Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel therapeutic strategies for stroke: The role of autophagy

Abstract Autophagy is an important biological mechanism involved in the regulation of numerous fundamental cellular processes that are mainly associated with cellular growth and differentiation. Autophagic pathways are vital for maintaining cellular homeostasis by enhancing the turnover of nonfunctional proteins and organelles. Neuronal cells, like other eukaryotic cells, are dependent on autophagy for neuroprotection in response to stress, but can also induce cell death in cerebral ischemia. Recent studies have demonstrated that autophagy may induce neuroprotection following acute brain injury, including ischemic stroke. However in some special circumstances, activation of autophagy can induce cell death, playing a deleterious role in the etiology and progression of ischemic stroke. Currently, there are no therapeutic options against stroke that demonstrate efficient neuroprotective abilities. In the present work, we will review the significance of autophagy in the context of ischemic stroke by first outlining its role in ischemic neuronal death. We will also highlight the potential therapeutic applications of pharmacological modulators of autophagy, including some naturally occurring polyphenolic compounds that can target this catabolic process. Our findings provide renewed insight on the mechanism of action of autophagy in stroke together with potential neuroprotective compounds, which may partially exert their function through enhancing mitochondrial function and attenuating damaging autophagic processes.
Dental caries experience in relation to body mass index and anthropometric measurements of rural children of Nellore district: A cross-sectional study

Context: The relationship between body mass index (BMI) and dental caries consists of multiple contributing factors. There have been no studies documented in the literature in this part of rural India assessing the prevalence of dental caries in relation to BMI. Hence, an attempt was made to study dental caries in relation to BMI and anthropometric measurements. Aims: The aims were to study dental caries experience in relation to BMI and anthropometric measurements of rural children in Nellore district. Settings and Design: A descriptive cross-sectional study was carried out in Nellore city. Subjects and Methods: A total of 1500 6- and 12-year-old children were examined. Dental caries was examined using the WHO dentition status criteria (1997) and 1-day diet chart was collected from each child followed by collection of anthropometric data. Statistical Analysis Used: Statistical analysis was performed using Chi-square test, Fisher's exact test, and Spearman's correlation test. Results: In the present study, out of all the participants, 59.2% of low weight children, 41.3% of normal weight children, and 25.7% of overweight-obese children were having dental caries. Dental caries was more among low weight children compared to normal weight and overweight-obese children and was statistically significant. Conclusions: All the anthropometric measurements were positively correlated with dental caries except height for age and BMI for age. There was an inverse graded association between the height for age and BMI for age with dental caries in 6- and 12-year-old children.
LncRNA BRE-AS1 interacts with miR-145-5p to regulate cancer cell proliferation and apoptosis in prostate carcinoma and has early diagnostic values

Long non-coding RNA (LncRNA) BRE-AS1 has recently proven to be a tumor suppressor in lung cancer. The present study aimed to investigate the involvement of lncRNA BRE-AS1 in prostate carcinoma (PC). In the present study we found that plasma BRE-AS1 and miR-145-5p were both down-regulated in PC patients than in healthy controls. Down-regulation of BRE-AS1 and miR-145-5p effectively distinguished early-stage PC patients from healthy controls. A significant and positive correlation between BRE-AS1 and miR-145–5p was only found in PC patients. BRE-AS1 overexpression mediated miR-145-5p up-regulation in PC cells, while miR-145-5p overexpression did not significantly affect BRE-AS1. Overexpression of BRE-AS1 and miR-145-5p led to inhibited proliferation and promoted apoptosis of PC cells. miR-145-5p inhibitor attenuated the effects of BRE-AS1 overexpression on cancer cell behaviors. Therefore, lncRNA BRE-AS1 may regulate cancer cell proliferation and apoptosis in PC by interacting with miR-145-5p.
Effect of Multidrug-Resistant 1 (MDR1) and CYP3A4*1B Polymorphisms on Cyclosporine-Based Immunosuppressive Therapy in Renal Transplant Patients

Background Immunosuppressive drugs such as cyclosporine A (CsA) are characterized by a narrow therapeutic range and high interindividual pharmacokinetic variations. Therefore, the effective monitoring of drug serum level is crucial for successful therapy. This variability can be caused by polymorphisms in genes encoding drug transporters and enzymes responsible for biotransformation. The aim of this study was to determine the relationship between CYP3A4*1B and MDR1 polymorphisms and dose requirements to achieve the target therapeutic range for CsA. Material/Method The study group consisted of 184 patients after kidney transplantation who were treated with immunosuppressive therapy. The MDR1 3435C>T and CYP3A4*1B polymorphisms were determined by the real-time PCR using the LightCycler® 480 device (Roche Diagnostics). Results Patients with the CYP3A4*1/*1 genotype received the lowest mean dose of CsA compared to CYP3A4*1/*1B, and had a higher average drug concentration in the blood. In the case of MDR1 3435C>T polymorphism, we observed that patients with the CC genotype received lower doses of CsA than patients with the CT and TT genotypes. Average drug concentration in the blood was comparable to individuals with different MDR-1 genotypes. Analysis of dependence between both polymorphisms and concentration/dose ratio showed no statistically significant differences. Conclusions The characterization of CYP3A4*1B and 3435C>T MDR1 polymorphism cannot provide useful guidance for individualizing CsA dosages in renal transplant patients by indicating the optimal dose of these drugs without exposing patients to possible adverse effects associated mainly with nephrotoxicity.
Relationship of callosities of the forefoot with foot deformity, Health Assessment Questionnaire Disability Index, and joint damage score in patients with rheumatoid arthritis

Abstract Objectives: We aimed to investigate the relationship of callosities of the forefoot with foot deformity, the Health Assessment Questionnaire Disability Index (HAQ-DI) and modified total Sharp score (TSS) in patients with rheumatoid arthritis (RA). Methods: A total of 202 patients and 404 feet were enrolled. We examined the prevalence of callosities. Clinical data included the HAQ-DI, TSS, hallux valgus angle (HVA), and calcaneal pitch angle (CPA). The analysis of factors associated with callosities of the forefoot was performed by comparing patients with and without callosities of the forefoot. Results: The prevalence of callosities was 31.2% of all patients and 24.0% of all feet. The patients with callosities of the forefoot had significantly higher TSS of the foot. The presence of callosities affected the HAQ-DI walking score. HVA and CPA were identified as being associated with callosities of the forefoot. Analyzing from the cutoff values, the odds ratios of HVA, CPA, and HVA and (combined) CPA were 4.64, 1.73, and 2.99, respectively. Conclusion: Hallux valgus and flatfoot were related to callosities of the forefoot in RA. This study suggested that to prevent callosities of the forefoot, early diagnosis and foot care for hallux valgus and flatfoot are needed in daily practice.
Evaluation of an In-Ear Sensor for Quantifying Head Impacts in Youth Soccer

Background: Wearable sensor systems have the potential to quantify head kinematic responses of head impacts in soccer. However, on-field use of sensors (eg, accelerometers) remains challenging, owing to poor coupling to the head and difficulties discriminating low-severity direct head impacts from inertial loading of the head from human movements, such as jumping and landing. Purpose: To test the validity of an in-ear sensor for quantifying head impacts in youth soccer. Study Design: Descriptive laboratory study. Methods: First, the sensor was mounted to a Hybrid III headform and impacted with a linear impactor or a soccer ball. Peak linear acceleration (PLA), peak rotational acceleration (PRA), and peak rotational velocity (PRV) were obtained from both systems; random and systematic errors were calculated with Hybrid III as reference. Then, 6 youth soccer players wore sensors and performed a structured training protocol, including heading and nonheading exercises; they also completed 2 regular soccer sessions. For each accelerative event recorded, PLA, PRA, and PRV outputs were compared with video recordings. Receiver operating characteristic curves were used to determine the sensor’s discriminatory capacity in both on-field settings, establishing cutoff values for predicting outcomes. Results: For the laboratory tests, the random error was 11% for PLA, 20% for PRA, and 5% for PRV; the systematic error was 11%, 19%, and 5%, respectively. For the structured training protocol, heading events resulted in higher absolute values (PLA = 15.6g± 11.8g) than nonheading events (PLA = 4.6g± 1.2g); the area under the curve was 0.98 for PLA. In regular training sessions, the area under the curve was >0.99 for PLA. A 9g cutoff value yielded a positive predictive value of 100% in the structured training protocol versus 65% in the regular soccer sessions. Conclusion: The in-ear sensor displayed considerable random error and substantially overestimated head impact exposure. Despite the sensor’s excellent on-field accuracy for discriminating headings from other accelerative events in youth soccer, absolute values must be interpreted with caution, and there is a need for secondary means of verification (eg, video analysis) in real-life settings. Clinical Relevance: Wearable sensor systems can potentially provide valuable insights into head impact exposures in contact sports, but their limitations require careful consideration.
Women’s Experiences and Perceptions of Depression in India: A Metaethnography

In India, social determinants of health, including poverty, domestic violence, and inadequate social support disproportionately affect women, leaving them more vulnerable to depression than men. We conducted a metaethnography to synthesize qualitative data from 13 studies (1987–2017) that explored women’s experiences and perceptions of depression in India. We used a feminist standpoint to critically examine how gender shapes these experiences and perceptions. Indian women’s experiences of depression were embedded in their social worlds. Women perceived interpersonal conflict, caregiving burden, domestic violence, financial insecurity, adverse reproductive events and widowhood as causes of depression. Women used cultural expressions to describe physical, emotional, and cognitive distress. The detrimental impact of discriminatory social conditions, gender inequalities, and traditional gender roles on Indian women’s mental health highlights the need for gender-sensitive mental health research and practice that can attend to women’s sociocultural context and promote values of gender equality and social justice.
Pathologising diversity: medical websites offering female genital cosmetic surgery in Australia

Abstract Female genital cosmetic surgery (FGCS) is increasingly popular. Medical organisations report concern about adverse outcomes and inadequate clinical indications. Given the Internet’s role in health decisions, we aimed to discover what was being communicated about FGCS on Australian provider websites. Thematic analysis of 31 prominent websites identified six themes: seeking aesthetic perfection; resisting natural diversity; gaining from FGCS; indications for surgery; a simple procedure; and ethical practice. Desirable vulvas were represented as ‘neat’ and ‘youthful’. Sites promoted a discourse in which to be ‘feminine’ means having no visible sex organs, consistent with the historical repression of women’s sexuality. FGCS was constructed as a simple and empowering solution, improving women’s comfort, hygiene, self-esteem and sexual relationships. The apparent primary concern was commercial. Attention was rarely paid to ethics. Sites reinforced women’s responsibility to strive for aesthetic perfection, implied that vulvar diversity is pathological, made unfounded claims for the benefits of FGCS and downplayed adverse consequences. Findings have implications for public health and medical authorities in countries where FGCS is practised and advertised. Enforcing the first do no harm principle would reduce websites’ capacity to promote discourses and practices that damage women’s bodies and wellbeing.
Environmental Variations in Mycobacterium ulcerans Transcriptome: Absence of Mycolactone Expression in Suboptimal Environments

Buruli ulcer is a neglected tropical infectious disease, produced by the environmentally persistent pathogen Mycobacterium ulcerans (MU). Neither the ecological niche nor the exact mode of transmission of MU are completely elucidated. However, some environmental factors, such as the concentration in chitin and pH values, were reported to promote MU growth in vitro. We pursued this research using next generation sequencing (NGS) and mRNA sequencing to investigate potential changes in MU genomic expression profiles across in vitro environmental conditions known to be suitable for MU growth. Supplementing the growth culture medium in either chitin alone, calcium alone, or in both chitin and calcium significantly impacted the MU transcriptome and thus several metabolic pathways, such as, for instance, those involved in DNA synthesis or cell wall production. By contrast, some genes carried by the virulence plasmid and necessary for the production of the mycolactone toxin were expressed neither in control nor in any modified environments. We hypothesized that these genes are only expressed in stressful conditions. Our results describe important environmental determinants playing a role in the pathogenicity of MU, helping the understanding of its complex natural life cycle and encouraging further research using genomic approaches.
Antioxidant Activities of Vaccinium vitis-idaea L. Leaves within Cultivars and Their Phenolic Compounds

Lingonberry leaves are the subject of numerous studies because of antioxidant properties, positive influence on the health and potential use in the prevention and treatment of chronic diseases. In this work, the radical scavenging, reducing, chelating activities, and phenolic composition of ten lingonberry leaves cultivars, one subspecies, and one variety were investigated. Furthermore, the antioxidant activity of individual phenolic compounds, that can be found in lingonberry leaves, were analyzed, and structure-activity relationship was determined. Wide diversity for phenolic profile and antioxidant properties of lingonberry leaves has been observed in the present material. Cultivars ‘Kostromskaja rozovaja’, ‘Rubin’, and Vaccinium vitis-idaea var. leucocarpum surpassed all others tested cultivars and lower taxa by contents of phenolic compounds and antioxidant activity. Leaves of lingonberry cultivars and lower taxa are rich in arbutin, flavonol glycosides, proanthocyanidins, and the latter were considered to be the major contributor to antioxidant properties of lingonberry leaves.
Age and Sex-Dependent Differences in the Neurochemical Characterization of Calcitonin Gene-Related Peptide-Like Immunoreactive (CGRP-LI) Nervous Structures in the Porcine Descending Colon

Neurons of the enteric nervous system (ENS) may undergo changes during maturation and aging, but knowledge of physiological stimuli-dependent changes in the ENS is still fragmentary. On the other hand, the frequency of many ENS-related intestinal illnesses depends on age and/or sex. The double immunofluorescence technique was used to study the influence of both of these factors on calcitonin gene-related peptide (CGRP)—positive enteric nervous structures—in the descending colon in young and adult female and castrated male pigs. The influence of age and gender on the number and neurochemical characterization (i.e., co-localization of CGRP with substance P, nitric oxide synthase, galanin, cocaine- and amphetamine-regulated transcript peptide and vesicular acetylcholine transporter) of CGRP-positive nerve structures in the colonic wall has been shown. These observations strongly suggest the participation of CGRP in adaptive processes in the ENS during GI tract maturation. Moreover, although the castration of males may mask some aspects of sex-dependent influences on the ENS, the sex-specific differences in CGRP-positive nervous structures were mainly visible in adult animals. This may suggest that the distribution and exact role of this substance in the ENS depend on the sex hormones.
Evaluation of the AGE/sRAGE Axis in Patients with Multiple Myeloma

Glycative stress influences tumor progression. The aim of the present study was to evaluate the advanced glycation end products/soluble receptor of advanced glycation end products (AGE/sRAGE) axis in patients with multiple myeloma (MM). Blood samples were taken from 19 patients affected by MM and from 16 sex-matched and age-matched healthy subjects. AGE and sRAGE axis were dosed in patients with MM and matched with controls. AGEs were measured by spectrofluorimetric methods. Blood samples for the determination of sRAGE were analyzed by ELISA. AGE levels were significantly reduced in patients with respect to controls. Instead, sRAGE was significantly elevated in patients affected by MM compared to healthy subjects. Moreover, we showed that there was a statistically significant difference in sRAGE according to the heavy and light chain. IgA lambda had significantly higher sRAGE values than IgA kappa, IgG kappa, and IgG Lambda MM patients. From our data emerges the role of the sRAGE/AGE axis in MM. Since AGE is a positive regulator of the activity of RAGE, circulating sRAGE concentrations may reflect RAGE expression and may be raised in parallel with serum AGE concentrations as a counter-system against AGE-caused tissue damage. Serum concentrations of AGE and sRAGE could therefore become potential therapeutic targets.
Probing initial transient oligomerization events facilitating Huntingtin fibril nucleation at atomic resolution by relaxation-based NMR

Significance Huntington’s disease is a fatal neurodegenerative condition arising from polyglutamine expansion within the Huntingtin protein leading to fibril accumulation in neurons. The initial multimerization events occur on the submillisecond timescale and involve sparsely populated species that can be probed at atomic resolution by NMR. Using a minimalistic construct comprising the N-terminal amphiphilic domain and seven glutamines, we uncover a branched oligomerization pathway, one leading to a tetramer comprising a dimer of coiled-coil helical dimers, and the other resulting in a nonproductive, partially helical, dimer. The results illuminate the contribution of the N-terminal amphiphilic domain in prenucleation events that precede fibril formation. The N-terminal region of the huntingtin protein, encoded by exon-1, comprises an amphiphilic domain (httNT), a polyglutamine (Qn) tract, and a proline-rich sequence. Polyglutamine expansion results in an aggregation-prone protein responsible for Huntington’s disease. Here, we study the earliest events involved in oligomerization of a minimalistic construct, httNTQ7, which remains largely monomeric over a sufficiently long period of time to permit detailed quantitative NMR analysis of the kinetics and structure of sparsely populated (≲2%) oligomeric states, yet still eventually forms fibrils. Global fitting of concentration-dependent relaxation dispersion, transverse relaxation in the rotating frame, and exchange-induced chemical shift data reveals a bifurcated assembly mechanism in which the NMR observable monomeric species either self-associates to form a productive dimer (τex ∼ 30 μs, Kdiss ∼ 0.1 M) that goes on to form a tetramer (τex≲25 μs; Kdiss ∼ 22 μM), or exchanges with a “nonproductive” dimer that does not oligomerize further (τex ∼ 400 μs; Kdiss ∼ 0.3 M). The excited state backbone chemical shifts are indicative of a contiguous helix (residues 3–17) in the productive dimer/tetramer, with only partial helical character in the nonproductive dimer. A structural model of the productive dimer/tetramer was obtained by simulated annealing driven by intermolecular paramagnetic relaxation enhancement data. The tetramer comprises a D2 symmetric dimer of dimers with largely hydrophobic packing between the helical subunits. The structural model, validated by EPR distance measurements, illuminates the role of the httNT domain in the earliest stages of prenucleation and oligomerization, before fibril formation.
Congenital Zika Syndrome: The Main Cause of Death and Correspondence Between Brain CT and Postmortem Histological Section Findings

Abstract In the present case series, the cause of death of infants diagnosed with congenital Zika syndrome (CZS) was lung disease (pneumonia and sepsis with massive pulmonary aspiration), probably secondary to dysphagia and reflux. The main findings in infants with a confirmed diagnosis of CZS who died were as follows: (1) calcification and hypoplasia of the lentiform nuclei, hypoplasia of the caudate nuclei, and calcification at the cortical-subcortical junction was noted in all cases (100%) and calcification of the caudate nuclei was noted in 66.7% of cases; (2) calcification in the brainstem and along the lateral wall of the lateral ventricles was noted in only the case with arthrogryposis (33.3%); and (3) lesions in the posterior fossa (hypoplasia of the brainstem and cerebellum) were noted in two cases (66.7%), including the case with arthrogryposis. The findings concerning calcifications and brain malformations obtained from non-contrast computed tomography (CT) demonstrated good agreement with findings obtained from the postmortem pathological analysis; however, CT failed to detect discontinuity of the pia mater with heterotopia, invasion of the cerebral tissue into the subarachnoid space, and discontinuity of the ependyma in the lateral ventricles with gliosis; this last feature was only imaged in the most severe case of extreme microcephaly with a simplified gyral pattern. Only histopathology showed grouped calcifications associated with scattered calcifications suggestive of the neuron morphology.