Miracle-dz/UniFAR-FTUs huggingface dataset:
Ceftriaxone Treatment Affects EAAT2 Expression and Glutamatergic Neurotransmission and Exerts a Weak Anticonvulsant Effect in Young Rats

Epilepsy is a common neurological disorder. Despite the availability of a wide range of antiepileptic drugs, these are unsuccessful in preventing seizures in 20–30% of patients. Therefore, new pharmacological strategies are urgently required to control seizures. Modulation of glutamate uptake may have potential in the treatment of pharmacoresistant forms of epilepsy. Previous research showed that the antibiotic ceftriaxone (CTX) increased the expression and functional activity of excitatory amino acid transporter 2 (EAAT2) and exerted considerable anticonvulsant effects. However, other studies did not confirm a significant anticonvulsant effect of CTX administration. We investigated the impacts of CTX treatment on EAAT expression and glutamatergic neurotransmission, as well its anticonvulsant action, in young male Wistar rats. As shown by a quantitative real-time polymerase chain reaction (qPCR) assay and a Western blot analysis, the mRNA but not the protein level of EAAT2 increased in the hippocampus following CTX treatment. Repetitive CTX administration had only a mild anticonvulsant effect on pentylenetetrazol (PTZ)-induced convulsions in a maximal electroshock threshold test (MEST). CTX treatment did not affect the glutamatergic neurotransmission, including synaptic efficacy, short-term facilitation, or the summation of excitatory postsynaptic potentials (EPSPs) in the hippocampus and temporal cortex. However, it decreased the field EPSP (fEPSP) amplitudes evoked by intense electrical stimulation. In conclusion, in young rats, CTX treatment did not induce overexpression of EAAT2, therefore exerting only a weak antiseizure effect. Our data provide new insight into the effects of modulation of EAAT2 expression on brain functioning.
Establishing neuronal diversity in the spinal cord: a time and a place

ABSTRACT The vertebrate spinal cord comprises multiple functionally distinct neuronal cell types arranged in characteristic positions. During development, these different types of neurons differentiate from transcriptionally distinct neural progenitors that are arrayed in discrete domains along the dorsal-ventral and anterior-posterior axes of the embryonic spinal cord. This organization arises in response to morphogen gradients acting upstream of a gene regulatory network, the architecture of which determines the spatial and temporal pattern of gene expression. In recent years, substantial progress has been made in deciphering the regulatory network that underlies the specification of distinct progenitor and neuronal cell identities. In this Review, we outline how distinct neuronal cell identities are established in response to spatial and temporal patterning systems, and outline novel experimental approaches to study the emergence and function of neuronal diversity in the spinal cord. Summary: This Review summarizes the spatial and temporal gene regulatory patterning systems that produce the diversity and organization of neurons in the vertebrate spinal cord.
Pediatric Pulmonology

Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology, and Genetics, Universidad de La Laguna, San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Universidad de La Laguna, San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain Department of Veterinary Medicine, University of Cambridge, Cambridge, UK Department of Medicine, University of California, San Francisco, San Francisco, California Bay Area Pediatrics, Oakland, California Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain Genomics Division, Instituto Tecnológico y de Energías Renovables (ITER), Granadilla, Santa Cruz de Tenerife, Spain Instituto de Tecnologías Biomédicas (ITB), Universidad de La Laguna, San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain
Comparison of the Effect of Two Hyaluronic Acid Preparations on Fibroblast and Endothelial Cell Functions Related to Angiogenesis

Hyaluronic acid (HA) is used in substitutive and aesthetic medicine with various applications. Ultrapure absorbable HA (Bioregen®) and a mix of reticulated and free low molecular weight HA (Regenyal Idea Bioexpander®) (both provided by Regenyal Laboratories Srl, San Benedetto del Tronto (AP), Italy) represent a reliable hydrating device and skin filler, useful for skin blemishes, lines and wrinkles, and lip widening, respectively. The commercial products are known for their safety, but data on the molecular, cellular, and tissue responses are lacking. We aimed to evaluate the bioavailability and the pro-angiogenic features of the products Bioregen® and Bioexpander® in vitro on cultured endothelial cells (ECs) and dermal fibroblasts in vivo when injected into experimental animals. When added to fibroblasts and ECs, Bioexpander® induced cell migration. The two HA preparations were well tolerated, while a transient proangiogenic behavior of Bioexpander®, when implanted subcutaneously in mice, was found. The neovascular response was evident in the first week with higher levels of VEGF and FGF-2 before undergoing regression. In conclusion, our data strengthen the safety of HA synthetic preparations both in vitro and in vivo. Even if a proangiogenic response is documented, it is modest and transient, leading to tissue recovery and absence of an inflammatory infiltrate.
Short-term effects of postural control by standing on a tilting board in patients with Parkinson’s disease

ABSTRACT Background: People with Parkinson’s disease (PD) often have backward displacement of their center of pressure (COP) during quiet standing and reduced stability limits, as compared to healthy controls. These kinetic characteristics may induce postural instability in people with PD. Objective: To investigate the short-term effects on COP displacements during quiet standing and forward leaning brought about by the post-incline leaning after-effects in people with PD. Methods: Twenty participants with PD were randomly divided into two groups (tilting and control groups). The tilting group was required to stand upright quietly on a tilting board angled to raise the front part of the feet. The control group was asked to voluntarily lean their bodies forward as far as possible. The total time of the intervention was 60 seconds for each group. The COP displacements during quiet standing and forward leaning were recorded before and after the intervention. Results: In the tilting group, the COP significantly shifted forward after the intervention compared to that before the intervention during quiet standing as well as forward stability limits; this did not happen in the control group. Conclusions: The post-incline leaning after-effects may induce the short-term effects of forward shifting of COP during quiet standing and expand the forward stability limits in people with PD.
Reasons for discordances between ultrasonography and magnetic resonance imaging in the evaluation of the ankle, hindfoot and heel of the patients with rheumatoid arthritis.

AIM To compare the ultrasonography (US) performance with magnetic resonance imaging (MRI) in identifying pathology in ankles, hindfeet and heels of rheumatoid arthritis (RA) patients and to evaluate the reasons for discordances between the two imaging methods. MATERIAL AND METHODS RA patients were enrolled and evaluated using the Clinical Disease Activity Index (CDAI) and the Disease Activity Score 28 with C-reactive Protein (DAS28-CRP). The ankle (tibiotalar joint, tendons), hindfoot (talonavicular, subtalar joints) and heel of the most symptomatic or dominant foot (for the asymptomatic patient)were evaluated by two pairs of examiners using US and contrast-enhanced MRI. RESULTS Totally, 105 joints, 245 tendons and 35 heels in 35 patients [mean age 59.2±11.25 years old, median disease duration 36 (16.5-114), mean CDAI 19.87±12.7] were evaluated. The interobserver agreements between the two sonographers, and the two radiologists were good and very good (k=0.624-0.940). The overall agreement between US and MRI was very good for subcalcaneal panniculitis (k=0.928, p<0.001), moderate for synovitis (k=0.463, p<0.001) and tenosynovitis (k=0.514, p<0.001), fair for osteophytes (k=0.260, p=0.004), and poor for erosions (k=0.063, p=0.308) and heel's structures. MRI found more erosions, synovitis, osteophytes,tenosynovitis and retrocalcaneal bursitis, but US found more enthesophytes and plantar fasciitis. Many of the discordancesbetween the two imaging techniques have explanations related to the technique itself or definition of the pathologic findings. CONCLUSIONS US is comparable to MRI for the evaluation of ankle, hindfoot and heel in RA patients and discordances in theinterpretation of the pathological findings/normal structures must be carefully analyzed.
Tissue Sodium Content and Arterial Hypertension in Obese Adolescents

Early-onset obesity is known to culminate in type 2 diabetes, arterial hypertension and subsequent cardiovascular disease. The role of sodium (Na+) homeostasis in this process is incompletely understood, yet correlations between Na+ accumulation and hypertension have been observed in adults. We aimed to investigate these associations in adolescents. A cohort of 32 adolescents (13–17 years), comprising 20 obese patients, of whom 11 were hypertensive, as well as 12 age-matched controls, underwent 23Na-MRI of the left lower leg with a standard clinical 3T scanner. Median triceps surae muscle Na+ content in hypertensive obese (11.95 mmol/L [interquartile range 11.62–13.66]) was significantly lower than in normotensive obese (13.63 mmol/L [12.97–17.64]; p = 0.043) or controls (15.37 mmol/L [14.12–16.08]; p = 0.012). No significant differences were found between normotensive obese and controls. Skin Na+ content in hypertensive obese (13.33 mmol/L [11.53–14.22] did not differ to normotensive obese (14.12 mmol/L [13.15–15.83]) or controls (11.48 mmol/L [10.48–12.80]), whereas normotensive obese had higher values compared to controls (p = 0.004). Arterial hypertension in obese adolescents is associated with low muscle Na+ content. These findings suggest an early dysregulation of Na+ homeostasis in cardiometabolic disease. Further research is needed to determine whether this association is causal and how it evolves in the transition to adulthood.
Deep biomarkers of aging and longevity: from research to applications

Multiple recent advances in machine learning enabled computer systems to exceed human performance in many tasks including voice, text, and speech recognition and complex strategy games. Aging is a complex multifactorial process driven by and resulting in the many minute changes transpiring at every level of the human organism. Deep learning systems trained on the many measurable features changing in time can generalize and learn the many biological processes on the population and individual levels. The deep age predictors can help advance aging research by establishing causal relationships in non-linear systems. Deep aging clocks can be used for identification of novel therapeutic targets, evaluating the efficacy of the various interventions, data quality control, data economics, prediction of health trajectories, mortality, and many other applications. Here we present the current state of development of the deep aging clocks in the context of the pharmaceutical research and development and clinical applications.
Emerging role of histone deacetylase inhibitors in the treatment of diffuse large B-cell lymphoma

Abstract Although current immunochemotherapy has increased the therapeutic efficacy in diffuse large B-cell lymphoma (DLBCL), there are still some patients who present unfavorable outcomes. Novel effective treatment strategies are needed to improve the prognosis of DLBCL. In this review, we discussed the functional mechanisms and therapeutic applications of histone deacetylases inhibitors (HDIs) in DLBCL from preclinical and clinical studies. The mechanistic rationale of HDIs involved a wide range of effects including the regulation of transcription factors, tumor suppressors, and cell surface molecules. Histone deacetylases inhibitors as monotherapy performed limited activity in the treatment of DLBCL in present clinical trials, but its combination with other regimens has emerged as potential treatment candidates with generally acceptable and manageable adverse effects. Further investigation on the anti-tumor mechanisms of HDIs and ongoing clinical trials will hopefully facilitate the application of HDIs in patients with DLBCL.
An isogenic hiPSC-derived BBB-on-a-chip.

The blood-brain barrier (BBB) is composed of brain microvascular endothelial cells (BMECs) that regulate brain homeostasis, and astrocytes within the brain are involved in the maintenance of the BBB or modulation of its integrity in disease states via secreted factors. A major challenge in modeling the normal or diseased BBB is that conventional in vitro models lack either the physiological complexity of the BBB or key functional features such as formation of a sufficiently tight barrier. In this study, we utilized human induced pluripotent stem cell (hiPSC)-derived BMECs in a BBB-on-a-chip device that supports flow and coculture with an astrocyte-laden 3D hydrogel. The BMECs are separated from the hydrogel by a porous membrane with either 0.4 or 8.0 μm pore size, making the device suitable for studying the transport of molecules or cells, respectively, across the BBB. In addition, all cells seeded in the device are differentiated from the same hiPSC line, which could enable genetic and rare disease modeling. Formation of a confluent BMEC barrier was confirmed by immunocytochemistry of tight junction proteins and measurement of fluorescein permeability. Integrity of the barrier was further assessed by performing impedance spectroscopy in the device. Finally, the ability of this device to recapitulate a disease model of BBB disruption was demonstrated, with apical addition of TGF-β1 leading to transendothelial electrical resistance reduction and indicators of astrocyte activation. These results demonstrate the utility of the fabricated device for a broad range of applications such as drug screening and mechanistic studies of BBB disruption.
Impact of early weaning on small intestine, metabolic, immune and endocrine system development, growth and body composition in artificially reared lambs1.

This study evaluated the effect of early weaning (EW) of artificially-reared lambs using a restricted milk replacer (MR) feeding and step-down weaning system on the short- and long-term effects on growth, feed intake, selected blood metabolites and hormones, body composition and small intestine development. Mixed-sex twin-born 2-5 d old lambs were randomly allocated to individual pens and fed MR at 20% of initial individual BW in wk 1 and 15% in wk 2 followed by weaning off MR by the end of wk 4 (EW; n=16) or wk 6 (Control; Ctrl, n=16) using a step-down procedure. Concentrate starter and fiber diets were offered ad libitum to wk 9, then gradually removed over a 10 d period. All lambs were managed as a single group on pasture from wk 6 to 16 of the trial. Feed intake was recorded daily in the first 6 wks, and BWs recorded weekly. At wk 2, 4, 6 and 8, and pre- and post-clostridial vaccination at wk 8, blood samples were collected for analysis of selected blood metabolites, IGF-1 and immune function. Body composition was evaluated in 8 animals per group at wk 4 and 16 after euthanasia, and duodenal samples collected for histomorphometric evaluation. Early weaned lambs had lower DM, ME, CP and NDF intake than Ctrl lambs at 21, 15, 21 and 36 d of rearing respectively (P < 0.001) driven by lower intakes of MR from d 15 (P < 0.001) as per the experimental design, and lower total DMI of fiber (P = 0.001) from 21 to 42 d of rearing. Lamb BW tended (P = 0.097) to be lower in EW than Ctrl lambs from five to 10 wks of rearing, with lower ADG in EW lambs from wk 3 to 6 (P = 0.041). Early weaning had negligible effects on duodenal morphology, organ and carcass weights at wk 4 and 16. Plasma metabolites (urea nitrogen, triglycerides, NEFA, glucose and total protein) were similar between groups, while beta-hydroxybutyrate was greater in EW than Ctrl lambs at wk 4 and 6 (P = 0.018) but not wk 8 indicative of early rumen development. Serum IGF-1 tended to be lower in EW than Ctrl lambs from wk 2 to 6 only (P = 0.065). All lambs developed antibody responses post-vaccination but there was no effect of treatment (P = 0.528) indicating similar immune function. The results of this study illustrate that artificially-reared lambs can be weaned off MR by 4 or 6 wks of rearing without compromising growth, small intestine morphology, major organ development and body composition, nor immune function at either 4 (pre-weaning) or 16 (post-weaning) wks of age.
Lead-Free Perovskites for Lighting and Lasing Applications: A Minireview

Research on materials with perovskite crystal symmetry for photonics applications represent a rapidly growing area of the photonics development due to their unique optical and electrical properties. Among them are high charge carrier mobility, high photoluminescence quantum yield, and high extinction coefficients, which can be tuned through all visible range by a controllable change in chemical composition. To date, most of such materials contain lead atoms, which is one of the obstacles for their large-scale implementation. This disadvantage can be overcome via the substitution of lead with less toxic chemical elements, such as Sn, Bi, Yb, etc., and their mixtures. Herein, we summarized the scientific works from 2016 related to the lead-free perovskite materials with stress on the lasing and lighting applications. The synthetic approaches, chemical composition, and morphology of materials, together with the optimal device configurations depending on the material parameters are summarized with a focus on future challenges.
Artificial turf infill associated with systematic toxicity in an amniote vertebrate

Significance Athletes and children are playing on artificial turfs. However, the health risk associated with exposure to crumb rubber from artificial turfs is unknown for higher vertebrates. Here, we employed chicken embryo as a developing amniote vertebrate model to show that toxic leachate from artificial athletic turf infill impairs the early development of chicken, notably brain and cardiovascular system. This study triggers a scientific discussion as to whether crumb rubber is an appropriate infill material for artificial fields. Artificial athletic turf containing crumb rubber (CR) from shredded tires is a growing environmental and public health concern. However, the associated health risk is unknown due to the lack of toxicity data for higher vertebrates. We evaluated the toxic effects of CR in a developing amniote vertebrate embryo. CR water leachate was administered to fertilized chicken eggs via different exposure routes, i.e., coating by dropping CR leachate on the eggshell; dipping the eggs into CR leachate; microinjecting CR leachate into the air cell or yolk. After 3 or 7 d of incubation, embryonic morphology, organ development, physiology, and molecular pathways were measured. The results showed that CR leachate injected into the yolk caused mild to severe developmental malformations, reduced growth, and specifically impaired the development of the brain and cardiovascular system, which were associated with gene dysregulation in aryl hydrocarbon receptor, stress-response, and thyroid hormone pathways. The observed systematic effects were probably due to a complex mixture of toxic chemicals leaching from CR, such as metals (e.g., Zn, Cr, Pb) and amines (e.g., benzothiazole). This study points to a need to closely examine the potential regulation of the use of CR on playgrounds and artificial fields.
Deciphering the Biological Mechanisms Underlying the Genome-Wide Associations between Computerized Device Use and Psychiatric Disorders

Computerized device use (CDU) is societally ubiquitous but its effects on mental health are unknown. We performed genetic correlation, Mendelian randomization, and latent causal variable analyses to identify shared genetic mechanisms between psychiatric disorders (Psychiatric Genomics Consortium; 14,477 < N < 150,064) and CDU (UK Biobank; N = 361,194 individuals). Using linkage disequilibrium score regression, we detected strong genetic correlations between “weekly usage of mobile phone in last 3 months” (PhoneUse) vs. attention deficit hyperactivity disorder (ADHD; rg = 0.425, p = 4.59 × 10−29) and “plays computer games” (CompGaming) vs. schizophrenia (SCZ; rg = −0.271, p = 7.16 × 10−26). Focusing on these correlations, we used two sample MRs to detect the causal relationships between trait pairs by treating single nucleotide polymorphisms as non-modifiable risk factors underlying both phenotypes. Significant bidirectional associations were detected (PhoneUse→ADHD β = 0.132, p = 1.89 × 10−4 and ADHD→PhoneUse β = 0.084, p = 2.86 × 10−10; CompGaming→SCZ β = −0.02, p = 6.46 × 10−25 and CompGaming→SCZ β = −0.194, p = 0.005) and the latent causal variable analyses did not support a causal relationship independent of the genetic correlations between these traits. This suggests that molecular pathways contribute to the genetic overlap between these traits. Dopamine transport enrichment (Gene Ontology:0015872, pSCZvsCompGaming = 2.74 × 10−10) and DRD2 association (pSCZ = 7.94 × 10−8; pCompGaming = 3.98 × 10−25) were detected in SCZ and CompGaming and support their negative correlative relationship. FOXP2 was significantly associated with ADHD (p = 9.32 × 10−7) and PhoneUse (p = 9.00 × 10−11) with effect directions concordant with their positive genetic correlation. Our study demonstrates that epidemiological associations between psychiatric disorders and CDUs are due, in part, to the molecular mechanisms shared between them rather than a causal relationship. Our findings imply that biological mechanisms underlying CDU contribute to the psychiatric phenotype manifestation.
SEDENTARY BEHAVIOR IN KITCHEN IS LIABLE TO FAT ACCUMULATION AND CARDIO-METABOLIC RISK

ABSTRACT Objective: Sedentary habits are considered one of the most important reasons for various cardiovascular complication and risks. Taking into this account the objective of the present study was to to explore the empirical association between accumulation of fat and heart health status among nonsedentary and sedentary habits in kitchen of our modernized society. Method: The current study included 100 women (22-40 years old). Workers who met the inclusion criteria were assigned in to two groups: Group (I) Non-sedentary workers (n-58) and Group (II) - sedentary workers (n-42). Commonly, workers which used to do simple movement work in kitchen were considered as control and which mostly worked at one place in kitchen for more than 6-hours of total working schedule (8–hours). were included in sedentary workers, Anthropometric measurement like body fat ( (%waist circumference(WC), waist hip (WH) ratio, and heart rate variability(HRV) were measured and analyzed by the independent student ʻtʼ test, followed by Pearson correlation and Linear regression. Result: we observed, there was significant increase in body fat ( (%, WC, WH ratio and sympathetic dominance among sedentary participants when compare to non-sedentary participants. There was significant negative correlation between LF and HF, body fat and HF, as well as WH ratio and HF, and significant positive correlation between body fat and LF as well as WH ratio and LF. Conclusion: These results suggest that sedentary behaviour in kitchen is associated with accumulation of adiposity and alteration of sympatho-vagal balance, may lead to cardiometabolic risk in adult women. Key words: Body fat distribution, Heart rate variability, Sedentary habit, physical activity.