The current landscape of exercise and female fertility research: a narrative review.

In brief: Females with obesity may experience infertility and can improve their fertility through exercise. This review found that most exercise interventions improve fertility outcomes regardless of technique, intensity, or duration. More detailed reporting through the lens of exercise prescription should be included in future studies. Abstract: Female infertility disproportionately affects people with obesity. Exercise often improves fertility outcomes for this population, however, there is limited prescriptive evidence. Specifically, there is a lack of information on the ideal type, frequency, intensity, and setting of exercise to improve fertility outcomes. Using principles of exercise prescription, this review aimed to describe the scope of exercise interventions that have been explored and fertility outcomes measured for people with female infertility and obesity. A search was completed in PubMed, Embase, Cochrane, and CINAHL, identifying 16 relevant published articles. Overall, exercise had a positive impact on female fertility outcomes in people with obesity, though there were large variations in the exercise interventions prescribed and outcomes measured. Cyclic exercise (i.e. walking and cycling) was the most common technique incorporated, though a combination of cyclic, acyclic (i.e. circuit training and boot camp), or individualization was often used. Several fertility outcomes were reported; however, the rate of conception, pregnancy, and live birth rates were the most common, which, we suggest, should always be reported in fertility intervention research. We stress that future studies provide more thorough descriptions of their implemented exercise interventions to facilitate reproducibility and comparisons between studies. Closer attention to the principles of exercise prescription when developing and reporting exercise interventions will help improve fertility outcomes, mainly live birth rates, for those with female infertility and obesity.

Adverse Childhood Experiences Predict Diurnal Cortisol Throughout Gestation.

OBJECTIVE: Adverse childhood experiences (ACEs) are associated with negative prenatal and perinatal health outcomes and may, via these pathways, have intergenerational effects on child health and development. We examine the impact of ACEs on maternal salivary cortisol, a key measure of prenatal biology previously linked with pregnancy-related health outcomes. METHODS: Leveraging assessments across three trimesters, we used linear mixed-effects models to analyze the influence of ACEs on maternal prenatal diurnal cortisol patterns in a diverse cohort of pregnant women (analytic sample, n = 207). Covariates included comorbid prenatal depression, psychiatric medications, and sociodemographic factors. RESULTS: Maternal ACEs were significantly associated with flatter diurnal cortisol slopes (i.e., less steep decline), after adjusting for covariates, with effects consistent across gestation (estimate = 0.15, standard error = 0.06, p = .008). CONCLUSIONS: ACEs experienced before pregnancy may have a robust and lasting influence on maternal prenatal hypothalamic-pituitary-adrenal activity throughout gestation, a key biological marker associated with perinatal and child health outcomes. The findings suggest one route of intergenerational transmission of early adverse experiences and underscore the potential value of assessing prepregnancy adverse experiences for promoting perinatal and maternal and child health.

Prenatal perfluoroalkyl substances exposure and maternal sex steroid hormones across pregnancy.

BACKGROUND: Poly- and perfluoroalkyl substances (PFAS) are ubiquitous and persistent environmental contaminants that may act as endocrine disruptors in utero, but the specific endocrine pathways are unknown. OBJECTIVE: We examined associations between maternal serum PFAS and sex steroid hormones at three time points during pregnancy. METHODS: Pregnant women participating in the Understanding Pregnancy Signals and Infant Development (UPSIDE) study contributed biospecimens, questionnaire, and medical record data in each trimester (n = 285). PFAS (including perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA)) were analyzed in second-trimester serum samples by high-performance liquid chromatography and tandem mass spectrometry (LC-MS/MS). Total testosterone [TT], free testosterone [fT], estrone [E1], estradiol [E2], and estriol [E3]) were measured by LC-MS/MS in serum samples from each trimester. Linear mixed models with random intercepts were used to examine associations between log-transformed PFAS concentrations and hormone levels, adjusting for covariates, and stratifying by fetal sex. Results are presented as the mean percentage difference (Δ%) in hormone levels per ln-unit increase in PFAS concentration. RESULTS: In adjusted models, PFHxS was associated with higher TT (%Δ = 20.0, 95%CI: 1.7, 41.6), particularly among women carrying male fetuses (%Δ = 15.3, 95%CI: 1.2, 30.7); this association strengthened as the pregnancy progressed. PFNA (%Δ = 7.9, 95%CI: 3.4, 12.5) and PFDA (%Δ = 7.2, 95%CI: 4.9, 9.7) were associated with higher fT, with associations again observed only in women carrying male fetuses. PFHxS was associated with higher levels of E2 and E3 in women carrying female fetuses (%Δ = 13.2, 95%CI: 0.5, 29.1; %Δ = 17.9, 95%CI: 3.2, 34.8, respectively). No associations were observed for PFOS and PFOA. CONCLUSION: PFHxS, PFNA, and PFDA may disrupt androgenic and estrogenic pathways in pregnancy in a sex-dependent manner.

Associations between neighborhood stress and maternal sex steroid hormones in pregnancy.

BACKGROUND: Neighborhood stressors (e.g., crime and deprivation) have been associated with adverse pregnancy outcomes including preterm birth and low birth weight. A potential mechanism is disruption of maternal endocrine pathways. While stress hormones (e.g., cortisol) have received much attention, other relevant hormones, including sex steroids, have been overlooked. METHODS: Pregnant women in the Understanding Pregnancy Signals and Infant Development (UPSIDE) study contributed biospecimens, questionnaires, and medical record data (n = 262). In each trimester, maternal serum total testosterone [TT], estrone, estradiol, and estriol were measured using LC/MS-MS and serum free testosterone was measured by equilibrium dialysis. In the third trimester, participants reported on neighborhood stress over the last year through the validated City Stress Inventory. We examined two subscales: 11-item neighborhood disorder (e.g., vacant buildings, crime) and 7-item exposure to violence (personal experiences of violence). Composite scores were calculated and examined categorically (quartile (Q) for neighborhood disorder and any/none for exposure to violence). We fitted linear mixed models examining associations between neighborhood stressors and sex steroid hormones across pregnancy as well as trimester-specific linear regression models, all adjusting for confounders. Secondarily, we stratified by fetal sex. Results are presented as percentage change (∆%) and 95% confidence interval (CI) in hormones. RESULTS: Most participants (73%) reported one or more exposures to neighborhood disorder; 22% reported any exposure to violence. In adjusted models, neighborhood disorder was associated with higher TT across pregnancy (Q2: %∆= 37.3, 95%CI: 13.2, 66.5; Q3: %∆= 22.2, 95%CI: 1.2, 47.5; and Q4: %∆= 25.7, 95%CI: 1.6, 55.3), with the strongest associations observed in the third trimester (Q2: %∆= 38.0, 95%CI: 10.6, 72.1; Q3: %∆= 29.2, 95%CI: 4.4, 59.9; and Q4: %∆=33.4, 95%CI: 4.9, 69.6). In stratified models, neighborhood disorder was associated with higher TT among women carrying male fetuses (%∆ range: 48.2-84.8). Exposure to violence was not associated with any hormones. CONCLUSION: Neighborhood disorder is associated with higher maternal testosterone levels, which may have implications for maternal and child health. Additional research is needed to understand the mechanisms by which neighborhood stress impacts endocrine physiology.

Skin and Disease in Early Modern Medicine: Jan Jessen's De cute, et cutaneis affectibus (1601).

This article examines skin and disease in early modern medicine through the writings of the little-known Bohemian physician Jan Jessen (1566-1621). In 1601, Jessen published De cute, et cutaneis affectibus, a set of twenty-one theses dedicated to the question of whether skin disease existed. In considering Jessen and his relationship to a broader world of writing, this article makes three arguments. First, it suggests that, contrary to existing historiography, the question of skin disease was a common sixteenth-century concern. Second, it posits a professional channel for this concern, which arose from surgery and disease, rather than from anatomy and physiology. Finally, rather than positioning Jessen at the forefront of discovery, I suggest his text functions as a representative case study. It allows us to see material change in medicine within a stable Galenic framework.

Changes in the use of the Mental Health Act 1983 in England 1984/85 to 2015/16.

BACKGROUND: Concerns have been raised about the increase in the use of involuntary detentions under the Mental Health Act in England over a number of years, and whether this merits consideration of legislative change.AimsTo investigate changes in the rate of detentions under Part II (civil) and Part III (forensic) sections of the Mental Health Act in England between 1984 and 2016. METHOD: Retrospective analysis of data on involuntary detentions from the National Archives and NHS Digital. Rates per 100 000 population were calculated with percentage changes. The odds of being formally admitted to a National Health Service hospital compared with a private hospital were calculated for each year. RESULTS: Rates of detention have at least trebled since the 1980s and doubled since the 1990s. This has been because of a rise in Part II (civil) sections. Although the overall rate of detentions under Part III (forensic) sections did not rise, transfers from prison increased and detentions by the courts reduced. The odds of being detained in a private hospital increased fivefold. CONCLUSIONS: The move to community-based mental health services in England has paradoxically led to an increase in the number of people being detained in hospital each year, and in particular an inexorable rise in involuntary admissions. This is likely to be partly because of improved case finding with an increased focus on treatment and risk management, and partly because of changes in legislation. An increasing proportion of this government-funded care is being provided by private hospitals.Declaration of interestNone.

Variability in size-selective mortality obscures the importance of larval traits to recruitment success in a temperate marine fish.

In fishes, the growth-mortality hypothesis has received broad acceptance as a driver of recruitment variability. Recruitment is likely to be lower in years when the risk of starvation and predation in the larval stage is greater, leading to higher mortality. Juvenile snapper, Pagrus auratus (Sparidae), experience high recruitment variation in Port Phillip Bay, Australia. Using a 5-year (2005, 2007, 2008, 2010, 2011) data set of larval and juvenile snapper abundances and their daily growth histories, based on otolith microstructure, we found selective mortality acted on larval size at 5 days post-hatch in 4 low and average recruitment years. The highest recruitment year (2005) was characterised by no size-selective mortality. Larval growth of the initial larval population was related to recruitment, but larval growth of the juveniles was not. Selective mortality may have obscured the relationship between larval traits of the juveniles and recruitment as fast-growing and large larvae preferentially survived in lower recruitment years and fast growth was ubiquitous in high recruitment years. An index of daily mortality within and among 3 years (2007, 2008, 2010), where zooplankton were concurrently sampled with ichthyoplankton, was related to per capita availability of preferred larval prey, providing support for the match-mismatch hypothesis. In 2010, periods of low daily mortality resulted in no selective mortality. Thus both intra- and inter-annual variability in the magnitude and occurrence of selective mortality in species with complex life cycles can obscure relationships between larval traits and population replenishment, leading to underestimation of their importance in recruitment studies.

Transcranial magnetic stimulation enhances the specificity of multiple sclerosis diagnostic criteria: a critical narrative review.

Background: Multiple sclerosis (MS) is an immune-mediated neurodegenerative disease that involves attacks of inflammatory demyelination and axonal damage, with variable but continuous disability accumulation. Transcranial magnetic stimulation (TMS) is a noninvasive method to characterize conduction loss and axonal damage in the corticospinal tract. TMS as a technique provides indices of corticospinal tract function that may serve as putative MS biomarkers. To date, no reviews have directly addressed the diagnostic performance of TMS in MS. The authors aimed to conduct a critical narrative review on the diagnostic performance of TMS in MS. Methods: The authors searched the Embase, PubMed, Scopus, and Web of Science databases for studies that reported the sensitivity and/or specificity of any reported TMS technique compared to established clinical MS diagnostic criteria. Studies were summarized and critically appraised for their quality and validity. Results: Seventeen of 1,073 records were included for data extraction and critical appraisal. Markers of demyelination and axonal damage-most notably, central motor conduction time (CMCT)-were specific, but not sensitive, for MS. Thirteen (76%), two (12%), and two (12%) studies exhibited high, unclear, and low risk of bias, respectively. No study demonstrated validity for TMS techniques as diagnostic biomarkers in MS. Conclusions: CMCT has the potential to: (1) enhance the specificity of clinical MS diagnostic criteria by "ruling in" true-positives, or (2) revise a diagnosis from relapsing to progressive forms of MS. However, there is presently insufficient high-quality evidence to recommend any TMS technique in the diagnostic algorithm for MS.

Enteric Dysbiosis in Children With Autism Spectrum Disorder and Associated Response to Stress.

Background Microbiome studies in humans, though limited, have facilitated the evaluation of the potential connection between the microbiome and brain function. Children with autism spectrum disorder (ASD) have several behavioral challenges and avoidant/restrictive food intake disorder, which may contribute to gut microbiome dysbiosis. Aim The aim of this study is to examine the extent to which the gut microbiome of children with ASD differs in comparison to children with neurotypical development (CWND) and to assess whether a probiotic intervention has the potential to influence the gut microbiome in mediating positive behavior change and stress regulation. Methods This pilot study collected data from three children with ASD and four CWND before and after a four-week probiotic intervention. Data collection included microbiome diversity screening from stool samples as well as the following biophysiological measures: salivary alpha-amylase (sAA) levels, response to simulated stressor and calming stimulus (behavior), including pulse rate, galvanic skin response, and pupil diameter (PD). In addition, telomere length was assessed. All measures, except for telomere length, were repeated after the four-week intervention on the ASD and CWND groups for pre-/post-comparison. Data analysis consisted of multivariate analyses, including ANOVA. Results While greater heterogeneity in the ASD group was evident in all measures, the gut microbiome of participants who received probiotic intervention differed from pretreatment results within and across the groups investigated. Further, the biophysiological parameter sAA displayed a significant increase between baseline and exposure to stress in both groups, whereas PD increased in both groups from baseline, F(11, 26615) = 123.43, p = 0.00. Conclusion Though gut microbiome diversity is diminished in children with ASD compared to CWND, the gap is narrowed following a brief probiotic intervention. The results suggest that probiotic interventions have the potential to rescue microbiome diversity and abundance, potentially supporting stress regulation in pediatric populations.

National Trends and Outcomes of Acute Myocardial Infarction After Transcatheter Aortic Valve Replacement.

BACKGROUND: Prior studies have reported decreased use of an invasive approach for acute myocardial infarction (AMI) in patients undergoing transcatheter aortic valve replacement (TAVR). OBJECTIVES: The aim of this study was to determine whether prior TAVR affects the use of subsequent coronary revascularization and outcomes of AMI in a contemporary national data set. METHODS: Consecutive TAVR patients from 2016 to 2022 were identified from the U.S. Vizient Clinical Data Base who were hospitalized after the index TAVR hospitalization with ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation myocardial infarction (NSTEMI). Patients with STEMI or NSTEMI with or without prior TAVR from the same time period were compared for the use of coronary angiography, revascularization, and in-hospital outcomes. Propensity score matching was used to account for imbalances in patient characteristics. RESULTS: Among 206,229 patients who underwent TAVR, the incidence of STEMI was 25 events per 100,000 person-years of follow-up, and that of NSTEMI was 229 events per 100,000 person-years. After propensity matching, the use of coronary revascularization was similar in the prior TAVR and no TAVR cohorts in both the STEMI (65.3% vs 63.9%; P = 0.81) and NSTEMI (41.4% vs 41.7%; P = 0.88) subgroups. Compared with patients without prior TAVR, in-hospital mortality was higher in the prior TAVR cohort in patients with STEMI (27.1% vs 16.7%; P = 0.03) and lower in those with NSTEMI (5.8% vs 8.2%; P = 0.02). CONCLUSIONS: In this large, national retrospective study, AMI events after TAVR were infrequent. There were no differences in the use of coronary revascularization for STEMI or NSTEMI in TAVR patients compared with the non-TAVR population. In-hospital mortality for STEMI is higher in TAVR patients compared with those without prior TAVR.

The role of prenatal maternal sex steroid hormones in weight and adiposity at birth and growth trajectories during infancy.

Objective: Intrauterine factors can impact fetal and child growth and may underlie the developmental origins of childhood obesity. Sex steroid hormone exposure during pregnancy is a plausible target because of the impact on placental vascularization, nutrient transportation, bone growth, adipogenesis, and epigenetic modifications. In this study we assessed maternal sex steroid hormones in each trimester in relation to birthweight, neonatal adiposity, and infant growth trajectories, and evaluate sensitive windows of development. Methods: Participants from a prospective pregnancy cohort who delivered at term were included in the analysis (n=252). Estrone, estradiol, and estriol, as well as total and free testosterone throughout gestation were assessed using high-performance liquid chromatography and tandem mass spectrometry. Path analyses were used to assess the direct associations of sex steroid hormones in each trimester with birth outcomes and infant growth trajectories (birth to 12 months) adjusting for covariates and considering moderation by sex. Results: The associations between prenatal sex steroid hormones and fetal/infant growth varied by sex and hormone assessment timing. First trimester estrone were associated with higher birthweight z-scores (ß=0.37, 95%CI: 0.02, 0.73) and truncal skinfold thickness (TST) at birth (ß=0.94, 95%CI: 0.34, 1.54) in female infants. Third trimester total testosterone was associated with higher TST at birth (ß=0.61, 95%CI: 0.02, 1.21) in male infants. First trimester estrone/estradiol and first and third trimesters testosterone were associated with lower probabilities of high stable weight trajectory compared to low stable weight trajectory (Estrone: ß=-3.87, 95%CI: -6.59, -1.16; First trimester testosterone: ß=-3.53, 95%CI: -6.63, -0.43; Third trimester testosterone: ß=-3.67, 95%CI: -6.66, -0.69) during infancy in male infants. Conclusions: We observed associations between prenatal sex steroid hormone exposure and birthweight, neonatal adiposity and infant growth that were sex and gestational timing dependent. Our findings suggest further investigation on additional mechanisms linking prenatal sex steroid exposure and fetal/postnatal growth is needed.

Lower corticospinal excitability and greater fatigue among people with multiple sclerosis experiencing pain.

Introduction: Persons with multiple sclerosis (MS) frequently report pain that negatively affects their quality of life. Evidence linking pain and corticospinal excitability in MS is sparse. We aimed to (1) examine differences in corticospinal excitability in MS participants with and without pain and (2) explore predictors of pain. Methods: Sixty-four participants rated their pain severity on a visual analog scale (VAS). Transcranial magnetic stimulation (TMS) and validated clinical instruments characterized corticospinal excitability and subjective disease features like mood and fatigue. We retrieved information on participants' prescriptions and disability status from their clinical records. Results: Fifty-five percent of participants reported pain that affected their daily functioning. Persons with pain had significantly greater fatigue and lower area under the excitatory motor evoked potential (MEP) recruitment curve (eREC AUC), a measure of total corticospinal excitability. After controlling for age, disability status, and pain medications, increased fatigue and decreased eREC AUC together explained 40% of the variance in pain. Discussion: Pain in MS is multifactorial and relates to both greater fatigue and lesser corticospinal excitability. Future work should better characterize relationships between these outcomes to develop targeted pain interventions such as neuromodulation. Summary: We examined pain in MS. Individuals with pain had higher fatigue and lower corticospinal excitability than those without pain. These outcomes significantly predicted self-reported pain.

Sharing the Details: Implementing and Evaluating the Integration of New York State AIDS Institute Health Equity Competencies for Health Care Providers into Clinical Training Activities.

Background: The New York State (NYS) Department of Health (DOH) AIDS Institute (AI) Clinical Education Initiative (CEI) trains the NYS health care workforce to improve health outcomes related to HIV, sexual health, hepatitis C, and for people who use drugs. Methods: In 2019, CEI began consistently integrating health equity into CEI activities through a working group that mapped NYS DOH AI health equity competencies for providers onto planned clinical education. We conducted a convergent mixed methods study on qualitative and quantitative participant feedback form (PFF) data to evaluate these competencies between April 1, 2021, and September 30, 2022, and conducted an annual survey of NYS clinician needs in 2021 and 2022. Results: The CEI Health Equity Working Group analyzed 25 measures within 4 health equity competencies that were grouped into 4 interventions: resources, internal tools, activity creation, and evaluation. Eighty-nine percent of PFF respondents (n=20,166) strongly agreed/agreed that CEI activities included multiple viewpoints; qualitative comments described informative and helpful activities. When asked how they address patient-identified social determinants of health (SDOH) needs, 84% and 71% of annual survey respondents reported they made the highest number of referrals for health insurance coverage assistance in 2021 and 2022, respectively. Discussion: CEI continues to address participant feedback and seamless incorporation of health equity components into their work. Health Equity Implications: Health equity in clinical practice and trainings is crucial in acknowledging and addressing SDOH that continue to impact NYS clinicians and their patients.

Recombinant Pichinde viral vector expressing tuberculosis antigens elicits strong T cell responses and protection in mice.

Introduction: Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) remains a major global health threat. The only available vaccine Bacille Calmette-Guérin (BCG) does not prevent adult pulmonary TB. New effective TB vaccines should aim to stimulate robust T cell responses in the lung mucosa to achieve high protective efficacy. We have previously developed a novel viral vaccine vector based on recombinant Pichinde virus (PICV), a non-pathogenic arenavirus with low seroprevalence in humans, and have demonstrated its efficacy to induce strong vaccine immunity with undetectable anti-vector neutralization activity. Methods: Using this tri-segmented PICV vector (rP18tri), we have generated viral vectored TB vaccines (TBvac-1, TBvac-2, and TBvac-10) encoding several known TB immunogens (Ag85B, EsxH, and ESAT-6/EsxA). A P2A linker sequence was used to allow for the expression of two proteins from one open-reading-frame (ORF) on the viral RNA segments. The immunogenicity of TBvac-2 and TBvac-10 and the protective efficacy of TBvac-1 and TBvac-2 were evaluated in mice. Results: Both viral vectored vaccines elicited strong antigen-specific CD4 and CD8 T cells through intramuscular (IM) and intranasal (IN) routes as evaluated by MHC-I and MHC-II tetramer analyses, respectively. The IN inoculation route helped to elicit strong lung T cell responses. The vaccine-induced antigen-specific CD4 T cells are functional, expressing multiple cytokines as detected by intracellular cytokine staining. Finally, immunization with TBvac-1 or TBvac-2, both expressing the same trivalent antigens (Ag85B, EsxH, ESAT6/EsxA), reduced Mtb lung tissue burden and dissemination in an aerosol challenge mouse model. Conclusions: The novel PICV vector-based TB vaccine candidates can express more than two antigens via the use of P2A linker sequence and elicit strong systemic and lung T cell immunity with protective efficacy. Our study suggests the PICV vector as an attractive vaccine platform for the development of new and effective TB vaccine candidates.

Understanding Immune Responses to Lassa Virus Infection and to Its Candidate Vaccines.

Lassa fever (LF) is a deadly viral hemorrhagic fever disease that is endemic in several countries in West Africa. It is caused by Lassa virus (LASV), which has been estimated to be responsible for approximately 300,000 infections and 5000 deaths annually. LASV is a highly pathogenic human pathogen without effective therapeutics or FDA-approved vaccines. Here, we aim to provide a literature review of the current understanding of the basic mechanism of immune responses to LASV infection in animal models and patients, as well as to several of its candidate vaccines.

Transcranial magnetic stimulation maps the neurophysiology of chronic noncancer pain: A scoping review.

BACKGROUND: Chronic noncancer pain is a global public health challenge. It is imperative to identify biological markers ("biomarkers") to understand the mechanisms underlying chronic pain and to monitor pain over time and after interventions. Transcranial magnetic stimulation (TMS) is a promising method for this purpose. OBJECTIVES: To examine differences in TMS-based outcomes between persons with chronic pain and healthy controls (HCs) and/or before versus after pain-modulating interventions and relationships between pain measures and TMS outcomes; To summarize the neurophysiological mechanisms underlying chronic pain as identified by TMS. METHODS: We searched the PubMed database for literature from January 1, 1985, to June 9, 2020, with the keywords "pain" and "transcranial magnetic stimulation." Eligible items included original studies of adult human participants with pain lasting for ≥ 6 months. We completed a narrative synthesis of the study findings stratified by chronic pain etiology (primary pain, neuropathic pain, and secondary musculoskeletal pain). RESULTS: The search yielded 1265 records. The final 12 articles included 244 patients with chronic pain (192 females, aged 35-65 years) and 169 HCs (89 females, aged 28-59 years). Abnormalities in TMS outcomes that reflect GABAergic and glutamatergic activities were associated with many of the disorders studied and were distinct for each pain etiology. Chronic primary pain is characterized by reduced intracortical inhibition and corticospinal excitability, chronic neuropathic pain shows evidence of increased excitation and disinhibition, and chronic secondary musculoskeletal pain involves low corticospinal excitability. DISCUSSION: TMS could be a useful tool for delineating the neurophysiological underpinnings of chronic pain syndromes.

Prenatal diurnal cortisol: Normative patterns and associations with affective symptoms and stress.

The hypothalamic-pituitary-adrenal (HPA) axis in pregnancy has attracted considerable research attention, in part, because it may be a mechanism by which diverse prenatal exposures alter perinatal and child health outcomes. Symptoms of affective disturbance and stress are among the most-studied prenatal factors associated with HPA axis alterations, but there remains uncertainty about the nature of the association because of the limitations to, and variability in, data collection and analytic approaches. The current study capitalized on a prospective, longitudinal pregnancy cohort that examined salivary diurnal cortisol, collected at 5 time points across the day, at each trimester in a diverse sample of women. Detailed data on affective symptoms and major life events were collected at each trimester, as were data on health behaviors, medication, and socio-demographics. Results indicated modest stability of individual differences in diurnal cortisol across pregnancy, which was evident for diurnal slope (ICC = .20) and measures of total output (area under the curve, ICC = .25); substantial gestation-related increases in total cortisol output across pregnancy was also observed (p < .001). Adjusting for health behaviors, medication, and socio-demographic covariates, elevated levels of depressive symptoms and major life events were significantly (p < .05) associated with a higher morning awakening value and flatter diurnal slope, which was evident across all trimesters. In addition to the normative gestation-related changes in cortisol production, our results demonstrate selective but robust associations between psychological symptoms, stressors, and the HPA axis across gestation, and suggest both methodological and mechanistic strategies for future study.

Pathogenicity and virulence mechanisms of Lassa virus and its animal modeling, diagnostic, prophylactic, and therapeutic developments.

Lassa fever (LF) is a deadly viral hemorrhagic disease that is endemic to West Africa. The causative agent of LF is Lassa virus (LASV), which causes approximately 300,000 infections and 5,000 deaths annually. There are currently no approved therapeutics or FDA-approved vaccines against LASV. The high genetic variability between LASV strains and immune evasion mediated by the virus complicate the development of effective therapeutics and vaccines. Here, we aim to provide a comprehensive review of the basic biology of LASV and its mechanisms of disease pathogenesis and virulence in various animal models, as well as an update on prospective vaccines, therapeutics, and diagnostics for LF. Until effective vaccines and/or therapeutics are available for use to prevent or treat LF, a better level of understanding of the basic biology of LASV, its natural genetic variations and immune evasion mechanisms as potential pathogenicity factors, and of the rodent reservoir-vector populations and their geographical distributions, is necessary for the development of accurate diagnostics and effective therapeutics and vaccines against this deadly human viral pathogen.