the study, in which 287 (47.8%) were boys. Based on microscopical diagnosis of malaria, 306 (51.00%) children with malaria parasitaemia had parasite density> 500 parasites/ µ l. Malaria parasitaemia was relatively higher in children aged 5-9 years. Conclusion: There is still a high prevalence of hospital-based malaria among children aged 1-day to18 years in the urban areas of Jos, north central Nigeria. Consequently, there is a need to intensify effort on malaria treatment, control and prevention in these areas. conducted among children attending the Emergency Paeditaric Unit, Special Care Baby Unit, Paediatric Outpatient Department including the immunization unit of JUTH and the primary health care centers (PHCs) including those who came to the PHCs solely for the purpose of the study.
Democracy and resilient pro-social behavioral change: an experimental study

Both experimental and empirical studies have shown that democratically imposing a policy that encourages cooperation may increase its effectiveness by enhancing the voters’ cooperation behavior. But, do those involved in the democratic decision-making process change their behavior when faced with an exogenously implemented rule? This paper experimentally shows that the voters that are involved in a successful democratic selection of a policy behave more pro-socially as consistent with recent studies. My experiment moreover shows that such a successful democratic imposition of the policy may increase the voters’ level of cooperation even when the policy is undemocratically imposed.
Prevalence of Skin Diseases in Kavre District, Nepal

Background Skin is the major interface of human to the environment . It is the major susceptible organ for any disease. Wide prevalence of skin diseases in the community is a well established fact. Objectve The aim of this study is to determine the prevalence of skin diseases among the general population of Kavre District,Nepal . Methods This is a hospital based, retrospective study done among all the patients visiting Dhulikhel Hospital, Kathmandu University Teaching Hospital, in Dhulikhel, Kavre during the year 2007-2008 AD. Data were obtained from the hospital out-patient records and analyzed. The total number of patients who visited the hospital were 74,279 (male-30,809 female- 43,470), out of which 7374 (9 .92 %), male 4155, female 3219, visited the Dermatology Department. Among this total study population now comparative study of the prevalence of skin diseases was performed based on sex, age and type of dermatological condition. Results The overall prevalence of skin diseases were 9.92% with slight higher rates seen among males ( 56.34 %) than females (43.65 %). Non-infective conditions , 6063 ( 82.22% ) outweighed infective conditions 1311 (17.78 %), commonest one being the pigmentary disorders (32.56 %) and in the age group 16-35 years old (31.23% ). Conclusion This study demonstrates that skin diseases are one of the most prevalent disease condition among the general population, representing a major public health problem. Keywords Prevalence; infective diseases; non-infective diseases. DOI: http://dx.doi. org/10.3126/njdvl.v9i1. 5761 NJDVL 2010; 9(1): 7-9
Mechanical ventilation and acute lung injury in emergency department patients with severe sepsis and septic shock: an observational study.

OBJECTIVES The objectives were to characterize the use of mechanical ventilation in the emergency department (ED), with respect to ventilator settings, monitoring, and titration and to determine the incidence of progression to acute lung injury (ALI) after admission, examining the influence of factors present in the ED on ALI progression. METHODS This was a retrospective, observational cohort study of mechanically ventilated patients with severe sepsis and septic shock (June 2005 to May 2010), presenting to an academic ED with an annual census of >95,000 patients. All patients in the study (n = 251) were analyzed for characterization of mechanical ventilation use in the ED. The primary outcome variable of interest was the incidence of ALI progression after intensive care unit (ICU) admission from the ED and risk factors present in the ED associated with this outcome. Secondary analyses included ALI present in the ED and clinical outcomes comparing all patients progressing to ALI versus no ALI. To assess predictors of progression to ALI, significant variables in univariable analyses at a p ≤ 0.10 level were candidates for inclusion in a bidirectional, stepwise, multivariable logistic regression analysis. RESULTS Lung-protective ventilation was used in 68 patients (27.1%) and did not differ based on ALI status. Delivered tidal volume was highly variable, with a median tidal volume delivered of 8.8 mL/kg ideal body weight (IBW; interquartile range [IQR] = 7.8 to 10.0) and a range of 5.2 to 14.6 mL/kg IBW. Sixty-nine patients (27.5%) in the entire cohort progressed to ALI after admission to the hospital, with a mean (±SD) onset of 2.1 (±1) days. Multivariable logistic regression analysis demonstrated that a higher body mass index (BMI), higher Sequential Organ Failure Assessment (SOFA) score, and ED vasopressor use were associated with progression to ALI. There was no association between ED ventilator settings and progression to ALI. Compared to patients who did not progress to ALI, patients progressing to ALI after admission from the ED had an increase in mechanical ventilator duration, vasopressor dependence, and hospital length of stay (LOS). CONCLUSIONS Lung-protective ventilation is uncommon in the ED, regardless of ALI status. Given the frequency of ALI in the ED, the progression shortly after ICU admission, and the clinical consequences of this syndrome, the effect of ED-based interventions aimed at reducing the sequelae of ALI should be investigated further.
History and physical examination plus laboratory testing for the diagnosis of adult female urinary tract infection.

BACKGROUND Emergency physicians often encounter females presenting with symptoms suggestive of urinary tract infections (UTIs). The diagnostic accuracy of history, physical examination, and bedside laboratory tests for female UTIs in emergency departments (EDs) have not been quantitatively described. OBJECTIVES This was a systematic review to determine the utility of history and physical examination (H&P) and urinalysis in diagnosing uncomplicated female UTI in the ED. METHODS The medical literature was searched from January 1965 through October 2012 in PUBMED and EMBASE using the following criteria: Patients were females greater than 18 years of age in the ED suspected of having UTIs. Interventions were H&P and urinalysis used to diagnose a UTI. The comparator was UTI confirmed by a positive urine culture. The outcome was operating characteristics of the interventions in diagnosing a UTI. Study quality was assessed using Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2). Sensitivity, specificity, and likelihood ratios (LRs) were calculated using Meta-DiSc. RESULTS Four studies (pooled n = 948) were included with UTI prevalence ranging from 40% to 60%. H&P variables all had positive LRs (+LR, range = 0.8 to 2.2) and negative LRs (-LR, range = 0.7 to 1.0) that are insufficient to significantly alter pretest probability of UTI. Only a positive nitrite reaction (+LR = 7.5 to 24.5) was useful to rule in a UTI. To rule out UTI, only a negative leukocyte esterase (LE; -LR = 0.2) or blood reaction on urine dipstick (-LR = 0.2) were significantly accurate. Increasing pyuria directly correlated with +LR, and moderate pyuria (urine white blood cells [uWBC] > 50 colony-forming units [CFUs]/ml) and moderate bacteruria were good predictors of UTI (+LR = 6.4 and 15.0, respectively). CONCLUSIONS No single H&P finding can accurately rule in or rule out UTI in symptomatic women. Urinalysis with a positive nitrite or moderate pyuria and/or bacteruria are accurate predictors of a UTI. If the pretest probability of UTI is sufficiently low, a negative urinalysis can accurately rule out the diagnosis.
Laboratory testing of individuals with severe α1-antitrypsin deficiency in three European centres

α1-Antitrypsin (AT) deficiency is a hereditary disorder that may lead to early-onset emphysema, and chronic liver disease later in life. Although there are validated methods for testing, the vast majority of α1-AT-deficient individuals remain undiagnosed. Recommendations have been published for the testing and diagnosis of α1-AT deficiency; however, guidelines on best practice are not well established. In our article, we review the developments in diagnostic techniques that have taken place in recent years, and describe the practices used in our three European centres. The determination of the level of α1-AT and genotyping are reported as the main diagnostic steps, whereas isoelectric focusing (also referred to as phenotyping) is reserved for confirmatory analysis. The following recommendations for best practice are put forward: detection of all PiZZ and other severe deficiency individuals; automated genotyping; preparation of reference standards; quality control programmes; development of standard operating procedure documents; and standardised methods for the collection of dried blood samples. Closer cooperation between laboratories and the sharing of knowledge are recommended, with the objectives of improving the efficiency of the diagnosis of severe α1-AT deficiency, increasing the numbers of individuals who are detected with the disorder, and assisting the establishment of new patient identification programmes.
Polymorphisms in the type IV collagen α3 gene and the risk of COPD

A number of genome-wide linkage analyses have identified the 2q33.3–2q37.2 region as the most likely to contain the genes that contribute to the susceptibility to chronic obstructive pulmonary disease (COPD). It was hypothesised that the type IV collagen α3 (COL4A3) gene, which is one of the genes located in the 2q33.3–2q37.2 region, may act as a low-penetrance susceptibility gene for COPD. To test this hypothesis, the association of COL4A3 -1162T>C, IVS2+12C>A, P141L, G162E, H451R, P574L and *315C>A polymorphisms with the risk of COPD was investigated in a case–control study of 311 COPD patients and 386 controls. The presence of at least one 451R allele was associated with a significantly higher risk of COPD compared with the 451 H/H genotype (adjusted odds ratio 1.48, 95% confidence interval (1.03–2.14)). When the subjects were stratified according to age and COPD severity, the 451R allele was associated with a significantly higher risk of COPD only in younger individuals with severe COPD (3.02 (1.37–6.67)). In conclusion, these findings suggest that the type IV collagen α3 gene contributes to the genetic susceptibility to chronic obstructive pulmonary disease.
Asymmetric dimethylarginine and asthma

To the Editor: With interest we have read the letter by Lau et al. [1] regarding circulating asymmetric dimethylarginine (ADMA) in a cohort of children with asthma from the Australian Childhood Asthma Prevention Study. ADMA, a product of protein degradation, is an endogenous nitric oxide synthase inhibitor that has been shown to be increased in mouse models of allergic airway inflammation and to be associated with airways hyperresponsiveness in these animals [2]. ADMA has also been reported to be increased in sputum samples [2] and exhaled breath condensates [3] from paediatric patients with asthma. Increased ADMA in serum has recently been found to be associated with the severity of symptoms in late-onset asthma and obesity [4]. Lau et al. [1] found no difference in …
Faecal metabolite profiling identifies medium-chain fatty acids as discriminating compounds in IBD

Background Bacteria play a role in the onset and perpetuation of intestinal inflammation in IBD. Compositional alterations may also change the metabolic capacities of the gut bacteria. Objective To examine the metabolic activity of the microbiota of patients with Crohn's disease (CD), UC or pouchitis compared with healthy controls (HC) and determine whether eventual differences might be related to the pathogenesis of the disease. Methods Faecal samples were obtained from 40 HC, 83 patients with CD, 68 with UC and 13 with pouchitis. Disease activity was assessed in CD using the Harvey–Bradshaw Index, in UC using the UC Disease Activity Index and in pouchitis using the Pouchitis Disease Activity Index. Metabolite profiles were analysed using gas chromatography–mass spectrometry. Results The number of metabolites identified in HC (54) was significantly higher than in patients with CD (44, p<0.001), UC (47, p=0.042) and pouchitis (43, p=0.036). Multivariate discriminant analysis predicted HC, CD, UC and pouchitis group membership with high sensitivity and specificity. The levels of medium-chain fatty acids (MCFAs: pentanoate, hexanoate, heptanoate, octanoate and nonanoate), and of some protein fermentation metabolites, were significantly decreased in patients with CD, UC and pouchitis. Hexanoate levels were inversely correlated to disease activity in CD (correlation coefficient=−0.157, p=0.046), whereas a significant positive correlation was found between styrene levels and disease activity in UC (correlation coefficient=0.338, p=0.001). Conclusions Faecal metabolic profiling in patients with IBD relative to healthy controls identified MCFAs as important metabolic biomarkers of disease-related changes. Trial Registration No: NCT 01666717.