Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional electrical stimulation following nerve injury in a large animal model

Introduction: Controversy exists over the effects of functional electrical stimulation (FES) on reinnervation. We hypothesized that intramuscular FES would not delay reinnervation after recurrent laryngeal nerve (RLn) axonotmesis. Methods: RLn cryo‐injury and electrode implantation in ipsilateral posterior cricoarytenoid muscle (PCA) were performed in horses. PCA was stimulated for 20 weeks in eight animals; seven served as controls. Reinnervation was monitored through muscle response to hypercapnia, electrical stimulation and exercise. Ultimately, muscle fiber type proportions and minimum fiber diameters, and RLn axon number and degree of myelination were determined. Results: Laryngeal function returned to normal in both groups within 22 weeks. FES improved muscle strength and geometry, and induced increased type I:II fiber proportion (p = 0.038) in the stimulated PCA. FES showed no deleterious effects on reinnervation. Discussion: Intramuscular electrical stimulation did not delay PCA reinnervation after axonotmesis. FES can represent a supportive treatment to promote laryngeal functional recovery after RLn injury. Muscle Nerve 59:717–725, 2019
Health Symptoms Associated with Pesticides Exposure among Flower and Onion Pesticide Applicators in Arusha Region

Introduction: Pesticides are extensively used in agriculture to control harmful pests and prevent crop yield losses or product damage. In Tanzania several studies have been conducted on health effects of pesticides on agricultural workers. However, there are few studies on neurological health symptoms associated with pesticide exposure in flower and onion farms. Objective: The objective of this cross-sectional study was to assess health symptoms associated with pesticide exposure among flower and onion pesticide applicators in the Arusha region, Tanzania. Methods: Data on demographic variables and health symptoms associated with pesticide exposure were collected from 140 males who were employed in spraying pesticides on flower and onion farms in Arusha, Meru and Karatu districts between April and May 2017. The study participants were interviewed using a structured questionnaire with questions focusing sociodemographic characteristics, occupation, pesticide exposure, common type of pesticide used in the area and neurological symptoms experienced during and after pesticide spraying. To determine the intensity of pesticide exposure, acetylcholinesterase assay was done by using the Test-mate Model 400 device with a photometric sensor. Results: Ninety-five percent of pesticide applicators reported handling organophosphate pesticides. Body weakness was the most frequently reported neurological symptom (57.1%) followed by perspiration and headache (40.7%), poor appetite and depression (29.3%) and irritation (26.4%). About 27% of pesticide applicators had an acetylcholinesterase level below the limit value. Conclusion: A high proportion of neurological health symptoms and cholinesterase test depression was noted among pesticide applicators in both farms. There is a need to conduct further studies to ascertain causality for such high instances of neurological symptoms.
Pulmonary , gastrointestinal and urogenital pharmacology Therapeutic e ff ects of the rhSOD 2-Hirudin fusion protein on bleomycin-induced pulmonary fi brosis in mice

Idiopathic pulmonary fibrosis (IPF) is a disease with a poor prognosis and high mortality, posing a major threat to human health. Increased levels of inflammatory cytokines, reactive oxygen species and coagulation cascade have been extensively reported in IPF. We previously fused Hirudin and human manganese superoxide dismutase (hSOD2) to generate a dual-feature fusion protein, denoted as rhSOD2-Hirudin fusion protein. In this study, 3(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) and Hydroxyproline (HYP) assays were used to investigate the effects of rhSOD2-Hirudin protein on thrombin-induced fibroblast proliferation and collagen accumulation in vitro. Subsequently, the mice model of pulmonary fibrosis induced by bleomycin was used for evaluating the anti-inflammatory and anti-fibrotic effects of rhSOD2Hirudin protein in vivo. Results showed that rhSOD2-Hirudin protein could inhibit the proliferation of fibroblasts and reduce the HYP production in vitro by inhibiting the activity of thrombin. In vivo experiments showed that lung inflammation and fibrosis were significantly decreased in rhSOD2-Hirudin protein-treated mice. Furthermore, rhSOD2-Hirudin protein treatment reduced profibrotic protein and gene expression while reducing the number of inflammatory cells in the lung. In conclusion, rhSOD2-Hirudin protein can effectively attenuate pulmonary fibrosis in vitro and in vivo, mainly by inhibiting the activity of thrombin meanwhile increasing SOD2 levels prevent cells from being damaged by reactive oxygen species, thereby mitigating IPF progression. This study provided important information on the feasibility and efficacy of rhSOD2-Hirudin protein as a novel therapeutic agent for IPF.
Resolution of human ribosomal DNA occurs in anaphase, dependent on tankyrase 1, condensin II, and topoisomerase IIα

In this paper by Daniloski et al., the authors investigated the timing and mechanism of the resolution of the ribosomal DNA (rDNA) repeats during chromosome segregation in human cells. They found that resolution of human rDNA occurs in anaphase after the bulk of the genome, dependent on tankyrase 1, condensin II, and topoisomerase II.
A Proposed Inflammatory Score of Circulating Cytokines/Adipokines Associated with Resistant Hypertension, but Dependent on Obesity Parameters

Background There is evidence that subclinical systemic inflammation is present in resistant hypertension (RHTN). Objective The aim of the study was to develop an integrated measure of circulating cytokines/adipokines involved in the pathophysiology of RHTN. Methods RHTN (n = 112) and mild to moderate hypertensive (HTN) subjects (n=112) were studied in a cross-sectional design. Plasma cytokines/adipokines (TNF-alpha, interleukins [IL]-6, -8, -10, leptin and adiponectin) values were divided into tertiles, to which a score ranging from 1 (lowest tertile) to 3 (highest tertile) was assigned. The inflammatory score (IS) of each subject was the sum of each pro-inflammatory cytokine scores from which anti-inflammatory cytokines (adiponectin and IL-10) scores were subtracted. The level of significance accepted was alpha = 0.05. Results IS was higher in RHTN subjects compared with HTN subjects [4 (2-6) vs. 3 (2-5); p = 0.02, respectively]. IS positively correlated with body fat parameters, such as body mass index (r = 0.40; p < 0.001), waist circumference (r = 0.30; p < 0.001) and fat mass assessed by bioelectrical impedance analysis (r = 0.31; p < 0.001) in all hypertensive subjects. Logistic regression analyses revealed that IS was an independent predictor of RHTN (OR = 1.20; p = 0.02), independent of age, gender and race, although it did not remain significant after adjustment for body fat parameters. Conclusion A state of subclinical inflammation defined by an IS including TNF-alpha, IL-6, IL-8, IL-10, leptin and adiponectin is associated with obese RHTN. In addition, this score correlates with obesity parameters, independently of hypertensive status. The IS may be used for the evaluation of conditions involving low-grade inflammation, such as obesity-related RHTN. Indeed, it also highlights the strong relationship between obesity and inflammatory process.
The Contribution of Pluripotent Stem Cell (PSC)-Based Models to the Study of Fragile X Syndrome (FXS)

Fragile X syndrome (FXS) is the most common heritable form of cognitive impairment. It results from a deficiency in the fragile X mental retardation protein (FMRP) due to a CGG repeat expansion in the 5′-UTR of the X-linked FMR1 gene. When CGGs expand beyond 200 copies, they lead to epigenetic gene silencing of the gene. In addition, the greater the allele size, the more likely it will become unstable and exhibit mosaicism for expansion size between and within tissues in affected individuals. The timing and mechanisms of FMR1 epigenetic gene silencing and repeat instability are far from being understood given the lack of appropriate cellular and animal models that can fully recapitulate the molecular features characteristic of the disease pathogenesis in humans. This review summarizes the data collected to date from mutant human embryonic stem cells, induced pluripotent stem cells, and hybrid fusions, and discusses their contribution to the investigation of FXS, their key limitations, and future prospects.
Improving GP communication in consultations on medically unexplained symptoms: a qualitative interview study with patients in primary care.

BACKGROUND Many GPs find the care of patients with medically unexplained symptoms (MUS) challenging. Patients themselves are often not satisfied with the care they receive. AIM To explore the problems patients with MUS experience in communication during consultations, with the aim of improving such consultations DESIGN AND SETTING: A qualitative analysis of semi-structured interviews. METHOD GP consultations were videorecorded and the GPs were asked immediately afterwards whether MUS were presented. Patients in these MUS consultations were asked to reflect on the consultation in a semi-structured interview while watching a recording of their own consultation. RESULTS Of the 393 videorecorded consultations, 43 contained MUS. Patients who did identified six categories of problems. First, they reported a mismatch between the GP's and their own agenda. Second, patients indicated that the GP evoked an uncomfortable feeling in them during the consultation. Third, they found that GPs did not provide a specific management plan for their symptoms. Fourth, patients indicated that the GP was not well prepared for the consultation. Fifth, they perceived prejudices in the GP during the consultation. Finally, one patient found that the GP did not acknowledge a limited understanding of the origin of the symptoms. CONCLUSION According to patients, GPs can improve their consultations on MUS by making genuine contact with their patients, by paying more attention to the patient's agenda, and by avoiding evoking uncomfortable feelings and displaying prejudices. They should prepare their consultations and focus on the issues that matter to patients, for example, symptom management. GPs should be honest to patients when they do not understand the origin of symptoms.
Genetic Diversity of Serum Proteins in Some Muslim Populations of India

Abstract The Muslim population of India is known for its historical and socioreligious significance. Literature on the genetic structure of this segment of India's population is scanty. Therefore we have investigated the allele frequency distribution of haptoglobin (HP) and transferrin (TF) phenotypes among the Muslims to explore the genetic diversity of the Muslim immigrant populations of Aligarh. Aligarh is a city in Uttar Pradesh, India (latitude 27°54′N, longitude 78°5′E), situated 130 km southeast of Delhi. The population is mainly represented by Muslim immigrants from the eastern, northern, southern, and western regions of India and from abroad. Differences in allele frequencies of both HP and TF were statistically significant for the population of immigrants from western India and insignificant for others. The alleles HP*2 and TF*C2 show maximum frequencies in the southern population (0.882 and 0.822, respectively) followed by the eastern population (0.862 and 0.807) and the northern population (0.806 and 0.650). In the northern population a third allele, TF*C3, is also detected, with a mean frequency of 0.044. The average heterozygosity (HL) values for HP and TF are 0.273 and 0.361, respectively, and the pooled values for gene diversity parameters for both loci are HT = 0.4294 ± 0.0351, HS = 0.4225 ± 0.0271, and DST = 0.0069 ± 0.0051. The pooled GST value is 0.0153 ± 0.0108. The magnitude of these values indicates genetic similarity among the investigated populations. Our AMOVA results also demonstrate similarity among populations of the same geographic region. However, we note substantial differentiation among different regions (ΦCT = 0.221). The UPGMA dendrogram shows a cluster between the eastern and southern populations, to which the northern population joins. Our results reveal genetic similarity among different immigrant populations, with the western population being the most distant. Therefore the present study on culturally, geographically, and linguistically different endogamous groups of Muslims may have significance in understanding their genetic relationship.
Clonotypic Diversity of the T-cell Receptor Corroborates the Immature Precursor Origin of Cutaneous T-cell Lymphoma

Purpose: Mycosis fungoides is one of the most common types of extranodal T-cell lymphomas, considered to be caused by malignant transformation of the mature T cells residing in the skin. However, some clinical observations such as the multifocal distribution of mycosis fungoides lesions or patterns of relapse after radiotherapy are not readily explainable by the mature T-cell origin theory. Experimental Design: We have performed a detailed analysis of T-cell receptor (TCR) rearrangements in single malignant cells and in biopsies from mycosis fungoides tumors composed of >80% of malignant cells using next-generation sequencing (NGS) to pinpoint the relationship between neoplastic cells in mycosis fungoides. We have also aimed to detect malignant, circulating T-cell by whole blood TCR sequencing. Results: We found a substantial clonal heterogeneity in the mycosis fungoides samples with regards to TCR, and we demonstrated that lymphoma cells harboring identical TCRγ sequences may harbor different TCRα and β sequences. Lack of absolute TCRα, -β, -γ monoclonality was further confirmed by TCR amplification and sequencing from microdissected lymphoma cells. We have also found the TCR rearrangements characteristic for lymphoma cells in patients' peripheral blood despite the lack of leukemic blood involvement; however, the circulating TCRγ clonotype did not always represent the dominant cutaneous clonotype. Conclusions: These findings can be explained by a model where malignant transformation takes place during early T-cell development giving rise to circulating premalignant clones, which home to the skin producing clinically apparent lesions of cutaneous lymphoma. Therapeutic strategies in T-cell lymphoma should therefore target those early lymphoma precursor cells.
Transcranial Direct Current Stimulation Reduces Craving in Substance Use Disorders: A Double-blind, Placebo-Controlled Study.

OBJECTIVES The use of transcranial direct current stimulation (tDCS) in addiction disorders is still on its rise in comparison with pharmacological and psychotherapeutic strategies that still show low level of evidence. In this study, we aimed to evaluate the efficacy of the anodic tDCS for the short-term treatment of substance craving and other psychiatric symptoms. METHODS In this randomized, double-blind, sham-controlled trial, inclusion criteria included the diagnosis of substance use disorder and/or gambling disorder. The protocol includes 5 consecutive days of active or sham tDCS session. Cathode was placed over the left dorsolateral prefrontal cortex. Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Young Mania Rating Scale, Barratt Impulsiveness Scale, South Oaks Gambling Screen, and visual analog scale (VAS) 1 to 10 for craving were administered at the baseline (T0) and after 5 days of treatment (T1). RESULTS Thirty-four treatment-seeking subjects were randomized to sham (n = 16) and active stimulation (n = 18) groups. A statistically significant reduction of values at T1 was found in all subjects considering VAS (P < 0.001), Hamilton Depression Rating Scale (P < 0.001), Hamilton Anxiety Rating Scale (P < 0.001), and Barratt Impulsiveness Scale 11 (P = 0.032). A significant reduction for VAS craving in favor of the active stimulation (P = 0.011) was found. CONCLUSIONS Our findings reveal a statistically significant rapid reduction of craving in the active tDCS group on the right dorsolateral prefrontal cortex with respect to sham group, confirming the scientific literature trend. Large samples, with maintenance tDCS therapy and long-term follow-up, are required to establish the potential of this noninvasive and easily delivered brain stimulation strategy.
Estimating Disease Prevalence and Incidence Using Administrative Data: Some Assembly Required

The prevalence and incidence of a disease are among the most fundamental measures in epidemiology. Prevalence is a measure of the burden of disease in a population in a given location and at a particular time, as represented in a count of the number of people affected. Counts of the number of people with a disease are required to plan appropriately for their healthcare needs. For example, large numbers of patients with rheumatoid arthritis will necessitate training and staffing with more rheumatologists than if the number of patients with the disease was low; similarly, having many patients with osteoarthritis will require more orthopedic surgeons and surgical beds. Prevalence estimates, which adjust these counts to the size of the source population, are also useful clinically in providing context for diagnostic decision making. Knowing that coronary artery disease is much more common than myocarditis is helpful in evaluating patients with anterior chest pain. Prevalence may also be used to compare disease burden across locations or time periods. However, because prevalence is determined by not only the number of persons affected but also their survival, prevalence is a less useful measure than incidence rates in studies of etiology. Incidence rates represent the number of new cases of disease among the number of susceptible persons in a given location and over a particular span of time. The primary value of incidence rates is in studies of disease etiology, by comparing how the rates vary among different subgroups or with different exposures. To provide prevalence and incidence rate estimates that are both reliable and generalizable, studies must include a sample large enough to capture most (if not all) cases and sufficiently distributed, both geographically and sociologically, to be representative of the general population. With uncommon diseases, including most autoimmune rheumatic diseases, the challenge is multiplied … Address correspondence to Dr. M. Ward, Building 10 CRC, Room 4-1339, 10 Center Drive, Bethesda, MD 20892-1468. E-mail: wardm1{at}mail.nih. gov
Sex differences in the relationship between cognitive impairment and overweight or obesity in late life

Abstract The relationship between body weight changes in late life and cognitive function is controversial. We investigated whether weight gain or loss in late life affected cognitive function in community-dwelling older adults over a 3-year period. Our study used data from the Survey of Living Conditions and Welfare Needs of Korean Older Persons and included 3859 subjects (aged ≥65 years) with normal cognition at baseline. At baseline and the 3-year follow-up, body weight and height were measured, and cognitive function was assessed using the mini-mental state examination. Based on their body mass index (BMI) at baseline and follow-up, we divided the subjects into 4 groups: weight gain (baseline BMI <23 kg/m2 and follow-up BMI ≥23 kg/m2); weight loss (baseline BMI ≥23 kg/m2 and follow-up BMI <23 kg/m2); stable overweight/obese (BMI ≥23 kg/m2 at both visits); and stable non-overweight/obese (BMI <23 kg/m2 at both visits). Incidence rates (IRs) of cognitive impairment per 100 persons and IR ratios (IRRs) were calculated for each group and adjusted for confounding variables. At the 3-year follow-up, 610 cases of cognitive impairment (15.8%) were identified. The stable overweight/obese group had the lowest IR (14.0, 95% confidence interval [CI] 12.45–15.71) and was therefore used as the reference group when calculating IRRs for cognitive impairment. When men and women were evaluated separately, IRs between groups were significantly different only for women. The stable non-overweight/obese group (IRR 1.65, 95% CI 1.22–2.22) and the weight gain group (IRR 1.93, 95% CI 1.24–3.01) had higher IRs than those in the stable overweight/obese group. As a gain or loss of adiposity, the IR of the weight gain group (IRR 1.17, 95% CI 0.74–1.84) was not different from that of the stable non-overweight/obese group. Also, the IR of weight loss group (IRR 1.09, 95% CI 0.71–1.67) was not significantly different from that of the stable overweight/obese group. We suggest that overweight or obese older women at baseline had cognitive benefits. However, additional gain or loss of adiposity in late life did not affect the risk of cognitive impairment.
Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio as Prognostic Hematologic Markers of Bell's Palsy: A Meta-analysis.

OBJECTIVE Bell's palsy (BP) is the most common cause of unilateral peripheral facial paralysis, and inflammation has been proposed as the main pathological cause. The study aim was to investigate the relationship between hematologic inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), and BP. DATA SOURCES The following key words were used to search PubMed and Scopus for English language articles: Bell's palsy, facial palsy, facial paresis or facial paralysis, neutrophil, lymphocyte, and platelet. STUDY SELECTION Articles related to BP with NLR or PLR data. DATA EXTRACTION The data included patient profiles, House-Brackmann score, treatment modality, NLR, and PLR. DATA SYNTHESIS Seven articles were selected. A random effect model was used to analyze the aggregated data. Six of these articles that included the NLR and two that included the PLR of BP and control patients were analyzed for the difference between BP and control patients. Three articles that included the NLR of the recovery and nonrecovery groups were analyzed for the relationship between NLR and recovery. CONCLUSIONS The NLR was significantly higher for the BP patients than for the controls. Furthermore, the NLR was significantly lower for the recovery group than for the nonrecovery group. A high NLR was associated with poor prognosis and related to the severity of facial nerve inflammation. There was no significant difference between the PLRs of the BP patients and controls. The NLR, but not the PLR, was found to be a useful prognostic indicator of BP.