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SARS-CoV-2 results on male duplication: need to males be troubled??
Interpretation of transcriptomic experiments is hindered by many problems including false positives/negatives inherent to big-data methods and changes in gene nomenclature. To find the most consistent effect of stress on brain transcriptome, we retrieved data from 79 studies applying animal models and 3 human studies investigating post-traumatic stress disorder (PTSD). The analyzed data were obtained either with microarrays or RNA sequencing applied to samples collected from more than 1887 laboratory animals and from 121 human subjects. Based on the initial database containing a quarter million differential expression effect sizes representing transcripts in three species, we identified the most frequently reported genes in 223 stress-control comparisons. Additionally, the analysis considers sex, individual vulnerability and contribution of glucocorticoids. We also found an overlap between gene expression in PTSD patients and animals which indicates relevance of laboratory models for human stress response. Our analysis points to genes that, as far as we know, were not specifically tested for their role in stress response (Pllp, Arrdc2, Midn, Mfsd2a, Ccn1, Htra1, Csrnp1, Tenm4, Tnfrsf25, Sema3b, Fmo2, Adamts4, Gjb1, Errfi1, Fgf18, Galnt6, Slc25a42, Ifi30, Slc4a1, Cemip, Klf10, Tom1, Dcdc2c, Fancd2, Luzp2, Trpm1, Abcc12, Osbpl1a, Ptp4a2). Provided transcriptomic resource will be useful for guiding the new research.Diabetes mellitus refers to a group of metabolic disorders which affect how the body uses glucose impacting approximately 9% of the population worldwide. This review covers the most recent technological advances envisioned to control and/or reverse Type 1 diabetes mellitus (T1DM), many of which will also prove effective in treating the other forms of diabetes mellitus. Current standard therapy for T1DM involves multiple daily glucose measurements and insulin injections. Advances in glucose monitors, hormone delivery systems, and control algorithms generate more autonomous and personalised treatments through hybrid and fully automated closed-loop systems, which significantly reduce hypo- and hyperglycaemic episodes and their subsequent complications. Bi-hormonal systems that co-deliver glucagon or amylin with insulin aim to reduce hypoglycaemic events or increase time spent in target glycaemic range, respectively. this website Stimuli responsive materials for the controlled delivery of insulin or glucagon are a promising alternative to glucose monitors and insulin pumps. By their self-regulated mechanism, these "smart" drugs modulate their potency, pharmacokinetics and dosing depending on patients' glucose levels. Islet transplantation is a potential cure for T1DM as it restores endogenous insulin and glucagon production, but its use is not yet widespread due to limited islet sources and risks of chronic immunosuppression. New encapsulation strategies that promote angiogenesis and oxygen delivery while protecting islets from recipients' immune response may overcome current limiting factors.Pharmaceutical products can activate immune cells, suppress their function, or change the immune responses to traditional immunologically active agonists such as those present in microbes. Therefore, the assessment of immunostimulation, immunosuppression, and immunomodulation comprises the backbone of immunotoxicity studies of new drug entities. Depending on physicochemical properties (e.g., size, charge, surface functionalities, hydrophobicity), nanoparticles can be immunostimulatory, immunosuppressive, and immunomodulatory. Various methods and experimental frameworks have been established to support preclinical translational studies of nanotechnology-based drug products. Immunophenotyping after the exposure of cells or preclinical animal models to nanoparticles can provide critical information about the changes in both the numbers of immune cells and their activation status. However, this methodology is underutilized in preclinical studies of engineered nanomaterials. Herein, we review current literature about varieties of instrumentation and methods utilized for immunophenotyping, discuss their advantages and limitations, and propose a roadmap for applying immunophenotyping to support preclinical immunological characterization of nanotechnology-based formulations.HSV-1/hPD-1 is composed of engineered herpes simplex virus type-1 and two inserted copies of the human PD-1 antibody sequence. It is a novel oncolytic virus product designed to cure malignancies. The objective of this study was to estimate its toxicity in mice. In the single-dose toxicity study, no mortality and abnormal symptoms were observed in animals injected with 4.0 × 107 pfu/mouse dose. In the repeat-dose toxicity study, HSV-1/hPD-1 in animals intramuscularly treated with 1.0 × 107, 2.0 × 107, or 4.0 × 107 pfu/mouse doses was well tolerated in terms of clinical observation, body weight, food consumption, hematology and biochemistry indexes, T lymphocyte counting, immune reaction, and organ weight, except for some histopathological changes, such as the irreversible degeneration of the sciatic nerve, which was considered related to the adopted administration route. Synchronously, a biodistribution study in mice was performed to examine whether HSV-1/hPD-1 could spread to the injection site, gonads, liver, lung, heart, mesenteric and inguinal lymph nodes, skin, dorsal root ganglia, and blood, and then be gradually eliminated. Thus, two safety dose levels-the maximum tolerance dose of 4.0 × 107 pfu/mouse and the no-observed-adverse-effect-level dose of 1.0 × 107 pfu/mouse-were determined to help design patients' dose regimens. Our research data have been successfully accepted for investigational new drug (IND) application in China.The efficacy of double manual cleaning (DMC) with enzymatic detergent followed by alkaline detergent on biofilm removal on hinged surgical instruments was compared to automated cleaning. Biofilm-covered haemostatic forceps were divided into four groups positive control (soaked in sterile water); DMC; DMC plus extra brushing of the inner hinge; and automated cleaning. All DMC, DMC plus brushing the hinge, and automated cleaning significantly (P less then 0.001) reduced 94.8%, 99.8%, and 100% viable bacteria and 82.3%, 93.8%, and 95.1% residual protein, respectively, compared to positive control. DMC instruments had significantly more viable bacteria (P less then 0.05) and residual protein (P less then 0.01) than those in instruments subjected to DMC with hinge brushing and automated cleaning. However, there was no significant difference in residual protein between DMC with hinge brushing and automated cleaning. In sterilizing service units with no access to automated cleaning equipment, it is important to brush the inner hinge during manual cleaning, and DMC plus brushing the inner hinge could be considered a viable alternative for cleaning hinged surgical instruments.Microbiological diagnosis of equine respiratory infections is essential for disease management. However, reliable diagnosis can be a challenge due to colonization of the upper respiratory tract (URT) by a diverse microbial population, and because there is a lack of studies with samples from healthy animals. Aiming to guide adequate URT culture, this work reports culturable microbial population from the URT of 1,010 apparently healthy horses from 341 farms in Southern Brazil and identifies the putative presence of pathogenic microorganisms. Nasal swabs were cultured in 5% blood agar, and the isolates were phenotypically identified to genus level. A diverse respiratory microbial population was found, mostly composed of Gram-positive bacteria, including Staphylococcus spp., Bacillus spp., Streptococcus spp. and Corynebacterium spp. The microbiological profile from the nasal cavity of 911 horses was described, with the five most common profiles being (1) Staphylococcus sp. + Gram-negative bacilli (12.67%), (2) Staphylococcus sp. in pure culture (12.47%), (3) Staphylococcus sp. + Bacillus sp. (10.10%), (4) Gram-negative bacilli in pure culture (6.93%), and (5) Staphylococcus sp. + Bacillus sp. + Gram-negative bacilli (6.73%). Streptococcus equi equi and Rhodococcus equi were detected in 34 horses (3.37%), demonstrating the presence of pathogenic bacteria along with commensal microorganisms in apparently healthy animals. The disclosed data may guide and facilitate microbiological diagnosis of URT infection in horses. The significant presence of Gram-negative bacilli was evidenced, as well as the occurrence of relevant pathogens, such as S. equi equi and R. equi, thus helping to improve diagnosis and antimicrobial therapy.Autologous cancer vaccines (ACV) are an emerging option for adjuvant cancer treatment in veterinary medicine. With this form of active immunotherapy, the patient's tumor cells are processed ex vivo and returned to the patient with the goal of stimulating an immune response to unique, patient-specific antigens. The case accession database at Torigen was queried to identify horses that underwent biopsy or surgical resection of their primary tumor and received at least one subcutaneous dose of an adjuvanted whole-cell autologous cancer vaccine. The records were then reviewed for any reported adverse events (AE). Forty-one horses met the inclusion criteria and received 252 doses of Torigen's ACV (ACV-T). There were seven AEs reported in four horses, which were associated with 1.6% of the administered doses of the ACV-T. Of the reported AE, all were characterized as mild. The ACV-T appears to be well tolerated by horses, and may be useful as a treatment option for owners who are concerned about AEs that can occur with other types of adjuvant cancer therapy. Additional studies are warranted to evaluate the efficacy of this ACV in horses with solid tumors.Seasonal effects on the oral sugar test (OST), used to monitor insulin dysregulation (ID) status to help reduce laminitis risk, are poorly understood in the ID horse. Resting, (basal) insulin (T0) and 60-minute (T60) OST (0.15 mL/Kg BW Karo Light Corn Syrup) insulin responses were evaluated, once per each season over 2 years, in ID (n = 11 14.9 ± 4.3 years; mean ± SD) and non-insulin dysregulated (NID n = 11 16.4 ± 5.3 years; mean ± SD) horses housed on the same farm. Seasonal morphometric measurements were collected bodyweight (BW), body-condition scores (BCS), and cresty neck scores (CNS). Seasonal forage from paddocks and hay were collected and analyzed. Insulin was measured by RIA. Data were analyzed via Minitab Software 20.2 (mixed effects model). Season had no effect on BW (P = .99); however, BCS and CNS were higher in ID versus NID in the spring, summer and fall (P .2) analytes varied across season. ID horses consistently had higher T0, T60 insulin concentrations versus NID (P less then .02). Season had no effect on NID T0 insulins (P = .31), but T60 values were higher in the spring versus summer (P = .01). ID horses' T0 & T60 insulins were higher in spring than fall and summer (P less then .01 & P less then .05) and winter T60 was higher than fall (P = .04). ID horses changed their ID categorization across season, with T0 confirming ID status only 56% of the time whilst T60 confirmed 94% of the time. Therefore, regardless of seasonal changes, if the OST was used, ID diagnosis would be more consistent.
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