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Abstract Background Duplication, followed by fixation or random loss of novel genes, contributes to genome evolution. Particular outcomes of duplication events are possibly associated with pathogenic life histories in fungi. To date, differential gene gain and loss have not been studied at genomic scales in fungal pathogens, despite this phenomenon's known importance in virulence in bacteria and viruses. Results To determine if patterns of gene duplication differed between pathogens and non-pathogens, we identified gene families across nine euascomycete and two basidiomycete species. Gene family size distributions were fit to power laws to compare gene duplication trends in pathogens versus non-pathogens. Fungal phytopathogens showed globally altered patterns of gene duplication, as indicated by differences in gene family size distribution. We also identified sixteen examples of gene family expansion and five instances of gene family contraction in pathogenic lineages. Expanded gene families included those predicted to be important in melanin biosynthesis, host cell wall degradation and transport functions. Contracted families included those encoding genes involved in toxin production, genes with oxidoreductase activity, as well as subunits of the vacuolar ATPase complex. Surveys of the functional distribution of gene duplicates indicated that pathogens show enrichment for gene duplicates associated with receptor and hydrolase activities, while euascomycete pathogens appeared to have not only these differences, but also significantly more duplicates associated with regulatory and carbohydrate binding functions. Conclusion Differences in the overall levels of gene duplication in phytopathogenic species versus non-pathogenic relatives implicate gene inventory flux as an important virulence-associated process in fungi. We hypothesize that the observed patterns of gene duplicate enrichment, gene family expansion and contraction reflect adaptation within pathogenic life histories. These adaptations were likely shaped by ancient, as well as contemporary, intimate associations with monocot hosts.

There are sparse data on the role of the vaginal microbiome (VMB) in pregnancy among pregnant women living with HIV (PWLWH) and its association with spontaneous preterm birth (sPTB). We conducted a scoping review to assess associations between vaginal microbiota and sPTB among PWLWH. Three studies were included, representing a total of 180 PWLWH out of 652 total pregnancies. All studies used modern DNA sequencing methods (16S rRNA amplification, metagenomics, or metatranscriptomics). PWLWH had higher VMB richness and diversity compared to HIV-uninfected pregnant women and higher sPTB rates in two of three studies. A higher proportion of sPTB among PWLWH was observed in those with Lactobacillus-deficient, anaerobe-dominant vaginal microbiota. In two of three studies, higher concentrations of vaginal inflammation markers were associated with increased VMB richness and diversity. HIV status was independently associated with sPTB. It is unclear if increased vaginal microbial diversity among PWLWH or increased vaginal inflammation contributes more to PTB, but HIV does appear to alter the VMB in pregnant individuals and may also affect PTB rates in microbiome-independent pathways. Given the limited number of studies, heterogeneity in sample size, sample collection methods, and inconsistent results it is difficult to causally link HIV, VMB, inflammatory cytokines, and sPTB., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The perinatal transmission of HIV is preventable through a regimen that includes testing of all pregnant individuals, antiretroviral treatment (ART) for the pregnant individual, prophylactic or preventative ART for the infant, and cesarean section delivery for mothers with HIV viremia at the time of delivery. Under this protocol, the United States has seen a significant decline in the perinatal transmission of HIV and achieved a perinatal HIV transmission rate of 0.9% in 2019. However, despite this progress nationally and after zero transmissions in 2021, Maryland recorded 6 cases of perinatal HIV diagnoses in 2022. Each of the 3 major referral centers for pediatric HIV patients in Maryland reported 2 new cases in 2022. A root cause analysis of the cases identified risk factors including delayed entry into perinatal and HIV care, premature birth, maternal adherence challenges in the setting of substance use and other adverse social determinants of health, and failure to diagnose maternal HIV infection in a timely way. All patients were successfully linked to care and initiated on ART. Multiple factors contributed to the 2022 increase in cases of perinatal HIV in Maryland. To achieve and then sustain the elimination of perinatal HIV transmission, the constancy of systems that eliminate barriers for all pregnant people to access testing, prevention, and treatment is critical., (Copyright © 2024 by the American Academy of Pediatrics.)

Background: Breast cancer brain metastasis is a rising occurrence, necessitating a better understanding of the mechanisms involved for effective management. Breast cancer brain metastases diverge notably from the primary tumor, with gains in kinase and concomitant losses of steroid signaling observed. In this study, we explored the role of the kinase receptor RET in promoting breast cancer brain metastases and provide a rationale for targeting this receptor., Methods: RET expression was characterized in a cohort of patients with primary and brain metastatic tumors. RET functionality was assessed using pharmacological inhibition and gene silencing in patient-derived brain metastatic tumor explants and in vivo models, organoid models, and brain organotypic cultures. RNA sequencing was used to uncover novel brain metastatic relevant RET mechanisms of action., Results: A statistically significant enrichment of RET in brain metastases was observed in estrogen receptor-positive breast cancer, where it played a role in promoting cancer cell adhesion, survival, and outgrowth in the brain. In vivo, RET overexpression enhanced brain metastatic competency in patient-derived models. At a mechanistic level, RET overexpression was found to enhance the activation of gene programs involved in cell adhesion, requiring EGFR cooperation to deliver a pro-brain metastatic phenotype., Conclusion: Our results illustrate, for the first time, the role of RET in regulating colonization and outgrowth of breast cancer brain metastasis and provide data to support the use of RET inhibitors in the management strategy for patients with breast cancer brain metastases., (© The Author(s) 2024. Published by Oxford University Press.)

This review illuminates the complex interplay between various maternal microbiomes and their influence on preterm birth (PTB), a driving and persistent contributor to neonatal morbidity and mortality. Here, we examine the dynamics of oral, gastrointestinal (gut), placental, and vaginal microbiomes, dissecting their roles in the pathogenesis of PTB. Importantly, focusing on the vaginal microbiome and PTB, the review highlights (1) a protective role of Lactobacillus species; (2) an increased risk with select anaerobes; and (3) the influence of social health determinants on the composition of vaginal microbial communities., Competing Interests: Disclosure None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Syphilis incidence is increasing among reproductive-aged women, and previous sexually transmitted infections (STIs) are a risk factor for subsequent STIs. This study aimed to determine syphilis incidence after a chlamydia, gonorrhea, or HIV diagnosis, and identify characteristics associated with higher syphilis incidence rates among reproductive-aged women in 1 mid-Atlantic city., Methods: A retrospective cohort of 85,113 chlamydia, gonorrhea, and HIV diagnoses occurring between 2009 and 2021 and among women aged 13 to 50 years was constructed using public health surveillance data. Cumulative incidence curves were estimated to examine time to early syphilis (i.e., primary, secondary, or early latent) diagnosis, and multivariable analyses determined incidence rate ratios by age (<25 vs. ≥25 years) and number of prior STI diagnoses (0 vs. ≥1) during the study period, stratified by STI., Results: There were 85,113 reportable STI diagnoses and 646 syphilis diagnoses in the cohort. Approximately 1 of 150 chlamydia, 1 of 100 gonorrhea, and 1 of 50 HIV diagnoses were followed by a syphilis diagnosis within 5 years. Cumulative incidence of syphilis differed significantly by STI diagnosis ( P < 0.001). In multivariable analysis, syphilis incidence rates were higher among women diagnosed with ≥1 (vs. 0) prior STI regardless of STI type ( P < 0.05) and among women ≥25 (vs. <25) years old diagnosed with gonorrhea ( P < 0.05)., Conclusions: There were significant differences in syphilis incidence by prior STI type, number of STIs, and age. Our data support targeted screening for syphilis among women with a history of STIs, parwomen with ≥1 prior STI diagnosis, and older women diagnosed with gonorrhea., Competing Interests: Conflict of Interest and Sources of Funding: None declared., (Copyright © 2024 American Sexually Transmitted Diseases Association. All rights reserved.)

Previous work has shown that activation of tiger salamander retinal radial glial cells by extracellular ATP induces a pronounced extracellular acidification, which has been proposed to be a potent modulator of neurotransmitter release. This study demonstrates that low micromolar concentrations of extracellular ATP similarly induce significant H + effluxes from Müller cells isolated from the axolotl retina. Müller cells were enzymatically isolated from axolotl retina and H + fluxes were measured from individual cells using self-referencing H + -selective microelectrodes. The increased H + efflux from axolotl Müller cells induced by extracellular ATP required activation of metabotropic purinergic receptors and was dependent upon calcium released from internal stores. We further found that the ATP-evoked increase in H + efflux from Müller cells of both tiger salamander and axolotl were sensitive to pharmacological agents known to interrupt calmodulin and protein kinase C (PKC) activity: chlorpromazine (CLP), trifluoperazine (TFP), and W-7 (all calmodulin inhibitors) and chelerythrine, a PKC inhibitor, all attenuated ATP-elicited increases in H + efflux. ATP-initiated H + fluxes of axolotl Müller cells were also significantly reduced by amiloride, suggesting a significant contribution by sodium-hydrogen exchangers (NHEs). In addition, α-cyano-4-hydroxycinnamate (4-cin), a monocarboxylate transport (MCT) inhibitor, also reduced the ATP-induced increase in H + efflux in both axolotl and tiger salamander Müller cells, and when combined with amiloride, abolished ATP-evoked increase in H + efflux. These data suggest that axolotl Müller cells are likely to be an excellent model system to understand the cell-signaling pathways regulating H + release from glia and the role this may play in modulating neuronal signaling. NEW & NOTEWORTHY Glial cells are a key structural part of the tripartite synapse and have been suggested to regulate synaptic transmission, but the regulatory mechanisms remain unclear. We show that extracellular ATP, a potent glial cell activator, induces H + efflux from axolotl retinal Müller (glial) cells through a calcium-dependent pathway that is likely to involve calmodulin, PKC, Na + /H + exchange, and monocarboxylate transport, and suggest that such H + release may play a key role in modulating neuronal transmission.

To describe predictors of patient satisfaction with pain control including opioid prescribing practices, patients undergoing minor gynaecologic and urogynaecologic surgeries were included in a prospective cohort study. Satisfaction with postoperative pain control by opioid prescription status was analysed using bivariate analysis and multivariable logistic regression, controlling for potential confounders. Among participants completing both postoperative surveys, 112/141 (79.4%) reported pain control satisfaction by day 1-2 and 118/137 (86.1%) by day 14. While we were underpowered to detect a true difference in satisfaction by opioid prescription, there were no differences in opioid prescription among patients satisfied with pain control [52% vs. 60% ( p  = .43) among satisfied patients at day 1-2 and 58.5% vs. 37% ( p  = .08) at day 14]. Significant predictors of pain control satisfaction were postoperative day (POD) 1-2 average pain at rest [aOR 0.72 (95% CI 0.52-0.99), p  = .04], rating of shared decision-making [aOR 1.16 (95% CI 1.004-1.34), p  = .04], amount of pain relief [aOR 1.28 (95% CI 1.07-1.54), p  = .008) and POD 14 shared decision-making rating [aOR 1.45 (95% CI 1.19-1.77), p  = .002].Impact Statement What is already known on this subject? There are little data published on opioid prescription rates after minor gynaecologic procedures and no formal evidence-based guidance for gynaecologic providers for opioid prescribing. Few publications describe rates of opioid prescription and use following minor gynaecologic procedures. In the setting of a dramatic escalation of opioid misuse in the United States over the last decade, we sought to describe our practice of opioid prescription following minor gynaecologic procedures and answer the question of whether patient satisfaction is affected by opioid prescription, fill and use. What do the results of this study add? Though underpowered to detect our primary outcome, our results suggest that patient satisfaction with pain control may primarily be significantly affected by the patient's subjective assessment of shared decision-making with the gynaecologist. What are the implications of these findings for clinical practice and/or further research? Ultimately, these preliminary findings suggest a larger cohort is needed to answer the question of whether pain control satisfaction is influenced by receipt/fill/use of opioids after minor gynaecologic surgery.

Behavioral contrast is defined as a change in reinforcement conditions in one context that causes a change in behavior in the opposite direction in another, unchanged context. Although behavioral contrast has implications for applied behavior analysts, researchers have not examined ramifications or identified common methods of mitigating contrast in applied settings. Therefore, we surveyed Board Certified Behavior Analysts in an exploratory investigation to determine practitioner experiences with behavioral contrast. Participants' responses reflected a variety of themes: contrast resulted in conversations with stakeholders; supporting stakeholders and mitigating factors are important; contrast is due to inconsistencies across settings; and contrast affects stakeholder buy-in, hurts rapport or relationships, and produces negative emotions. Our results suggest that contrast is not an innocuous occurrence in applied settings. We recommend a variety of areas for future research to further predict and control contrast and to identify the extent to which it affects clinical practice., (© 2023 Society for the Experimental Analysis of Behavior (SEAB).)

Microbiome science offers a glimpse into personalized medicine by characterizing health and disease states according to an individual's microbial signatures. Without a critical examination of the use of race as a variable, microbiome studies may be susceptible to the same pitfalls as other areas of science grounded in racist biology. We will examine the use of race as a biological variable in pregnancy-related microbiome research. Emerging data from studies that investigate the intestinal microbiome in pregnancy suggest strong influence of a poor diet on adverse pregnancy outcomes. Differences in the vaginal microbiome implicated in adverse pregnancy outcomes are frequently attributed to race. We review evidence that links systemic racism to pregnancy health outcome differences with a focus on the vaginal and intestinal microbiomes as well as diet. We also review how structural racism ultimately contributes to inequitable access to healthy food and higher risk environmental exposures among pregnant people of lower socioeconomic status and exacerbates common pregnancy comorbidities., Competing Interests: Financial Disclosure Anna Maya Powell receives royalty payments from UpToDate for authorship. The other authors did not report any potential conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

The ShcA adapter protein is necessary for early embryonic development. The role of ShcA in development is primarily attributed to its 52 and 46 kDa isoforms that transduce receptor tyrosine kinase signaling through the extracellular signal regulated kinase (ERK). During embryogenesis, ERK acts as the primary signaling effector, driving fate acquisition and germ layer specification. P66Shc, the largest of the ShcA isoforms, has been observed to antagonize ERK in several contexts; however, its role during embryonic development remains poorly understood. We hypothesized that p66Shc could act as a negative regulator of ERK activity during embryonic development, antagonizing early lineage commitment. To explore the role of p66Shc in stem cell self-renewal and differentiation, we created a p66Shc knockout murine embryonic stem cell (mESC) line. Deletion of p66Shc enhanced basal ERK activity, but surprisingly, instead of inducing mESC differentiation, loss of p66Shc enhanced the expression of core and naive pluripotency markers. Using pharmacologic inhibitors to interrogate potential signaling mechanisms, we discovered that p66Shc deletion permits the self-renewal of naive mESCs in the absence of conventional growth factors, by increasing their responsiveness to leukemia inhibitory factor (LIF). We discovered that loss of p66Shc enhanced not only increased ERK phosphorylation but also increased phosphorylation of Signal transducer and activator of transcription in mESCs, which may be acting to stabilize their naive-like identity, desensitizing them to ERK-mediated differentiation cues. These findings identify p66Shc as a regulator of both LIF-mediated ESC pluripotency and of signaling cascades that initiate postimplantation embryonic development and ESC commitment.

Vulvovaginitis occurs in mostly reproductive aged women. Recurrent vaginitis affects overall quality of life, with a large financial burden on the patient, family, and health system. This review discusses a clinician's approach to vulvovaginitis with specific attention to the 2021 updated Center for Disease Control and Prevention guidelines. The authors discuss the role of the microbiome in vaginitis and evidence-based approaches for diagnosis and treatment of vaginitis. This review also provides updates on new considerations, diagnosis, management, and treatment of vaginitis. Desquamative inflammatory vaginitis and genitourinary syndrome of menopause are discussed as differential diagnosis of vaginitis symptoms., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Shared decision making for infant feeding in the context of HIV in high-resourced settings is necessary to acknowledge patient autonomy, meet increasing patient requests and address the changing reality of perinatal HIV care. In low-to middle-income countries (LMIC), where the majority of individuals living with HIV reside, persons with HIV are recommended to breastfeed their infants. In the setting of maternal anti-retroviral therapy (ART) use throughout pregnancy, viral suppression and appropriate neonatal post-exposure prophylaxis (PEP) use, updated information indicates that the risk of HIV transmission through breastmilk may be between 0.3 and 1%. While not endorsing or recommending breastfeeding, the United States' DHHS perinatal guidelines are similarly pivoting, stating that individuals should "receive patient-centred, evidence-based counselling on infant feeding options." Similar statements appear in the British, Canadian, Swiss, European, and Australasian perinatal guidelines. We assembled a multi-disciplinary group at our institution to develop a structured shared decision-making process and protocol for successful implementation of breastfeeding. We recommend early and frequent counselling about infant feeding options, which should include well known benefits of breastfeeding even in the context of HIV and the individual's medical and psychosocial circumstances, with respect and support for patient's autonomy in choosing their infant feeding option., Competing Interests: AMP receives royalties from UpToDate for authorship. JRA previously received HRSA-Ryan White Part A, C, D institutional funding; CDC/HRSA renumeration for serving on a data safety and monitoring board (HIV/STD/Viral Hepatitis panel); payment for participation in faculty workshops from the University of Pittsburgh, DKB Med Inc and AIDS Healthcare Foundation. KM (the Well Project) has received unrestricted funding from ViiV Healthcare, Gilead and Merck., (© 2023 The Author(s).)

HIV infection is a clinically significant public health disease and contributes to increased risk of maternal and fetal morbidity and mortality. HIV pregnancy studies use outcome measures as metrics to show how people with HIV feel, function, or survive. These endpoints are crucial for tracking the evolution of HIV illness over time, assessing the effectiveness of antiretroviral therapy (ART), and comparing outcomes across studies. Although the need for ideal outcome measures is widely acknowledged, selecting acceptable outcome measures for these HIV pregnancy studies can be challenging. We discuss the many outcome measures that have been implemented over time to assess HIV in pregnancy studies, their benefits, and drawbacks. Finally, we offer suggestions for improving the reporting of outcome measures in HIV in pregnancy studies. Medical professionals can best care for pregnant women living with HIV receiving ART by having a thorough understanding of these outcome metrics., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Rates of unintended pregnancy may be higher in women living with human immunodeficiency virus (WLWH) than in the general population, and it is unclear how populations of WLWH with intended and unintended pregnancy differ. We compared baseline characteristics and outcomes between WLWH with intended and unintended pregnancy. Materials and Methods: We conducted a retrospective analysis of WLWH enrolled in a human immunodeficiency virus (HIV) and Pregnancy clinic from 2003 to 2014. Data were analyzed using descriptive statistics, chi-square test, Student's t -test, one-way analysis of variance, and linear and logistic regression analysis. Two-tailed p -value <0.05 was considered significant. The study was approved by the Johns Hopkins University School of Medicine Institutional Review Board. Results: Sixty-nine (27.1%) of 255 women reported an intended pregnancy. Women with intended pregnancy (WWIP) were more likely to be older, White, married, privately insured, and college educated. WWIP were less likely to use tobacco (15.9% vs. 44.2%, p  < 0.001), alcohol (2.9% vs. 11.1%, p  = 0.041), opiates (0.0% vs. 19.3%, p  < 0.001), or cocaine (2.9% vs. 21.0%, p  < 0.001) during pregnancy, more likely to disclose their HIV status to the father of the baby by delivery (100.0% vs. 15.8%, p  < 0.001), and more likely to receive less effective contraception at delivery (condoms 14.9% vs. 4.8%, p  = 0.024; sterilization 11.9% vs. 22.1%, p  = 0.028). In multivariate regression analysis, pregnancy intendedness was an important predictor of nondetectable viral load at pregnancy entry but not at delivery. Conclusions: WLWH vary in their baseline characteristics and pregnancy outcomes depending on pregnancy intendedness, highlighting the need to improve pregnancy timing in WLWH and intensify interventions for women with unintended pregnancy.

Background: Maternal markers of intestinal immune activation may be used to predict preterm birth (PTB) in pregnant women living with HIV., Methods: This study used de-identified samples from the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) Protocol P1025 study. Singleton pregnancies with ≥3 ml plasma available and HIV viral load ≤400 copies/ml within 4 weeks of specimen collection were included. Frequency matching of PTB cases and term birth controls was performed on basis of maternal race, number of available plasma specimens, and timing of plasma sample collection in a 1:1 ratio. Plasma progesterone, 25-hydroxy vitamin D, soluble CD14, intestinal fatty acid binding protein (I-FABP), Lipopolysaccharide (LPS)-binding protein, and inflammatory cytokines (IL-1B, IFN-gamma, IL-6, TNF-alpha) were measured. Generalized mixed linear regression modeling was used to examine the association between PTB and biomarkers, adjusting for covariates and confounders. Data analyses were performed using SAS 9.4 (Cary, NC)., Results: We included 104 PTB compared to 104 controls. Third trimester log2 IL-1B was lower among PTB versus term birth controls by univariate analysis (-1.50 ± 2.26 vs. -.24 ± 2.69, p = .01) though this association was no longer significant by regression modeling. In an uncontrolled, exploratory sub-analysis, subjects with prior PTB had increased odds of PTB with higher I-FABP [aOR 2.72, 95% CI 1.18-6.24] and lower IFN-gamma [aOR .23, 95% CI .12-.41] after adjustment for covariates and confounders., Conclusions: Intestinal immune activation measured by soluble CD14 or intestinal fatty acid binding protein was not associated with preterm birth among pregnant women with low-level HIV viremia., (© 2023 The Authors. American Journal of Reproductive Immunology published by John Wiley & Sons Ltd.)

Germ cell development requires interplay between factors that balance cell fate and division. Early in their development, germ cells in many organisms divide mitotically with incomplete cytokinesis. Key regulatory events then lead to the specification of mature gametes, marked by the switch to a meiotic cell cycle program. Though the regulation of germ cell proliferation and meiosis are well understood, how these events are coordinated during development remains incompletely described. Originally characterized in their role as nucleo-cytoplasmic shuttling proteins, β-importins exhibit diverse functions during male and female gametogenesis. Here, we describe novel, distinct roles for the β-importin, Transportin-Serine/Arginine rich (Tnpo-SR), as a regulator of the mitosis to meiosis transition in the Drosophila ovary. We find that Tnpo-SR is necessary for germline stem cell (GSC) establishment and self-renewal, likely by controlling the response of GSCs to bone morphogenetic proteins. Depletion of Tnpo-SR results in germ cell counting defects and loss of oocyte identity. We show that in the absence of Tnpo-SR, proteins typically suppressed in germ cells when they exit mitosis fail to be down-regulated, and oocyte-specific factors fail to accumulate. Together, these findings provide new insight into the balance between germ cell division and differentiation and identify novel roles for β-importins in germ cell development., Competing Interests: Declaration of competing interest The authors declare no competing conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The ability to conduct spatially controlled RNA interference (RNAi) for gene knockdown using the UAS/Gal4 system is among the most appealing techniques available for analysis of gene function in the Drosophila ovary. While gene knockdown experiments in somatic cells in the developing organism (i.e., embryos and larvae) are effectively and commonly performed, the use of RNAi in adult ovarian cells can be hampered by the unintended deleterious effects of Gal4 expression in "off-target" developing tissues. Mosaic analysis overcomes these problems by imparting temporal and spatial control over gene manipulation, providing a useful tool to compare manipulated cells with wild-type cells in the same tissue. Here, we provide a method to utilize the UAS/Gal4 system in combination with the Flippase (FLP)-Flippase Recognition Target (FRT) system to generate positively labeled "FLP-Out" clones expressing a chosen RNAi in both the germline and the soma in the Drosophila ovary. This protocol outlines each step of the generation of clones and the selection of appropriate fly stocks and reagents, providing a guide to this powerful tool in the Drosophila genetic toolbox. These techniques allow for RNAi analysis within a specific cell type, providing an opportunity to study a variety of unique aspects of cell function that would not be possible in more traditional RNAi-based experiments., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Inhalation is a critical route for occupational exposure. To protect workers from adverse effects, health-based exposure limits (HBELs) are derived using chemical-specific information including inhalation bioavailability. Inhalation bioavailability of large proteins is well studied and generally accepted to be 1% or less. However, the inhalation bioavailability of peptides and proteins 1-10 kDa in size is not well defined. The goal of this study was to expand upon previous analyses and evaluate the inhalation bioavailability of small peptides. Inhalation bioavailability data for 72 peptides and protein samples ranging from 1.1 to 10.9 kDa in size were evaluated. The median inhalation bioavailability was 20%, which is in agreement with previously published analyses. Inhalation bioavailabilities for the vast majority were below 50%. Interestingly, species, peptide size, and peptide identity did not correlate with inhalation bioavailability. Other factors including inhalation dosimetry, peptide degradation, and chemical characteristics also decrease the amount of peptide available for absorption. Together, the median bioavailability of 20% is likely an appropriate estimate of systemic exposure and is sufficiently protective in most cases for the purposes of occupational exposure safety. Thus, in the absence of peptide-specific data or concerns, an inhalation bioavailability default of 20% is recommended for 1-10 kDa peptide and proteins., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ernest Fung reports a relationship with Cardno ChemRisk that includes: employment. Jillian Parker reports a relationship with Cardno ChemRisk that includes: employment. Alexandra Powell reports a relationship with Cardno ChemRisk that includes: employment. Andrew Maier reports a relationship with Cardno ChemRisk that includes: employment. All the authors are employed by ChemRisk, a consulting firm that provides scientific advice to the government, corporations, law firms and various scientific/professional organizations. All research efforts in this presentation were funded solely by ChemRisk. No entity outside of ChemRisk funded, reviewed, or provided input of the research contained within this publication., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Person-centred care (PCC) meets the needs of individuals by increasing convenience, providing supportive and culturally appropriate services to diverse populations, and engaging families, communities, and stakeholders in planning and provision of care. While the evidence demonstrates that PCC approaches can lead to clinical improvements across the HIV care continuum, it is not yet well defined in the context of HIV service delivery., Methods: A systematic review was conducted to define PCC practices for HIV treatment services in health facilities in sub-Saharan Africa. Data synthesis led to the development of a PCC framework including domain and sub-domain development. The study team used the Effective Public Health Project Practice tool for quantitative studies to assess the quality of the included studies., Results: Thirty-one studies from 12 countries met the inclusion criteria, including 56,586 study participants (females 42%-100% and males 0%-58%), resulting in three major domains and 11 sub-domains. These include staffing (sub-domains of composition, availability, and competency); service delivery standards (sub-domains of client feedback mechanisms; service efficiency and integration; convenience and access; and digital health worker support tools); and direct client support services (sub-domains of psychosocial services, logistics support, client-agency, and digital client support tools). Twenty-five of the person-centred interventions within these domains resulted in improvements in linkage to care, treatment retention, and/or viral suppression., Conclusions: The PCC framework can help to provide a more consistent classification of HIV treatment interventions and will support improved assessment of these interventions to ensure that people receive personalised care., (© 2022 The Authors Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

Competing Interests: Financial Disclosure Chailee F. Moss reports that their institution receives grant funding from Merck, Inc. for an HPV vaccination trial. Anna Maya Powell disclosed currently receiving payments from UpToDate. The other authors did not report any potential conflicts of interest.

Species of camel spiders in the family Eremobatidae are an important component of arthropod communities in arid ecosystems throughout North America. Recently, research demonstrated that the evolutionary history and biogeography of the family are poorly understood. Herein we explore the biogeographic history of this group of arachnids using genome-wide single nucleotide polymorphism (SNP) data, morphology, and distribution modelling to study the eremobatid genus Eremocosta, which contains exceptionally large species distributed throughout North American deserts. Relationships among sampled species were resolved with strong support and they appear to have diversified within distinct desert regions along an east-to-west progression beginning in the Chihuahuan Desert. The unexpected phylogenetic position of some samples suggests that the genus may contain additional, morphologically cryptic species. Geometric morphometric analyses reveal a largely conserved cheliceral morphology among Eremocosta spp. Phylogeographic analyses indicate that the distribution of E. titania was substantially reduced during the last glacial maximum and the species only recently colonized much of the Mojave Desert. Results from this study underscore the power of genome-wide data for unlocking the genetic potential of museum specimens, which is especially promising for organisms like camel spiders that are notoriously difficult to collect., (© 2021. The Author(s).)

Small alterations in extracellular H + can profoundly alter neurotransmitter release by neurons. We examined mechanisms by which extracellular ATP induces an extracellular H + flux from Müller glial cells, which surround synaptic connections throughout the vertebrate retina. Müller glia were isolated from tiger salamander retinae and H + fluxes examined using self-referencing H + -selective microelectrodes. Experiments were performed in 1 mM HEPES with no bicarbonate present. Replacement of extracellular sodium by choline decreased H + efflux induced by 10 µM ATP by 75%. ATP-induced H + efflux was also reduced by Na + /H + exchange inhibitors. Amiloride reduced H + efflux initiated by 10 µM ATP by 60%, while 10 µM cariporide decreased H + flux by 37%, and 25 µM zoniporide reduced H + flux by 32%. ATP-induced H + fluxes were not significantly altered by the K + /H + pump blockers SCH28080 or TAK438, and replacement of all extracellular chloride with gluconate was without effect on H + fluxes. Recordings of ATP-induced H + efflux from cells that were simultaneously whole cell voltage clamped revealed no effect of membrane potential from -70 mV to 0 mV. Restoration of extracellular potassium after cells were bathed in 0 mM potassium produced a transient alteration in ATP-dependent H + efflux. The transient response to extracellular potassium occurred only when extracellular sodium was present and was abolished by 1 mM ouabain, suggesting that alterations in sodium gradients were mediated by Na + /K + -ATPase activity. Our data indicate that the majority of H + efflux elicited by extracellular ATP from isolated Müller cells is mediated by Na + /H + exchange. NEW & NOTEWORTHY Glial cells are known to regulate neuronal activity, but the exact mechanism(s) whereby these "support" cells modulate synaptic transmission remains unclear. Small changes in extracellular levels of acidity are known to be particularly powerful regulators of neurotransmitter release. Here, we show that extracellular ATP, known to be a potent activator of glial cells, induces H + efflux from retinal Müller (glial) cells and that the bulk of the H + efflux is mediated by Na + /H + exchange.

The coronavirus disease 2019 pandemic has altered medical practice in unprecedented ways. Although much of the emphasis in obstetrics and gynecology to date has been on the as yet uncertain effects of coronavirus disease 2019 in pregnancy and on changes to surgical management, the pandemic has broad implications for ambulatory gynecologic care. In this article, we review important ambulatory gynecologic topics such as safety and mental health, reproductive life planning, sexually transmitted infections, and routine screening for breast and cervical cancer. For each topic, we review how care may be modified during the pandemic, provide recommendations when possible on how to ensure continued access to comprehensive healthcare at this time, and discuss ways that future practice may change. Social distancing requirements may place patients at higher risk for intimate partner violence and mental health concerns, threaten continued access to contraception and abortion services, affect prepregnancy planning, interrupt routine screening for breast and cervical cancer, increase risk of sexually transmitted infection acquisition and decrease access to treatment, and exacerbate already underlying racial and minority disparities in care and health outcomes. We advocate for increased use of telemedicine services with increased screening for intimate partner violence and depression using validated questionnaires. Appointments for long-acting contraceptive insertions can be prioritized. Easier access to patient-controlled injectable contraception and pharmacist-provided hormonal contraception can be facilitated. Reproductive healthcare access can be ensured through reducing needs for ultrasonography and laboratory testing for certain eligible patients desiring abortion and conducting phone follow-up for medication abortions. Priority for in-person appointments should be given to patients with sexually transmitted infection symptoms, particularly if at risk for complications, while also offering expedited partner therapy. Although routine mammography screening and cervical cancer screening may be safely delayed, we discuss society guideline recommendations for higher-risk populations. There may be an increasing role for patient-collected human papillomavirus self-samples using new cervical cancer screening guidelines that can be expanded considering the pandemic situation. Although the pandemic has strained our healthcare system, it also affords ambulatory clinicians with opportunities to expand care to vulnerable populations in ways that were previously underutilized to improve health equity., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective  Bacterial vaginosis (BV) is associated with vitamin D deficiency and poor pregnancy outcomes. We studied a nested cohort from a randomized controlled trial to investigate the association between BV and vitamin D concentration in pregnancy. Study Design  Subjects with randomly assigned 400 versus 4,400 IU of daily cholecalciferol (vitamin D 3 ) had vaginal swabs collected for Gram staining and Nugent score calculation, as well as plasma 25-hydroxyvitamin D (25(OH)D) measurement at three pregnancy time points. Results  Fifty-two (21.2%) of the 245 women included in the analysis were diagnosed with BV at study entry. Women with BV were also more likely to be African American ( p  < 0.0001) and have lower 25(OH)D concentrations at 22 to 24 weeks' gestation ( p  = 0.03). There were no differences in pregnancy outcomes of interest within this group compared with the remaining study subjects. In mixed regression modeling, while race ( p  = 0.001) and age ( p  = 0.03) were significant predictors of BV prevalence independently, 25(OH)D concentration ( p  = 0.81), gestational age ( p  = 0.06), and body mass index ( p  = 0.87) were not. Conclusion  Neither vitamin D deficiency in early pregnancy nor supplementation decreased BV incidence during pregnancy. Pregnancy outcomes (preterm birth and hypertensive disorders of pregnancy) were similar among women with and without BV.

Objective: Evidence supports an inverse association between vitamin D and bacterial vaginosis (BV) during pregnancy. Furthermore, both the vaginal microbiome and vitamin D status correlate with pregnancy outcome. Women of African ancestry are more likely to experience BV, to be vitamin D deficient, and to have certain pregnancy complications. We investigated the association between vitamin D status and the vaginal microbiome., Study Design: Subjects were assigned to a treatment (4400 IU) or a control group (400 IU vitamin D daily), sampled three times during pregnancy, and vaginal 16S rRNA gene taxonomic profiles and plasma 25-hydroxyvitamin D [25(OH)D] concentrations were examined., Result: Gestational age and ethnicity were significantly associated with the microbiome. Megasphaera correlated negatively (p = 0.0187) with 25(OH)D among women of African ancestry. Among controls, women of European ancestry exhibited a positive correlation between plasma 25(OH)D and L. crispatus abundance., Conclusion: Certain vaginal bacteria are associated with plasma 25(OH)D concentration.

Purpose: We sought to determine if infants born in rural counties had an increased risk of contracting HIV., Methods: Data were obtained from the South Carolina Department of Health and Environmental Control for all women living with HIV delivering from 2004 to 2014. In this retrospective cohort study, maternal and neonatal outcomes from urban and rural counties were compared. Binomial statistical analyses were conducted using Wilcoxon Rank Sum Tests, χ2 or Fisher's exact tests. Logistic regression analyses were performed to evaluate factors associated with perinatal HIV infection., Findings: Six hundred and sixty-six women living with HIV had 868 pregnancies and delivered 885 infants; 17% (148) were born in rural counties. Eleven infants (1.2%) were diagnosed with perinatal HIV infection. The proportion of women taking antenatal antiretroviral therapy (ART) was similar between rural and urban counties (84% vs 87%; P = .3), but women in urban counties were more likely to have an HIV RNA viral load <40 copies/mL before delivery (32% vs 42%; P = .05). Factors associated with perinatal HIV infection were intra- and postpartum maternal HIV diagnosis (aOR 61.4 [95% CI: 6.7-562.5]; P < .001), parenteral drug use (aOR 7.5 [1.6-34.7]; P = .01), and preterm birth (<37 weeks gestation) (aOR 4.6 [1.2-17.8]; P = .3)., Conclusions: Delivery in a rural county was not associated with an increased risk of perinatal HIV transmission. Women delivering in rural counties taking ART were less likely to have HIV viral suppression, which is a risk factor for perinatal HIV infection., (© 2018 National Rural Health Association.)

Background: Our primary objective was to determine the rate of persistent Trichomonas infection among pregnant women posttreatment. The secondary objective was to determine if oral multidose metronidazole was associated with fewer cases of persistent Trichomonas compared with single-dose treatment., Methods: This is a retrospective cohort study of women diagnosed with genital Trichomonas vaginalis from 2008 to 2017. We calculated the rate of persistent Trichomonas by dividing the number of positive Trichomonas tests collected 21 days or longer posttreatment by the total number of women treated and retested. Bivariate analysis was performed to compare the rates of positive tests after single and multidose metronidazole. Multivariate logistic regression was used to evaluate factors associated with persistent infection., Results: Five hundred forty-two women with 565 pregnancies were diagnosed with Trichomonas infection. The majority of subjects were prescribed either single-dose (n = 352) or multidose metronidazole (n = 74). Posttreatment Trichomonas tests were collected 21 days or longer in 326 subjects and 44% (143) were positive. Rates of positive Trichomonas tests among women receiving single-dose and multidose regimens were similar (45% vs. 40%, P = 0.50). Women who had ≥1 pregnancy affected by Trichomonas infection were more likely to have a positive test posttreatment (adjusted odds ratio, 20.1; 95% confidence interval, 1.9-215.3). Obese women were less likely to have a positive test posttreatment (adjusted odds ratio, 0.3; 95% confidence interval, 0.1-0.9)., Conclusions: Given high rates of positive Trichomonas tests and increased detection with nucleic acid amplification tests (NAATs), all pregnant women should be retested with NAATs approximately 3 weeks posttreatment. Further studies are needed to determine the most effective treatment of Trichomonas infection in pregnant women.

In HIV infection, increased adverse perinatal outcomes reported among HIV-associated pregnancies are not fully understood. Currently, microbial product translocation (MT) from a permeable mucosa is demonstrated as a driver of inflammation, and may contribute to preterm delivery in HIV. Here, our results showed that plasma LPS levels (a representative marker of MT) were increased in HIV-infected women in the first and second trimester. Progesterone levels were significantly decreased in HIV-infected subjects in the first trimester and second trimester. There were significant inverse correlations between plasma LPS and progesterone in the first and second trimester. These results suggested heightened systemic MT and decreased plasma progesterone levels in HIV-infected pregnant women may play a role in increased incidence of preterm delivery., (Published by Elsevier B.V.)

Background: Elimination of perinatal transmission is possible but limited by missed care opportunities. Our objective was to investigate the effects of HIV-centered obstetric care (HCC) on missed care opportunities and perinatal HIV transmission in 2 obstetric cohorts at our institution from 2000 to 2014., Methods: This was a retrospective cohort study of HIV-exposed mother-infant pairs delivering from 2000 to 2014, analyzed according to SQUIRE 2.0 (Standards for Quality Improvement Reporting Excellence) guidelines. Before 2009, women received care in high-risk obstetric care (HRC); subsequently, an HCC service was established. Women who received HRC vs HCC obstetric care were compared to determine differences in maternal and neonatal outcomes. Continuous variables were compared with Student t test and Wilcoxon rank sum tests. Categorical variables were compared using χ test and Fisher exact test. Logistic regression analyses were performed to determine factors associated with outcomes of interest., Results: Over 14 years, 161 women delivered 217 HIV-exposed infants; 78 (36%) women received HCC. Two perinatal HIV transmissions (1.5%) occurred in HRC group compared with none in the HCC group (P = 0.3). Women in HCC were more likely to have HIV RNA viral load <1000 copies per milliliter at delivery (12% vs 26%, P = 0.02), have a contraception plan before delivery (93% vs 60%, P < 0.001), return for postpartum evaluation (80% vs 63%, P = 0.01), and have undetectable HIV viral load postpartum (50 copies per milliliter vs 2067, P < 0.0001)., Conclusions: HCC can potentially reduce the risk of perinatal HIV transmission by improving maternal virologic control during pregnancy and postpartum and increasing postpartum contraceptive use.

Thirteen independent induced bovine trophectroderm (iBT) cell lines were established by reprogramming bovine fetal liver-derived fibroblasts after viral-vector transduction with either six or eight factors, including POU5F1 (OCT4), KLF4, SOX2, MYC, NANOG, LIN28, SV40 large T antigen, and hTERT. Light- and electron-microscopy analysis showed that the iBT cells had epithelial cell morphology typical of bovine trophectoderm cells. Reverse-transcription-PCR assays indicated that all of the cell lines expressed interferon-tau (IFNT) at passages 1 or 2. At later passages (≥ passage 8), however, immunoblot and antiviral activity assays revealed that more than half of the iBT cell lines had stopped expressing IFNT. Messenger RNAs specific to trophectoderm differentiation and function were found in the iBT cell lines, and 2-dimensional-gel analysis for cellular proteins showed an expression pattern similar to that of trophectoderm cell lines derived from bovine blastocysts. Integration of some of the human reprogramming factors, including POU5F1, KLF4, SOX2, MYC, NANOG, and LIN28, were detected by PCR, but their transcription was mostly absent in the iBT cell lines. Gene expression assessment of endogenous bovine reprogramming factor orthologs revealed endogenous bLIN28 and bMYC transcripts in all; bSOX2 and bNANOG in none; and bKLF4 and bPOU5F1 in less than half of the iBT cell lines. These results demonstrate that bovine trophectoderm can be induced via reprogramming factor expression from bovine liver-derived fibroblasts, although other fibroblast populations-e.g., derived from fetal thigh tissue-may produce similar results, albeit at lower frequencies., (© 2017 Wiley Periodicals, Inc.)

Background: Studies have shown that HIV infection is associated with an impaired influenza vaccine response. We examined the role of cellular phenotypes and function in influenza vaccine responsiveness in healthy controls and aviremic HIV-infected subjects on antiretroviral treatment (ART)., Methods: 16 healthy controls and 26 ART+ aviremic HIV+ subjects were enrolled in the current study. Blood was collected at pre-vaccination (D0), and on days 7-10 (D7) and 14-21 (D14) following the 2013-2014 seasonal influenza vaccine administrations. Subjects were classified as responders if neutralizing titers against H1N1 virus increased ⩾4-fold at D14 compared to D0. A serial analysis of B and CD4+ T cell frequencies and activation was performed on D0 and D7 by flow cytometry., Results: 9 of 26 (34.6%) HIV-infected individuals and 7 of 16 (43.8%) healthy controls were classified as responders to influenza vaccines. Total B cell apoptosis (annexin V) was increased on D7 post-vaccination in non-responders but not in responders among both controls and HIV+ subjects. Surface CD80 expression on memory B cells and intracellular CD40L expression on memory CD4+ T cells were induced on D7 in responders of controls but not in non-responders. The CD80 and CD40L induction was not demonstrable in HIV-infected subjects regardless of responders and non-responders. Memory CD4+ T cell cycling tended to increase on D7 in the four study groups but did not achieve significance. All the other parameters were indistinguishable between responders and non-responders, regardless of HIV-infection status., Conclusion: The perturbation of activation and apoptotic induction on B cells or CD4+ T cells after seasonal influenza vaccination in non-responders and HIV-infected subjects may help understand the mechanism of impaired vaccine responsiveness., (Copyright © 2016. Published by Elsevier Ltd.)

Multi-drug resistant bacteria are a persistent problem in modern health care, food safety and animal health. There is a need for new antimicrobials to replace over used conventional antibiotics. Here we describe engineered triple-acting staphylolytic peptidoglycan hydrolases wherein three unique antimicrobial activities from two parental proteins are combined into a single fusion protein. This effectively reduces the incidence of resistant strain development. The fusion protein reduced colonization by Staphylococcus aureus in a rat nasal colonization model, surpassing the efficacy of either parental protein. Modification of a triple-acting lytic construct with a protein transduction domain significantly enhanced both biofilm eradication and the ability to kill intracellular S. aureus as demonstrated in cultured mammary epithelial cells and in a mouse model of staphylococcal mastitis. Interestingly, the protein transduction domain was not necessary for reducing the intracellular pathogens in cultured osteoblasts or in two mouse models of osteomyelitis, highlighting the vagaries of exactly how protein transduction domains facilitate protein uptake. Bacterial cell wall degrading enzyme antimicrobials can be engineered to enhance their value as potent therapeutics.

Purpose: To assess patterns and outcomes of a "Treat and Extend" dosing regimen of ranibizumab in patients with age-related macular degeneration., Methods: Three hundred and thirty two treatment-naive age-related macular degeneration patients starting therapy with ranibizumab between January 1, 2011, and June 30, 2012, at the Ivey Eye Institute were reviewed, and 79 met inclusion criteria. Patients on Treat and Extend dosing regimen underwent an induction phase with monthly injections and then moved onto an extension phase. Change in visual acuity and central retinal thickness during the induction and extension phases were recorded., Results: During the induction phase, patients had a significant gain in vision and decrease in central retinal thickness (+8.4 letters, P < 0.001 and -81.3 μm, P < 0.001). During the extension phase, patients did not have significant change in vision (-0.5 letters, P = 0.81) and did not have significant change in central retinal thickness (-11.5 μm, P = 0.17). The average extension interval between treatments was 47.7 days, with patients receiving an average of 8.6 injections per year. Cost analysis showed it cost US $16,659 to treat 1 patient in the first year on Treat and Extend dosing regimen compared with US $20,614 on monthly dosing., Conclusion: Treat and Extend dosing regimen allows similar visual outcomes to monthly dosing, while reducing the total number of injections, visits, and overall cost.

Objectives: The aims of this study are to analyze a cohort of women with vulvovaginal symptoms and positive cultures for non-albicans Candida (NAC) to determine whether yeast was responsible for their symptoms and to evaluate the mycological effectiveness of various regimens., Methods: This observational study was performed from retrospective chart review of patients with positive NAC cultures between April 1, 2008, and January 31, 2011, at a tertiary care vaginitis center. Patient intake demographics were entered into a database. Follow-up visits were analyzed for data about patient treatments and outcomes. Patients were considered a clinical cure if their symptoms were significantly improved and mycologic cure (MC) if later yeast cultures were negative. If clinical symptoms improved at the same time as MC, the isolate was considered the proximate cause for the symptoms., Results: One hundred eight patients meeting entry criteria were analyzed. Boric acid was effective at obtaining MC in 32 (78%) of 41 patients with C. glabrata, 3 of 3 patients with C. tropicalis, and 3 of 3 patients with C. lusitaniae. Fluconazole was effective as initial treatment for 3 (60%) of 5 patients with C. glabrata and 13 (81%) of 16 patients with C. parapsilosis. In 52.7% of C. glabrata, 66.7% of C. parapsilosis, and 57.1% of C. tropicalis cases, effective antifungal therapy led to symptom improvement., Conclusions: In a tertiary care vaginitis center, NAC, when isolated on culture, caused clinically significant infections in approximately half of symptomatic patients. A majority of infections can be effectively treated with boric acid or fluconazole regardless of the non-albicans Candida species.

Bovine mastitis results in billion dollar losses annually in the USA alone. Streptococci are among the most relevant causative agents of this disease. Conventional antibiotic therapy is often unsuccessful and contributes to development of antibiotic resistance. Bacteriophage endolysins represent a new class of antimicrobials against these bacteria. In this work, we characterized the endolysins (lysins) of the streptococcal phages λSA2 and B30 and evaluated their potential as anti-mastitis agents. When tested in vitro against live streptococci, both enzymes exhibited near-optimum lytic activities at ionic strengths, pH, and Ca(2+) concentrations consistent with cow milk. When tested in combination in a checkerboard assay, the lysins were found to exhibit strong synergy. The λSA2 lysin displayed high activity in milk against Streptococcus dysgalactiae (reduction of CFU/ml by 3.5 log units at 100 μg/ml), Streptococcus agalactiae (2 log), and Streptococcus uberis (4 log), whereas the B30 lysin was less effective. In a mouse model of bovine mastitis, both enzymes significantly reduced intramammary concentrations of all three streptococcal species (except for B30 vs. S. dysgalactiae), and the effects on mammary gland wet weights and TNFα concentrations were consistent with these findings. Unexpectedly, the synergistic effect determined for the two enzymes in vitro was not observed in the mouse model. Overall, our results illustrate the potential of endolysins for treatment of Streptococcus-induced bovine mastitis.

An understanding of how the vaginal flora is influenced by hormonal status is crucial in distinguishing normal from abnormal secretions. New studies exploring the vaginal microbiome with culture-independent techniques have led to the discovery of previously uncultivable bacteria on a species level, and have contributed to a better understanding of disease processes including bacterial vaginosis. It is important to note that not all vaginal discharge is abnormal or infectious in etiology, but a thorough evaluation will help reassure both the patient and the provider.

Importance: Teleophthalmology has the potential to reduce costs and inconveniences associated with frequent patient visits. Evaluating teleophthalmology in the management of age-related macular degeneration (AMD) will allow for future implementation of this technology., Objective: To evaluate teleophthalmology as a tool for the screening and monitoring of neovascular AMD., Design, Setting, and Participants: Prospective, randomized clinical trial that included 106 referral eyes for suspected neovascular AMD and 63 eyes with stable neovascular AMD. New referrals for patients with suspected neovascular AMD and patients with stable neovascular AMD were randomized into either routine or teleophthalmologic groups. In the routine group, patients received clinical assessment and diagnostic imaging at a tertiary hospital-based retina clinic. In the teleophthalmologic group, patients received basic examination and diagnostic imaging at a stand-alone teleophthalmologic site, where patient information and imaging studies were acquired and electronically sent over to tertiary hospital-based retina specialists. Patients in the teleophthalmologic group were called back to the tertiary treatment center if the teleophthalmologic data set suggested pathology or was inconclusive for diagnosis., Main Outcomes and Measures: Patient wait times for diagnosis and/or treatment, referral accuracy, and visual outcome., Results: For neovascular AMD screening, the average referral-to-diagnostic imaging time was 22.5 days for the teleophthalmologic group and 18.0 days for the routine group, for a difference of 4.5 days (95% CI, 11.8 to -2.8 days; P = .23). The average diagnostic imaging to treatment time was 16.4 days for the teleophthalmologic group and 11.6 days for the routine group, for a difference of 4.8 days (95% CI, 10.7 to -1.1 days; P = .11). For neovascular AMD monitoring, the average recurrence to treatment time was shorter for the routine group (0.04 days) compared with 13.6 days for the teleophthalmologic group, for a difference of -13.5 days (95% CI, -18.2 to -9.0 days; P < .01). There was no difference identified between end-of-study visual acuities in the 2 groups (P = .99)., Conclusions and Relevance: A delay of referral to treatment time could not be identified when comparing teleophthalmologic screening for suspected neovascular AMD with retinal specialist-based screening. Teleophthalmologic monitoring for neovascular AMD recurrence resulted in longer wait times for treatment reinitiation, but no adverse visual outcomes were identified., Trial Registration: clinicaltrials.gov Identifier:NCT01581606.

Vulvovaginitis (VV) is one of the most commonly encountered problems by a gynecologist. Many women frequently self-treat with over-the-counter medications, and may present to their health-care provider after a treatment failure. Vulvovaginal candidiasis, bacterial vaginosis, and trichomoniasis may occur as discreet or recurrent episodes, and have been associated with significant treatment cost and morbidity. We present an update on diagnostic capabilities and treatment modalities that address recurrent and refractory episodes of VV., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: To provide a strategic framework for the prevention of bipolar disorder (BD) that incorporates a 'Big Data' approach to risk assessment for BD., Methods: Computerized databases (e.g., Pubmed, PsychInfo, and MedlinePlus) were used to access English-language articles published between 1966 and 2012 with the search terms bipolar disorder, prodrome, 'Big Data', and biomarkers cross-referenced with genomics/genetics, transcriptomics, proteomics, metabolomics, inflammation, oxidative stress, neurotrophic factors, cytokines, cognition, neurocognition, and neuroimaging. Papers were selected from the initial search if the primary outcome(s) of interest was (were) categorized in any of the following domains: (i) 'omics' (e.g., genomics), (ii) molecular, (iii) neuroimaging, and (iv) neurocognitive., Results: The current strategic approach to identifying individuals at risk for BD, with an emphasis on phenotypic information and family history, has insufficient predictive validity and is clinically inadequate. The heterogeneous clinical presentation of BD, as well as its pathoetiological complexity, suggests that it is unlikely that a single biomarker (or an exclusive biomarker approach) will sufficiently augment currently inadequate phenotypic-centric prediction models. We propose a 'Big Data'- bioinformatics approach that integrates vast and complex phenotypic, anamnestic, behavioral, family, and personal 'omics' profiling. Bioinformatic processing approaches, utilizing cloud- and grid-enabled computing, are now capable of analyzing data on the order of tera-, peta-, and exabytes, providing hitherto unheard of opportunities to fundamentally revolutionize how psychiatric disorders are predicted, prevented, and treated. High-throughput networks dedicated to research on, and the treatment of, BD, integrating both adult and younger populations, will be essential to sufficiently enroll adequate samples of individuals across the neurodevelopmental trajectory in studies to enable the characterization and prevention of this heterogeneous disorder., Conclusions: Advances in bioinformatics using a 'Big Data' approach provide an opportunity for novel insights regarding the pathoetiology of BD. The coordinated integration of research centers, inclusive of mixed-age populations, is a promising strategic direction for advancing this line of neuropsychiatric research., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)