Drosophila melanogaster sex peptide regulates mated female midgut morphology and physiology.

Drosophila melanogaster females experience a large shift in energy homeostasis after mating to compensate for nutrient investment in egg production. To cope with this change in metabolism, mated females undergo widespread physiological and behavioral changes, including increased food intake and altered digestive processes. The mechanisms by which the female digestive system responds to mating remain poorly characterized. Here, we demonstrate that the seminal fluid protein Sex Peptide (SP) is a key modulator of female post-mating midgut growth and gene expression. SP is both necessary and sufficient to trigger post-mating midgut growth in females under normal nutrient conditions, and likely acting via its receptor, Sex Peptide Receptor (SPR). Moreover, SP is responsible for almost the totality of midgut transcriptomic changes following mating, including up-regulation of protein and lipid metabolism genes and down-regulation of carbohydrate metabolism genes. These changes in metabolism may help supply the female with the nutrients required to sustain egg production. Thus, we report a role for SP in altering female physiology to enhance reproductive output: Namely, SP triggers the switch from virgin to mated midgut state.

Exploring Infant Feeding Experiences and Maternity Care Practices in Appalachia.

OBJECTIVES: Our aim was to explore postpartum individuals' experiences and perceptions of breastfeeding and International Board Certified Lactation Consultants' (IBCLC) knowledge and perceptions of maternity care practices and perceived barriers to breastfeeding among their patient populations in Appalachia. METHODS: Semistructured interviews were conducted with seven IBCLCs and seven postpartum individuals. Interviews were recorded and transcribed. Thematic analysis was conducted to determine emergent themes and subthemes related to knowledge/perceptions, experiences, and barriers to breastfeeding among postpartum individuals, as well as emergent themes associated with the knowledge and perceptions of maternity care practices, easy-/difficult-to-implement Baby-Friendly Hospital Initiative maternity care practices, and perceived barriers to breastfeeding among IBCLCs. RESULTS: Postpartum individuals recruited from an Appalachian obstetrics/gynecology clinic were aware of the benefits of breastfeeding, but their infant feeding journeys were more stressful than they expected, and they had limited access to lactation support and breastfeeding education/information. IBCLCs identified the benefits of the Baby-Friendly maternity care practices but mentioned some risks, especially when there is a lack of communication and coordination among providers. Environmental and informational barriers were identified by both postpartum individuals and IBCLCs as breastfeeding challenges potentially amenable to change. CONCLUSIONS: To support postpartum mothers in the Appalachian region, environmental barriers (eg, lack of lactation support) and informational barriers (eg, lack of prenatal education) need to be addressed.

Medical and surgical nurses' experiences of modifying and implementing contextually suitable Safewards interventions into medical and surgical hospital wards.

AIM: To explore general nurses' experiences of modifying and implementing contextually suitable Safewards interventions into medical and surgical hospital wards. DESIGN: Qualitative action research was used working with nurses as co-researchers. METHODS: Pre-implementation focus groups were conducted in April 2022 to understand and explore the current strategies nurses utilized to avert, respond to or decrease violence. Following this, two Safewards interventions were modified by the nurses on the wards. Post-implementation focus groups were conducted in October 2022, to explore the nurses' experience of implementing Safewards interventions and the effect on their nursing practice. Data were analysed using Braun and Clarke's framework for thematic analysis. RESULTS: Three themes emerged from the analysis of the pre-implementation focus groups that reflected the type of violence experienced by these nurses and the context within which they occurred: 'the space is hectic'; 'it can feel like a battlefield'; and 'the aftermath'. These themes encompass the nurses' experience of violence from patients and their visitors. Following the implementation of two modified Safewards interventions, the analysis of the focus groups reflected a change in nursing skills to avert or respond to violence: 'Safewards in action'; 'empathy and self-reflection'; and 'moving forward'. CONCLUSION: Safewards interventions can be successfully modified and used in general hospital wards and influence nursing practice to manage patient and visitor violence. IMPLICATIONS FOR THE PROFESSION: In the interests of safety, successful interventions to reduce violence towards general hospital nurses should be a priority for managers and healthcare organizations. Averting, mitigating and managing violence can decrease the negative professional and personal effect on nurses and ultimately improve well-being, job satisfaction and retention rates. Furthermore, decreasing violence or aggressive incidents leads to a safer patient experience and decreased number of nursing errors ultimately improving patient experiences and outcomes. Understanding nurses' experiences of violence and working with them to explore and develop contextually relevant solutions increases their capacity to respond to and avert violent incidents. Contextually modified Safewards interventions offer one such solution and potentially has wider implications for healthcare settings beyond the specific wards studied. IMPACT: This study addressed the implementation of modified Safewards strategies in medical and surgical wards to prevent violence. Three themes emerged from the analysis of the pre-implementation focus groups that reflected the type of violence experienced by these nurses and the context within which they occurred. Following the implementation of two modified Safewards interventions, the post-implementation focus groups reported positive changes to their practices using the modified resources to prevent violence from patients and their visitors. Mental health interventions, such as those used in the Safewards model can be modified and provide a tool kit of interventions that can be used by medical and surgical nurses. REPORTING METHOD: This paper has adhered to the COREQ guidelines. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. WHAT DOES THIS PAPER CONTRIBUTE TO THE WIDER GLOBAL CLINICAL COMMUNITY?: This paper outlines and discusses the action research approach undertaken to work with general hospital nurses to modify mental health nurses' Safewards interventions into their clinical practice. This paper provides evidence of the 'real world' application of Safewards interventions by medical and surgical nurses in general hospital wards. This paper presents qualitative findings based on focus group methods to highlight the narratives of general nurses and their experiences of violence.

Exposure to polycyclic aromatic hydrocarbons during pregnancy and breast tissue composition in adolescent daughters and their mothers: a prospective cohort study.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAH), which are found in air pollution, have carcinogenic and endocrine disrupting properties that might increase breast cancer risk. PAH exposure might be particularly detrimental during pregnancy, as this is a time when the breast tissue of both the mother and daughter is undergoing structural and functional changes. In this study, we tested the hypothesis that ambient PAH exposure during pregnancy is associated with breast tissue composition, measured one to two decades later, in adolescent daughters and their mothers. METHODS: We conducted a prospective analysis using data from a New York City cohort of non-Hispanic Black and Hispanic mother-daughter dyads (recruited 1998-2006). During the third trimester of pregnancy, women wore backpacks containing a continuously operating air sampling pump for two consecutive days that measured ambient exposure to eight carcinogenic higher molecular weight nonvolatile PAH compounds (Σ8 PAH) and pyrene. When daughters (n = 186) and mothers (n = 175) reached ages 11-20 and 29-55 years, respectively, optical spectroscopy (OS) was used to evaluate measures of breast tissue composition (BTC) that positively (water content, collagen content, optical index) and negatively (lipid content) correlate with mammographic breast density, a recognized risk factor for breast cancer. Multivariable linear regression was used to evaluate associations between ambient PAH exposure and BTC, overall and by exposure to household tobacco smoke during pregnancy (yes/no). Models were adjusted for race/ethnicity, age, and percent body fat at OS. RESULTS: No overall associations were found between ambient PAH exposure (Σ8 PAH or pyrene) and BTC, but statistically significant additive interactions between Σ8 PAH and household tobacco smoke exposure were identified for water content and optical index in both daughters and mothers (interaction p values < 0.05). Σ8 PAH exposure was associated with higher water content (ßdaughters = 0.42, 95% CI = 0.15-0.68; ßmothers = 0.32, 95% CI = 0.05-0.61) and higher optical index (ßdaughters = 0.38, 95% CI = 0.12-0.64; ßmothers = 0.38, 95% CI = 0.12-0.65) in those exposed to household tobacco smoke during pregnancy; no associations were found in non-smoking households (interaction p values < 0.05). CONCLUSIONS: Exposure to ambient Σ8 PAH and tobacco smoke during pregnancy might interact synergistically to impact BTC in mothers and daughters. If replicated in other cohorts, these findings might have important implications for breast cancer risk across generations.

Mother and Daughter Perspectives on Genetic Counseling and Testing of Adolescents for Hereditary Breast Cancer Risk.

OBJECTIVE: To evaluate the risks, benefits, and utility of testing for adult-onset hereditary breast and ovarian cancer (HBOC) in adolescents and young adults. STUDY DESIGN: We evaluated interest in genetic testing of adolescents for adult-onset HBOC genes through semistructured interviews with mothers and adolescents who had previously participated in breast cancer research or had pursued (mothers) clinical testing for HBOC. RESULTS: The majority of mothers (73%) and daughters (75%) were interested in the daughter having genetic testing and were motivated by the future medical utility and current social utility of relieving anxiety and allowing them to prepare. Mothers and daughters both reported that approximately 3 years in the future was the best time to test the daughter regardless of the current age of the daughter. Overall, both mothers and daughters expressed the importance of the involvement of the mother to provide educational and emotional support but ultimately it was the daughter's decision to test. Balancing the independence and maturity of the daughter while reinforcing communication and support within the dyad was a prominent theme throughout the interviews. CONCLUSIONS: There is interest among some high-risk adolescents and young adults to engage in genetic counseling and undergo testing. Providing pretest and posttest genetic counseling, assessing preferences for parent involvement, and offering psychosocial support may be important if genetic testing for HBOC is offered to adolescents and young adults before age 25 years.

Community-Onset Venous Thromboembolism in Children: Pediatric Emergency Medicine Perspectives.

Pediatric venous thromboembolism (VTE) is a condition increasingly encountered by emergency medicine physicians. Unfortunately, despite increased incidence, the diagnosis of pediatric VTE relies on a high index of suspicion from clinicians. Delays in diagnosis and initiation of treatment can lead to poor outcomes in children, including an increased risk of mortality from pulmonary embolism, increased risk of VTE recurrence, and the development of the post-thrombotic syndrome. The majority of pediatric VTE events are associated with the presence of at least one underlying prothrombotic risk. Timely recognition of these risk factors in the emergency department (ED) setting is paramount for a prompt diagnosis and treatment initiation. Compared with children with hospital-acquired VTE, children presenting to the ED with new onset VTE tend to be older (>11 years of age), have a lower incidence of co-morbidities, and present more frequently with a deep venous thrombosis of the lower extremity. Currently, there are no validated pediatric-specific VTE clinical pretest probability tools that reliably assist with the accurate and timely diagnosis of pediatric VTE. Compression ultrasound with Doppler is the most common imaging modality used for VTE diagnosis, and low molecular weight heparins are the most common anticoagulants initiated in children presenting with VTE in the ED. Special consideration should be given to patients who present to the ED already on anticoagulation therapy who may require acute management for clinically-significant bleeding or change in antithrombotic therapy approach for progression/recurrence of VTE.

She's got nerve: roles of octopamine in insect female reproduction.

The biogenic monoamine octopamine (OA) is a crucial regulator of invertebrate physiology and behavior. Since its discovery in the 1950s in octopus salivary glands, OA has been implicated in many biological processes among diverse invertebrate lineages. It can act as a neurotransmitter, neuromodulator and neurohormone in a variety of biological contexts, and can mediate processes including feeding, sleep, locomotion, flight, learning, memory, and aggression. Here, we focus on the roles of OA in female reproduction in insects. OA is produced in the octopaminergic neurons that innervate the female reproductive tract (RT). It exerts its effects by binding to receptors throughout the RT to generate tissue- and region-specific outcomes. OA signaling regulates oogenesis, ovulation, sperm storage, and reproductive behaviors in response to the female's internal state and external conditions. Mating profoundly changes a female's physiology and behavior. The female's OA signaling system interacts with, and is modified by, male molecules transferred during mating to elicit a subset of the post-mating changes. Since the role of OA in female reproduction is best characterized in the fruit fly Drosophila melanogaster, we focus our discussion on this species but include discussion of OA in other insect species whenever relevant. We conclude by proposing areas for future research to further the understanding of OA's involvement in female reproduction in insects.

Parallel assembly of actin and tropomyosin, but not myosin II, during de novo actin filament formation in live mice.

Many actin filaments in animal cells are co-polymers of actin and tropomyosin. In many cases, non-muscle myosin II associates with these co-polymers to establish a contractile network. However, the temporal relationship of these three proteins in the de novo assembly of actin filaments is not known. Intravital subcellular microscopy of secretory granule exocytosis allows the visualisation and quantification of the formation of an actin scaffold in real time, with the added advantage that it occurs in a living mammal under physiological conditions. We used this model system to investigate the de novo assembly of actin, tropomyosin Tpm3.1 (a short isoform of TPM3) and myosin IIA (the form of non-muscle myosin II with its heavy chain encoded by Myh9) on secretory granules in mouse salivary glands. Blocking actin polymerization with cytochalasin D revealed that Tpm3.1 assembly is dependent on actin assembly. We used time-lapse imaging to determine the timing of the appearance of the actin filament reporter LifeAct-RFP and of Tpm3.1-mNeonGreen on secretory granules in LifeAct-RFP transgenic, Tpm3.1-mNeonGreen and myosin IIA-GFP (GFP-tagged MYH9) knock-in mice. Our findings are consistent with the addition of tropomyosin to actin filaments shortly after the initiation of actin filament nucleation, followed by myosin IIA recruitment.

Feasibility and Outcomes Associated With the Use of 2.6-Fr Double-Lumen PICCs in Neonates.

BACKGROUND: Low birth-weight infants' survival continues to improve and there is increased need to provide secure vascular access. This study examines safety of larger peripherally inserted central catheters (PICCs) that offer greater utility. PURPOSE: To determine feasibility of 2.6-French (Fr) double-lumen PICCs in newborns and compare noninfectious complications such as thrombus formation, catheter breakage, infiltration, and accidental dislodgment and central line-associated bloodstream infection (CLABSI) rate with that of newborn infants treated with 1.9-Fr single- and double-lumen PICCs. METHODS: Infants requiring PICCs were admitted in our 69-bed level IV neonatal intensive care unit from September 2006 to May 2015. Two distinct groups were compared: the 1.9-Fr-(single-lumen [n = 105] and double-lumen [n = 27])-and 2.6-Fr double-lumen PICCs (n = 111). Data obtained included birth weight and weight at insertion, gestational age at birth and corrected gestation age at insertion, indication, catheter days, indication for removal, and complications: noninfectious and infectious. Univariate and multivariate statistical analysis evaluated data. RESULTS: There were no differences regarding gestational age at birth and insertion and indications for placement of 2.6-Fr double-lumen (n =111) and 1.9-Fr both single- and double-lumen (n = 132) PICCs. The same was noted between the groups' complications. Noninfectious complications were more common in PICCs with peripheral tip location in all groups. IMPLICATIONS FOR PRACTICE: Consider use of 2.6-Fr PICCs in a neonatal intensive care unit when the utility of blood administration and sampling is required. IMPLICATIONS FOR RESEARCH: Examine line migration and CLABSI associated with sampling and blood administration.

Comparison of methods to assess onset of breast development in the LEGACY Girls Study: methodological considerations for studies of breast cancer.

BACKGROUND: Younger age at onset of breast development, which has been declining in recent decades, is associated with increased breast cancer risk independent of age at menarche. Given the need to study the drivers of these trends, it is essential to validate methods to assess breast onset that can be used in large-scale studies when direct clinical assessment of breast onset is not feasible. METHODS: Breast development is usually measured by Tanner stages (TSs), assessed either by physical examination or by mother's report using a picture-based Sexual Maturation Scale (SMS). As an alternative, a mother-reported Pubertal Development Scale (PDS) without pictures has been used in some studies. We compared agreement of SMS and PDS with each other (n = 1022) and the accuracy of PDS with clinical TS as a gold standard for the subset of girls with this measure (n = 282) using the LEGACY cohort. We further compared prediction of breast onset using ROC curves and tested whether adding urinary estrone 1-glucuronide (E1G) improved the AUC. RESULTS: The agreement of PDS with SMS was high (kappa = 0.80). The sensitivity of PDS vs clinical TS was 86.6%. The AUCs for PDS alone and SMS alone were 0.88 and 0.79, respectively. Including E1G concentrations improved the AUC for both methods (0.91 and 0.86 for PDS and SMS, respectively). CONCLUSIONS: The PDS without pictures is a highly accurate, sensitive, and specific method for assessing breast onset, especially in settings where clinical TS is not feasible. In addition, it is comparable to SMS methods with pictures and thus easier to implement in large-scale studies, particularly phone-based interviews where pictures may not be available. Urinary E1G can improve accuracy over than PDS or SMS alone.

Hyperspectral microscopy can detect metabolic heterogeneity within bovine post-compaction embryos incubated under two oxygen concentrations (7% versus 20%).

STUDY QUESTION: Can we separate embryos cultured under either 7% or 20% oxygen atmospheres by measuring their metabolic heterogeneity? SUMMARY ANSWER: Metabolic heterogeneity and changes in metabolic profiles in morula exposed to two different oxygen concentrations were not detectable using traditional fluorophore and two-channel autofluorescence but were detectable using hyperspectral microscopy. WHAT IS KNOWN ALREADY: Increased genetic and morphological blastomere heterogeneity is associated with compromised developmental competence of embryos and currently forms the basis for embryo scoring within the clinic. However, there remains uncertainty over the accuracy of current techniques, such as PGS and time-lapse microscopy, to predict subsequent pregnancy establishment. STUDY DESIGN, SIZE, DURATION: The impact of two oxygen concentrations (7% = optimal and 20% = stressed) during post-fertilisation embryo culture was assessed. Cattle embryos were exposed to the different oxygen concentrations for 8 days (D8; embryo developmental competence) or 5 days (D5; metabolism measurements). Between 3 and 4 experimental replicates were performed, with 40-50 embryos per replicate used for the developmental competency experiment, 10-20 embryos per replicate for the fluorophore and two-channel autofluorescence experiments and a total of 21-22 embryos used for the hyperspectral microscopy study. PARTICIPANTS/MATERIALS, SETTING, METHODS: In-vitro produced (IVP) cattle embryos were utilised for this study. Post-fertilisation, embryos were exposed to 7% or 20% oxygen. To determine impact of oxygen concentrations on embryo viability, blastocyst development was assessed on D8. On D5, metabolic heterogeneity was assessed in morula (on-time) embryos using fluorophores probes (active mitochondria, hydrogen peroxide and reduced glutathione), two-channel autofluorescence (FAD and NAD(P)H) and 18-channel hyperspectral microscopy. MAIN RESULTS AND THE ROLE OF CHANCE: Exposure to 20% oxygen following fertilisation significantly reduced total blastocyst, expanded and hatched blastocyst rates by 1.4-, 1.9- and 2.8-fold, respectively, compared to 7% oxygen (P < 0.05), demonstrating that atmospheric oxygen was a viable model for studying mild metabolic stress. The metabolic profiles of D5 embryos was determined and although metabolic heterogeneity was evident within the cleavage stage (i.e. arrested) embryos exposed to fluorophores, there were no detectable difference in fluorescence intensity and pattern localisation in morula exposed to the two different oxygen concentrations (P > 0.05). While there were no significant differences in two-channel autofluorescent profiles of morula exposed to 7% and 20% oxygen (main effect, P > 0.05), morula that subsequently progressed to the blastocyst stage had significantly higher levels of FAD and NAD(P)H fluorescence compared to arrested morula (P < 0.05), with no change in the redox ratio. Hyperspectral autofluorescence imaging (in 18-spectral channels) of the D5 morula revealed highly significant differences in four features of the metabolic profiles of morula exposed to the two different oxygen concentrations (P < 0.001). These four features were weighted and their linear combination revealed clear discrimination between the two treatment groups. LIMITATIONS, REASONS FOR CAUTION: Metabolic profiles were assessed at a single time point (morula), and as such further investigation is required to determine if differences in hyperspectral signatures can be detected in pre-compaction embryos and oocytes, using both cattle and subsequently human models. Furthermore, embryo transfers should be performed to determine the relationship between metabolic profiles and pregnancy success. WIDER IMPLICATIONS OF THE FINDINGS: Advanced autofluorescence imaging techniques, such as hyperspectral microscopy, may provide clinics with additional tools to improve the assessment of embryos prior to transfer. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Australian Research Council Centre of Excellence for Nanoscale BioPhotonics (CE140100003). The Fluoview FV10i confocal microscope was purchased as part of the Sensing Technologies for Advanced Reproductive Research (STARR) facility, funded by the South Australian Premier's Science and Research Fund. The authors declare there are no conflict of interest.

Cumulin, an Oocyte-secreted Heterodimer of the Transforming Growth Factor-ß Family, Is a Potent Activator of Granulosa Cells and Improves Oocyte Quality.

Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are oocyte-specific growth factors with central roles in mammalian reproduction, regulating species-specific fecundity, ovarian follicular somatic cell differentiation, and oocyte quality. In the human, GDF9 is produced in a latent form, the mechanism of activation being an open question. Here, we produced a range of recombinant GDF9 and BMP15 variants, examined their in silico and physical interactions and their effects on ovarian granulosa cells (GC) and oocytes. We found that the potent synergistic actions of GDF9 and BMP15 on GC can be attributed to the formation of a heterodimer, which we have termed cumulin. Structural modeling of cumulin revealed a dimerization interface identical to homodimeric GDF9 and BMP15, indicating likely formation of a stable complex. This was confirmed by generation of recombinant heterodimeric complexes of pro/mature domains (pro-cumulin) and covalent mature domains (cumulin). Both pro-cumulin and cumulin exhibited highly potent bioactivity on GC, activating both SMAD2/3 and SMAD1/5/8 signaling pathways and promoting proliferation and expression of a set of genes associated with oocyte-regulated GC differentiation. Cumulin was more potent than pro-cumulin, pro-GDF9, pro-BMP15, or the two combined on GC. However, on cumulus-oocyte complexes, pro-cumulin was more effective than all other growth factors at notably improving oocyte quality as assessed by subsequent day 7 embryo development. Our results support a model of activation for human GDF9 dependent on cumulin formation through heterodimerization with BMP15. Oocyte-secreted cumulin is likely to be a central regulator of fertility in mono-ovular mammals.

Using the Assessment for Signal Clients as a feedback tool for reducing treatment failure.

OBJECTIVE: The Clinical Support Tools (CSTs) were developed to help therapists organize and target potential problems that might account for negative outcomes in psychotherapy. The core of CST feedback is the Assessment for Signal Clients. The purpose of this study was to describe and identify patterns of problems that typically characterize off-track cases. METHOD: The responses and scores from 107 off-track clients from a hospital-based outpatient clinic were analyzed. RESULTS: A cluster analysis of the 107 off-track clients revealed three client types: those whose problems were characterized by alliance and motivational difficulties; those characterized by social support and life event difficulties; and those whose problems had an indistinguishable pattern. Log-linear modeling showed that if patients had less therapeutic alliance problems they were also less likely to have motivational problems. Findings were also consistent with the cluster analysis, which showed that a relatively higher percentage of not-on-track participants received signal alerts for the social support items and scale. CONCLUSIONS: Individuals whose progress goes off-track while in psychotherapy appear to have their greatest difficulty with social support, followed closely by motivation for therapy and therapeutic alliance.

Determining the Diagnostic Accuracy of the Test of Integrated Language and Literacy Skills for College Students.

PURPOSE: This study sought to determine whether the Test of Integrated Language and Literacy Skills (TILLS; Nelson et al., 2016) can accurately identify language disorders in college-aged adults. METHOD: Fifty-nine college students between the ages of 18 and 23 years were administered the test battery validated by Fidler et al. (2011) for the diagnosis of language disorders as well as the Identification Core (ID Core) subtests of the TILLS validated for ages 12-18 years. Sensitivity and specificity information was calculated for the TILLS at various cut-scores to determine the diagnostic accuracy of the ID Core for this population. Discriminant function analysis was also performed to determine if sensitivity and specificity could be improved using empirically derived discriminant scores. RESULTS: The recommended cut-score of 42 for ages 12-18 years underidentified individuals with language disorders in this sample. An adjusted cut-score of 51 maximized sensitivity and specificity to acceptable levels. Discriminant function analysis also yielded acceptable sensitivity and specificity (> 80%). CONCLUSION: Using either an adjusted cut-score for the ID Core or weighted discriminant scores, the TILLS can be used to accurately differentiate between college-aged adults with and without language disorders.

Trends and factors associated with receipt of human papillomavirus (HPV) vaccine in private, public, and alternative settings in the United States.

BACKGROUND: One of the goals of the President's Cancer Panel was to maximize access to human papillomavirus (HPV) vaccination through expansion of alternative settings for receiving the vaccine, such as in public health settings, schools, and pharmacies. METHODS: In a cross-sectional analysis, we utilized the National Immunization Survey-Teen data from 2014 to 2020 (n = 74,645) to describe trends and factors associated with HPV vaccine uptake in private, public, and alternative settings. We calculated annual percent change (APC) between 2014 and 2020, estimating rate of HPV vaccine uptake across settings. Using multinomial logistic regression, we estimated the odds of receipt of HPV vaccine in public health settings and other alternative settings compared to private healthcare settings, adjusting for sociodemographic covariates. RESULTS: We found a 5 % annual increase in the use of private facilities between 2014-2018 (APC = 5.3; 95 % CI 3.4, 7.1), and almost 7 % between 2018-2020 (APC = 6.7; 95 % CI 1.4, 12.3). Adjusted multinomial logistic regression analyses found that odds of receiving vaccinations at a public facility vs. a private facility increased almost two times for adolescents living below poverty (aOR = 1.82, 95 % CI: 1.60, 2.08) compared to above poverty. Additionally, adolescents without physician recommendations had lower odds of receiving vaccines at public versus private facilities (aOR = 1.75, 95 % CI: 1.44, 2.12). Finally, odds of receiving HPV vaccines at public facilities vs. private facilities decreased by 33 % for White adolescents (aOR = 0.67, 95 % CI: 0.57, 0.78) versus Black adolescents. CONCLUSIONS: Sociodemographic factors such as race, and socioeconomic factors such as poverty level, and receipt of physician HPV recommendations are associated with receiving the vaccine at private settings vs. public health facilities and alternative settings. This information is important in strengthening alternative settings for HPV vaccine uptake to increase access to the vaccine among disadvantaged individuals.

Urinary Androgens Provide Additional Evidence Related to Metabolism and Are Correlated With Serum Androgens in Girls.

Context: Androgen levels are generally measured in serum samples, but urine may be a more feasible option, especially in children, as it is a noninvasive alternative. Objective: To assess the correlations of 10 urinary androgen metabolites with 4 serum androgens [dehydroepiandrosterone-sulfate (DHEA-S), androstenedione, and total and free testosterone] and assess if their correlations differ by participant characteristics. Methods: Our study consisted of 44 girls, ages 6-13, who participated in the New York site of the LEGACY Girls Study and had both serum and urine samples collected at the same visit. We performed Pearson's correlation coefficient tests between 4 serum and 10 individual urinary metabolite measures and their sum. We examined the influence of participant characteristics on the magnitude and direction of the correlations. Results: The summed urinary metabolite measures had the highest correlation with free testosterone in serum (global sum, r = 0.83) and correlated least with DHEA-S in serum (global sum, r = 0.64). The correlation between individual urinary metabolites and serum androgens ranged from 0.08 to 0.84.Two 11-oxygenated urinary metabolites (5α-androstane-3α-ol-11,17-dione5ß-androstane-3α,11ß-diol-17-one) were weakly correlated with all serum androgens. Participant age, weight, height, waist:hip ratio, and pubic hair growth stage changed the correlations between urinary and serum androgens measures between 10% and 213%. Conclusion: The sum of urinary androgen metabolites was a good marker of circulating androstenedione, testosterone, and free testosterone. Individual urinary metabolites provide additional information about the metabolic processes of disease development compared to the antecedent serum androgens.

Considerations for instituting pediatric pulmonary embolism response teams: A tool kit.

The incidence of pediatric pulmonary embolism (PE) has increased by 200 % in the last decade, but at a single center, it is still infrequent. Given the unique epidemiologic features of pediatric PE, diagnosis is often delayed, and the management is empiric, based on individual physician experience or preference. Thus, there is a strong need for center-specific uniform management of pediatric PE patients. In adults, the development of pulmonary embolism response teams (PERTs) or PE critical care pathways has shortened the time to diagnosis and the initiation of definitive management. Evidence to support an improvement in PE outcomes after the development of PERTs does not exist in children. Nonetheless, we have summarized the practical practice guidelines that physicians and institutions can adopt to establish their institutional PERTs or critical pathways. We also provide strategies for resource-challenged institutions for partnering with centers with expertise in the management of pediatric PE.

Compromised transcription-mRNA export factor THOC2 causes R-loop accumulation, DNA damage and adverse neurodevelopment.

We implicated the X-chromosome THOC2 gene, which encodes the largest subunit of the highly-conserved TREX (Transcription-Export) complex, in a clinically complex neurodevelopmental disorder with intellectual disability as the core phenotype. To study the molecular pathology of this essential eukaryotic gene, we generated a mouse model based on a hypomorphic Thoc2 exon 37-38 deletion variant of a patient with ID, speech delay, hypotonia, and microcephaly. The Thoc2 exon 37-38 deletion male (Thoc2Δ/Y) mice recapitulate the core phenotypes of THOC2 syndrome including smaller size and weight, and significant deficits in spatial learning, working memory and sensorimotor functions. The Thoc2Δ/Y mouse brain development is significantly impacted by compromised THOC2/TREX function resulting in R-loop accumulation, DNA damage and consequent cell death. Overall, we suggest that perturbed R-loop homeostasis, in stem cells and/or differentiated cells in mice and the patient, and DNA damage-associated functional alterations are at the root of THOC2 syndrome.

Bacterial pericarditis associated with a hepatic abscess in a cat.

Case summary: An 8-year-old male neutered domestic shorthair cat presented collapsed and was subsequently diagnosed with a pericardial effusion based on ultrasound imaging. A laboratory analysis of pericardial fluid revealed a septic pericardial effusion and further diagnostics, including abdominal ultrasound and fluid analysis, revealed a concurrent hepatic abscess. Bacterial isolation and identification from both septic foci revealed Escherichia coli. Therapeutic measures included a combination of medical and surgical intervention, the latter including a pericardiectomy, cholecystectomy, liver lobectomy and splenectomy. Relevance and novel information: Septic pericarditis is one of the least reported causes of feline pericardial effusion. This case report describes bacterial pericarditis in a cat, suspected to be derived from a hepatic abscess via haematological spread. In this case, a favourable response was achieved with both surgical and medical management.