Miracle-dz/UniFAR-FTUs huggingface dataset:
Iron Supplementation Therapy, A Friend and Foe of Mycobacterial Infections?

Iron is an essential element that is required for oxygen transfer, redox, and metabolic activities in mammals and bacteria. Mycobacteria, some of the most prevalent infectious agents in the world, require iron as growth factor. Mycobacterial-infected hosts set up a series of defense mechanisms, including systemic iron restriction and cellular iron distribution, whereas mycobacteria have developed sophisticated strategies to acquire iron from their hosts and to protect themselves from iron’s harmful effects. Therefore, it is assumed that host iron and iron-binding proteins, and natural or synthetic chelators would be keys targets to inhibit mycobacterial proliferation and may have a therapeutic potential. Beyond this hypothesis, recent evidence indicates a host protective effect of iron against mycobacterial infections likely through promoting remodeled immune response. In this review, we discuss experimental procedures and clinical observations that highlight the role of the immune response against mycobacteria under various iron availability conditions. In addition, we discuss the clinical relevance of our knowledge regarding host susceptibility to mycobacteria in the context of iron availability and suggest future directions for research on the relationship between host iron and the immune response and the use of iron as a therapeutic agent.
Effects of Long-Term Storage at −80 °C on the Human Plasma Metabolome

High-quality biological samples are required for the favorable outcome of research studies, and valid data sets are crucial for successful biomarker identification. Prolonged storage of biospecimens may have an artificial effect on compound levels. In order to investigate the potential effects of long-term storage on the metabolome, human ethylenediaminetetraacetic acid (EDTA) plasma samples stored for up to 16 years were analyzed by gas and liquid chromatography-tandem mass spectrometry-based metabolomics. Only 2% of 231 tested plasma metabolites were altered in the first seven years of storage. However, upon longer storage periods of up to 16 years and more time differences of few years significantly affected up to 26% of the investigated metabolites when analyzed within subject age groups. Ontology classes that were most affected included complex lipids, fatty acids, energy metabolism molecules, and amino acids. In conclusion, the human plasma metabolome is adequately stable to long-term storage at −80 °C for up to seven years but significant changes occur upon longer storage. However, other biospecimens may display different sensitivities to long-term storage. Therefore, in retrospective studies on EDTA plasma samples, analysis is best performed within the first seven years of storage.
Effects of Cariprazine, Aripiprazole, and Olanzapine on Mouse Fibroblast Culture: Changes in Adiponectin Contents in Supernatants, Triglyceride Accumulation, and Peroxisome Proliferator-Activated Receptor-γ Expression

Background and Objectives: The use of the dopamine-partial agonist subclass (also termed dopamine stabilizers) of atypical antipsychotics for the treatment of negative schizophrenia symptoms and some mood disorders has increased recently. Similar to other second-generation antipsychotics (SGAs), aripiprazole (ARI) and cariprazine (CAR) also influence food intake, but the peripheral effects of these drugs on adipose–tissue homeostasis, including adipokine secretion as well as lipo- and adipogenesis, are not fully elucidated. In this study, we explored the adipocyte-related mechanisms induced by second-generation antipsychotics (SGAs), leading to changes in peripheral signals involved in energy homeostasis. Materials and Methods: CAR, a new SGA, was compared with ARI and olanzapine (OLA), using cell cultures to study adipogenesis, and the expression levels of peroxisome proliferator-activated receptor-γ (PPAR-γ) was measured in adipocytes derived from mouse fibroblasts, by western blotting on days 7, 14, and 21 postinduction. The triglyceride (TG) content of the cells was also evaluated on day 15 using Oil Red O staining, and the adiponectin (AN) content in the cell culture supernatants was quantified on days 7 and 15 by enzyme-linked immunosorbent assay. Cells were treated with two concentrations of ARI (0.5 and 20 µg/mL), OLA (1 and 20 µg/mL), and CAR (0.1 and 2 µg/mL). Results: Both concentrations of ARI and OLA, as well as the lower concentration of CAR, significantly increased the TG contents. The AN levels in the supernatants were significantly increased by the higher concentration of ARI on days 7 and 15 (p < 0.05). Although PPAR-γ levels were not significantly affected by ARI and OLA, the lower concentration of CAR induced a significant time-dependent decrease in PPAR-γ expression (p < 0.05). Conclusions: The in vitro adipogenesis considered from TG accumulation, AN secretion, and PPAR-γ expression was differently influenced by ARI, CAR, and OLA. Understanding the adipocyte-related mechanisms of antipsychotics could contribute to understanding their weight-influencing effect.
Structural Insights into the Molecular Evolution of the Archaeal Exo-β-d-Glucosaminidase

The archaeal exo-β-d-glucosaminidase (GlmA), a thermostable enzyme belonging to the glycosidase hydrolase (GH) 35 family, hydrolyzes chitosan oligosaccharides into monomer glucosamines. GlmA is a novel enzyme in terms of its primary structure, as it is homologous to both GH35 and GH42 β-galactosidases. The catalytic mechanism of GlmA is not known. Here, we summarize the recent reports on the crystallographic analysis of GlmA. GlmA is a homodimer, with each subunit comprising three distinct domains: a catalytic TIM-barrel domain, an α/β domain, and a β1 domain. Surprisingly, the structure of GlmA presents features common to GH35 and GH42 β-galactosidases, with the domain organization resembling that of GH42 β-galactosidases and the active-site architecture resembling that of GH35 β-galactosidases. Additionally, the GlmA structure also provides critical information about its catalytic mechanism, in particular, on how the enzyme can recognize glucosamine. Finally, we postulate an evolutionary pathway based on the structure of an ancestor GlmA to extant GH35 and GH42 β-galactosidases.
Abdominal magnetic resonance imaging: Optimization and artifact suppression

Optimized spin-echo images must contain adequate tissue contrast, which can be realized by selecting proper repetition time, echo time, and flip angle. Although conventional T2-weighted images have long acquisition time and limited signal-to-noise ratio (SNR), multiecho conjugate techniques address both of these problems. SNR, resolution, and anatomic coverage are interrelated issues that must be addressed together. Motion artifact reduction techniques include averaging, physiologic monitoring, gradient-moment nulling, spatial presaturation, and fat suppression. Best results are obtained by combining multiple methods when possible.
A large-scale drug screen identifies selective inhibitors of class I HDACs as a potential therapeutic option for SHH medulloblastoma.

BACKGROUND Medulloblastoma (MB) is one of the most frequent malignant brain tumors of children, and a large set of these tumors is characterized by aberrant activation of the Sonic hedgehog (SHH) pathway. While some tumors initially respond to inhibition of the SHH pathway component Smoothened (SMO), tumors ultimately recur due to downstream resistance mechanisms, indicating a need for novel therapeutic options. METHODS Here we performed a targeted small molecule screen on a stable, SHH-dependent murine MB cell line (SMB21). Comprehensive isotype profiling of histone deacetylase (HDAC) inhibitors was performed, and effects of HDAC inhibition were evaluated both in cell lines sensitive and resistant to SMO inhibition. Lastly, distinct mouse models of SHH MB were used to demonstrate pharmacologic efficacy in vivo. RESULTS A subset of the HDAC inhibitors tested significantly inhibit tumor growth of SMB21 cells by preventing SHH pathway activation. Isotype profiling of HDAC inhibitors, together with genetic approaches suggested that concerted inhibition of multiple class I HDACs is necessary to achieve pathway inhibition. Of note, class I HDAC inhibitors were also efficacious in suppressing growth of diverse SMO inhibitor-resistant clones of SMB21 cells. Finally, we show that the novel HDAC inhibitor Quisinostat targets multiple class I HDACs, is well tolerated in mouse models and robustly inhibits growth of SHH MB cells in vivo as well as in vitro. CONCLUSIONS Our data provide strong evidence that Quisinostat or other class I HDAC inhibitors might be therapeutically useful for patients with SHH MB including those resistant to SMO inhibition.
Menopause Rating Scale: Validation and Applicability in Nepalese Women.

BACKGROUND Menopausal Rating Scale is one of the globally used tools to assess quality of life in menopause and peri-menopause. The aim of this study is to validate the standard menopausal rating scale in Nepalese menopausal women and to test menopausal symptoms during clinical consultation at hospital. METHODS Cross sectional validation study at Paropakar Maternity and Women's Hospital, Thapathali, Kathmandu. Five-step language translation of menopausal rating scale from English to Nepali, questionnaire clarity assessment with gynecologists and Likert scale questionnaire based interview to the clients. Reliability and validity tests applied. Each component of rating scale analyzed. RESULTS Nepali version of menopausal rating scale developed. Acceptable level (Cronbach's Alpha = 0.77) of tools reliability obtained. Barlett's test of sphericity was highly significant and Pearson correlation between variables was significant. Average age of menarche was 15 years, and mean and modal value of menopause was 48 and 50 years respectively. First menopausal symptom was vasomotor flush in 62%, one-forth didn't experience flush, half experienced mild to moderate flush and rest one-fourth had severe to very severe form; 50% had significant sleep, bladder and sexual dysfunction. Three-fourth had vaginal dryness and musculoskeletal problem. One-half had some degree of mental dysfunction. CONCLUSIONS Nepali version of menopausal rating scale developed. Baseline menopausal parameters obtained.
Fish, Shellfish, and Children’s Health: An Assessment of Benefits, Risks, and Sustainability

American children eat relatively little fish and shellfish in comparison with other sources of animal protein, despite the health benefits that eating fish and shellfish may confer. At the same time, fish and shellfish may be sources of toxicants. This report serves to inform pediatricians about available research that elucidates health risks and benefits associated with fish and shellfish consumption in childhood as well as the sustainability of fish and shellfish harvests.
Composite Learning Enhanced Robot Impedance Control

The desired impedance dynamics can be achieved for a robot if and only if an impedance error converges to zero or a small neighborhood of zero. Although the convergence of impedance errors is important, it is seldom obtained in the existing impedance controllers due to robots modeling uncertainties and external disturbances. This brief proposes two composite learning impedance controllers (CLICs) for robots with parameter uncertainties based on whether a factorization assumption is satisfied or not. In the proposed control designs, the convergence of impedance errors, reflected by the convergence of parameter estimation errors and some auxiliary errors, is achieved by using composite learning laws under a relaxed excitation condition. The theoretical results are proven based on the Lyapunov theory. The effectiveness and advantages of the proposed CLICs are validated by simulations on a parallel robot in three cases.
Occupational health surveillance: pulmonary function testing and oxidative stress among photocopying workers in Pakistan.

BACKGROUND The photocopying occupation contributes to various health issues in workers. Elevated levels of oxidative stress have been found to be associated with respiratory problems in occupational workers. The intention of the current research is to evaluate the association between the pulmonary function parameters, a biomarker of oxidative stress, and the photocopying occupation in Lahore, Pakistan. MATERIAL AND METHODS The study was performed on a group of photocopying operators (N = 100) and a control group (N = 100). A structured questionnaire was developed to gather the demographic attributes. Lung function testing was done with the spirometer. The blood lipid peroxides level, as thiobarbituric acid reactive substances (TBARS), was assessed spectrophotometrically. RESULTS A statistically significant reduction was found in the pulmonary function parameters as compared to the control group. In the study group, the prevalence of respiratory symptoms, including cough (31%), sneezing (18%), wheezing (9%) and breathing issues (19%), was high as compared to the control group. A significantly higher plasma TBARS concentration was observed in the photocopying workers. A negative correlation prevailed between FVC (-0.081), FVC% predicted (-0.038) and FEV1 (-0.043), and the duration of exposure. CONCLUSIONS The study showed that the occupational exposure could have a significant effect on the normal pulmonary function and the oxidative potential of well-being. The profound emissions in the vicinity of photocopying centers may be responsible for the variations in the pulmonary function parameters and oxidative stress. Med Pr. 2019;70(4).
Bacterial Community Composition in Central European Running Waters Examined by Temperature Gradient Gel Electrophoresis and Sequence Analysis of 16S rRNA Genes

ABSTRACT The bacterial community composition in small streams and a river in central Germany was examined by temperature gradient gel electrophoresis (TGGE) with PCR products of 16S rRNA gene fragments and sequence analysis. Complex TGGE band patterns suggested high levels of diversity of bacterial species in all habitats of these environments. Cluster analyses demonstrated distinct differences among the communities in stream and spring water, sandy sediments, biofilms on stones, degrading leaves, and soil. The differences between stream water and sediment were more significant than those between sites within the same habitat along the stretch from the stream source to the mouth. TGGE data from an entire stream course suggest that, in the upper reach of the stream, a special suspended bacterial community is already established and changes only slightly downstream. The bacterial communities in water and sediment in an acidic headwater with a pH below 5 were highly similar to each other but deviated distinctly from the communities at the other sites. As ascertained by nucleotide sequence analysis, stream water communities were dominated by Betaproteobacteria (one-third of the total bacteria), whereas sediment communities were composed mainly of Betaproteobacteria and members of the Fibrobacteres/Acidobacteria group (each accounting for about 25% of bacteria). Sequences obtained from bacteria from water samples indicated the presence of typical cosmopolitan freshwater organisms. TGGE bands shared between stream and soil samples, as well as sequences found in bacteria from stream samples that were related to those of soil bacteria, demonstrated the occurrence of some species in both stream and soil habitats. Changes in bacterial community composition were correlated with geographic distance along a stream, but in comparisons of different streams and rivers, community composition was correlated only with environmental conditions.
Erythrocytes as a source of essential lipids for Treponema hyodysenteriae

Mammalian erythrocytes were tested as a nutrient source for the spirochete Treponema hyodysenteriae, the etiologic agent of swine dysentery. Brain heart infusion (BHI) broth did not support growth of T. hyodysenteriae B204 or B78. However, BHI broth supplemented with washed bovine erythrocytes, erythrocyte membranes, or cholesterol was an excellent culture medium for these strains (4 X 10(8) to 10(9) cells per ml, final population densities). Small amounts of cholesterol (3 to 10 micrograms/ml of medium) were required for maximum cell yields of strain B204. Of various sterols and sterol-like compounds tested, cholestanol and sitosterol could substitute for cholesterol. BHI-dehydrated medium extracted with CHCl3-CH3OH (2:1, vol/vol) to remove lipids was used to prepare lipid-depleted culture broth. Lipid-depleted broth supplemented only with cholesterol did not support T. hyodysenteriae B204 growth. However, this same broth supplemented either with vesicles made from cholesterol and phosphatidylcholine or with washed erythrocytes was a good culture medium for the spirochete. Thus, both cholesterol and a phospholipid are needed for T. hyodysenteriae growth in lipid-depleted broth. Mammalian erythrocytes can be used by the spirochete as a source of these lipids.
Retinal miRNA Functions in Health and Disease

The health and function of our visual system relies on accurate gene expression. While many genetic mutations are associated with visual impairment and blindness, we are just beginning to understand the complex interplay between gene regulation and retinal pathologies. MicroRNAs (miRNAs), a class of non-coding RNAs, are important regulators of gene expression that exert their function through post-transcriptional silencing of complementary mRNA targets. According to recent transcriptomic analyses, certain miRNA species are expressed in all retinal cell types, while others are cell type-specific. As miRNAs play important roles in homeostasis, cellular function, and survival of differentiated retinal cell types, their dysregulation is associated with retinal degenerative diseases. Thus, advancing our understanding of the genetic networks modulated by miRNAs is central to harnessing their potential as therapeutic agents to overcome visual impairment. In this review, we summarize the role of distinct miRNAs in specific retinal cell types, the current knowledge on their implication in inherited retinal disorders, and their potential as therapeutic agents.
Brain computer interface prototypes for upper limb rehabilitation: A review of principles and experimental results

In this paper we review and discuss three novel Brain Computer Interface (BCI) prototypes for upper limb motor function rehabilitation after stroke or brain injury, recently developed at the Laboratory for Biomedical Engineering and Technologies, University of Belgrade - School of Electrical Engineering. All three systems combine movement imagery as a control strategy and functional electrical stimulation (FES) for executing the action and delivering sensory feedback. The BCI system I is a hybrid version comprising both steady state visual evoked potentials (SSVEP) and event related desynchronization (ERD) based modalities for automated selection and triggering of three FES patterns for assistance of grasping. This system was tested in 6 healthy subjects, and all of them were able to control the device with positive predictive value in a range 0.7-0.96 and with true positive rate in a range 0.89-1. BCI system II is a cue-based version of ERD-driven BCI for FES control and was tested in 4 subjects that achieved positive predictive value of 1 and true positive rate in a range 0.8-1. BCI system III is asynchronous version of an ERD-operated brain switch for triggering of FES and it was tested in 4 subject with results for positive predictive value and true positive rate in ranges 0.66-0.92 and 0.81-0.94 respectively.
Anticholinergic burden of patients with dementia attending a Psychiatry of Later Life service

Objectives Older adults with dementia are particularly vulnerable to adverse outcomes resulting from anticholinergic use. We aimed to: (i) Examine the anticholinergic burden of patients with dementia attending a Psychiatry of Later Life (PLL) service (ii) Examine concomitant prescription of acetylcholinesterase inhibitors (AChEIs) and anticholinergics and (iii) Compare the Anticholinergic Cognitive Burden (ACB) scale with a recently published composite list of anticholinergics. Methods Retrospective chart review of new referrals with a diagnosis of dementia (n = 66) seen by the PLL service, Tallaght University Hospital, Dublin, Ireland, over a consecutive period of 4 months. Results The mean ACB score was 2.2 (range = 0–9, SD = 2.1). 37.9% (n = 25) had a clinically significant ACB score (>3) and 42.1% (n = 8) of those taking AChEIs had a clinically significant ACB score. A significantly greater number of medications with anticholinergic activity were identified using the composite list versus the traditional ACB scale (2.3 v.1.5, p = 0.001). Conclusions We demonstrated a significant anticholinergic burden amongst patients with dementia attending a specialist PLL service. There was no difference in anticholinergic burden between groups prescribed and not prescribed AChEIs, indicating that these medications are being prescribed without discontinuation of potentially inappropriate medications with anticholinergic activity. The true anticholinergic burden experienced by patients may be underestimated by the use of the ACB score alone, although the clinical significance of this finding is unclear. Calculation of true clinical anticholinergic burden load and its translation to a specific rating scale remains a challenge.
Aspirin plus clopidogrel versus aspirin mono-therapy for ischemic stroke: a meta-analysis

Abstract Objectives. Stroke is a common condition after a transient ischemic attack (TIA) or minor ischemic stroke (IS). Adding clopidogrel to aspirin may yield more beneficial outcomes than aspirin mono-therapy; meanwhile, the risk of bleeding in the acute phase remains poorly understood. Therefore, there is increasing emphasis on the risks and benefits of clopidogrel with aspirin compared with aspirin mono-therapy in an effort to treat TIA/IS. Design. We searched several electronic databases, including PubMed, Cochrane, and Embase, to identify eligible randomized controlled trials (RCTs) based on the index words comparing dual-antiplatelet therapy to aspirin mono-therapy for secondary stroke prevention updated to December, 2018. Results. A total of 11 RCTs met our inclusion criteria. The pooled analysis showed that clopidogrel plus aspirin was associated with a trend toward a reduction in recurrent IS (RR = 0.72, 95%CI = 0.65–0.81, p < .001), but not the recurrent stroke rate (RR = 0.81, 95% CI = 0.63‐1.03, p = .09) than aspirin mono-therapy. There were differences in bleeding episodes (RR = 1.81, 95%CI = 1.65–1.99, p < .001), moderate-severe major bleeding (RR = 1.64, 95% CI = 1.24‐2.16, p = .0005), or mild bleeding (RR = 2.25, 95%CI = 1.54–3.31, p < .001) between the study groups. Meanwhile, no benefit of reducing the risk of intracranial hemorrhage with dual-antiplatelet therapy was found in TIA/IS patients (RR = 1.44, 95% CI = 0.95–2.19, p = .09). Conclusions. The addition of clopidogrel to aspirin for patients with TIA or IS appeared to significantly reduce the risk of IS recurrence with a possible increase in the risk of bleeding compared with aspirin alone.