Search

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.

Objectives: Female sexual dysfunction (FSD), a common concern affecting women of all ages, is often mediated by important psychological factors. Resilience has been shown to correlate with psychological well-being across different groups of people. The aim of this study was to assess if there is an association between resilience and FSD., Study Design: This cross-sectional study included 4,366 women (mean [SD] age, 51.7 [11]) seen in women's health clinics at 1 of 3 geographic Mayo Clinic locations. Participants completed the Brief Resilience Scale, the Female Sexual Function Index (FSFI), and the Female Sexual Distress Scale-Revised (FSDS-R)., Main Outcome Measures: We used univariate and multivariable logistic regression analyses to assess associations between resilience, sexual function, and sexual distress, adjusting for potential confounding variables., Results: FSD criteria (FSFI ≤26.55 and FSDS-R ≥ 11) were met by 55.8 % of women. Low, normal, and high levels of resilience were reported by 17.3 %, 57.1 %, and 25.6 % of participants, respectively. The univariate analysis showed that higher resilience was associated with lower sexual distress, lower odds of FSD, and better sexual function. Multivariable analysis adjusted for potential confounders showed that the association persisted and that higher resilience correlated with better sexual function and lower odds of FSD., Conclusions: In this large cross-sectional study, women with higher resilience scores had better sexual function and lower odds of FSD. Additional studies with diverse women are needed to confirm this association and to determine whether women with FSD could benefit from enhancing resilience as a therapeutic strategy., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to evolve carrying flexible amino acid substitutions in the spike protein's receptor binding domain (RBD). These substitutions modify the binding of the SARS-CoV-2 to human angiotensin-converting enzyme 2 (hACE2) receptor and have been implicated in altered host fitness, transmissibility, and efficacy against antibody therapeutics and vaccines. Reliably predicting the binding strength of SARS-CoV-2 variants RBD to hACE2 receptor and neutralizing antibodies (NAbs) can help assessing their fitness, and rapid deployment of effective antibody therapeutics, respectively. Here, we introduced a two-step computational framework with 3-fold validation that first identified dissociation constant as a reliable predictor of binding affinity in hetero- dimeric and trimeric protein complexes. The second step implements dissociation constant as descriptor of the binding strengths of SARS-CoV-2 variants RBD to hACE2 and NAbs. Then, we examined several variants of concerns (VOCs) such as Alpha, Beta, Gamma, Delta, and Omicron and demonstrated that these VOCs RBD bind to the hACE2 with enhanced affinity. Furthermore, the binding affinity of Omicron variant's RBD was reduced with majority of the RBD-directed NAbs, which is highly consistent with the experimental neutralization data. By studying the atomic contacts between RBD and NAbs, we revealed the molecular footprints of four NAbs (GH-12, P2B-1A1, Asarnow_3D11, and C118)-that may likely neutralize the recently emerged Omicron variant-facilitating enhanced binding affinity. Finally, our findings suggest a computational pathway that could aid researchers identify a range of current NAbs that may be effective against emerging SARS-CoV-2 variants., (© 2023 Wiley Periodicals LLC.)

The current study aimed to develop broadly protective vaccines for avian influenza. In an earlier study, HA stalk (universal flu vaccine) was found to be broadly protective against different subtypes of influenza virus in mice. Hence, we were interested to know its breadth of protective efficacy either alone or combined with inactivated rgH5N2 (clade 2.3.2.1a) vaccine against challenge viruses of homologous H5N1, heterologous H5N8 (clade 2.3.4.4) and heterosubtypic H9N2 virus in specific pathogen-free chickens. The rgH5N2 vaccine alone or in combination with HA stalk elicited sufficient pre-challenge immunity in the form of haemagglutination inhibiting (HI) antibodies and neutralizing antibodies (MNT) against H5N1, H5N8, and H9N2 in chickens. The rgH5N2 vaccine alone or in combination with HA stalk also attenuated the shedding of H5N1, H5N8 and H9N2 in chickens and protected against the lethal challenge of H5N1 or H5N8. In contrast, all HA stalk immunised chickens died upon H5N1 or H5N8 challenge and H9N2 challenged chickens survived. Our study suggests that the rgH5N2 vaccine can provide clinical protection against H5N1, H5N8 and can attenuate the viral shedding of H9N2 in chickens., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The emergence of methicillin-resistant Staphylococcus aureus (MRSA) has increased and become a serious concern worldwide, including India. Additionally, MRSA isolates are showing resistance to other chemotherapeutic agents. Isolated and valuable reports on the prevalence of MRSA are available in India. There is no systematic review on the prevalence of MRSA in one place; hence, this study was planned. The overall prevalence of MRSA in humans in India was evaluated state-wise, zone-wise, and year-wise. A systematic search from PubMed, Indian journals, Google Scholar, and J-Gate Plus was carried out and retrieved 98 eligible articles published from 2015 to 2020 in India. The statistical analysis of data was conducted using R software. The overall prevalence of MRSA was 37% (95% CI: 32-41) from 2015 to 2019. The pooled prevalence of MRSA zone-wise was 41% (95% CI: 33-50), 43% (95% CI: 20-68), 33% (95% CI: 24-43), 34% (95% CI: 26-42), 36% (95% CI: 25-47), and 40% (95% CI: 23-58) for north, east, west, south, central, and northeast region-zones, respectively. The state-wise stratified results showed a predominance of MRSA in Jammu and Kashmir with 55% (95% CI: 42-67) prevalence, and the lowest was 21% (95% CI: 11-34) in Maharashtra. The study indicated that the prevalence data would help in formulating and strict implementation of control measures in hospital areas to prevent the outbreak of MRSA infection and management of antibiotic usage., (The OMJ is Published Bimonthly and Copyrighted 2022 by the OMSB.)

Objectives: Female sexual dysfunction (FSD) affects women of all ages. It is often a multifactorial problem with a strong psychosocial component. Mindfulness may help alleviate FSD with nonjudgmental, present-moment awareness and decreased emotional reactivity. The goal of this study was to assess the association between dispositional or trait mindfulness and FSD., Study Design: In this cross-sectional study at a tertiary care women's health clinic, 1718 cisgender women (mean age, 51.9 years) completed the Mindfulness Attention Awareness Scale (MAAS), Female Sexual Function Index (FSFI), and Female Sexual Distress Scale-Revised (FSDS-R)., Main Outcome Measures: Regression analysis was used to test the associations of mindfulness, sexual function, and sexual distress with univariate and multivariable analyses, adjusting for potential confounders., Results: Within the sample, 57% of women met FSD criteria (FSFI scores ≤26.55 and FSDS-R ≥ 11). On univariate analysis, higher MAAS scores, signifying greater mindfulness, were associated with higher (better) sexual function scores, lower sexual distress scores, and lower odds of FSD. This association persisted on multivariable analysis after adjusting for potential confounders., Conclusions: Higher trait mindfulness was associated with better sexual function, lower sexual distress, and lower likelihood of FSD. Further studies are needed to assess the role of mindfulness in mitigating FSD., Competing Interests: Richa Sood's husband is the owner/CEO of Global Center for Resiliency and Well-being and The GRIT Institute.Ekta Kapoor has received consultant fees for Astellas Pharmaceuticals, personal fees from CogniMed, personal fees from Med Learning Group, consultant fees and grant support from Mithra Pharmaceuticals, personal fees from PriMed, and consultant fees from Womaness, all of which are outside the scope of the submitted work.All other authors declare that they have no competing interests., (Copyright © 2022. Published by Elsevier B.V.)

Natural infections with HoBi-like pestivirus (HoBiPeV) have been detected in cattle in South America, Europe and Asia with a range of clinical manifestations including fatal mucosal disease (MD). In India, although HoBiPeV in cattle has been reported, there is no information on currently circulating HoBiPeV strains and associated severe clinical disease. Between September 2018 and December 2019, suspected cases of bovine viral diarrhoea with severe disease in cattle were noticed in farmers' small holdings in Tamil Nadu State. To determine the extent of pestivirus infection, blood, serum, nasal or oral swab samples of 46 cattle from 18 villages were tested. Based on the real-time RT-PCR, antigen ELISA and nucleotide sequencing results, pestivirus was detected in nine cattle from eight villages in two districts and all pestiviruses were identified as HoBiPeV. All nine HoBiPeV-infected cattle displayed clinical signs resembling MD and HoBiPeV isolates (n = 9) obtained were characterized at genetic and antigenic level. Phylogenetic analyses based on 5'-untranslated regions (5'-UTR), N pro and combined 5'-UTR-N pro gene sequences revealed that eight HoBiPeV isolates clustered into a clade, distinct from all reported HoBiPeV clades (a-d), whereas one belonged to HoBiPeV-d clade, thus providing evidence of emergence of a novel HoBiPeV clade (e). This was also supported by HoBiPeV-e clade-specific amino acid substitutions in N pro and the antigenic reactivity patterns. The study demonstrates the existence and independent evolution of five HoBiPeV clades (four main clades) globally and surprisingly three exclusive to India. Also we confirm first HoBiPeV occurrence in southern India with predominant prevalence of HoBiPeV-e strains. Besides demonstrating increased HoBiPeV genetic diversity, here we show association of HoBiPeV with severe clinical disease involving fatalities highlighting impact of HoBiPeV on cattle health. The emergence of a novel HoBiPeV lineage provides new insights on global HoBiPeV epidemiology and genetic diversity reiterating the need for continuous monitoring of HoBiPeV in India., (© 2021 Wiley-VCH GmbH.)

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., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

We report here a targeted risk-based study to investigate the presence of influenza A viruses at the migratory-wild-domestic bird interface across the major wetlands of central India's Maharashtra state during the winter migration season. The H9N2 viruses have been isolated and confirmed in 3.86% (33/854) of the fecal samples of resident birds. To investigate the genetic pools of H9N2 circulating in resident birds, we sequenced two isolates of H9N2 from distant wetlands. Sequence and phylogenetic analyses have shown that these viruses are triple reassortants, with HA, NA, NP, and M genes belonging to G1 sub-lineage (A/quail/Hong Kong/G1/1997), PB2, PB1, and NS genes originating from the prototype Eurasian lineage (A/mallard/France/090360/2009) and PA gene deriving from Y439/Korean-like (A/duck/Hong Kong/Y439/97) sub-lineage. It was confirmed not only that four of their gene segments had a high genetic association with the zoonotic H9N2 virus, A/Human/India/TCM2581/2019, but also that they had many molecular markers associated with mammalian adaptation and enhanced virulence in mammals including the unique multiple basic amino acids, KSKR↓GLF at the HA cleavage site, and analog N-and O-glycosylation patterns on HA with that of the zoonotic H9N2 virus. Furthermore, future experiments would be to characterize these isolates biologically to address the public health concern. Importantly, due to the identification of these viruses at a strategic geographical location in India (a major stop-over point in the Central Asian flyway), these novel viruses also pose a possible threat to be exported to other regions via migratory/resident birds. Consequently, systematic investigation and active monitoring are a prerequisite for identifying and preventing the spread of viruses of zoonotic potential by enforcing strict biosecurity measures., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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.

Introduction: Mindfulness is a promising intervention for female sexual dysfunction (FSD); however, of the mindfulness interventions studied, few treat the woman and her partner., Aim: We developed a brief online mindfulness, resilience, and psychoeducation intervention, Stress Management and Resiliency Training for Sexuality (Sex SMART), for women with sexual health concerns and their partners., Methods: Women with female sexual interest/arousal disorder and their partners were recruited between February 24, 2015, and October 6, 2016, and randomized to treatment or control groups (received educational pamphlets). The treatment intervention comprised of an online SMART and sexual health psychoeducation module., Main Outcome Measures: The Female Sexual Function Index (FSFI), Female Sexual Distress Scale-Revised (FSDS-R), Sexual Desire Inventory-2 (SDI-2), Revised Dyadic Adjustment Scale (RDAS), International Index of Erectile Function (IIEF), and other subjective measures were used to assess sexual function and sexual distress at baseline and 12 weeks., Results: The study included 60 women and their partners (30 couples in each group). In both groups, sexual function by total FSFI scores and sexual distress scores significantly improved at 12 weeks compared with baseline, with no significant between-group differences (FSFI effect estimate for Sex SMART vs control = +1.4 (90% CI [-0.6 to +3.4]; P=.13). Both participants and partners randomized to the intervention reported significantly improved attitude and feelings, comfort as a sexual person, and subjective sexual functioning at 12 weeks. The findings provide preliminary evidence for efficacy of an online intervention for couples with sexual health problems., Conclusions: A brief online mindfulness, resilience, and psychoeducation-based intervention showed no significant improvement in many outcomes (FSFI, FSDS-R, SDI-2, RDAS) of sexual health versus controls. Although this is the first online randomized controlled trial to evaluate a mindfulness-based therapy intervention, it was limited by its lack of population diversity and high attrition rate. Significant improvements in subjective sexual health and partner sexual function by the International Index of Erectile Function were reported only in the intervention group. Rullo JE, Sood R, Fokken SC, et al. Couples' Use of Online Stress Management and Resiliency Training for Sexual Health Concerns: A Randomized Controlled Trial. Sex Med 2021;9:100404., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kalaiyarasu, Bhatia, Mishra, Senthil Kumar, Kumar, Sood, Rajukumar, Ponnusamy, Desai and Singh.)

Ovine herpesvirus 2 (OvHV-2) is the causative agent of sheep-associated malignant catarrhal fever (SA-MCF), a highly fatal disease syndrome that predominantly affects susceptible hosts of the order Artiodactyla . In this study, an in-depth clinico-molecular investigation of SA-MCF disease in a morbid 50-days-old cattle calf ( Bos taurus indicus ) and asymptomatic infection in the in-contact reservoir hosts, sheep ( Ovis aries ), and goat ( Capra hircus ) housed on a farm located in the Southern India is reported. An OIE recommended SA-MCF type-specific PCR confirmed the etiological agent as OvHV-2. The genetic characterization and phylogenetic analyses based on the glycoprotein B (gB) gene indicate that three genetic variants of OvHV-2 had infected the animal cluster of this study. As the OvHV-2 infection eventually lead to the death of the cattle calf, and the fact that its gB sequence carried four unique amino acid substitutions (N169S, L594P, I645V, and V730A), an investigation of these substitutions impact on its stability and molecular flexibility was carried out. The mapping of these amino acid substitutions on the three-dimensional structure of gB coupled with supplementary investigations showed that these substitutions conveyed the molecular flexibility to the gB, at the cost of its stability. Future studies would be to investigate whether these gB substitutions have any impact on membrane fusion activity using a virus-free cell-to-cell membrane fusion assay. The study also highlights the importance of adopting stringent biosecurity measures where mixed animal farming is a common practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kumar, Sood, Pateriya, Venkatesakumar, Ramprabhu, Dixit, Bhatia and Singh.)

Lumpy skin disease (LSD) caused by lumpy skin disease virus (LSDV) inflicts significant economic losses in cattle production with impact on livelihoods of smallholders. This study reports the first occurrence of LSD in cattle in India and analyses epidemiological and genetic characterization data from LSD outbreaks in five districts of Odisha state in August 2019. In all, 182 of 2,539 cattle were affected with an apparent morbidity rate of 7.1% and no mortality. Out of 102 samples from 60 LSD suspected and 17 asymptomatic in-contact cattle tested, 29.87% cattle were positive by capripoxvirus generic PCR and 37.66% were positive by LSDV real-time PCR. All the in-contact cattle tested were negative for LSDV. Among affected cattle, LSDV genome was detected more in scabs (79.16%) than blood (31.81%) and frozen bull semen (20.45%). Differential diagnosis by PCR was negative for pseudo-LSD, buffalopox, cowpox, pseudo-cowpox and bovine papular stomatitis. Five selected PCR and real-time PCR-positive LSDV DNA were sequenced in three genomic regions, P32 (LSDV074), F (LSDV117) and RPO30 (LSDV036). Phylogenetic analysis based on partial P32 and F gene sequences and complete RPO30 gene sequences showed that all the five Indian LSDV strains were identical and clustered with other field strains of LSDV circulating globally. However, the F and RPO30 gene sequence analyses revealed that Indian LSDV strains are genetically closer to the South African NI2490/KSGP-like strains than the strains detected in Europe, which was rather surprising. The present study established the existence of LSDV in India and involvement of LSDV field strains in the outbreaks. Additionally, we provided evidence of LSDV shedding in semen of naturally infected bulls. Further studies are required to determine the source of LSD introduction, extent of spread, modes of transmission and impact on dairy cattle production in India and effective control measures must be undertaken urgently., (© 2020 Blackwell Verlag GmbH.)

Background: Obesity and female sexual dysfunction (FSD) are prevalent conditions, and both are associated with significant adverse effects on health and well-being., Aim: To investigate the association between body mass index and FSD, as well as potential moderators., Methods: This cross-sectional study was performed by analyzing medical records of 6,688 women seeking consultation for menopause-related or sexual health-related concerns at women's health clinics at Mayo Clinic Rochester, MN, and Scottsdale, AZ, between May 1, 2015, and September 15, 2019., Outcomes: Female sexual function was assessed by the Female Sexual Function Index, and sexual distress was assessed by the Female Sexual Distress Scale-Revised., Results: Being overweight or obese was associated with a lack of sexual activity. Among sexually active women, those who were overweight or obese had lower Female Sexual Function Index total scores and sexual function domain scores (indicating worse sexual function), including sexual arousal, lubrication, satisfaction, orgasm, and pain, and higher levels of sexual distress than those with normal weight. However, on multivariable analysis, these associations were found to be mediated by other factors, including age, level of education, reproductive stage, medication use, and mood disturbances, which are known to impact body weight and sexual function in women., Clinical Implications: Overweight and obesity were associated with sexual inactivity and greater odds of having FSD, which should prompt proactive assessment of sexual function., Strengths and Limitations: The strengths of this study include the large cohort size and assessment of sexual problems in addition to sexual distress, a key component of the definition of sexual dysfunction. This study also took into account multiple potential moderating factors. Limitations include the cross-sectional design, which precludes determination of causality as well as lack of diversity in the cohort, potentially limiting generalizability of results. In addition, sexual function was not assessed in women reporting no recent sexual activity, which may confound results., Conclusion: Overweight/obesity and FSD are highly prevalent conditions, which appear to be indirectly associated. These results highlight the need to identify and address FSD in all overweight and obese women, with particular attention to potential contributing factors. Faubion SS, Fairbanks F, Kuhle CL, et al. Association Between Body Mass Index and Female Sexual Dysfunction: A Cross-sectional Study from the Data Registry on Experiences of Aging, Menopause, and Sexuality. J Sex Med 2020;17:1971-1980., (Copyright © 2020 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: Hypertensive disorders of pregnancy and menopausal symptoms, specifically vasomotor symptoms, have both been associated with cardiovascular disease risk in women. However, data are sparse on the association between these two female-specific cardiovascular risk factors. This study was conducted to investigate the association between a history of a hypertensive disorder of pregnancy and menopausal symptoms., Methods: This was a cross-sectional study of women aged 40 to 65 years seen for specialty consultation in women's health clinics at Mayo Clinic Rochester, MN and Scottsdale, AZ, between May, 2015 and September, 2019. A self-reported history of hypertensive disorders of pregnancy served as the independent variable, and menopause symptoms as assessed by the Menopause Rating Scale were the primary outcome measure., Results: Of 2,684 women included in the analysis, 180 had a self-reported history of a hypertensive disorder of pregnancy. The total menopausal symptom scores as well as somatic and psychological domain scores were higher in women with a history of a hypertensive disorder of pregnancy compared to women without a history of a hypertensive disorder of pregnancy or to women without a pregnancy. On multivariable analysis, women with a hypertensive disorder of pregnancy using hormone therapy had significantly higher total menopause symptom scores than women with no such history., Conclusions: In this large cross-sectional study, a history of hypertensive disorders of pregnancy was associated with more bothersome menopausal symptoms. Additional study is needed to determine the strength of this association, underlying mechanisms of the association, and clinical implications for cardiovascular risk prediction in women., Competing Interests: Financial disclosure/conflicts of interest: EK: Consultant for Mithra Pharmaceuticals and Astellas Pharmaceuticals., (Copyright © 2020 by The North American Menopause Society.)

Accurate and rapid diagnosis of Influenza A viruses (IAVs) is challenging because of multiple strains circulating in humans and animal populations, and the emergence of new strains. In this study, we demonstrate a simple and rapid strategy for visual detection of multiple strains of IAVs (H1 to H16 subtypes) using peptide nucleic acid (PNA) as a biosensor and unmodified gold nanoparticles (AuNPs) as a reporter. The design principle of the assay is based on the color change on account of free PNA-induced aggregation of AuNPs in the presence of non-complementary viral RNA sequence and vice-versa. The assay could detect IAV RNA with a visual limit of detection of 2.3 ng. The quantification of RNA with a considerable accuracy on a simple spectrophotometer was achieved on plotting the PNA-induced colorimetric changes (absorption ratio of A 640 /A 520 ) in the presence of a varying concentration of complementary RNA. As a proof-of-concept, the visual assay was validated on 419 avian clinical samples and receiver operating characteristic (ROC) curve analysis showed a high diagnostic specificity (96.46%, 95% CI = 93.8 to 98.2) and sensitivity (82.41%, 95% CI = 73.9 to 89.1) when RT-qPCR was used as reference test. Hence, the simplicity, rapidity, and universality of this strategy make it a potential candidate visual assay for clinical diagnosis and surveillance of IAVs, especially in the resource-limited settings. The proposed strategy establishes new avenues for developing a simple and rapid diagnostic system for viral infections and biomolecules., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: Understanding gender differences in self-perception of health (SPH) and self-efficacy can inform the design of tailored programs to improve health behaviors. We aimed to assess gender-specific differences in SPH and self-efficacy for maintaining wellness habits at a work-place wellness center. Methods: A workplace wellness center member survey was conducted in 2016. Information about SPH and self-efficacy to maintain wellness habits was assessed. Data were analyzed to assess gender differences in SPH and self-efficacy. Results: The survey was completed by 2784 members (mean age, 49.2 years; 68.2% women). SPH was similar between genders despite more men reporting health problems such as hypertension, diabetes, high cholesterol, and cigarette smoking. Women had higher self-efficacy about maintaining healthy diet, but the difference was not clinically meaningful. Women had lower self-efficacy in their ability to maintain physical activity. Conclusions: In this large cohort of worksite wellness center members, men and women had similar self-perception of health despite higher disease burden among men. Women had lower self-efficacy in their ability to maintain physical activity level but similar self-efficacy for maintaining healthy diet. These differences may inform the design of tailored wellness programs to meet the needs of both genders.

Objective: 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., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: Dr A. Sood is the owner of Global Center for Resiliency and Well-Being. Dr R. Sood is the spouse of Dr A. Sood. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.

Bovine leukaemia virus (BLV) causes enzootic leucosis in cattle and is prevalent worldwide. Although recent studies have shown that BLV strains can be classified into 10 distinct genotypes, no information is available regarding the BLV genotype prevalent in cattle in India. To determine the genetic variability in BLV, in this study, 118 adult dairy cows from three states of India were screened for BLV infection by env gp51-specific ELISA and nested PCR. Of the 33 cows found positive by both PCR and ELISA, 10 selected BLV strains were subjected to molecular characterization. Phylogenetic analyses of partial and full-length env gp51 gene sequences of Indian BLV strains and other geographical diverse BLV strains representing all the 10 genotypes revealed that Indian strains belonged to BLV genotype 6. Although Indian strains showed close genetic proximity with the strains circulating in South America, they were classified into a new subgenotype within genotype 6. Alignment of deduced amino acid sequences in gp51 demonstrated substitutions mainly in conformational epitope G, neutralizing domain 2 and linear epitope D, with a novel mutation (threonine to alanine at residue 252) found in D-epitope of all the Indian BLV strains. Although serological evidence of BLV infection in India has been reported earlier, this study on molecular characterization of BLV strains established the existence of BLV genotype 6 in India. Additionally, the results of this study highlight the importance of genetic analysis of geographically diverse BLV strains to understand BLV global genetic diversity and further studies are required to determine BLV genetic diversity and extent of BLV infection in cattle in India., (© 2018 Blackwell Verlag GmbH.)

Background: Since ancient times, potential of plants in research and medicine have found pronounced applications, due to better therapeutic value. To meet the mounting demands for commercial nanoparticles, novel eco-friendly methods of synthesis has led to a remarkable progress via unfolding a green synthesis protocol towards metallic nanoparticles synthesis., Hypothesis/purpose: This review highlights the biological synthesis of various metallic nanoparticles as safe, cost effective process, where the phytochemicals present in extract such as flavonoid, phenols, terpenoids act as capping, reducing and stabilizing agents. Moreover, due to their nano size, the nanoparticles directly bind to bacterial strains leading to higher antimicrobial activity., Conclusion: Nano-sized dosage systems have a potential for enhancing the activity and overcoming problems associated with phyto medicines. Hence, synthesis of metallic nanoparticles using various plant extracts, emerge as safe alternative to conventional methods for biomedical applications., (Copyright © 2017. Published by Elsevier GmbH.)

The present study deals with sequential optimization strategy based on Box-Behnken method to optimize the process variables for efficient production of Ocimum sanctum synthesized silver nanoparticles using biological synthesis. Four substantial factors influencing the dependent variables viz size, zeta potential, Polydispersity index (PDI) and yield were identified as silver nitrate concentration, temperature, amount of plant extract and stirring speed as independent variables. The contribution of the studied factors in monitoring dependent variables was evaluated via analysis of variance. The validity of the model developed was verified, and the statistical analysis showed that the optimal operational conditions were AgNO 3 concentration 5.29 mM, temperature 60 °C, agitation speed of 500 rpm and plant extract 2.24% (w/v) which primes to form silver nanoparticles of smallest size 83.41 nm and 0.24 with maximum zeta potential of -20.20mV and Yield of 18.62. In addition, the optimized AgNPs were characterized using DLS, TEM, FE-SEM and UV-vis analysis. The topical formulation was prepared by incorporation of optimized AgNPs into the carbopol gel base. Further, the gel was evaluated in vivo using the rat model of skin wound healing. The measurement of the wound areas was performed on 2nd, 4th, 6th, 8th, 10th, 12th and 14th days and the percentage of wound closures were calculated accordingly. By the 14th day, silver nanoparticle gel showed 96.20% wound healing activity compared with that of the standard as well as control base. The antibacterial inhibitory efficiency of prepared nano gel was found similar to the commercial product against the Staphylococcus aureus, E. coli and Pseudomonas aeruginosa., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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.

We tested 65 highly pathogenic avian influenza (HPAI) A(H5N1) viruses, isolated from avian species in India between 2006 and 2015, for susceptibility to the FDA approved neuraminidase (NA) inhibitors (NAIs), oseltamivir and zanamivir using a phenotypic fluorescence-based assay. The overall incidence of resistant variants among HPAI A(H5N1) viruses was 7.69% (5/65). The NA inhibition assay identified 3 viruses resistant to oseltamivir (N294S substitution, N2 numbering) and 2 cross-resistant to oseltamivir and zanamivir (E119A or I117V+E119A substitutions), all of which belonged to hemagglutinin (HA) clade 2.2 (5/17) and predominantly circulated in Indian poultry during 2006-2010. In comparison to E119A substitution alone, viruses with I117V+E119A double substitutions showed greater reduction in susceptibility to both oseltamivir and zanamivir. The NAI resistance-associated NA markers, identified in this study, were as a result of naturally occurring mutations. Of note, 48 viruses of HA clade 2.3.2.1 that circulated in Indian poultry during 2011-2015 were susceptible to both oseltamivir and zanamivir. It is essential to monitor NAI susceptibility among human and avian HPAI A(H5N1) viruses that would provide baseline data to develop strategies for pandemic preparedness and therapeutic interventions., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The present study was aimed at generating a reassortant vaccine candidate virus with clade 2.3.2.1 Hemagglutinin (HA) and its evaluation in a challenge study for protection against homologous (2.3.2.1 clade) and heterologous (2.2 clade) highly pathogenic avian influenza (HPAI) H5N1 viruses. Plasmid-based reverse genetics technique was used to rescue a 5 + 3 reassortant H5N2 strain containing the modified HA of H5N1 (clade 2.3.2.1), the Neuraminidase (NA) of H9N2, the Matrix (M) of H5N1 and the internal genes of A/WSN/33 H1N1. In addition, another 6 + 2 reassortant virus containing modified HA from H5N1 (clade 2.3.2.1), the NA from H9N2 and the internal genes of A/WSN/33 H1N1 was also rescued. The 5 + 3 reassortant H5N2 virus could grow to a higher titer in both MDCK cells and chicken eggs compared to the 6 + 2 reassortant H5N2 virus. The vaccine containing the inactivated 5 + 3 reassortant H5N2 virus was used in a two-dose immunization regime which protected specific pathogen free (SPF) chickens against two repeated challenges with homologous 2.3.2.1 clade and heterologous 2.2 clade HPAI H5N1 viruses. The 5 + 3 reassortant H5N2 virus based on clade 2.3.2.1 generated in this study can be effective in protecting chickens in the case of an outbreak caused by antigenically different clade 2.2 HPAI H5N1 viruses and opens the way to explore its applicability as potential vaccine candidate especially in the Asian countries reporting these clades frequently. The study also indicates that sequential immunization can broaden protection level against antigenically diverse strains of H5N1 viruses., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Dehydroepiandrosterone (DHEA) is helpful for treating vaginal symptoms. This secondary analysis evaluated the impact of vaginal DHEA on hormone concentrations, bone turnover, and vaginal cytology in women with a cancer history., Methods: Postmenopausal women, diagnosed with breast or gynecologic cancer, were eligible if they reported at least moderate vaginal symptoms. Participants could be on tamoxifen or aromatase inhibitors (AIs). Women were randomized to 3.25 versus 6.5 mg/day of DHEA versus a plain moisturizer (PM) control. Sex steroid hormone levels, biomarkers of bone formation, vaginal pH, and maturation index were collected at baseline and 12 weeks. Analysis included independent t tests and Wilcoxon rank tests, comparing each DHEA arm with the control., Results: Three hundred forty-five women contributed evaluable blood and 46 contributed evaluable cytology and pH values. Circulating DHEA-S and testosterone levels were significantly increased in those on vaginal DHEA in a dose-dependent manner compared to PM. Estradiol was significantly increased in those on 6.5 mg/day DHEA but not in those on 3.25 mg/day DHEA (p < 0.05 and p = 0.05, respectively), and not in those on AIs. Biomarkers of bone formation were unchanged in all arms. Maturation of vaginal cells was 100% (3.25 mg/day), 86% (6.5 mg/day), and 64% (PM); pH decreased more in DHEA arms., Conclusion: DHEA resulted in increased hormone concentrations, though still in the lowest half or quartile of the postmenopausal range, and provided more favorable effects on vaginal cytology, compared to PM. Estrogen concentrations in women on AIs were not changed. Further research on the benefit of vaginal DHEA is warranted in hormone-dependent cancers.

The Women's Health Clinic (WHC) at Mayo Clinic in Rochester, Minnesota, has provided consultative care to women with menopausal and sexual health concerns since 2005. Clinical information on the 8688 women seen in the WHC through May 2017 who gave consent for the use of their medical records in research is contained in the Data Registry on Experiences of Aging, Menopause, and Sexuality (DREAMS). Initially, DREAMS was created to improve the clinical care of women, but it has become a valuable research tool. About 25% of the DREAMS women have been seen in the WHC 2 or more times, allowing for passive longitudinal follow-up. Additionally, about 25% of the DREAMS women live in the 27-county region included in the expanded Rochester Epidemiology Project medical records linkage system, providing additional information on those women. The cohort has been used to investigate associations between: caffeine intake and vasomotor symptom bother; recent abuse (physical, sexual, verbal, and emotional) and menopausal symptoms; specific menopausal symptoms and self-reported view of menopause; and obstructive sleep apnea risk and vasomotor symptom severity and the experience of vasomotor symptoms in women older than 60 years. A study nearing completion describes a clinical series of over 3500 women presenting for sexual health consultation by sexual function domain and by decade of life. Other studies under way are determining correlates with sexual health and dysfunction. Planned studies will investigate associations between the experience with menopause and the risk of disease., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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., (Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: Equine influenza is a major health problem of equines worldwide. The polymerase genes of influenza virus have key roles in virus replication, transcription, transmission between hosts and pathogenesis. Hence, the comprehensive genetic and codon usage bias of polymerase genes of equine influenza virus (EIV) were analyzed to elucidate the genetic and evolutionary relationships in a novel perspective., Results: The group - specific consensus amino acid substitutions were identified in all polymerase genes of EIVs that led to divergence of EIVs into various clades. The consistent amino acid changes were also detected in the Florida clade 2 EIVs circulating in Europe and Asia since 2007. To study the codon usage patterns, a total of 281,324 codons of polymerase genes of EIV H3N8 isolates from 1963 to 2015 were systemically analyzed. The polymerase genes of EIVs exhibit a weak codon usage bias. The ENc-GC3s and Neutrality plots indicated that natural selection is the major influencing factor of codon usage bias, and that the impact of mutation pressure is comparatively minor. The methods for estimating host imposed translation pressure suggested that the polymerase acidic (PA) gene seems to be under less translational pressure compared to polymerase basic 1 (PB1) and polymerase basic 2 (PB2) genes. The multivariate statistical analysis of polymerase genes divided EIVs into four evolutionary diverged clusters - Pre-divergent, Eurasian, Florida sub-lineage 1 and 2., Conclusions: Various lineage specific amino acid substitutions observed in all polymerase genes of EIVs and especially, clade 2 EIVs underwent major variations which led to the emergence of a phylogenetically distinct group of EIVs originating from Richmond/1/07. The codon usage bias was low in all the polymerase genes of EIVs that was influenced by the multiple factors such as the nucleotide compositions, mutation pressure, aromaticity and hydropathicity. However, natural selection was the major influencing factor in defining the codon usage patterns and evolution of polymerase genes of EIVs.

Objectives: Bioidentical hormone therapy (BHT) is available in the United States in formulations that have been approved by the Food and Drug Administration (FDA) but also in formulations that have not been so approved. The aim of this study was to evaluate the knowledge, beliefs, and prescribing practices of BHT among healthcare providers., Study Design: A cross-sectional self-selected responder survey was conducted of health care providers attending primary care Continuing Medical Education (CME) conferences in the United States from May 2012 to April 2013. The questionnaire consisted of 26 items assessing knowledge, beliefs, and current practice around BHT., Results: A total of 366 survey responses were analyzed. Though 69.8% of respondents accurately identified the definition of BHT, only 45.3% were aware that BHT is available in FDA-approved products and 34.2% of respondents incorrectly identified that BHT is available only in custom-compounded formulations. Of those who had prescribed CC-BHT, less than half agreed with the statement "I am comfortable prescribing BHT" (45.4%)., Conclusions: Our study showed that many practitioners are unaware that bioidentical hormones are available in FDA-approved products. Knowledge gaps identified by this survey highlight the need for and importance of education to further dispel misinformation surrounding the topic., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Decision making regarding the use of menopausal hormone therapy (MHT) for the treatment of bothersome menopausal symptoms in a cancer survivor can be complex, and includes assessment of its impact on disease-free or overall survival. Estrogen receptors are present in several cancer types, but this does not always result in estrogen-mediated tumor proliferation and adverse cancer-related outcomes. Estrogen may even be protective against certain cancers. Menopausal hormone therapy is associated with an increased risk of recurrence and mortality after diagnosis of some cancer types, but not others. We provide a narrative review of the medical literature regarding the risk of cancer recurrence and associated mortality with initiation of MHT after the diagnosis of breast, gynecologic, lung, colorectal, hematologic cancers, and melanoma. Menopausal hormone therapy may be considered for management of bothersome menopausal symptoms in women with some cancer types (e.g., colorectal and hematologic cancer, localized melanoma, and most cervical, vulvar and vaginal cancers), while nonhormonal treatment options may be preferred for others (e.g., breast cancer). In women with other cancer types, recommendations are less straightforward, and the use of MHT must be individualized., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The study was designed to characterize and compare chicken bone marrow and peripheral blood monocyte derived dendritic cells (chBM-DC and chMoDC) and to evaluate inflammatory cytokine and chemokine alterations in response upon LPS stimulation. Typical morphology was observed in DCs from 48h of culture using recombinant chicken GM-CSF and IL-4. Maturation of DCs with LPS (1μg/ml) showed significant up regulation of mRNA of surface markers (CD40, CD80, CD83, CD86, MHC-II and DC-LAMP (CD208)), pro-inflammatory cytokines (IL-1β, IL-6, TNF-α (LITAF)), iNOS, chemokine CXCli2 and TLRs4 and 15. Basal level of TLR1 mRNA expression was higher followed by TLR15 in both DCs irrespective of their origin. Expression of iNOS and CXCLi2 mRNA in mature DCs of both origins were higher than other surface molecules and cytokines studied. Hence, its level of expression can also be used as an additional maturation marker for LPS induced chicken dendritic cell maturation along with CD83 and CD40. LPS matured DCs of both origins upregulated IL-12 and IFN-γ. Based on CD40 and CD83 mRNA expression, it was observed that LPS induced the maturation in both DCs, but chMoDCs responded better in expression of surface markers and inflammatory mediator genes., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: Several studies describe "elder abuse" among residents of nursing homes, but this issue is less well studied among independently functioning, community-based women. The current study was undertaken to report rates of self-reported intimate partner violence - with a focus on verbal abuse - among older women within a private tertiary women's health clinic., Methods: This study focused on women who completed a questionnaire on domestic abuse., Results: A total of 1389 women with a median age of 55 years (range: 50, 90) are the focus of this report. Most 1102 (79%) were married. Within this group, 100 (7%) women reported verbal abuse within the last year. Rates of physical and sexual abuse were much lower with 9 women (1%) and 2 (<1%), respectively. In univariate analyses, being divorced, being an alcoholic, and having suffered prior abuse were associated with reported verbal abuse. In multivariate analyses, self-reported alcoholism and physical abuse were independently associated with reported verbal abuse., Conclusion: This study found a notable rate of patient-reported verbal abuse in older women within a private, tertiary women's health clinic., Implications: This observation should prompt healthcare providers to ask about intimate partner violence - and specifically verbal abuse - regardless of healthcare setting., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: The aim of the study was to determine whether there is an association between current menopausal symptom bother and a history of abuse (physical, sexual, or emotional/verbal) in the last year., Methods: A cross-sectional survey was completed using the Data Registry on Experiences of Aging, Menopause, and Sexuality and the Menopause Health Questionnaire. Data from the Menopause Health Questionnaire were collected from 4,956 women seen consecutively for menopause consultation in the Women's Health Clinic at Mayo Clinic (Rochester, MN) from January 1, 2006 through October 7, 2014. Data from 3,740 women were included in the analysis. Menopausal symptom ratings were compared between women reporting a history of abuse (physical, sexual, or emotional/verbal) in the last year and those not using a two-sample t test. Analysis of covariance was used to assess whether abuse was associated with menopausal symptom bother after adjusting for baseline participant characteristics., Results: Of the 3,740 women, 253 (6.8%) reported experiencing one or more forms of abuse in the last year, the majority (96%) of which was verbal/emotional abuse. Those reporting abuse in the last year had higher (P < 0.001) mean total menopausal symptom bother scores. Consistent findings were obtained from multivariable analyses adjusting for all demographic and substance use characteristics., Conclusions: In the present study from the Data Registry on Experiences of Aging, Menopause, and Sexuality, menopausal symptom bother scores were directly associated with recent self-reported abuse.

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.

Emergence of antiviral resistance among H5N1 avian influenza viruses is the major challenge in the control of pandemic influenza. Matrix 2 (M2) inhibitors (amantadine and rimantadine) and neuraminidase inhibitors (oseltamivir and zanamivir) are the two classes of antiviral agents that are specifically active against influenza viruses and are used for both treatment and prophylaxis of influenza infections. Amantadine targets the M2 ion channel of influenza A virus and interrupts virus life cycle through blockade of hydrogen ion influx. This prevents uncoating of the virus in infected host cells which impedes the release of ribonucleoprotein required for transcription and replication of virion in the nucleus. The present study was carried out to review the status of amantadine resistance in H5N1 viruses isolated from India and to study their replicative capability. Results of the study revealed resistance to amantadine in antiviral assay among four H5N1 viruses out of which two viruses had Serine 31 Asparagine (AGT-AAT i.e., S31N) mutation and two had Valine 27 Alanine (GTT-GCT i.e., V27A) mutation. The four resistant viruses not only exhibited significant difference in effective concentration 50% (EC50) values of amantadine hydrochloride from that of susceptible viruses (P < 0.0001) but also showed significant difference between two different types (S31N and V27A) of mutant viruses (P < 0.05). Resistance to amantadine could also be demonstrated in a simple HA test after replication of the viruses in MDCK cells in presence of amantadine. The study identifies the correlation between in vitro antiviral assay and presence of established molecular markers of resistance, the retention of replicative capacity in the presence of amantadine hydrochloride by the resistant viruses and the emergence of resistant mutations against amantadine among avian influenza viruses (H5N1) without selective drug pressure., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The recurrent circulation of highly pathogenic avian influenza (HPAI) H5N1 in Indian poultry since 2006 resulted in emergence of the viruses of distinct antigenic clades of haemagglutinin (HA) with the majority of the H5N1 outbreaks since 2011 belonging to clade 2.3.2.1. The present study was aimed to characterize the antigenic profile of a collection of H5N1 HPAI viruses of clade 2.3.2.1 isolated in India by applying antigenic cartography, serological data and phylogenetic analysis. Eleven H5N1 viruses (2 of clade 2.2 and 9 of clade 2.3.2.1) were selected based on genetic analysis and were further characterized by antigenic cartography analysis based on cross HI (hemagglutination inhibition) data. This study highlights the intercladal antigenic differences between clades 2.3.2.1 and 2.2 and the intracladal antigenic divergence among the clade 2.3.2.1 viruses. Five viruses of clade 2.3.2.1 were also studied for analysis of glycosylation pattern of Hemagglutinin (HA) gene and the growth kinetics analysis in MDCK cells in which the viruses CL03485/H5N1 and 03CL488/H5N1 showed better replication kinetics than other viruses. The study presents a baseline data of antigenicity and other factors that can be used in the selection of suitable H5 vaccine strains or HA donor viruses to develop H5 vaccine strains by reverse genetics or other methods for control of currently circulating H5N1 viruses in Indian region., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: We assessed the association between caffeine intake and menopausal symptom bother, particularly vasomotor symptoms., Methods: A cross-sectional survey was conducted using the Menopause Health Questionnaire, which is a comprehensive survey of menopause-related health information. Questionnaires were completed by 2,507 consecutive women who presented with menopausal concerns at the Women's Health Clinic at Mayo Clinic (Rochester, MN) between July 25, 2005 and July 25, 2011. Data from 1,806 women who met all inclusion criteria were analyzed. Menopausal symptom ratings were compared between women who used caffeine and women who did not use caffeine using two-sample t test and analysis of covariance, with smoking and menopause status included as covariates. In all cases, two-tailed P < 0.05 was considered statistically significant., Results: Caffeine use was positively associated with mean (SD) vasomotor symptom scores (2.30 [0.91] vs 2.15 [0.94], P = 0.011). This finding remained significant after adjustment for menopause status and cigarette smoking (P = 0.027)., Conclusions: Caffeine use is associated with greater vasomotor symptom bother in postmenopausal women.

Women with a prior hysterectomy with and without oophorectomy represent special cohorts among those who require menopausal hormone therapy (HT), as a progestogen is not required for endometrial protection. This is relevant in light of recent research demonstrating superiority of estrogen therapy alone compared with estrogen plus a progestogen with respect to breast cancer risk and perhaps even cardiovascular protection. No longer is it appropriate to lump all HT regimens together when advising patients. Unfortunately, there is a general reluctance in the healthcare community to prescribe HT even a decade after publication of the results of the Women's Health Initiative trial. However, with subsequent research showing a favorable benefit/risk balance of short-term estrogen therapy in symptomatic, recently menopausal women, especially those who have undergone hysterectomy with oophorectomy, the need for educating patients and providers on the matter cannot be overemphasized.

Malignant catarrhal fever (MCF) is a fatal herpesvirus infection of domestic and wild ruminants, with a short and dramatic clinical course characterized primarily by high fever, severe depression, swollen lymph nodes, salivation, diarrhea, dermatitis, neurological disorders, and ocular lesions often leading to blindness. In the present study, fatal clinical cases of sheep associated malignant catarrhal fever (SA-MCF) were identified in cattle in the state of Karnataka. These cases were initially presented with symptoms of diarrhea, respiratory distress, conjunctivitis, and nasal discharges. Laboratory diagnosis confirmed the detection of ovine herpesvirus-2 (OvHV-2) genome in the peripheral blood samples of two ailing animals. The blood samples collected subsequently from sheep of the neighboring areas also showed presence of OvHV-2 genome indicating a nidus of infection in the region. The positive test results were further confirmed by nucleotide sequencing of the OIE approved portion of tegument gene as well as complete ORF8 region of the OvHV-2 genome. Phylogenetic analysis based on the sequence of the latter region indicated close genetic relationship with other OvHV-2 reported elsewhere in the world.

Highly pathogenic Avian influenza (HPAI) is a notifiable viral disease caused by avian influenza type A viruses of the Orthomyxoviridae family. Type A influenza genome consists of eight segments of negative-sense RNA. RNA segment 2 encodes three proteins, PB1, PB1-F2, and N40, which are translated from the same mRNA by ribosomal leaky scanning and reinitiation. Since these proteins are critical for viral replication and pathogenesis, targeting their expression can be one of the approaches to control and resist HPAI. MicroRNAs are short noncoding RNAs that regulate a variety of biological processes such as cell growth, tissue differentiation, apoptosis, and viral infection. In this study, a set of 300 miRNAs expressed in chicken lungs were screened against the HPAI virus (H5N1) segment 2 with different screening parameter like thermodynamic stability of heteroduplex, seed sequence complementarity, conserved target sequence, and target-site accessibility for identifying miRNAs that can potentially target the transcript of segment 2 of H5N1. Chicken miRNAs gga-mir-133c, gga-mir-1710, and gga-mir-146c* are predicted to target the expression of PB1, PB1-F2, and N40 proteins. This indicates that chicken has genetic potential to resist/tolerate H5N1 infection and these can be suitably exploited in designing strategies for control of avian influenza in chicken.

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.

Malignant catarrhal fever (MCF) is a fatal lymphoproliferative disease affecting bovids, cervids and other ruminant species caused by viruses belonging to subfamily Gammaherpesvirinae, genus Macavirus. Among the 10 MCF viruses known to cause the disease, alcelaphine herpesvirus 1 (AlHV-1) and ovine herpesvirus 2 (OvHV-2) are the two most widely prevalent causative organisms. The AlHV-1 naturally infects wildebeest and causes wildebeest associated MCF (WA-MCF) in cattle in regions of African sub-continent. The OvHV-2 is prevalent in all varieties of domestic sheep as a sub-clinical infection and causes sheep associated MCF (SA-MCF) in susceptible ruminants in most regions of the world. In India, the detection of cases of SA-MCF in cattle and OvHV-2 infection in sheep during the last decade has established the presence of the virus in native sheep of the country. The present review presents up to date information on various aspects of SA-MCF and its causative agent OvHV-2 with special reference to Indian scenario.

The present study was carried out with an aim to develop anti-nucleoprotein (anti-NP) monoclonal antibodies (MAbs) for use in immunodiagnostic testing for detection of avian influenza virus (AIV) antigen or antibodies. The NP gene of AIV, cloned in pET vector, was expressed in Escherichia coli BL 21 strain to produce a 6x-His tagged recombinant NP (rNP) antigen of ∼61 kDa molecular weight as soluble fraction. The rNP antigen was detected in soluble fraction of bacterial cell lysate with anti-His HRPO conjugate and reacted with the reference AIV antibody positive serum in immunoblotting. The rNP was used to immunize BALB/c mice to produce hybridoma secreting anti-NP MAbs. Out of 11 anti-NP MAbs produced, 8D2-H5, 8D2-H9, and 6D11-A7 were of IgM isotype and 5D10-C9 and 5D10-F11 were of IgG2b type, while 3F3-D2, 7D2-C9, 7D2-G7, and 7D2-G8 were of IgG1 isotype. The MAbs 3F3-D2 and 7D2-G8 showed high intensity positive reaction with rNP and a low intensity reaction with H5N1 virus in Western blot analysis. The anti-NP MAbs produced in the present work may be valuable in developing a competitive ELISA or immunochromatographic strip test-based assays for the rapid diagnosis of avian influenza.

Objective: Bioidentical compounded hormone therapy is popular among patients, but providers do not have pharmacokinetic information or dosing guidelines for these preparations. Our objective was to compare the pharmacokinetics of the commonly used compounded preparations with conventional hormonal preparations that are considered bioequivalent in practice., Methods: We conducted a randomized, blinded, four-arm 16-day clinical trial of forty postmenopausal women assigned to one of three doses of a compounded estrogen cream (Bi-est (80:20); 2.0, 2.5, or 3.0 mg)+compounded oral progesterone 100 mg, or to a conventional estradiol patch (Vivelle-Dot™ 0.05 mg)+Prometrium™ 100mg. Serum levels of estrone, estradiol, estriol, and progesterone were obtained at multiple time intervals during the first 24-h, and at steady-state., Results: Results were analyzable for 37/40 women. Study medications were well tolerated. The AUC at 24h and at steady-state for estrogens remained consistently lower for all doses of Bi-est tested relative to the patch. The difference was statistically significant for Bi-est 2.0mg (AUC-estradiol=181 vs. 956; p<0.001) and 2.5mg (AUC-estradiol=286 vs. 917; p<0.001). Estriol levels remained low in all study arms. Serum progesterone levels were comparable in conventional vs. compounded groups., Conclusions: This pharmacokinetic trial showed that the currently used doses of compounded hormones yield lower levels of estrogen compared to the standard-dose estradiol patch. To find comparable doses, further studies are needed. This successfully conducted randomized controlled study attests to the feasibility of using a similar design in the setting of a larger clinical trial., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective: Paced breathing (slow, deep, diaphragmatic breathing) reduces central sympathetic activity and facilitates the relaxation response. The present study was designed to assess the feasibility of and to obtain initial efficacy estimates of two paced-breathing programs, compared with usual breathing, for the frequency and severity of hot flashes., Methods: We designed a 9-week, randomized, three-arm, parallel-group, blinded (investigator) phase II clinical trial. Using an audio CD, participants in the active arms practiced paced breathing at 6 breaths/minute for 15 minutes, either once or twice a day, whereas the control arm practiced usual breathing at 14 breaths/minute for 10 minutes/day. Feasibility was assessed through self-report questionnaires; percent reduction and effect size estimates were determined using changes in hot flash frequency and scores within each group., Results: Of the 92 eligible participants, 68 (74%) completed the study. Most women reported that the intervention was easy to do (79%) and of appropriate duration (71%). They could practice exercises as taught (61%) and could practice on most days (65%). Participants in all arms reported hot flash reductions during the 9 weeks: 52% for paced breathing twice a day, 42% for paced breathing once a day, and 46% for usual breathing., Conclusions: The paced-breathing intervention is feasible. Although paced breathing twice a day seems to be the most helpful dose, efforts to intensify paced breathing once a day may be more practical for widespread dissemination. The efficacy and overall clinical impact of paced-breathing exercises on hot flash reduction require further evaluation in an adequately powered, placebo-controlled, randomized phase III clinical trial.

Crude extracts of leaves and bark of E. jambolana were tested for antiviral activity against highly pathogenic avian influenza virus (H5N1) by CPE reduction assay in three different layouts to elucidate virucidal, post-exposure and preexposure antiviral activity of the extracts. The cold and hot aqueous extracts of bark and hot aqueous extract of leaves of E. jambolana showed significant virucidal activity (100% inhibition) which was further confirmed in virus yield reduction assay (-98 to 99% reduction) and by egg based in ovo assay. The selective index (CC50/EC50) of hot aqueous extract (248) and cold aqueous extract (43.5) of bark of E. jambolana showed their antiviral potential against H5N1 virus. The significant virucidal activity of leaves and bark of E. jambolana merits further investigation as it may provide alternative antiviral agent for managing avian influenza infections in poultry farms and potential avian-human transmission.

Menstrual migraine and other hormonally related headaches are common in women. Falling estrogen levels or estrogen withdrawal after periods of sustained higher levels can trigger migraine. It makes sense to target this trigger for management of hormonally related headaches, particularly when nonhormonal strategies have been unsuccessful. Decision making regarding the use of hormonal contraception and menopausal hormone therapy is complex and commonly driven by other factors, but hormonal manipulation can potentially improve the course of migraine. Providers caring for migraineurs are appropriately concerned about stroke risk. Estrogen-containing hormonal contraceptives are relatively contraindicated for women who have migraine with aura. Postmenopausal hormone therapy is acceptable for women with a history of migraine. For these women, transdermal estradiol is recommended. Estrogen replacement is important for women who undergo an early menopause, whether natural or induced. Practical strategies for hormonal manipulation in the management of migraine and other hormonally related headaches are presented.