Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of dehydroepiandrosterone replacement on vascular function in primary and secondary adrenal insufficiency: a randomized crossover trial.

CONTEXT Patients with Addison's disease and hypopituitarism have increased mortality, chiefly related to vascular disease. Both diseases are characterized by dehydroepiandrosterone (DHEA) deficiency, yet this is not usually corrected. It is unclear whether treatment of these conditions with DHEA improves cardiovascular risk. OBJECTIVE The aim of the study was to evaluate the effects of DHEA on arterial stiffness and endothelial function in subjects with Addison's disease and hypopituitarism. DESIGN AND INTERVENTION Forty subjects (20 with Addison's disease, 20 with panhypopituitarism) were assigned to consecutive 12-wk treatment periods of DHEA 50 mg or placebo in a randomized, double-blind, crossover design separated by an 8-wk washout. MAIN OUTCOME MEASURES Primary outcome parameters were measures of arterial stiffness [augmentation index, central blood pressure, brachial and aortic pulse wave velocity (PWV)] and endothelial function. Serum androgens, anthropometry, and metabolic biochemistry (lipids, homeostasis model of assessment for insulin resistance, high sensitivity C-reactive protein, adiponectin, plasminogen activator inhibitor-1) were also assessed. RESULTS Despite normalization of DHEA sulfate, androstenedione, and testosterone (females), DHEA replacement did not affect augmentation index, aortic PWV, brachial PWV, central blood pressure, or endothelial function. DHEA did not affect any anthropometric or metabolic measures, apart from a small reduction in high-density lipoprotein cholesterol (-0.08 mmol/liter; P = 0.007; 95% confidence interval for the difference, -0.13 to -0.02 mmol/liter). CONCLUSIONS Short-term DHEA supplementation does not significantly affect measures of arterial stiffness or endothelial function in patients with adrenal insufficiency.
Strong evidence from studies with brachymorphic mice and pentachlorophenol that 1'-sulfoöxysafrole is the major ultimate electrophilic and carcinogenic metabolite of 1'-hydroxysafrole in mouse liver.

The role of sulfation of 1'-hydroxysafrole in the formation of hepatic macromolecular adducts and in hepatic tumor formation in mice given 1'-hydroxysafrole was investigated by the use of: (a) mice treated with the specific sulfotransferase inhibitor pentachlorophenol; and (b) brachymorphic mice, which are characterized by a deficiency in the hepatic synthesis of 3'-phosphoadenosine 5'-phosphosulfate. Cytosolic sulfotransferase activity for 1'-hydroxysafrole in both mouse and rat liver was significantly inhibited by 10 microM pentachlorophenol, usually by greater than 90%. Prior administration of nontoxic amounts of pentachlorophenol, either in the diet of adult female CD-1 mice or by i.p. injection of 12-day-old male C57BL/6 X C3H F1 (hereafter called B6C3F1) mice, resulted in an 85% decrease in the level of adducts formed from 1'-hydroxysafrole in hepatic DNA and RNA as compared to those of non-pentachlorophenol-treated animals. Likewise, the chronic administration of a nontoxic level of pentachlorophenol in the diet of adult female CD-1 mice strongly inhibited hepatic tumor induction by long-term dietary administration of either safrole or 1'-hydroxysafrole. Initiation of hepatic tumors by a single i.p. injection of 1'-hydroxysafrole to 12-day-old male B6C3F1 mice was strongly inhibited by prior treatment with pentachlorophenol. Under these conditions, the hepatocarcinogenicity of diethylnitrosamine was not inhibited by pentachlorophenol. Supplementation with adenosine triphosphate and sulfate of hepatic cytosols from adult female or 12-day-old brachymorphic progeny of a B6C3 background outbred to B6C3F1 mice (B6C3F2), of either sex, resulted in 5- to 10-fold less binding of 1'-hydroxysafrole to added RNA than when cytosols from phenotypically normal B6C3F2 mice were used. On administration of [3H]-1'-hydroxysafrole to adult female or 12-day-old brachymorphic B6C3F2 mice of either sex, the levels of hepatic DNA and RNA adducts were 7- to 12-fold lower than those obtained in phenotypically normal B6C3F2 mice of the same age and sex. Brachymorphic mice were also much less responsive than their phenotypically normal littermates to the induction of liver tumors by 1'-hydroxysafrole; lower incidences were observed both when the carcinogen was fed chronically to adult females and when it was administered to males only prior to weaning. Thus, all of these data strongly support the conclusion that 1'-sulfoöxysafrole is the major ultimate electrophilic and tumor-initiating metabolite of 1'-hydroxysafrole.
Unique characteristic features of stimulated Brillouin scattering in small-core photonic crystal fibers

We present extensive stimulated Brillouin scattering (SBS) results from experiments and modeling for four different photonic crystal fibers (PCFs) with core diameters ranging from 8 to 1.7 μm. These results reveal several SBS characteristic features of small-core PCFs, high thresholds, and acoustic peaks, which are due to their antiguiding nature and highly multimode acoustic character. The nature of what we believe to be new acoustic modes is examined in the light of the large variations observed in the Brillouin gain, Brillouin threshold, and Brillouin shift with decreasing core diameter and optical wavelength.
Global analysis of the rat and human platelet proteome – the molecular blueprint for illustrating multi‐functional platelets and cross‐species function evolution

Emerging evidences indicate that blood platelets function in multiple biological processes including immune response, bone metastasis and liver regeneration in addition to their known roles in hemostasis and thrombosis. Global elucidation of platelet proteome will provide the molecular base of these platelet functions. Here, we set up a high‐throughput platform for maximum exploration of the rat/human platelet proteome using integrated proteomic technologies, and then applied to identify the largest number of the proteins expressed in both rat and human platelets. After stringent statistical filtration, a total of 837 unique proteins matched with at least two unique peptides were precisely identified, making it the first comprehensive protein database so far for rat platelets. Meanwhile, quantitative analyses of the thrombin‐stimulated platelets offered great insights into the biological functions of platelet proteins and therefore confirmed our global profiling data. A comparative proteomic analysis between rat and human platelets was also conducted, which revealed not only a significant similarity, but also an across‐species evolutionary link that the orthologous proteins representing “core proteome”, and the “evolutionary proteome” is actually a relatively static proteome.
Effects associated with on- and off-label stimulant treatment of core autism and ADHD symptoms exhibited by children with autism spectrum disorder

Abstract Objective: Families of children with autism spectrum disorder are barraged by different treatment options. Some of these options have the support of empirical evidence while others do not. Stimulant treatments are typically utilized to treat symptoms of ADHD indicating an on-label use of such treatment. Methods: This study examines the association of stimulant treatment with the on- (symptoms of ADHD) and off- (symptoms of ASD) label symptoms among children with ASD via a non-clinical, population-based sample. Results: Results indicate no significant association of stimulant treatment with a reduction of on- or off-label symptoms among children with ASD. Conclusion: Stimulant medications utilized in the treatment of DSM core symptoms of autism spectrum disorder would be considered an off-label use because there is limited evidence to support that stimulants are effective in treating core symptoms of ASD, which is supported by the results of the current study.
Method to Detect Floating-Point Absorption and Cancellation Phenomena in Software-Critical Design Models

Airborne critical systems that use real numbers in their algorithms can be considerably affected by the floating-point discretized representation. This limitation in the representation is the cause of many problems already known while running software with floating-point variables such as loss of precision in arithmetic operations. This work presents a method for detecting floating-point absorption and cancellation phenomena using static analysis in software design models. Our method uses a range analysis tool that operates over SCADE model to propagate the range of the internal variables and, then, each addition and subtraction operation in the model is analyzed to check the occurrence of the floating-point absorption and cancellation phenomena. The results are presented in an HTML report containing absorption alerts and cancellations charts providing the number of canceled bits for each sub-range in order to permit better assessment of the impact of each detected cancellation. In order to validate the proposed method, we compare the results of our proposed method with the results obtained by an alternative validation method developed using the source code as input and the Frama-C EVA to propagate internal ranges. The method can be used as an early design analysis enabling the cheaper detection and treatment of floating-point anomalies.
The role of some cyclorrhaphan flies as carriers of human helminths in Malaysia

Abstract. The role of some adult flies (Diptera: Cyclorrhapha) as carriers of helminth parasites of man was studied at four sites in Malaysia: a refuse dump, where no helminth‐positive flies were detected, and in three peri‐domestic situations where four species of flies carried up to three types of nematodes.
Patients’ Attitudes Towards Medical Students in a Teaching Family Practice: A Sri Lankan Experience

Background: Faculty of Medicine, University of Kelaniya, Sri Lanka conducts a one month under graduate training programme during their fourth year at the University family practice centre. Students get training in history taking, clinical examination, patient management and practice management during this attachment. This study was conducted to look at the patients’ attitude towards student participation during consultation. Materials and Methods: This was a descriptive cross sectional study. All the patients who were 16 years and above during a 2 month period were included in the study. Structured questionnaire was administered by demonstrators following a consultation where students were present. Their demographic data, number of consultations with student participation and questions related to presence of students at various stages of the consultation were asked. Results: Total of 85 patients took part in the study and 81.3% of them were females. 88.8% were of the opinion that they benefited by the interaction with medical students while 93.8% thought students understood their problems. 26.3% patients preferred a medical student of the same sex during consultation while 71.3 had not expressed any opinion in this regard. Only 3.8% and 5% wanted the doctor alone during history taking and examination respectively. Almost every patient was happy that they could help the undergraduate training. Discussion: As expected results of the study showed that patients were willing to take part in undergraduate training without any reservation. These results are compatible with the previous studies done in the western world and data is not available form either Sri Lanka or other Asian countries.
Silver as an antimicrobial: facts and gaps in knowledge

Silver has been used for centuries. Today, silver and silver nanoparticles (AgNPs) are used in a wide range of healthcare, food industry, domiciliary applications, and are commonly found in hard surface materials and textiles. Such an extensive use raises questions about its safety, environmental toxicity and the risks associated with microbial resistance and cross-resistance. If the mechanisms of antimicrobial action of ionic silver (Ag+) have been studied, there is little understanding of AgNPs interactions with microorganisms. There have been excellent reviews on the bacterial resistance mechanisms to silver, but there is a paucity of information on resistance to AgNPs. Silver toxicity and accumulation in the environment has been studied and there is a better understanding of silver concentration and species in different environmental compartments. However, owing to the increased applications of silver and AgNPs, questions remain about the presence and consequences of AgNPs in the environment. This review provides an historical perspective of silver usage, an overview of applications, and combined information of microbial resistance and toxicity. Owing the evidence provided in this review, a call for a better understanding and control of silver usage, and for tighter regulations of silver and AgNPs usage is proposed.
Anti-miRNA-23a oligonucleotide suppresses glioma cells growth by targeting apoptotic protease activating factor-1.

BACKGROUND Abnormal expression of microRNAs (miRNAs) is closely related to glioma, which is one of the most common malignant brain tumors. The current study is to identify the key miRNAs involved in the pathogenesis of glioma and to discover novel therapeutic targets for this disease. MATERIALS AND METHODS Total RNA was extracted from glioma tissues of 100 patients. The microRNA microarray and the northern blot were used to detect the changes of miRNAs expression in 7 pairs of glioma specimens. Relative expressions of miR-23a were validated by real-time reverse transcription polymerase chain reaction (RT-PCR) with specific Taqman probes. In order to evaluate the role of miR-23a, the miR-23a mimics and anti-miR-23a oligonucleotides were transfected to glioma cell lines; the cell proliferation, apoptosis, cell cycle percentage, cell migration and invasion abilities were evaluated in vitro. The target genes of miR-23a were also investigated using the bioinformatics tools. The expression of the apoptotic protease activating factor-1 (APAF1), which might be one of the direct targets of miR-23a, was also analyzed using the luciferase reporter assay and western blot analysis in 293T cells and glioma cell line, respectively. RESULTS The microRNA microarray and the northern blot results showed that the expressions of miR-23a in glioma tissues were significantly upregulated. The miR-23a expression levels identified using real time RT-PCR in tumor tissues of 79 samples were higher than in the matched adjacent tissues. By transfection of anti-miR-23a oligonucleotide, the results showed that the proliferation, migration, and invasion of glioma cell lines were significantly suppressed. The bioinformatics searching results showed that APAF1 might be a direct target gene of miR-23a, and it was supported by the luciferase reporter gene assay and western blot analysis results. Finally, experiments showed that overexpression of APAF1 suppressed glioma cell growth and promoted cell apoptosis. CONCLUSIONS Our findings characterized the expression properties of miR-23a, contributed to the function and molecular mechanism of miR-23a in glioma and implied that miR-23a might be employed as novel prognostic markers and therapeutic targets of glioma.
Alteration of human UDP-glucuronosyltransferase UGT2B17 regio-specificity by a single amino acid substitution.

The glucuronidation of steroid hormones is catalyzed by a family of UDP-glucuronosyltransferase (UGT) enzymes. Previously, two cDNA clones, UGT2B15 and UGT2B17, which encode UGT enzymes capable of glucuronidating C19steroids, were isolated and characterized. These proteins are 95% identical in primary structure; however, UGT2B17 is capable of conjugating C19steroid molecules at both the 3alpha and 17beta-OH positions, whereas UGT2B15 is only active at the 17beta-OH position. To identify the amino acid residue(s) which may account for this difference in substrate specificity, a comprehensive study on the role of 15 residues which differ between UGT2B15 and UGT2B17 was performed by site-directed mutagenesis. The stable expression of UGT2B17 mutant proteins into HK293 cells demonstrated that the mutation of isoleucine 125, valine 181 and valine 455 to the residues found in UGT2B15 did not alter enzyme activity nor substrate specificity. Furthermore, mutation of the variant residues in UGT2B15 (serine 124, asparagine 125, phenylalanine 165) to the amino acid residues found in UGT2B17 did not alter enzyme activity nor substrate specificity. However, mutation of the serine residue at position 121 of UGT2B17 to a tyrosine, as found in UGT2B15, abolished the ability of UGT2B17 to conjugate androsterone at the 3alpha position, but still retained activity for dihydrotestosterone and 5alpha-androstane-3alpha, 17beta-diol, which have an OH-group at the 17beta position. Interestingly, mutation of tyrosine 121 in UGT2B15 to a serine abolished activity for C19steroids. It is suggested that the serine residue at position 121 in UGT2B17 is required for activity towards the 3alpha and not for the 17beta position of C19steroids, whereas the tyrosine 121 in UGT2B15 is necessary for UGT activity. Despite the high homology between UGT2B15 and UGT2B17, it is apparent that different amino acid residues in the two proteins are required to confer conjugation of C19steroid molecules.
Exercise training inhibits inflammatory cytokines and more than prevents myocardial dysfunction in rats with sustained β‐adrenergic hyperactivity

Myocardial hypertrophy and dysfunction occur in response to excessive catecholaminergic drive. Adverse cardiac remodelling is associated with activation of proinflammatory cytokines in the myocardium. To test the hypothesis that exercise training can prevent myocardial dysfunction and production of proinflammatory cytokines induced by β‐adrenergic hyperactivity, male Wistar rats were assigned to one of the following four groups: sedentary non‐treated (Con); sedentary isoprenaline treated (Iso); exercised non‐treated (Ex); and exercised plus isoprenaline (Iso+Ex). Echocardiography, haemodynamic measurements and isolated papillary muscle were used for functional evaluations. Real‐time RT‐PCR and Western blot were used to quantify tumour necrosis factor α, interleukin‐6, interleukin‐10 and transforming growth factor β1 (TGF‐β1) in the tissue. NF‐κB expression in the nucleus was evaluated by immunohistochemical staining. The Iso rats showed a concentric hypertrophy of the left ventricle (LV). These animals exhibited marked increases in LV end‐diastolic pressure and impaired myocardial performance in vitro, with a reduction in the developed tension and maximal rate of tension increase and decrease, as well as worsened recruitment of the Frank–Starling mechanism. Both gene and protein levels of tumour necrosis factor α and interleukin‐6, as well as TGF‐β1 mRNA, were increased. In addition, the NF‐κB expression in the Iso group was significantly raised. In the Iso+Ex group, the exercise training had the following effects: (1) it prevented LV hypertrophy; (ii) it improved myocardial contractility; (3) it avoided the increase of proinflammatory cytokines and improved interleukin‐10 levels; and (4) it attenuated the increase of TGF‐β1 mRNA. Thus, exercise training in a model of β‐adrenergic hyperactivity can avoid the adverse remodelling of the LV and inhibit inflammatory cytokines. Moreover, the cardioprotection is related to beneficial effects on myocardial performance.
A Case of Metoclopramide-induced Oculogyric Crisis in a 16-year-old Girl with Cystic Fibrosis

Oculogyric crisis is a neurologic reaction characterized by bilateral dystonic elevation of visual gaze as well as hyperextension of the neck. This reaction is most commonly explained as an adverse effect of numerous medications, such as dopamine receptor blocking agents or neuroleptic medications and traditional antipsychotic or antiemetic drugs, such as prochlorperazine or metoclopramide. A case of oculogyric crisis induced by metoclopramide is described in this paper.
Work-related problems in multiple sclerosis: a literature review on its associates and determinants

Abstract Purpose: To explore which variables are associated to or determinants of work-related difficulties or unemployment in persons with multiple sclerosis (MS). Method: Papers published between 1993 and February 2015 were included. Quality was judged as poor, acceptable, good or excellent. Determinants were extracted from prospective and retrospective data, associated variables from cross-sectional data; variables were grouped by similarity. Evidence was judged as strong if there were at least two good studies reporting the same results; limited if there was only one good and some acceptable studies. Results: Forty-two papers were selected, for a total of 31 192 patients (75% females). Work-related difficulties were referred as unemployment, lower amount of worked hours or job cessation. Strong evidence of impact over work-related difficulties was found for a core set of variables, i.e. expanded disability status scale, MS duration, patients’ age, fatigue and walking problems. Little evidence exists on the impact of contextual factors. Discussion: Most of the variables identified as associated to or determinants of work-related difficulties can be treated through rehabilitative interventions. It is important that future research addresses not only unemployment issues in MS, but also the amount and severity of problems affecting work-related tasks relying on specific assessment instruments. Implications for Rehabilitation Multiple sclerosis (MS) affects young persons of working age and limitation in work activities is part of MS-related disability, but they are not consistently addressed in MS research: EDSS, MS duration, patients’ age, fatigue, walking problems, cognitive and neuropsychological impairments were the factors most commonly found as associated to or determinant of difficulties with work. Evidence exists that rehabilitation interventions are effective for fatigue, cognitive impairment, mobility and walking difficulties. However, research did not address the impact of rehabilitation programmes on vocational outcomes. Rehabilitation researchers should include MS-specific assessment instruments for work-related difficulties to standardised clinical protocols, so that the benefits of rehabilitation on persons’ ability to work can be demonstrated directly: in this way, cost-benefit balance analyses can be added to the evaluation of treatment effectiveness.
Prediction of Violence on a Psychiatric Intensive Care Unit

The aim of the present study was to identify patients who were at particular risk of violent behaviour, over a period of one month in a psychiatric high dependency unit, and to examine whether particular patients could be identified at admission who would subsequently be violent. Medical records, and other documents for 52 inpatients were included. Demographic, historical and clinical data available at admission were noted. All violent incidents were recorded and classified. Seventeen of 52 patients committed physical violence, usually to the staff. Most incidents were carried out by a small number of individuals. Identifying the violent, using variables available at admission, was not possible. The ward admitted a group with a subsequent high rate of violence. Prediction within this high-risk group was not possible. Measures aimed at preventing violence on a local secure ward should apply to all patients and should not be targeted just at those that would appear to be the most likely to be violent.