Metabolic memory of Δ9-tetrahydrocannabinol exposure in pluripotent stem cells and primordial germ cells-like cells.

Cannabis, the most consumed illicit psychoactive drug in the world, is increasingly used by pregnant women. However, while cannabinoid receptors are expressed in the early embryo, the impact of phytocannabinoids exposure on early embryonic processes is lacking. Here, we leverage a stepwise in vitro differentiation system that captures the early embryonic developmental cascade to investigate the impact of exposure to the most abundant phytocannabinoid, Δ9-tetrahydrocannabinol (Δ9-THC). We demonstrate that Δ9-THC increases the proliferation of naive mouse embryonic stem cells (ESCs) but not of their primed counterpart. Surprisingly, this increased proliferation, dependent on the CB1 receptor binding, is only associated with moderate transcriptomic changes. Instead, Δ9-THC capitalizes on ESCs' metabolic bivalence by increasing their glycolytic rates and anabolic capabilities. A memory of this metabolic rewiring is retained throughout differentiation to Primordial Germ Cell-Like Cells in the absence of direct exposure and is associated with an alteration of their transcriptional profile. These results represent the first in-depth molecular characterization of the impact of Δ9-THC exposure on early stages of germline development.

Cannabis is the most widely used illicit drug in the world, with 4.3% of the global adult population estimated to have used it in the previous year. In particular, the consumption of cannabis by pregnant women has almost doubled in recent years and is particularly increased in those aged under 18. The main psychoactive component in cannabis, known as Δ9-THC, activates cannabinoid receptors in the brain, including the receptor CB1. Recent research has shown that CB1 is also active in the mouse embryo, but it remained unclear if Δ9-THC could also affect the development of an embryo. To better understand the potential effects of this exposure, scientists can study stem cells that develop into germ cells (which go on to form egg and sperm), which have been grown in the laboratory. Emerging research has shown that germ cells are particularly sensitive to changes in their environment and due to their role in reproduction, changes can have knock-on effects for embryos. Verdikt et al. studied the effects of Δ9-THC on mouse embryonic stem cells, finding that it caused them to multiply more quickly. This was dependent on both Δ9-THC binding to the CB1 receptor that causes the psychoactive effects of cannabis in the brain and an increased energy metabolism. Blocking an important metabolic pathway called glycolysis caused the Δ9-THC-treated cells to return to a normal multiplication rate. The exposed stem cells also gave rise to germ cells with abnormal metabolism and altered gene expression, suggesting that this metabolic 'memory' can be passed on to cells in the next developmental stage. Overall, the findings indicate that exposure to Δ9-THC alters the metabolism in early embryonic cells of mice and that these effects can be lasting. This emphasises the need for further research on the impact of cannabis use during pregnancy, particularly as the drug's availability is expected to increase significantly with changes in regulation. The work also contributes to research highlighting the inheritance of metabolism.

The nature of embryonic mosaicism across female age spectrum: an analysis of 21,345 preimplantation genetic testing for aneuploidy cycles.

Objective: To understand how mosaicism varies across patient-specific variables and clinics. Design: Cross-sectional cohort. Setting: Genetic testing laboratory. Patients: A total of 86,208 embryos from 17,366 patients underwent preimplantation genetic testing for aneuploidy using next-generation sequencing. Interventions: Mosaic embryos were classified as either low-level (20%-40%) or high-level (40%-80%) and by type of mosaic error: single segmental, complex segmental, single chromosome, or complex abnormal mosaic. The rate of mosaicism was stratified by the Society for Assisted Reproductive Technology age categories: <35 years, 35-37 years, 38-40 years, 41-42 years, and >42 years. Main Outcome Measures: Distribution of chromosomal findings and prevalence of mosaicism type by age. Probability of creating mosaic embryos in a subsequent cycle. Results: Among all embryos, 44% were euploid, 40.2% were aneuploid, and 15.8% were mosaic. Both low-level and high-level mosaicism were more prevalent among younger patients. Of all mosaic embryos, the youngest age cohort <35 years had the highest proportions of single and complex segmental mosaicism (37.9% and 6.8%, respectively), whereas those aged >42 years had the highest single whole chromosome and complex abnormal mosaicism (37.1% and 34.0%, respectively). Although there was variability in mosaic rates across clinics, the median mosaic rate over 3 years ranged from 14.48% to 17.72%. A diagnosis of a mosaic embryo in a previous cycle did not increase a patient's odds for having a mosaic embryo in a subsequent cycle. Conclusions: Mosaicism is overall higher in younger patients, but the complexity of mosaic errors increases with age. A history of mosaicism was not associated with mosaicism in subsequent cycles. Additional research is needed to understand the etiologies of the various subtypes of mosaic embryos and clinical outcomes associated with their transfer.

Saliva microbiome in relation to SARS-CoV-2 infection in a prospective cohort of healthy US adults.

BACKGROUND: The clinical outcomes of SARS-CoV-2 infection vary in severity, potentially influenced by the resident human microbiota. There is limited consensus on conserved microbiome changes in response to SARS-CoV-2 infection, with many studies focusing on severely ill individuals. This study aimed to assess the variation in the upper respiratory tract microbiome using saliva specimens in a cohort of individuals with primarily mild to moderate disease. METHODS: In early 2020, a cohort of 831 adults without known SARS-CoV-2 infection was followed over a six-month period to assess the occurrence and natural history of SARS-CoV-2 infection. From this cohort, 81 participants with a SARS-CoV-2 infection, along with 57 unexposed counterparts were selected with a total of 748 serial saliva samples were collected for analysis. Total bacterial abundance, composition, population structure, and gene function of the salivary microbiome were measured using 16S rRNA gene and shotgun metagenomic sequencing. FINDINGS: The salivary microbiome remained stable in unexposed individuals over the six-month study period, as evidenced by all measured metrics. Similarly, participants with mild to moderate SARS-CoV-2 infection showed microbiome stability throughout and after their infection. However, there were significant reductions in microbiome diversity among SARS-CoV-2-positive participants with severe symptoms early after infection. Over time, the microbiome diversity in these participants showed signs of recovery. INTERPRETATION: These findings demonstrate the resilience of the salivary microbiome in relation to SARS-CoV-2 infection. Mild to moderate infections did not significantly disrupt the stability of the salivary microbiome, suggesting its ability to maintain its composition and function. However, severe SARS-CoV-2 infection was associated with temporary reductions in microbiome diversity, indicating the limits of microbiome resilience in the face of severe infection. FUNDING: This project was supported in part by Danone North America and grants from the National Institutes of Health, United States.

Metabolic memory of Δ9-tetrahydrocannabinol exposure in pluripotent stem cells and primordial germ cells-like cells.

Cannabis, the most consumed illicit psychoactive drug in the world, is increasingly used by pregnant women. However, while cannabinoid receptors are expressed in the early embryo, the impact of phytocannabinoids exposure on early embryonic processes is lacking. Here, we leverage a stepwise in vitro differentiation system that captures early embryonic developmental cascade to investigate the impact of exposure to the most abundant phytocannabinoid, Δ9-tetrahydrocannabinol (Δ9-THC). We demonstrate that Δ9-THC increases the proliferation of naïve mouse embryonic stem cells (ESCs) but not of their primed counterpart. Surprisingly, this increased proliferation, dependent on the CB1 receptor binding, is only associated with moderate transcriptomic changes. Instead, Δ9-THC capitalizes on ESCs' metabolic bivalence by increasing their glycolytic rates and anabolic capabilities. A memory of this metabolic rewiring is retained throughout differentiation to Primordial Germ Cell-Like Cells in the absence of direct exposure and is associated with an alteration of their transcriptional profile. These results represent the first in-depth molecular characterization of the impact of Δ9-THC exposure on early stages of germline development.

Temporal changes in the systemic concentrations of retinoids in pregnant and postpartum women.

Retinoids and vitamin A are essential for multiple biological functions, including vision and immune responses, as well as the development of an embryo during pregnancy. Despite its importance, alterations in retinoid homeostasis during normal human pregnancy are incompletely understood. We aimed to characterize the temporal changes in the systemic retinoid concentrations across pregnancy and postpartum period. Monthly blood samples were collected from twenty healthy pregnant women, and plasma concentrations of retinol, all-trans-retinoic acid (atRA), 13-cis-retinoic acid (13cisRA), and 4-oxo-retinoic acids were measured using liquid chromatography-tandem mass spectrometry. Significant decreases in 13cisRA concentrations over the pregnancy were observed, with rebound increases in retinol and 13cisRA levels after delivery. Of note, atRA concentrations exhibited a unique temporal pattern with levels peaking at mid-pregnancy. While the 4-oxo-atRA concentration was below the limit of quantification, 4-oxo-13cisRA was readily detectable, and its temporal change mimicked that of 13cisRA. The time profiles of atRA and 13cisRA remained similar after correction by albumin levels for plasma volume expansion adjustment. Together, the comprehensive profiling of systemic retinoid concentrations over the course of pregnancy provides insights into pregnancy-mediated changes in retinoid disposition to maintain its homeostasis.

Transgenerational inheritance and its modulation by environmental cues.

The epigenome plays an important role in shaping phenotypes. However, whether the environment can alter an organism's phenotype across several generations through epigenetic remodeling in the germline is still a highly debated topic. In this chapter, we briefly review the mechanisms of epigenetic inheritance and their connection with germline development before highlighting specific developmental windows of susceptibility to environmental cues. We further discuss the evidence of transgenerational inheritance to a range of different environmental cues, both epidemiological in humans and experimental in rodent models. Doing so, we pinpoint the current challenges in demonstrating transgenerational inheritance to environmental cues and offer insight in how recent technological advances may help deciphering the epigenetic mechanisms at play. Together, we draw a detailed picture of how our environment can influence our epigenomes, ultimately reshaping our phenotypes, in an extended theory of inheritance.

Size optimization of carfilzomib nanocrystals for systemic delivery to solid tumors.

Carfilzomib (CFZ) is a second-generation proteasome inhibitor effective in blood cancer therapy. However, CFZ has shown limited efficacy in solid tumor therapy due to the short half-life and poor tumor distribution. Albumin-coated nanocrystal (NC) formulation was shown to improve the circulation stability of CFZ, but its antitumor efficacy remained suboptimal. We hypothesize that NC size reduction is critical to the formulation safety and efficacy as the small size would decrease the distribution in the reticuloendothelial system (RES) and selectively increase the uptake by tumor cells. We controlled the size of CFZ-NCs by varying the production parameters in the crystallization-in-medium method and compared the size-reduced CFZ-NCs (z-average of 168 nm, NC168) with a larger counterpart (z-average of 325 nm, NC325) as well as the commercial CFZ formulation (CFZ-CD). Both CFZ-NCs showed similar or higher cytotoxicity than CFZ-CD against breast cancer cells. NC168 showed greater uptake by cancer cells, less uptake by macrophages and lower immune cell toxicity than NC325 or CFZ-CD. NC168, but not NC325, showed a similar safety profile to CFZ-CD in vivo. The biodistribution and antitumor efficacy of CFZ-NCs in mice were also size-dependent. NC168 showed greater antitumor efficacy and tumor accumulation but lower RES accumulation than NC325 in 4T1 breast cancer model. These results support that NC formulation with an optimal particle size can improve the therapeutic efficacy of CFZ in solid tumors.

Obesity and reproduction.

PURPOSE OF REVIEW: The objective of this review is to highlight the recent literature on how obesity affects reproductive capacity in men and women. RECENT FINDINGS: The relationship between fertility and obesity is complex and involves the hypothalamic-pituitary-ovarian axis, neuroendocrine systems and adipose tissue. The exact pathophysiology of how obesity lowers fertility rates is unknown, but is likely multifactorial involving anovulation, insulin resistance and alterations in gonadotropins. In addition, there is controversy on whether oocyte quality or endometrial receptivity plays a larger role in obese infertile women. Data on effects of bariatric surgery and weight loss on obese infertile men and women are mixed. SUMMARY: Obesity alters the hormonal profile, gonadotropin secretion, embryo development and in-vitro fertilization outcomes in both men and women.

Faculty and applicant perceptions of virtual interviews on subspecialty fellowship match in obstetrics and gynecology.

BACKGROUND: In response to COVID-19, the AAMC recommended that hospitals conduct interviews in a virtual setting. OBJECTIVE: To evaluate whether fellowship video conference interviews (VCIs) are an acceptable alternative to in-person interviews from both the applicant and program perspectives. METHODS: Applicants and faculty from a single academic institution with five OBGYN subspecialty fellowship programs were invited to complete surveys regarding their experience using VCIs during the 2020 interview season. Survey responses used a 5-point Likert scale (strongly disagree to strongly agree). Comparative analyses between faculty and applicants responses to survey questions were performed with two-tailed Student's t-tests. RESULTS: 45 faculty members and 131 applicants received the survey. Response rate for faculty members and applicants was 95.6% (n = 43) and 46.6% (n = 61), respectively. Faculty and applicants agreed that the VCIs allowed them to accurately represent themselves (83.7% vs. 88.6%, p = 0.48). Most applicants (62.3%, n = 38) reported a fundamental understanding of the fellowship's culture. The majority of applicants (77.1%, n = 47) and faculty (72.1%, n = 31) agreed that they were able to develop connections during the virtual interview (p = 0.77). Faculty and applicants stated that VCIs assisted them in determining whether the candidate or program, respectively, was a good fit (83.7% vs. 67.2%, p = 0.98). CONCLUSIONS: The VCI fellowship recruitment process allowed OBGYN fellowship applicants and programs to accurately represent themselves compared to in-person interviews. Most applicants and faculty were able to develop relationships over the virtual platform. Although not explicitly assessed, it is possible that the virtual interviews can achieve a suitable match between applicant and program across all OBGYN subspecialty fellowships. The VCI process may be a long-term resolution to minimize both the financial burden and time commitment presented by traditional in-person interviews. Follow-up studies should assess the performance of the virtually selected fellows compared to those selected in previous years using traditional in-person interviews.

Examining the psychometric properties of the Integrative Hope Scale's English translation in a mixed-diagnostic community health sample.

OBJECTIVE: Our objective is to provide preliminary evidence of the English translation of the Integrative Hope Scale (IHS). Hope is a critical concept for recovery. Synthesizing from other hope models, Schrank and colleagues developed the IHS. Although translated into five languages, no known studies assess the IHS's English translation within a clinical sample. Additionally, no known studies investigate the IHS's relationships with mental health measures in a mixed-diagnostic clinical sample. METHOD: To address these gaps in the literature, we used confirmatory factor analyses, alpha, and omega reliability coefficients, and correlational analyses to assess the IHS within a suburban, mixed-diagnostic intensive outpatient community mental health sample (n = 125) in the midwestern United States. RESULTS: While poorest fit was found within the one-factor model, the four-factor oblique, higher-order, and bifactor models showed improved fit. Reliability for the total score was good, with subscales ranging from acceptable to good. Significant relationships were found for the IHS in expected directions with measures of hope and depression at a large effect size and anxiety and stress at a moderate effect size. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: This study provides preliminary evidence that the IHS may have the potential to serve as a central measure of hope. Given hope's role within recovery and given its relationships with mental health measures shown in this mixed-diagnostic clinical sample, the IHS should continue to be investigated by researchers, clinicians, and clients, especially in recovery-focused programs. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Elevated inflammatory fecal immune factors in men who have sex with men with HIV associate with microbiome composition and gut barrier function.

Introduction: People living with HIV infection (PLWH) exhibit elevated levels of gastrointestinal inflammation. Potential causes of this inflammation include HIV infection and associated immune dysfunction, sexual behaviors among men who have sex with men (MSM) and gut microbiome composition. Methods: To better understand the etiology of gastrointestinal inflammation we examined levels of 28 fecal soluble immune factors (sIFs) and the fecal microbiome in well-defined cohorts of HIV seronegative MSM (MSM-SN), MSM with untreated HIV infection (MSM-HIV) and MSM with HIV on anti-retroviral treatment (MSMART). Additionally, fecal solutes from these participants were used to stimulate T-84 colonic epithelial cells to assess barrier function. Results: Both MSM cohorts with HIV had elevated levels of fecal calprotectin, a clinically relevant marker of GI inflammation, and nine inflammatory fecal sIFs (GM-CSF, ICAM-1, IL-1ß, IL-12/23, IL-15, IL-16, TNF-ß, VCAM-1, and VEGF). Interestingly, four sIFs (GM-CSF, ICAM-1, IL-7 and IL-12/23) were significantly elevated in MSM-SN compared to seronegative male non-MSM. Conversely, IL-22 and IL-13, cytokines beneficial to gut health, were decreased in all MSM with HIV and MSM-SN respectively. Importantly, all of these sIFs significantly correlated with calprotectin, suggesting they play a role in GI inflammation. Principal coordinate analysis revealed clustering of fecal sIFs by MSM status and significant associations with microbiome composition. Additionally, fecal solutes from participants in the MSM-HIV cohort significantly decreased colonic transcellular fluid transport in vitro, compared to non-MSM-SN, and this decrease associated with overall sIF composition and increased concentrations of eight inflammatory sIFs in participants with HIV. Lastly, elevated levels of plasma, sCD14 and sCD163, directly correlated with decreased transcellular transport and microbiome composition respectively, indicating that sIFs and the gut microbiome are associated with, and potentially contribute to, bacterial translocation. Conclusion: Taken together, these data demonstrate that inflammatory sIFs are elevated in MSM, regardless of HIV infection status, and are associated with the gut microbiome and intestinal barrier function.

Quantifying Spin-Mixed States in Ferromagnets.

We quantify the presence of spin-mixed states in ferromagnetic 3D transition metals by precise measurement of the orbital moment. While central to phenomena such as Elliot-Yafet scattering, quantification of the spin-mixing parameter has hitherto been confined to theoretical calculations. We demonstrate that this information is also available by experimental means. Comparison of ferromagnetic resonance spectroscopy with x-ray magnetic circular dichroism results show that Kittel's original derivation of the spectroscopic g factor requires modification, to include spin mixing of valence band states. Our results are supported by ab initio relativistic electronic structure theory.

Assessing saliva microbiome collection and processing methods.

The oral microbiome has been connected with lung health and may be of significance in the progression of SARS-CoV-2 infection. Saliva-based SARS-CoV-2 tests provide the opportunity to leverage stored samples for assessing the oral microbiome. However, these collection kits have not been tested for their accuracy in measuring the oral microbiome. Saliva is highly enriched with human DNA and reducing it prior to shotgun sequencing may increase the depth of bacterial reads. We examined both the effect of saliva collection method and sequence processing on measurement of microbiome depth and diversity by 16S rRNA gene amplicon and shotgun metagenomics. We collected 56 samples from 22 subjects. Each subject provided saliva samples with and without preservative, and a subset provided a second set of samples the following day. 16S rRNA gene (V4) sequencing was performed on all samples, and shotgun metagenomics was performed on a subset of samples collected with preservative with and without human DNA depletion before sequencing. We observed that the beta diversity distances within subjects over time was smaller than between unrelated subjects, and distances within subjects were smaller in samples collected with preservative. Samples collected with preservative had higher alpha diversity measuring both richness and evenness. Human DNA depletion before extraction and shotgun sequencing yielded higher total and relative reads mapping to bacterial sequences. We conclude that collecting saliva with preservative may provide more consistent measures of the oral microbiome and depleting human DNA increases yield of bacterial sequences.

Maternal cecal microbiota transfer rescues early-life antibiotic-induced enhancement of type 1 diabetes in mice.

Early-life antibiotic exposure perturbs the intestinal microbiota and accelerates type 1 diabetes (T1D) development in the NOD mouse model. Here, we found that maternal cecal microbiota transfer (CMT) to NOD mice after early-life antibiotic perturbation largely rescued the induced T1D enhancement. Restoration of the intestinal microbiome was significant and persistent, remediating the antibiotic-depleted diversity, relative abundance of particular taxa, and metabolic pathways. CMT also protected against perturbed metabolites and normalized innate and adaptive immune effectors. CMT restored major patterns of ileal microRNA and histone regulation of gene expression. Further experiments suggest a gut-microbiota-regulated T1D protection mechanism centered on Reg3γ, in an innate intestinal immune network involving CD44, TLR2, and Reg3γ. This regulation affects downstream immunological tone, which may lead to protection against tissue-specific T1D injury.

Systems Analysis of Gut Microbiome Influence on Metabolic Disease in HIV-Positive and High-Risk Populations.

Poor metabolic health, characterized by insulin resistance and dyslipidemia, is higher in people living with HIV and has been linked with inflammation, antiretroviral therapy (ART) drugs, and ART-associated lipodystrophy (LD). Metabolic disease is associated with gut microbiome composition outside the context of HIV but has not been deeply explored in HIV infection or in high-risk men who have sex with men (HR-MSM), who have a highly altered gut microbiome composition. Furthermore, the contribution of increased bacterial translocation and associated systemic inflammation that has been described in HIV-positive and HR-MSM individuals has not been explored. We used a multiomic approach to explore relationships between impaired metabolic health, defined using fasting blood markers, gut microbes, immune phenotypes, and diet. Our cohort included ART-treated HIV-positive MSM with or without LD, untreated HIV-positive MSM, and HR-MSM. For HIV-positive MSM on ART, we further explored associations with the plasma metabolome. We found that elevated plasma lipopolysaccharide binding protein (LBP) was the most important predictor of impaired metabolic health and network analysis showed that LBP formed a hub joining correlated microbial and immune predictors of metabolic disease. Taken together, our results suggest the role of inflammatory processes linked with bacterial translocation and interaction with the gut microbiome in metabolic disease among HIV-positive and -negative MSM.IMPORTANCE The gut microbiome in people living with HIV (PLWH) is of interest since chronic infection often results in long-term comorbidities. Metabolic disease is prevalent in PLWH even in well-controlled infection and has been linked with the gut microbiome in previous studies, but little attention has been given to PLWH. Furthermore, integrated analyses that consider gut microbiome, together with diet, systemic immune activation, metabolites, and demographics, have been lacking. In a systems-level analysis of predictors of metabolic disease in PLWH and men who are at high risk of acquiring HIV, we found that increased lipopolysaccharide-binding protein, an inflammatory marker indicative of compromised intestinal barrier function, was associated with worse metabolic health. We also found impaired metabolic health associated with specific dietary components, gut microbes, and host and microbial metabolites. This study lays the framework for mechanistic studies aimed at targeting the microbiome to prevent or treat metabolic endotoxemia in HIV-infected individuals.

Influence of shrub willow buffers strategically integrated in an Illinois corn-soybean field on soil health and microbial community composition.

Soil serves many important ecological functions and is an integral part of our existence as a society. However, concerns for soil health are growing globally, in part due to the negative impacts of agricultural management on soil resources. The production of perennial bioenergy crops on marginal land in row-crop production systems is one solution that could improve land-use efficiency and address the sustainability of cropland management. Because the relationship between crop management and the environment is complex, more research is needed to evaluate the potential benefits perennial bioenergy crop production has on soil health, as well as other ecosystem services. In this study, shrub willow buffers were strategically integrated into a corn-soybean cropping system with the main objective of reducing nitrate-N leaching from grain crop production while producing biomass for bioenergy. Two buffer systems (defined by landscape positions) were included for comparison, one on marginal land with exposure to nitrate-N leaching from upslope grain (southern plots) and one on fertile soils with less nitrate-N leaching potential (northern plots). Evaluation of soil (chemistry, bulk density, microbial community) and shrub willow vegetation properties (fine roots, leaf litter decomposition, and nutrient uptake dynamics), showed that landscape position plays an important role in (1) the dynamics of soil chemical properties, (2) shrub willow's influence and productivity, and (3) the provision of additional ecosystem services such as reductions in nitrous oxide emissions and nitrate-N leaching. In addition, the combination of crop type and landscape position (N-grain, N-willow, S-grain, and S-willow) influenced the species composition of the soil microbial community, resulting in unique and identifiable communities. These results highlight the potential application of shrub willow buffers for ecosystem service provision and support of ecosystem processes; however, understanding the relationship between the microbial community, crop type, and landscape is important for understanding the sustainability of the design.

Availability of Fertility Preservation Information on the Websites of U.S. News and World Report Top-Ranked Pediatric Cancer Programs.

Purpose: To evaluate the availability of fertility preservation (FP) services and educational resources on the websites of top-ranked U.S. pediatric cancer programs. Methods: Cross-sectional survey of information and resources related to FP on websites from top-ranked pediatric cancer programs according to the 2018-2019 U.S.-News & World Report (USNWR) ranking. Factors that predicted the website availability of FP information or a fertility team were analyzed, as was availability in Spanish and for specific groups by sex and puberty status. As a surrogate marker of comprehensive oncological services, the availability of resources for psychological support was compared to FP. Results: A fertility team was referenced on the website of 36% of programs, but only 32% provided FP educational resources for patients. Among them, 100%, 93.8%, 93.8%, and 68.8% provided specific information for postpubertal females, prepubertal females, postpubertal males, and prepubertal males, respectively. The majority (93.8%) did not provide information in Spanish. The ranking on USNWR (p < 0.05) and patient volume (p < 0.05) positively correlated with the availability of FP information and fertility team on the program's website. Information regarding psychological support was provided more often than information regarding FP (96% vs. 32%, p < 0.05). Conclusion: The majority of the top-ranked pediatric cancer programs in the United States do not list FP resources or a fertility team on their website. The lack of resources is particularly concerning for the Spanish-speaking population, as well as for prepubertal males. This may be potentially hindering access to FP and contributing to health care disparities.

Measures of Patient Dissatisfaction With Health Care in Polycystic Ovary Syndrome: Retrospective Analysis.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common reproductive and metabolic disorder in women; however, many clinicians may not be well versed in scientific advances that aid understanding of the associated reproductive, metabolic, and psychological abnormalities. Women with PCOS are dissatisfied with health care providers, the diagnostic process, and the initial treatment of PCOS and seek information through alternative sources. This has affected the patient-physician relationship by allowing medical information acquired through the internet, whether correct or not, to become accessible to patients and reshape their health care perspective. Patient dissatisfaction with health care providers regarding PCOS raises questions about the responsibilities of academic institutions to adequately train and maintain the competence of clinicians and government agencies to sufficiently support scientific investigation in this field. OBJECTIVE: The primary aim was to examine internet searching behaviors of the public regarding PCOS vs another highly prevalent gynecologic disorder. The secondary aim was to explore satisfaction with health care among patients with PCOS and their internet use. The tertiary aim was to examine medical education in reproductive endocrinology and infertility (REI) during obstetrics and gynecology (Ob/Gyn) residency as a proxy for physician knowledge in this field. METHODS: Google search trends and StoryBase quantified monthly Google absolute search volumes for search terms related to PCOS and fibroids (January 2004 to December 2017; United States). The reproductive disorder, fibroids, was selected as a comparison group because of its high prevalence among women. Between female groups, monthly absolute search volumes and their trends were compared. A Web-based questionnaire (June 2015 to March 2018) explored health care experiences and the internet use of women with PCOS. REI rotation information during Ob/Gyn residency in the United States was obtained from the Association of Professors of Gynecology and Obstetrics website. RESULTS: For PCOS (R=0.89; P<.01), but not fibroids (R=0.09; P=.25), monthly absolute search volumes increased significantly. PCOS-related monthly absolute search volumes (mean 384,423 searches, SD 88,756) were significantly greater than fibroid-related monthly absolute search volumes (mean 348,502 searches, SD 37,317; P<.05). PCOS was diagnosed by an Ob/Gyn in 60.9% (462/759) of patients, and 57.3% (435/759) of patients were dissatisfied with overall care. Among patients with PCOS, 98.2% (716/729) searched for PCOS on the Web but only 18.8% (143/729) of patients joined an online PCOS support group or forum. On average, Ob/Gyn residencies dedicated only 4% (2/43) of total block time to REI, whereas 5.5% (11/200) of such residencies did not offer any REI rotations. CONCLUSIONS: Over time, PCOS has been increasingly searched on the Web compared with another highly prevalent gynecologic disorder. Patients with PCOS are dissatisfied with their health care providers, who would benefit from an improved understanding of PCOS during Ob/Gyn residency training.

Correction to: An exploration of Prevotella-rich microbiomes in HIV and men who have sex with men.

Following publication of the original article [1], the authors reported an error in Fig. 2. The original Fig. 2 has been incorrectly replaced with the Supplementary Fig. 2. The correct Fig. 2 is presented here.

Can gut microbiota of men who have sex with men influence HIV transmission?

Gaining a complete understanding of transmission risk factors will assist in efforts to reduce new HIV infections, especially within the disproportionally affected population of men who have sex with men (MSM). We recently reported that the fecal microbiota of MSM elevates immune activation in gnotobiotic mice and enhances HIV infection in vitro over that of fecal microbiota from men who have sex with women. We also demonstrated elevation of the gut homing marker CD103 (integrin αE) on CD4+ T cells by MSM-microbiota. Here we provide additional evidence that the gut microbiota is a risk factor for HIV transmission in MSM by showing elevated frequencies of the HIV co-receptor CCR5 on CD4+ T cells in human rectosigmoid colon biopsies. We discuss our interest in specific MSM-associated bacteria and propose the influx of CD103+ and CCR5+ CD4+ T cells into the colon as a potential link between the MSM microbiota and HIV transmission.