Miracle-dz/UniFAR-FTUs huggingface dataset:
Long‐term evaluation of cyclosporine and tacrolimus based immunosuppression in pediatric liver transplantation

Abstract: Both calcineurin inhibitors (CNIs), cyclosporine and tacrolimus, are widely used in pediatric liver transplant recipients and currently data are limited with regards to long‐term results using the one drug or the other in comparable low doses. We conducted the present study to assess the advantages and disadvantages of both drugs in children at least five yr post‐liver transplantation. A total of 129 children were enrolled in the study. Thirty‐eight of the children were switched to tacrolimus monotherapy for different reasons [steroid resistant graft rejection (n = 15), chronic rejection (n = 5), severe acute rejection (n = 4), repetitive acute graft rejection (n = 5), dysfunction of the transplant (n = 3), insufficient CsA metabolism (n = 3), hypertrichosis (n = 2), and CsA toxicity (n = 1)], four patients had primary tacrolimus therapy, and 87 patients are receiving cyclosporine. Mean trough levels were 5.3 ± 2.3 ng/mL (tacrolimus) and 73.6 ± 44.5 μ/L (cyclosporine), respectively at least five yr post‐orthotopic liver transplantation (OLT). There was no significant difference in the calculated glomerular filtration rate between children on cyclosporine and tacrolimus (142.7 + 39.5 mL/min/1.73 m2 vs. 151.1 ± 44.1 mL/min/1.73 m2). The incidence of arterial hypertension was 7.1% vs. 9.2%, that of hepatotoxicity was 0% vs. 2.3%. Cosmetic changes were found in more than one‐third of the patients on cyclosporine and in 4.8% of the patients receiving tacrolimus. Quality of life was excellent in both groups (self assessment). The impact of CNIs on chronic graft dysfunction cannot be assessed by our present study. We conclude from the results that cyclosporine and tacrolimus are both excellent drugs for maintenance immunosuppression in the long‐term course following pediatric liver transplantation. However, this retrospective analysis is limited by the bias between children on CsA as compared with patients receiving tacrolimus. A prospective randomized controlled trial is needed in order to assess which CNI is the best for children following OLT.
Effect of trehalose on protein structure

Trehalose is a ubiquitous molecule that occurs in lower and higher life forms but not in mammals. Till about 40 years ago, trehalose was visualized as a storage molecule, aiding the release of glucose for carrying out cellular functions. This perception has now changed dramatically. The role of trehalose has expanded, and this molecule has now been implicated in a variety of situations. Trehalose is synthesized as a stress‐responsive factor when cells are exposed to environmental stresses like heat, cold, oxidation, desiccation, and so forth. When unicellular organisms are exposed to stress, they adapt by synthesizing huge amounts of trehalose, which helps them in retaining cellular integrity. This is thought to occur by prevention of denaturation of proteins by trehalose, which would otherwise degrade under stress. This explanation may be rational, since recently, trehalose has been shown to slow down the rate of polyglutamine‐mediated protein aggregation and the resultant pathogenesis by stabilizing an aggregation‐prone model protein. In recent years, trehalose has also proved useful in the cryopreservation of sperm and stem cells and in the development of a highly reliable organ preservation solution. This review aims to highlight the changing perception of the role of trehalose over the last 10 years and to propose common mechanisms that may be involved in all the myriad ways in which trehalose stabilizes protein structures. These will take into account the structure of trehalose molecule and its interactions with its environment, and the explanations will focus on the role of trehalose in preventing protein denaturation.
Combined Effects of Alzheimer Risk Variants in the CLU and ApoE Genes on Ventricular Expansion Patterns in the Elderly

The C allele at the rs11136000 locus in the clusterin (CLU) gene is the third strongest known genetic risk factor for late-onset Alzheimer's disease (LOAD). A recent genome-wide association study of LOAD found the strongest evidence of association with CLU at rs1532278, in high linkage disequilibrium with rs11136000. Brain structure and function are related to the CLU risk alleles, not just in LOAD patients but also in healthy young adults. We tracked the volume of the lateral ventricles across baseline, 1-year, and 2-year follow-up scans in a large sample of elderly human participants (N = 736 at baseline), from the Alzheimer's Disease Neuroimaging Initiative, to determine whether these CLU risk variants predicted longitudinal ventricular expansion. The rs11136000 major C allele—previously linked with reduced CLU expression and with increased risk for dementia—predicted faster expansion, independently of dementia status or ApoE genotype. Further analyses revealed that the CLU and ApoE risk variants had combined effects on both volumetric expansion and lateral ventricle surface morphology. The rs1532278 locus strongly resembles a regulatory element. Its association with ventricular expansion was slightly stronger than that of rs11136000 in our analyses, suggesting that it may be closer to a functional variant. Clusterin affects inflammation, immune responses, and amyloid clearance, which in turn may result in neurodegeneration. Pharmaceutical agents such as valproate, which counteract the effects of genetically determined reduced clusterin expression, may help to achieve neuroprotection and contribute to the prevention of dementia, especially in carriers of these CLU risk variants.
Postdischarge geriatric assessment of hospitalized frail elderly patients.

BACKGROUND The diffusion of comprehensive geriatric assessment services has been rather limited in North America partly because of reimbursement and organizational constraints. OBJECTIVE To evaluate the impact of a comprehensive geriatric assessment intervention for frail older patients that is started before hospital discharge and is continued at home. METHODS Patients older than 65 years were selected who had either unstable medical problems, recent functional limitations, or potentially reversible geriatric clinical problems. Patients (n = 354) were randomly assigned to either the intervention group or a control group. Information on survival, readmissions, nursing home placement, medication use, and health status was collected at 30 and 60 days after hospital discharge. RESULTS No differences were observed between the two treatment groups in survival, hospital readmission, or nursing home placement by 60 days. After adjustment for baseline characteristics, no significant differences were observed between the two groups on measures of physical functioning, social functioning, role limitations, health perceptions, pain, mental health, energy and/or fatigue, health change, or overall well-being. CONCLUSIONS Although efficacy has been demonstrated for some forms of comprehensive geriatric assessment, the types of services that are easier to establish (inpatient consultation services and ambulatory assessment) have not been shown to improve outcomes. Our results indicate that outcomes are unaffected by a limited form of comprehensive geriatric assessment begun in the hospital and completed at home. Further efforts are needed to develop and to evaluate realistic approaches to comprehensive geriatric assessment.
Matrix Metalloproteinase-3 on Ligamentum Flavum in Degenerative Lumbar Spondylolisthesis

Study Design. Human ligamentum flavum (LF) was examined for the activity level of matrix metalloproteinase-3 (MMP-3) in degenerative spondylolithesis (DS) patients using immunohistochemistry, Western blot, reverse transcriptase-polymerase chain reaction (RT-PCR), and quantitative real-time PCR. Objective. To investigate the hypothesis that the activity of MMP-3 is elevated in LF of DS patients, which might contribute to DS pathogenesis. Summary of Background Data. MMP-3 is a proteinase produced by connective tissue cells and is responsible for the degradation and modification of extracellular matrix molecules. MMP-3 activity has been established in articular cartilage, synovial membrane, and intervertebral discs, but not in the LF. Methods. The experimental group consisted of 18 patients with DS and the control group consisted of 18 patients with spinal stenosis (SS) without any instabilities. MMP-3 expression was measured with in situ using immunohistochemistry and both for mRNA and protein levels. Results. The MMP-3 positive cell ratio in the LF observed in DS patients was substantially higher than in SS patients (P = 0.030). In Western blot, the average optical density (OD) of MMP-3 was higher in LF of DS than of SS (P = 0.028). There was greater MMP-3 expression in DS patients as quantified by RT-PCR (P = 0.004). Conclusion. Our study shows that MMP-3 expression in the LF of DS patients was significantly higher than in SS patients. Increased MMP-3 expression may be associated with the degenerative changes of LF in DS patients comprising one of the mechanisms of pathogenesis in DS.
Cellular Uptake of Clostridium botulinum C2 Toxin Requires Oligomerization and Acidification*

The actin-ADP-ribosylating binaryClostridium botulinum C2 toxin consists of two individual proteins, the binding/translocation component C2II and the enzyme component C2I. To elicit its cytotoxic action, C2II binds to a receptor on the cell surface and mediates cell entry of C2I via receptor-mediated endocytosis. Here we report that binding of C2II to the surface of target cells requires cleavage of C2II by trypsin. Trypsin cleavage causes oligomerization of the activated C2II (C2IIa) to give SDS-stable heptameric structures, which exhibit a characteristic annular or horseshoe shape and form channels in lipid bilayer membranes. Cytosolic delivery of the enzyme component C2I is blocked by bafilomycin but not by brefeldin A or nocodazole, indicating uptake from an endosomal compartment and requirement of endosomal acidification for cell entry. In the presence of C2IIa and C2I, short term acidification of the extracellular medium (pH 5.4) allows C2I to enter the cytosol directly. Our data indicate that entry of C2 toxin into cells involves (i) activation of C2II by trypsin-cleavage, (ii) oligomerization of cleaved C2IIa to heptamers, (iii) binding of the C2IIa oligomers to the carbohydrate receptor on the cell surface and assembly with C2I, (iv) receptor-mediated endocytosis of both C2 components into endosomes, and finally (v) translocation and release of C2I into the cytosol after acidification of the endosomal compartment.
A novel UWB bandpass filter and its application to UWB pulse generation

This paper presented an ultra-wideband (UWB) bandpass filter using broadside-coupled microstrip-coplanar waveguide structure. The filter consists of a microstrip line coupled to a coplanar waveguide (CPW) that was fabricated on the ground of the microstrip line. The proposed filter has been simulated, fabricated and measured for UWB system. The measured results of a 3-section filter demonstrated the best UWB performance around the world; bandwidth from 3.0 GHz to 10.63 GHz ((@-10 dB); insertion loss at central frequency about 0.32 dB and very flat over the whole band; group delay, which is important to an impulse radio UWB system, about 0.42 ns over the most central bund, and less than 0.95 ns over the whole band. The filter also exhibited a good performance outside the band, both at low frequency end (to meet FCC limit) and high frequency end higher than 18 GHz with insertion loss better than 30 dB. The developed bandpass filter has been successfully applied to the UWB pulse generation. The experimental results demonstrated that a step-like negative pulse with less than 5 ps failtime, generated from a pulse generator, was reshaped through the filter as a Gaussian doublet-like UWB pulse.
Bridging the gap: does a specialist eating disorder service, aimed at developing a continuum of community care, make a difference?

Objective: In 2010, the authors identified in a separate publication, Mind the evidence gap, the sparse evidence-base for the treatment of adult anorexia nervosa and barriers to accessing care. We report on the ensuing development, implementation and first 18-month results of a novel eating disorder service bridging the primary and specialist continuum of care in Victoria, Australia. Method: Using literature review, stakeholder, and consumer and carer consultation, a model for a community eating disorder service was developed and then implemented. All patients entering the service were then assessed at intake and, if they gave consent, at 12 month follow-up. Results: From December 2010 to July 2012, 208 patients accessed The Body Image Eating Disorders Treatment and Recovery Service (BETRS). Fifty-three per cent had a diagnosis of anorexia nervosa and the mean number of co-morbid psychiatric diagnoses was two. Twenty-three per cent attended a day patient programme and showed a significant improvement in their body mass index. Measures of depression, anxiety and eating disorder symptomatology showed a concomitant, significant decrease. Conclusions: The development of BETRS has led to markedly improved access and effectiveness of specialist services in the region.
The effect of happiness training on self-esteem in the mothers of children with cleft lip and palate in Isfahan 2015

BACKGROUND: Birth of a child with cleft lip and palate, as a crisis, can affect family relationships and interactions seriously and hence self-esteem in family members. The present study was conducted to investigate the effect of a happiness training program on self-esteem in the mothers of children with cleft lip and palate. MATERIALS AND METHODS: In this quasi-experimental study, 64 mothers of children with cleft lip and palate referring to health-care team in the Isfahan University Medical Sciences were enrolled by convenience random sampling. Then, the program of happiness training was implemented within 10 sessions, and a questionnaire of demographic characteristics and Coopersmith Self-Esteem Inventory was filled out before and 2 months after the last session. The data were analyzed by descriptive and analytical statistics (paired t-test, independent t-test, Chi-square, and Mann–Whitney) in SPSS 20 (SPSS Inc: Chicago), RESULTS: The mean age of the mothers in intervention and control groups was 33.3 ± 6.3 and 33.5 ± 5.8 years, respectively. The mean age of the children in the intervention and control groups was 6.34 ± 3.37 and 5.03 ± 3.36 years. Independent t-test indicated a significant difference in self-esteem mean score after training in the intervention and control groups. Moreover, paired t-test indicated a significant difference in self-esteem mean score between before and after training in the intervention group. CONCLUSION: In the light of the effect of happiness training on the promotion of self-esteem in children with cleft lip and palate, this program can be used as a care intervention to reduce psychological and mental problems and to enhance adjustment in parents.
Cross-Lagged Associations Between Children’s Stress and Adiposity: The Children’s Body Composition and Stress Study

Objective The public health threats stress and adiposity have previously been associated with each other. Longitudinal studies are needed to reveal whether this association is bidirectional and the moderating factors. Methods In the longitudinal Children’s Body Composition and Stress study, 316 children (aged 5–12 years) had measures of stress (questionnaires concerning negative life events, problem behavior, and emotions) and adiposity (body mass index, waist-to-height ratio, and fat percentage) in three waves at 1-year intervals. The bidirectionality of the association between stress and adiposity was examined using cross-lagged analyses. We tested moderation by cortisol and life-style (physical activity, screen time, food consumption, eating behavior and sleep duration). Results Adiposity (body mass index: &bgr; = 0.48 and fat percentage: &bgr; = 0.18; p < .001) were associated with subsequent increased stress levels, but stress was not directly related to subsequent increases in adiposity indices. Cortisol and life-style factors displayed a moderating effect on the association between stress and adiposity. Stress was positively associated with adiposity in children with high cortisol awakening patterns (&bgr; = 0.204; p = .020) and high sweet food consumption (&bgr; = 0.190; p = .031), whereas stress was associated with lower adiposity in the most active children (&bgr; = −0.163; p = .022). Conclusions Stress is associated with the development of children’s adiposity, but the effects depend on cortisol levels and life-style factors. This creates new perspectives for multifactorial obesity prevention programs. Our results also highlight the adverse effect of an unhealthy body composition on children’s psychological well-being.
Expression of heat shock protein in broiler embryo tissues after acute cold or heat stress

This study evaluated the expression of heat shock protein 70 kD (hsp70) in broiler chicken embryos subjected to cold (Experiment I) or high incubation temperature (Experiment II). In each experiment, fertile eggs were distributed in three incubators kept at 37.8°C. At day 13 (D13), D16, and D19 of incubation, the embryos were subjected to acute cold (32°C) or heat (40°C) for 4–6 hr. Immediately after cold or heat exposure, samples from the liver, heart, breast muscle, brain, and lungs of 40 embryos were taken per age and treatment (control or stressed embryos). A tissue pool from 10 embryos was used as 1 replication. The levels of hsp70 in each tissue sample was quantified by Western blot analysis. The data were analyzed in a 3 × 2 factorial arrangement of treatments with four replications. hsp70 was detected in all embryo tissues, and the brain contained 2‐ to 5‐times more hsp70 protein compared to the other tissues in either cold or heat stressed embryos. hsp70 increases were observed in the heart and breast muscle of cold stressed embryos at D16 and D19, respectively. Heat stressed embryos showed an increase of hsp70 in the heart at D13 and D19, and in the lung at D19 of incubation. Younger embryos had higher hsp70 synthesis than older embryos, irrespective of the type of thermal stressor. The results indicate that the expression of hsp70 in broiler chicken embryos is affected by cold and heat distress, and is tissue‐ and age‐dependent. Mol. Reprod. Dev. 67:172–177, 2004. © 2004 Wiley‐Liss, Inc.
Cytokine production at the site of disease in human tuberculosis

Clinical and immunologic evidence suggests that tuberculous pleuritis provides a model to understand protective immune mechanisms against Mycobacterium tuberculosis. We therefore evaluated the pattern of cytokine mRNA expression and cytokine production in pleural fluid and blood of patients with tuberculous pleuritis. RNA was extracted from mononuclear cells, reverse transcribed to cDNA, and amplified by polymerase chain reaction (PCR). After normalization for T-cell cDNA, cDNA from pleural fluid cells and peripheral blood mononuclear cells (PBMC) was amplified with cytokine-specific primers. PCR product was quantified by Southern blot. For the Th1 cytokines gamma interferon (IFN-gamma) and interleukin-2 (IL-2), PCR product was greater in pleural fluid than in blood, whereas PCR product for the Th2 cytokine IL-4 was decreased in pleural fluid compared with blood. Concentrations of IFN-gamma were elevated in pleural fluid compared with serum, but IL-2, IL-4, and IL-5 were not detectable. Mean concentrations of IFN-gamma and IL-2 in supernatants of M. tuberculosis-stimulated pleural fluid cells were significantly greater than corresponding concentrations in supernatants of stimulated PBMC. In situ hybridization showed that increased IFN-gamma production by pleural fluid cells was associated with a 20- to 60-fold increase in the frequency of antigen-reactive IFN-gamma-mRNA-expressing cells. Because IL-10 can be produced by T cells and macrophages, pleural fluid cells and PBMC were normalized for beta-actin cDNA content and then amplified by PCR with IL-10-specific primers. IL-10 mRNA was greater in pleural fluid cells than in PBMC and was expressed predominantly by macrophages. IL-10 concentrations were elevated in pleural fluid versus serum. These data provide strong evidence for compartmentalization of Th1 cytokines and IL-10 at the site of disease in humans with a resistant immune response to mycobacterial infection.
The effect of short-term hyperammonaemia on milk synthesis in dairy cows

To test the hypothesis that ammonia detoxification in ruminants consumes amino acids to the detriment of milk protein production, we infused four lactating dairy cows with ammonium acetate or sodium acetate in switchback experiments. Plasma ammonia concentrations increased to 411 μm within 1 h of the start of infusion of ammonium acetate at 567 mmol/h. The rate constant for ammonia clearance from plasma was 0·054/min and the half-life was 12·9 min. Infusion at 567 mmol/h for 1 h followed by 1 h without infusion, repeated four times between am- and pm-milking, caused a decrease in feed intake. Compared with sodium acetate, continuous infusion of ammonium acetate at 360 mmol/h throughout an entire 10-h milking interval increased plasma ammonia concentrations to 193 μm and caused a 20% decrease in milk, protein and lactose production with no effect on percentage composition of milk or the yield of milk fat. Arterial concentrations of glucose and non-esterified fatty acids tended to increase; there was no effect on arterial acetate, β-hydroxybutyrate or triacylglcerol, and branched-chain amino acids, Lys and Thr decreased. Mammary plasma flow, estimated by assuming 100% uptake/output of Phe+Tyr, was significantly correlated with milk yield. Mammary uptakes of acetate tended to be reduced by hyperammonaemia, but uptakes of other energy metabolites and amino acids were not affected. Thus, while an increase in amino acid consumption during hyperammonaemia was apparent from the drop in circulating concentrations of Leu, Ile, Val, Lys and Thr, there was no evidence to support the hypothesis that milk yield is affected by the lower concentrations. An ammonia-induced depression in feed intake may have caused the decrease in milk synthesis.
The earliest stages of adaptation in an experimental plant population: strong selection on QTLS for seed dormancy

Colonizing species may often encounter strong selection during the initial stages of adaptation to novel environments. Such selection is particularly likely to act on traits expressed early in development since early survival is necessary for the expression of adaptive phenotypes later in life. Genetic studies of fitness under field conditions, however, seldom include the earliest developmental stages. Using a new set of recombinant inbred lines, we present a study of the genetic basis of fitness variation in Arabidopsis thaliana in which genotypes, environments, and geographic location were manipulated to study total lifetime fitness, beginning with the seed stage. Large‐effect quantitative trait loci (QTLs) for fitness changed allele frequency and closely approached 90% in some treatments within a single generation. These QTLs colocated with QTLs for germination phenology when seeds were dispersed following a schedule of a typical winter annual, and they were detected in two geographic locations at different latitudes. Epistatically interacting loci affected both fitness and germination in many cases. QTLs for field germination phenology colocated with known QTLs for primary dormancy induction as assessed in laboratory tests, including the candidate genes DOG1 and DOG6. Therefore fitness, germination phenology, and primary dormancy are genetically associated at the level of specific chromosomal regions and candidate loci. Genes associated with the ability to arrest development at early life stages and assess environmental conditions are thereby likely targets of intense natural selection early in the colonization process.