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Several studies have demonstrated that Zika virus (ZIKV) damages testis and leads to infertility in mice; however, the infection in the epididymis, another important organ of male reproductive health, has gained less attention. Previously, we detected lesions in the epididymis in interferon type I and II receptor knockout male mice during ZIKV infection. Herein, the pathogenesis of ZIKV in the epididymis was further assessed in the infected mice after footpad inoculation. ZIKV efficiently replicated in the epididymis, and principal cells were susceptible to ZIKV. ZIKV infection disrupted the histomorphology of the epididymis, and the effects were characterized by a decrease in the thickness of the epithelial layer and an increase in the luminal diameter, especially at the proximal end. Significant inflammatory cell infiltration was observed in the epididymis accompanied by an increase in the levels of interleukin (IL)-6 and IL-28. The expression of tight junction proteins was downregulated and associated with disordered arrangement of the junctions. Importantly, the expression levels of aquaporin 1 and lipocalin 8, indicators of the absorption and secretion functions of the epididymis, were markedly reduced, and the proteins were redistributed. These events synergistically altered the microenvironment for sperm maturation, disturbed sperm transport downstream, and may impact male reproductive health. Overall, these results provide new insights into the pathogenesis of the male reproductive damage caused by ZIKV infection and the possible contribution of epididymal injury into this process. Therefore, male fertility of the population in areas of ZIKV epidemic requires additional attention.The CRISPR/Cas9 bacterial system has proven to be an powerful tool for genetic manipulation in several organisms, but the efficiency of sequence replacement by homologous direct repair (HDR) is substantially lower than random indel creation. Many studies focused on improving HDR efficiency using double sgRNA, cell synchronization cycle, and the delivery of single-stranded oligo DNA nucleotides (ssODN) with a rational design. In this study, we evaluate these three methods' synergistic effects to improve HDR efficiency. For our tests, we have chosen the TNFα gene (NM_000594) for its crucial role in various biological processes and diseases. For the first time, our results showed how the use of two sgRNA with asymmetric donor design and triple transfection events dramatically increase the HDR efficiency from an undetectable HDR event to 39% of HDR efficiency and provide a new strategy to facilitate CRISPR/Cas9-mediated human genome editing. Besides, we demonstrated that the TNFα locus could be edited with CRISPR/Cas9 methodology, an opportunity to safely correct, in the future, the specific mutations of each patient.Fragility fracture of the hip is associated with reduced functional status and mortality. Poor self-rated health (SRH) might be such an indicator. Our aim was to study if SRH was associated with hip fractures and all-cause mortality within the next 10 years in community-dwelling older women. A population-based sample of 350 women aged between 69 and 79 years (median 72.4) assessed their SRH by answering the question "How would you rate your health right now" by putting a mark on a visual-analogue scale (0-100 mm). Information on hip fracture and mortality over the next 10 years was retrieved from health care registers. The association between SRH and hip fracture and all-cause mortality was tested with a Cox proportional hazards regression model. SRH was divided into low, intermediate, and high (reference) assessed SRH. During the study, 40 hip fractures and 72 deaths occurred. The median value of SRH was 62 mm (IQR 50-81 mm). The age-adjusted hazard ratio (HR) for hip fracture was significantly higher in the group with low and intermediate SRH; HR 3.17 (95% CI 1.25-8.01), and HR 2.75 (95% CI 1.08-7.04), compared with high SRH. Adding bone mineral density (at the femoral neck) gave even greater risk. [https://www.selleckchem.com/products/nf-kb-activator-1.html find more] We did not find the hypothesized association between SRH and mortality. In our study, SRH indicated a higher risk of future hip fracture in older women. SRH might be a marker that could add information about the risk of hip fracture independently of bone mineral density.Phenotype Prediction Scores (PPS) might be powerful tools to predict traits or the efficacy of treatments based on combinations of Single-Nucleotide Polymorphism (SNPs) in large samples. We developed a novel method to produce PPS models for small samples sizes. The set of SNPs is first filtered on those known to be relevant in biological pathways involved in a clinical condition, and then further filtered repeatedly in a survival strategy to select stabile positive/negative risk alleles. This method is applied on Female Sexual Interest/Arousal Disorder (FSIAD), for which two subtypes has been proposed 1) a relatively insensitive excitatory system in the brain for sexual cues, and 2) a dysfunctional activation of brain mechanisms for sexual inhibition. A double-blind, randomized, placebo-controlled cross-over experiment was conducted on 129 women with FSIAD. The women received three different on-demand drug-combination treatments during 3 two-week periods testosterone (0.5 mg) + sildenafil (50 mg), testosterone (0.5 mg) + buspirone (10 mg), or matching placebos. The resulted PPS were independently validated on patient-level and group-level. The AUC scores for T+S of the derivation set was 0.867 (95% CI = 0.796-0.939; p less then 0.001) and was 0.890 (95% CI = 0.778-1.000; p less then 0.001) on the validation set. For T+B the AUC of the derivation set was 0.957 (95% CI = 0.921-0.992; p less then 0.001) and 0.869 (95% CI = 0.746-0.992; p less then 0.001) for the validation set. Both formulas could reliably predict for each drug who benefit from the on-demand drugs and could therefore be useful in clinical practice.In the 21st century, invasive animals rank second only to habitat destruction as the greatest threat to global biodiversity. Socially-acceptable and cost-effective strategies are needed to reduce the negative economic and environmental impacts of invasive animals. We investigated the potential for sodium nitrite (SN; CAS 7632-00-0) to serve as an avian toxicant for European starlings (Sturnus vulgaris L.). We also assessed the non-target hazard of an experimental formulation of SN that is being developed as a toxicant for invasive wild pigs (Sus scrofa L.). In gavage experiments with European starlings, we identified a lowest observed adverse effect level (LOAEL) for mortality of 2.40% technical SN (w/v; 120 mg SN/kg body mass) and a no observed adverse effect level (NOAEL) for mortality of 1.30% technical SN (65 mg/kg). The exposure of ten starlings to the experimental formulation of SN (10% SN pig toxicant) resulted in one starling mortality during four days of exposure to the toxic bait. Sodium nitrite toxicity presented a moderate hazard to European starlings; thus, the future development of SN as an avian toxicant is dependent upon its cost-effectiveness.