Explore the vast range of titles available.

To assess the impact of resilience, the ability to withstand and bounce back from adversity, on measures of well-being, self-reported stress, and mental health diagnoses. This study was a cross-sectional survey of participants seen at an executive health practice at Mayo Clinic, Rochester, Minnesota, from January 2012 through September 2016. Participants completed an anonymous survey that included demographic information and 3 validated survey instruments-the 10-item Connor-Davidson Resilience Scale (CD-RISC), the 12-item Linear Analogue Self-Assessment Scale (LASA), and the 14-item Perceived Stress Scale (PSS). Self-reported history of mental health diagnoses was also collected. CD-RISC scores were used to stratify participants into lower (<30), medium (30-34), or higher (≥35) resilience categories. Participants' LASA scores, PSS scores, and self-reported mental health diagnoses were compared among resilience categories. Of the 2,027 eligible participants, 1,954 met the study inclusion criteria as currently employed corporate-sponsored executive or business professionals (self-designated) who completed the CD-RISC survey. Most participants (62.5%) were aged 40 to 59 years. The majority were male (78.3%), white (95.3%), educated (86.2%), and in a committed relationship (89.7%). Among participants, 41.7% reported higher resilience, 34.3% had medium resilience, and 24.0% had lower resilience. The quality of life and overall LASA scores were positively associated with higher resilience (P < .001). PSS scores and self-reported mental health diagnoses were negatively associated with higher resilience (P < .001). These associations remained significant after adjusting for patient characteristics. In this cross-sectional survey of a large cohort of corporative executives, the lower-resilience cohort had a 4-fold higher prevalence of depression and an almost 3-fold higher prevalence of anxiety compared with the higher-resilience cohort. High resilience was positively associated with well-being and negatively associated with perceived stress. Our findings suggest that higher resilience in the executive workplace environment is associated with better mental health, reduced stress, and greater well-being.

Equine influenza viruses (EIVs) of H3N8 subtype are culprits of severe acute respiratory infections in horses, and are still responsible for significant outbreaks worldwide. Adaptability of influenza viruses to a particular host is significantly influenced by their codon usage preference, due to an absolute dependence on the host cellular machinery for their replication. In the present study, we analyzed genome-wide codon usage patterns in 92 EIV strains, including both H3N8 and H7N7 subtypes by computing several codon usage indices and applying multivariate statistical methods. Relative synonymous codon usage (RSCU) analysis disclosed bias of preferred synonymous codons towards A/U-ended codons. The overall codon usage bias in EIVs was slightly lower, and mainly affected by the nucleotide compositional constraints as inferred from the RSCU and effective number of codon (ENc) analysis. Our data suggested that codon usage pattern in EIVs is governed by the interplay of mutation pressure, natural selection from its hosts and undefined factors. The H7N7 subtype was found less fit to its host (horse) in comparison to H3N8, by possessing higher codon bias, lower mutation pressure and much less adaptation to tRNA pool of equine cells. To the best of our knowledge, this is the first report describing the codon usage analysis of the complete genomes of EIVs. The outcome of our study is likely to enhance our understanding of factors involved in viral adaptation, evolution, and fitness towards their hosts.

Elucidation of the molecular pathogenesis underlying virus-host interactions is important for the development of new diagnostic and therapeutic strategies against highly pathogenic avian influenza (HPAI) virus infection in chickens. However, the pathogenesis of HPAI virus in chickens is not completely understood. To identify the intracellular signaling pathways and critical host proteins associated with influenza pathogenesis, we analyzed the lung proteome of a chicken infected with HPAI H5N1 virus (A/duck/India/02CA10/2011/Agartala). Mass spectrometry data sets were searched against the chicken UniProt reference database. At the local false discovery rate level of 5%, a total of 3313 proteins with the presence of at least one unique peptide were identified in the chicken lung proteome datasets. Differential expression analysis of these proteins showed that 247 and 1754 proteins were downregulated at 12 h and 48 h postinfection, respectively. We observed expression of proteins of the predominant signaling pathways, including Toll-like receptors (TLRs), retinoic acid-inducible gene I-like receptors (RLRs), NOD-like receptors (NLRs), and JAK-STAT signaling. Activation of these pathways is associated with the cytokine storm effect and thus may be the cause of the severity of HPAI H5N1 infection in chickens. We also observed the expression of myeloid differentiation primary response protein (MyD88), inhibitor of nuclear factor kappa B kinase subunit beta (IKBKB), interleukin 1 receptor associated kinase 4 (IRAK4), RELA proto-oncogene NF-κB subunit (RELA), and mitochondrial antiviral signaling protein (MAVS), which are involved in critical signaling pathways, as well as other, less-commonly identified proteins such as hepatocyte nuclear factor 4 alpha (HNF4A), ELAV-like RNA binding protein 1 (ELAVL1), fibronectin 1 (FN1), COP9 signalosome subunit 5 (COPS5), cullin 1 (CUL1), breast cancer type 1 susceptibility protein (BRCA1), and the FYN proto-oncogene Src family tyrosine kinase (FYN) as main hub proteins that might play important roles in influenza pathogenesis in chickens. In summary, we identified the signaling pathways and the proteomic determinants associated with disease pathogenesis in chickens infected with HPAI H5N1 virus.

Hendra virus (HeV) and Nipah virus (NiV) are among a group of emerging bat-borne paramyxoviruses that have crossed their species-barrier several times by infecting several hosts with a high fatality rate in human beings. Despite the fatal nature of their infection, a comprehensive study to explore their evolution and adaptation in different hosts is lacking. A study of codon usage patterns in henipaviruses may provide some fruitful insight into their evolutionary processes of synonymous codon usage and host-adapted evolution. Here, we performed a systematic evolutionary and codon usage bias analysis of henipaviruses. We found a low codon usage bias in the coding sequences of henipaviruses and that natural selection, mutation pressure, and nucleotide compositions shapes the codon usage patterns of henipaviruses, with natural selection being more important than the others. Also, henipaviruses showed the highest level of adaptation to bats of the genus Pteropus in the codon adaptation index (CAI), relative to the codon de-optimization index (RCDI), and similarity index (SiD) analyses. Furthermore, a comparison to recently identified henipa-like viruses indicated a high tRNA adaptation index of henipaviruses for human beings, mainly due to F, G and L proteins. Consequently, the study concedes the substantial emergence of henipaviruses in human beings, particularly when paired with frequent exposure to direct/indirect bat excretions.

Many viruses that cause serious diseases in humans and animals, including the betacoronaviruses (beta-CoVs), such as SARS-CoV, MERS-CoV, and the recently identified SARS-CoV-2, have natural reservoirs in bats. Because these viruses rely entirely on the host cellular machinery for survival, their evolution is likely to be guided by the link between the codon usage of the virus and that of its host. As a result, specific cellular microenvironments of the diverse hosts and/or host tissues imprint peculiar molecular signatures in virus genomes. Our study is aimed at deciphering some of these signatures. Using a variety of genetic methods we demonstrated that trends in codon usage across chiroptera-hosted CoVs are collaboratively driven by geographically different host-species and temporal-spatial distribution. We not only found that chiroptera-hosted CoVs are the ancestors of SARS-CoV-2, but we also revealed that SARS-CoV-2 has the codon usage characteristics similar to those seen in CoVs infecting the Rhinolophus sp. Surprisingly, the envelope gene of beta-CoVs infecting Rhinolophus sp., including SARS-CoV-2, had extremely high CpG levels, which appears to be an evolutionarily conserved trait. The dissection of the furin cleavage site of various CoVs infecting hosts revealed host-specific preferences for arginine codons; however, arginine is encoded by a wider variety of synonymous codons in the murine CoV (MHV-A59) furin cleavage site. Our findings also highlight the latent diversity of CoVs in mammals that has yet to be fully explored.

The rapid evolution of SARS-CoV-2 variants, have posed significant public health challenges due to their heightened transmissibility and varying clinical outcomes. While the impact of these variants in humans has been extensively studied, their effect on domestic animals has not been explored thoroughly. Given the close contact between humans and pets, combined with documented cases of virus transmission from humans to domestic animals and the potential for these animals to act as viral reservoirs, highlights the importance of understanding the molecular dynamics of SARS-CoV-2 infection in them. Consequently, there is an increasing demand for infection models that closely mimic viral behavior in animal tissues. In vivo infection of cats or any other non-laboratory animal species is extremely resource intensive, time consuming, require ABSL3 facilities, and animal ethical clearances which are not practically possible for the majority of researchers. In this scenario the ex vivo cultures model can be an excellent alternative. Therefore, in this study, we have utilized an ex vivo lung explant culture model derived from domestic cats to examine the host’s response to Delta and Omicron variants of SARS-CoV-2 in cat lung explant culture. Comprehensive transcriptomic profiling at multiple time points post-infection revealed significant disruptions in genes associated with cell adhesion, structural components, extracellular matrix (ECM) organization and regulation, secreted and growth factors, and immune responses. Our study revealed that the Delta variant triggered early activation of genes associated with tissue damage as early as 12 hours post-infection (hpi). By 24 hpi, both the Delta and Omicron variants showed significant activation of these genes, with the Delta variant linked to the activation of a larger number of tissue damage-related genes. Notably, we identified several hub genes, including MMP9 , CCL5 , MCP-1/CCL2 , VWF , HGF , ANGPT1 , CD34 , CD68 , SPP1 , IGF1 , CSF1 , and VCL , involved in critical signaling pathways such as focal adhesion, PI3K-Akt signaling, and TNF signaling. These hub genes hold potential as valuable biomarkers. This study provides key insights into the pathogenesis of SARS-CoV-2 in cats and highlights the utility of ex vivo lung explant cultures as a platform for studying viral infections.

The constantly changing landscape regarding menopausal hormone therapy (MHT) has been challenging for providers caring for menopausal women. After a decade of fear and uncertainty regarding MHT, reanalysis of the Women's Health Initiative data and the results of recent studies have provided some clarity regarding the balance of risks and benefits of systemic MHT. Age and years since menopause are now known to be important variables affecting the benefit-risk profile. For symptomatic menopausal women who are under 60 years of age or within 10 years of menopause, the benefits of MHT generally outweigh the risks. Systemic MHT initiated early in menopause appears to slow the progression of atherosclerotic disease, thereby reducing the risk of cardiovascular disease and mortality. During this window of opportunity, MHT might also provide protection against cognitive decline. In older women and women more than 10 years past menopause, the risk-benefit balance of MHT is less favorable, particularly with regard to cardiovascular risk and cognitive impairment. For women entering menopause prematurely (<40 years), MHT ameliorates the risk of cardiovascular disease, osteoporosis, and cognitive decline. Nonoral administration of estrogen offers advantages due to the lack of first-pass hepatic metabolism, which in turn avoids the increased hepatic synthesis of clotting proteins, C-reactive protein, triglycerides, and sex hormone-binding globulin. The duration of combined MHT use is ideally limited to less than 5 years because of the known increase in breast cancer risk after 3-5 years of use. Limitations to use of estrogen only MHT are less clear, since breast cancer risk does not appear to increase with use of estrogen alone. For women under the age of 60 years, or within 10 years of onset of natural menopause, MHT for the treatment of bothersome menopausal symptoms poses low risk and is an acceptable option, particularly when nonhormonal management approaches fail.

Domestic ducks (Anas platyrhynchos domesticus) are resistant to most of the highly pathogenic avian influenza virus (HPAIV) infections. In this study, we characterized the lung proteome and phosphoproteome of ducks infected with the HPAI H5N1 virus (A/duck/India/02CA10/2011/Agartala) at 12 h, 48 h, and 5 days post-infection. A total of 2082 proteins were differentially expressed and 320 phosphorylation sites mapping to 199 phosphopeptides, corresponding to 129 proteins were identified. The functional annotation of the proteome data analysis revealed the activation of the RIG-I-like receptor and Jak-STAT signaling pathways, which led to the induction of interferon-stimulated gene (ISG) expression. The pathway analysis of the phosphoproteome datasets also confirmed the activation of RIG-I, Jak-STAT signaling, NF-kappa B signaling, and MAPK signaling pathways in the lung tissues. The induction of ISG proteins (STAT1, STAT3, STAT5B, STAT6, IFIT5, and PKR) established a protective anti-viral immune response in duck lung tissue. Further, the protein–protein interaction network analysis identified proteins like AKT1, STAT3, JAK2, RAC1, STAT1, PTPN11, RPS27A, NFKB1, and MAPK1 as the main hub proteins that might play important roles in disease progression in ducks. Together, the functional annotation of the proteome and phosphoproteome datasets revealed the molecular basis of the disease progression and disease resistance mechanism in ducks infected with the HPAI H5N1 virus.

Genitourinary syndrome of menopause (GSM), previously known as atrophic vaginitis or vulvovaginal atrophy, affects more than half of postmenopausal women. Caused by low estrogen levels after menopause, it results in bothersome symptoms, including vaginal dryness, itching, dyspareunia, urinary urgency and increased frequency, and urinary tract infections. Even though women with GSM can have sexual dysfunction that interferes with partner relationships, women are often embarrassed to seek treatment, and health care professionals do not always actively screen for GSM. As a result, GSM remains underdiagnosed and undertreated. Several effective treatments exist, but low-dose vaginal estrogen therapy is the criterion standard. It is effective and safe for most patients, but caution is suggested for survivors of hormone-sensitive cancers. Newer treatment options include selective estrogen receptor modulators, vaginal dehydroepiandrosterone, and laser therapy. Nonprescription treatments include vaginal lubricants, moisturizers, and dilators. Pelvic floor physical therapy may be indicated for some women with concomitant pelvic floor muscle dysfunction. Sex therapy may be helpful for women with sexual dysfunction. This concise review presents a practical approach to the evaluation and management of GSM for the primary care physician.

The study was aimed to evaluate the elicitation of highly pathogenic avian influenza (HPAI) virus (AIV) M2e and HA2-specific immunity in chicken to develop broad protective influenza vaccine against HPAI H5N1. Based on the analysis of Indian AIV H5N1 sequences, the conserved regions of extracellular domain of M2 protein (M2e) and HA2 were identified. Synthetic gene construct coding for M2e and two immunodominant HA2 conserved regions was designed and synthesized after codon optimization. The fusion recombinant protein (~38 kDa) was expressed in a prokaryotic system and characterized by Western blotting with anti-His antibody and anti-AIV polyclonal chicken serum. The M2e–HA2 fusion protein was found to be highly reactive with known AIV-positive and -negative chicken sera by ELISA. Two groups of specific pathogen-free (SPF) chickens were immunized (i/m) with M2e synthetic peptide and M2e–HA2 recombinant protein along with one control group with booster on the 14th day and 28th day with the same dose and route. Pre-immunization sera and whole blood were collected on day 0 followed by 3, 7, 14, 21, and 28 days and 2 weeks after the second booster (42 day). Lymphocyte proliferation assay by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) method revealed that the stimulation index (SI) was increased gradually from days 0 to 14 in the immunized group ( p < 0.05) than that in control chicken. Toll-like receptor (TLR) mRNA analysis by RT-qPCR showed maximum upregulation in the M2e–HA2-vaccinated group compared to M2e- and sham-vaccinated groups. M2e–HA2 recombinant protein-based indirect ELISA revealed that M2e–HA2 recombinant fusion protein has induced strong M2e and HA2-specific antibody responses from 7 days post-primary immunization, and then the titer gradually increased after booster dose. Similarly, M2e peptide ELISA revealed that M2e–HA2 recombinant fusion protein elicited M2e-specific antibody from day 14 onward. In contrast, no antibody response was detected in the chicken immunized with synthetic peptide M2e alone or control group. Findings of this study will be very useful in future development of broad protective H5N1 influenza vaccine targeting M2e and HA2.