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In settings with high HIV prevalence, cervical cancer incidence rates are up to six-fold higher than the global average of 13.1 cases per 100,000 women-years. To inform strategies for global cervical cancer elimination, we used a dynamic transmission model to evaluate scalable screening and treatment strategies, accounting for HIV-associated cancer risks and weighing prevention gains against overtreatment.We developed a dynamic model of HIV-HPV co-infection and disease progression, which we calibrated to KwaZulu-Natal, South Africa. Our baseline scenario reflects the current practice of HPV vaccination with a multi-visit screening and treatment strategy involving cytology and colposcopy triage. We evaluated 13 comparator scenarios with increased vaccination coverage and one-time, two-time or repeat HIV-targeted cervical cancer screening with the following single-visit strategies: HPV DNA testing, HPV genotyping, automated visual evaluation (AVE) and HPV DNA with AVE triage. In all scenarios, HIV antiretroviral therapy, condom use and voluntary male medical circumcision continue at baseline levels. We simulated cancer incidence under each scenario from 2020 to 2120 using the 25 best-fitting parameter sets. We present the median and range of model output from these simulations to account for parameter uncertainty.We estimate that cervical cancer incidence will decrease by 87% with the continuation of current cervical cancer and HIV prevention strategies, from an age-standardized rate per 100,000 women of 80.4 (range 58.2, 112.1) in 2020 to 10.7 (4.2, 29.9) in 2120. Scenarios scaling up vaccination and single-visit strategies resulted in near- and long-term gains. With repeat HIV-targeted screening, incidence rates were projected to be 29-34% lower in 2030 relative to the baseline scenario, and elimination (incidencelt;4/100,000) was achieved with HPV DNA testing in 2095 and with AVE in 2114. A strategy of HPV DNA with AVE triage optimized the tradeoff between cancer cases averted and overtreatment.Single-visit screening strategies could avert a substantial burden of cervical cancer and accelerate progress towards elimination in settings with a high burden of HIV. Increasing the screening frequency among women with HIV and reducing loss-to-follow-up for treatment will be key components of a successful elimination strategy.

Military-connected families face many challenges associated with military life transitions, including deployment separations. We report on a randomized controlled trial to evaluate the efficacy of Families OverComing Under Stress-Early Childhood (FOCUS-EC) delivered through an in-home, virtual telehealth platform. FOCUS-EC is a trauma-informed, family-centered preventive intervention designed to promote family resilience and well-being. Military-connected families with 3- to 6-year-old children (194 mothers; 155 fathers; 199 children) were randomized to FOCUS-EC or an online education condition. Parent psychological health symptoms, child behavior, parenting, and parent–child relationships were examined by parent-report and observed interaction tasks for up to 12 months. Longitudinal regression models indicated that FOCUS-EC families demonstrated significantly greater improvements than online education families in parent-reported and observational measures of child behavior, parenting practices, and parent–child interaction, as well as greater reductions in parent posttraumatic stress symptoms. Findings provide support for the benefit of a virtually-delivered preventive intervention for military-connected families.

Exposure to alcohol marketing is positively associated with alcohol consumption. However, few research studies have tested alcohol marketing's effect on other alcohol-related outcomes. Consequently, the current study sought to identify associations between exposure to alcohol marketing and alcohol-related consequences in young adults.

In vivo functional and structural brain imaging of synucleinopathies in humans have provided a rich new understanding of the affected networks across the cortex and subcortex. Despite this progress, the temporal relationship between α-synuclein (α-syn) pathology and the functional and structural changes occurring in the brain is not well understood., In vivo functional and structural brain imaging of synucleinopathies in humans have provided a rich new understanding of the affected networks across the cortex and subcortex. Despite this progress, the temporal relationship between α-synuclein (α-syn) pathology and the functional and structural changes occurring in the brain is not well understood. Here, we examine the temporal relationship between locomotor ability, brain microstructure, functional brain activity, and α-syn pathology by longitudinally conducting rotarod, diffusion magnetic resonance imaging (MRI), resting-state functional MRI (fMRI), and sensory-evoked fMRI on 20 mice injected with α-syn fibrils and 20 PBS-injected mice at three timepoints (10 males and 10 females per group). Intramuscular injection of α-syn fibrils in the hindlimb of M83+/− mice leads to progressive α-syn pathology along the spinal cord, brainstem, and midbrain by 16 weeks post-injection. Our results suggest that peripheral injection of α-syn has acute systemic effects on the central nervous system such that structural and resting-state functional activity changes occur in the brain by four weeks post-injection, well before α-syn pathology reaches the brain. At 12 weeks post-injection, a separate and distinct pattern of structural and sensory-evoked functional brain activity changes was observed that are co-localized with previously reported regions of α-syn pathology and immune activation. Microstructural changes in the pons at 12 weeks post-injection were found to predict survival time and preceded measurable locomotor deficits. This study provides preliminary evidence for diffusion and fMRI markers linked to the progression of synuclein pathology and has translational importance for understanding synucleinopathies in humans. SIGNIFICANCE STATEMENT α-Synuclein (α-syn) pathology plays a critical role in neurodegenerative diseases such as Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. The longitudinal effects of α-syn pathology on locomotion, brain microstructure, and functional brain activity are not well understood. Using high field imaging, we show preliminary evidence that peripheral injection of α-syn fibrils induces unique patterns of functional and structural changes that occur at different temporal stages of α-syn pathology progression. Our results challenge existing assumptions that α-syn pathology must precede changes in brain structure and function. Additionally, we show preliminary evidence that diffusion and functional magnetic resonance imaging (fMRI) are capable of resolving such changes and thus should be explored further as markers of disease progression.

Infants, toddlers, and preschool-aged children have unique developmental needs that render them vulnerable to challenges associated with parental military service. We used a sample of military-connected families with 3-6-year-old children (N = 104) to examine associations among children's socioemotional development and fathers' trauma-related deployment experiences, including perceived threat during deployment and exposure to combat and the aftermath of battle. Of these potential stressors, only paternal perceived threat during deployment was significantly associated with measures of mother-reported child adjustment. Fathers' perceived threat during deployment was associated with child behavior problems even after accounting for demographic variables and current paternal symptoms of posttraumatic stress, depression, and anxiety, β = .36, p = .007. The association between fathers' perceived threat during deployment and child behavior problems was mediated by several family processes related to emotion socialization, including father-reported sensitive parenting, indirect effect (IE) B = 0.106, 95% CI [0.009, 0.236]; parent-child dysfunctional interaction, IE B = 0.119, 95% CI [0.014, 0.252]; and mother-reported family emotional responsiveness, IE B = 0.119, 95% CI [0.011, 0.258]. Implications for future research on the intergenerational transmission of traumatic stress as well as prevention and intervention efforts for military-connected families with young children are discussed.

Objective: Alcohol marketing has proliferated on digital media, such as websites, social media, and apps. A systematic review was conducted to examine studies of associations between exposure to digital alcohol marketing and alcohol consumption. Method: Eight electronic databases were searched for “alcohol” and “marketing” through 14 February 2017. Studies were included if exposure to digital alcohol marketing and alcohol consumption, or related attitudes and intentions, were assessed. Studies were excluded if they only measured exposure to alcohol depictions posted online by family and friends. Study quality was also assessed. Results: In all, 25 studies were included, including 2 randomized controlled trials, 15 cross-sectional studies, and 8 prospective cohort studies. There was a consistent finding across studies that participation and engagement with digital alcohol marketing—such as clicking on an alcohol ad, visiting an alcohol-branded website, liking or sharing an ad on social media, or downloading alcohol-branded content—was positively associated with alcohol use. The effects of simple exposure to digital alcohol advertising were inconclusive. Proper blinding of subjects, measuring exposures before the outcomes, and measuring the exposures multiple times would improve study quality. Conclusions: Although more research is needed, existing studies suggest that engagement with digital alcohol marketing is positively associated with increased alcohol consumption and increased binge or hazardous drinking behavior. Governments should consider implementing digital alcohol marketing regulations under the precautionary principle as the alcohol industry’s self-regulated marketing codes are likely ineffective at protecting populations vulnerable to alcohol-related harm.

Human neurodegenerative diseases can be characterized as disorders of protein aggregation. As a key player in cellular autophagy and the ubiquitin proteasome system, p62 may represent an effective immunohistochemical target, as well as mechanistic operator, across neurodegenerative proteinopathies. In this study, 2 novel mouse-derived monoclonal antibodies 5G3 and 2A5 raised against residues 360–380 of human p62/sequestosome-1 were characterized via immunohistochemical application upon human tissues derived from cases of C9orf72-expansion spectrum diseases, Alzheimer disease, progressive supranuclear palsy, Lewy body disease, and multiple system atrophy. 5G3 and 2A5 reliably highlighted neuronal dipeptide repeat, tau, and α-synuclein inclusions in a distribution similar to a polyclonal antibody to p62, phospho-tau antibodies 7F2 and AT8, and phospho-α-synuclein antibody 81A. However, antibodies 5G3 and 2A5 consistently stained less neuropil structures, such as tau neuropil threads and Lewy neurites, while 2A5 marked fewer glial inclusions in progressive supranuclear palsy. Both 5G3 and 2A5 revealed incidental astrocytic tau immunoreactivity in cases of Alzheimer disease and Lewy body disease with resolution superior to 7F2. Through their unique ability to highlight specific types of pathological deposits in neurodegenerative brain tissue, these novel monoclonal p62 antibodies may provide utility in both research and diagnostic efforts.

This study documents disparities in the mental health burden of young adults in Rhode Island during the COVID-19 pandemic as it pertains to essential worker status, sexual orientation, gender identity, and childhood trauma. A cross-sectional web-based survey of young adults aged 18 to 25 years conducted between May and October of 2020 assessed anxiety symptoms, depressive symptoms, and thoughts of suicide. In fully adjusted regression models, (n =528 young adults) being an essential worker, a sexual minority, having lower relative SES, and having more adverse childhood experiences were significantly associated with negative mental health outcomes. In models adjusted for individual ACEs, exposure to mental illness in the household, physical violence between adults in the household, emotional abuse, and sexual abuse were independently associated with all three outcomes. Young adults most vulnerable and stigmatized in the community are also those who are most severely affected in terms of mental health.

This study evaluates the prevalence of autistic behaviors in fragile X syndrome as a function of infant diet. Retrospective survey data from the Fragile X Syndrome Nutrition Study, which included data on infant feeding and caregiver-reported developmental milestones for 190 children with fragile X syndrome enrolled in the Fragile X Online Registry with Accessible Database (FORWARD), were analyzed. Exploratory, sex-specific associations were found linking the use of soy-based infant formula with worse autistic behaviors related to language in females and self-injurious behavior in males. These findings prompt prospective evaluation of the effects of soy-based infant formula on disease comorbidities in fragile X syndrome, a rare disorder for which newborn screening could be implemented if there was an intervention. Gastrointestinal problems were the most common reason cited for switching to soy-based infant formula. Thus, these findings also support the study of early gastrointestinal problems in fragile X syndrome, which may underly the development and severity of disease comorbidities. In conjunction with comorbidity data from the previous analyses of the Fragile X Syndrome Nutrition Study, the findings indicate that premutation fragile X mothers should be encouraged to breastfeed.

Rationale: The contributions of diverse cell populations in the human lung to pulmonary fibrosis pathogenesis are poorly understood. Single-cell RNA sequencing can reveal changes within individual cell populations during pulmonary fibrosis that are important for disease pathogenesis. Objectives: To determine whether single-cell RNA sequencing can reveal disease-related heterogeneity within alveolar macrophages, epithelial cells, or other cell types in lung tissue from subjects with pulmonary fibrosis compared with control subjects. Methods: We performed single-cell RNA sequencing on lung tissue obtained from eight transplant donors and eight recipients with pulmonary fibrosis and on one bronchoscopic cryobiospy sample from a patient with idiopathic pulmonary fibrosis. We validated these data using in situ RNA hybridization, immunohistochemistry, and bulk RNA-sequencing on flow-sorted cells from 22 additional subjects. Measurements and Main Results: We identified a distinct, novel population of profibrotic alveolar macrophages exclusively in patients with fibrosis. Within epithelial cells, the expression of genes involved in Wnt secretion and response was restricted to nonoverlapping cells. We identified rare cell populations including airway stem cells and senescent cells emerging during pulmonary fibrosis. We developed a web-based tool to explore these data. Conclusions: We generated a single-cell atlas of pulmonary fibrosis. Using this atlas, we demonstrated heterogeneity within alveolar macrophages and epithelial cells from subjects with pulmonary fibrosis. These results support the feasibility of discovery-based approaches using next-generation sequencing technologies to identify signaling pathways for targeting in the development of personalized therapies for patients with pulmonary fibrosis.

Understanding the biological functions of tau variants can illuminate differential etiologies of Alzheimer’s disease (AD) and primary tauopathies. Though the end-stage neuropathological attributes of AD and primary tauopathies are similar, the etiology and behavioral outcomes of these diseases follow unique and divergent trajectories. To study the divergent physiological properties of tau variants on a uniform immunogenetic background, we created somatic transgenesis CNS models of tauopathy utilizing neonatal delivery of adeno-associated viruses expressing wild-type (WT) or mutant tau in non-transgenic mice. We selected four different tau variants—WT tau associated with AD, P301L mutant tau associated with frontotemporal dementia (FTD), S320F mutant tau associated with Pick’s disease and a combinatorial approach using P301L/S320F mutant tau. CNS-targeted expression of WT and P301L mutant tau results in robust tau hyperphosphorylation without tangle pathology, gradually developing age-progressive memory deficits. In contrast, the S320F variant, especially in combination with P301L, produces an AD-type tangle pathology, focal neuroinflammation and memory impairment on an accelerated time scale. Using the doubly mutated P301L/S320F tau variant, we demonstrate that combining different mutations can have an additive effect on neuropathologies and associated co-morbidities, possibly hinting at involvement of unique functional pathways. Importantly, we also show that overexpression of wild-type tau as well as an FTD-associated tau variant can lead to cognitive deficits even in the absence of tangles. Together, our data highlights the synergistic neuropathologies and associated cognitive and synaptic alterations of the combinatorial tau variant leading to a robust model of tauopathy.

OBJECTIVES: Breastfeeding is associated with numerous health benefits in infants, but early life nutrition has not been specifically studied in the neurodevelopmental disorder fragile X syndrome (FXS). Herein, we evaluate associations between the consumption of breast milk during infancy and the prevalence of autism, allergies, diabetes, gastrointestinal (GI) problems and seizures in participants with FXS. METHODS: The study design was a retrospective survey of families enrolled in the Fragile X Online Registry and Accessible Research Database (FORWARD). RESULTS: There was a 73% rate of breastfeeding in the enrolled participants with an 81% rate for at least 3 months, 73% for 6 months and 41% for 12 months of age or longer. There was a 1.7-fold reduction in the prevalence of autism in participants with FXS who were fed breast milk for 12 months or longer and a 1.9-fold decrease in autism in participants reporting no use of any infant formula (P

Importance Despite the widespread use of systemic antibiotics to prevent infections in surgically treated patients with fracture, high rates of surgical site infection persist. Objective To examine the effect of intrawound vancomycin powder in reducing deep surgical site infections. Design, Setting, and Participants This open-label randomized clinical trial enrolled adult patients with an operatively treated tibial plateau or pilon fracture who met the criteria for a high risk of infection from January 1, 2015, through June 30, 2017, with 12 months of follow-up (final follow-up assessments completed in April 2018) at 36 US trauma centers. Interventions A standard infection prevention protocol with (n = 481) or without (n = 499) 1000 mg of intrawound vancomycin powder. Main Outcomes and Measures The primary outcome was a deep surgical site infection within 182 days of definitive fracture fixation. A post hoc comparison assessed the treatment effect on gram-positive and gram-negative-only infections. Other secondary outcomes included superficial surgical site infection, nonunion, and wound dehiscence. Results The analysis included 980 patients (mean [SD] age, 45.7 [13.7] years; 617 [63.0%] male) with 91% of the expected person-time of follow-up for the primary outcome. Within 182 days, deep surgical site infection was observed in 29 of 481 patients in the treatment group and 46 of 499 patients in the control group. The time-to-event estimated probability of deep infection by 182 days was 6.4% in the treatment group and 9.8% in the control group (risk difference, –3.4%; 95% CI, –6.9% to 0.1%;P = .06). A post hoc analysis of the effect of treatment on gram-positive (risk difference, –3.7%; 95% CI, –6.7% to –0.8%;P = .02) and gram-negative-only (risk difference, 0.3%; 95% CI, –1.6% to 2.1%;P = .78) infections found that the effect of vancomycin powder was a result of its reduction in gram-positive infections. Conclusions and Relevance Among patients with operatively treated tibial articular fractures at a high risk of infection, intrawound vancomycin powder at the time of definitive fracture fixation reduced the risk of a gram-positive deep surgical site infection, consistent with the activity of vancomycin. Trial Registration ClinicalTrials.gov Identifier:NCT02227446

The World Health Organization announced an ambitious call for cervical cancer elimination worldwide. With existing prevention and treatment modalities, cervical cancer elimination is now within reach for high-income countries. Despite limited financing and capacity constraints in low-and-middle-income countries (LMICs), prevention and control efforts can be supported through integrated services and new technologies. We conducted this scoping review to outline a roadmap toward cervical cancer elimination in LMICs and highlight evidence-based interventions and research priorities to accelerate cervical cancer elimination. We reviewed and synthesized literature from 2010 to 2020 on primary and secondary cervical cancer prevention strategies. In addition, we conducted expert interviews with gynecologic and infectious disease providers, researchers, and LMIC health officials. Using these data, we developed a logic model to summarize the current state of science and identified evidence gaps and priority research questions for each prevention strategy. The logic model for cervical cancer elimination maps the needs for improved collaboration between policy makers, production and supply, healthcare systems, providers, health workers, and communities. The model articulates responsibilities for stakeholders and visualizes processes to increase access to and coverage of prevention methods. We discuss the challenges of contextual factors and highlight innovation needs. Effective prevention methods include HPV vaccination, screening using visual inspection and HPV testing, and thermocoagulation. However, vaccine coverage remains low in LMICs. New strategies, including single-dose vaccination could enhance impact. Loss to follow-up and treatment delays could be addressed by improved same-day screen-and-treat technologies. We provide a practical framework to guide cervical cancer elimination in LMICs. The scoping review highlights existing and innovative strategies, unmet needs, and collaborations required to achieve elimination across implementation contexts.

The World Health Organization announced an ambitious call for cervical cancer elimination worldwide. With existing prevention and treatment modalities, cervical cancer elimination is now within reach for high-income countries. Despite limited financing and capacity constraints in low-and-middle-income countries (LMICs), prevention and control efforts can be supported through integrated services and new technologies. We conducted this scoping review to outline a roadmap toward cervical cancer elimination in LMICs and highlight evidence-based interventions and research priorities to accelerate cervical cancer elimination. We reviewed and synthesized literature from 2010 to 2020 on primary and secondary cervical cancer prevention strategies. In addition, we conducted expert interviews with gynecologic and infectious disease providers, researchers, and LMIC health officials. Using these data, we developed a logic model to summarize the current state of science and identified evidence gaps and priority research questions for each prevention strategy. The logic model for cervical cancer elimination maps the needs for improved collaboration between policy makers, production and supply, healthcare systems, providers, health workers, and communities. The model articulates responsibilities for stakeholders and visualizes processes to increase access to and coverage of prevention methods. We discuss the challenges of contextual factors and highlight innovation needs. Effective prevention methods include HPV vaccination, screening using visual inspection and HPV testing, and thermocoagulation. However, vaccine coverage remains low in LMICs. New strategies, including single-dose vaccination could enhance impact. Loss to follow-up and treatment delays could be addressed by improved same-day screen-and-treat technologies. We provide a practical framework to guide cervical cancer elimination in LMICs. The scoping review highlights existing and innovative strategies, unmet needs, and collaborations required to achieve elimination across implementation contexts

A large number of adults and children consume soy in various forms, but little information is available regarding potential neurological side effects. Prior work indicates an association between the consumption of soy-based diets and seizure prevalence in mouse models of neurological disease and in children with autism. Herein, we sought to evaluate potential associations between the consumption of soy-based formula during infancy and disease comorbidities in persons with fragile X syndrome (FXS), while controlling for potentially confounding issues, through a retrospective case-control survey study of participants with FXS enrolled in the Fragile X Online Registry with Accessible Research Database (FORWARD). There was a 25% usage rate of soy-based infant formula in the study population. We found significant associations between the consumption of soy-based infant formula and the comorbidity of autism, gastrointestinal problems (GI) and allergies. Specifically, there was a 1.5-fold higher prevalence of autism, 1.9-fold GI problems and 1.7-fold allergies in participants reporting the use of soy-based infant formula. The major reason for starting soy-based infant formula was GI problems. The average age of seizure and allergy onset occurred long after the use of soy-based infant formula. We conclude that early-life feeding with soy-based infant formula is associated with the development of several disease comorbidities in FXS.

Alveolar epithelial cell (AEC) apoptosis, arising from mitochondrial dysfunction and mitophagy defects, is important in mediating idiopathic pulmonary fibrosis (IPF). Our group established a role for the mitochondrial (mt) DNA base excision repair enzyme, 8-oxoguanine-DNA glycosylase 1 (mtOGG1), in preventing oxidant-induced AEC mtDNA damage and apoptosis and showed that OGG1-deficient mice have increased lung fibrosis. Herein, we determined whether mice overexpressing the mtOGG1 transgene ( mtOgg1tg) are protected against lung fibrosis and whether AEC mtOGG1 preservation of mtDNA integrity mitigates phosphatase and tensin homolog-induced putative kinase 1 (PINK1) deficiency and apoptosis. Compared with wild type (WT), mtOgg1tg mice have diminished asbestos- and bleomycin-induced pulmonary fibrosis that was accompanied by reduced lung and AEC mtDNA damage and apoptosis. Asbestos and H2O2 promote the MLE-12 cell PINK1 deficiency, as assessed by reductions in the expression of PINK1 mRNA and mitochondrial protein expression. Compared with WT, Pink1-knockout ( Pink1-KO) mice are more susceptible to asbestos-induced lung fibrosis and have increased lung and alveolar type II (AT2) cell mtDNA damage and apoptosis. AT2 cells from Pink1-KO mice and PINK1-silenced (siRNA) MLE-12 cells have increased mtDNA damage that is augmented by oxidative stress. Interestingly, mtOGG1 overexpression attenuates oxidant-induced MLE-12 cell mtDNA damage and apoptosis despite PINK1 silencing. mtDNA damage is increased in the lungs of patients with IPF as compared with controls. Collectively, these findings suggest that mtOGG1 maintenance of AEC mtDNA is crucial for preventing PINK1 deficiency that promotes apoptosis and lung fibrosis. Given the key role of AEC apoptosis in pulmonary fibrosis, strategies aimed at preserving AT2 cell mtDNA integrity may be an innovative target.

This study tested child characteristics (temperamental executive control and negative reactivity) and maternal characteristics (parenting behaviors and maternal depressive symptoms) as predictors of a mother's emotion-related socialization behaviors (ERSBs). Further, parenting behaviors and ERSBs were examined as predictors of children's emotion knowledge, social competence, and adjustment problems. ERSBs and children's emotion knowledge were tested as mediators of the effects of child and parent characteristics on adjustment. A community sample (N = 306) of mothers and children (36-40 months at T1) were assessed 4 times, once every 9 months, and assessments included maternal reports of depressive symptoms, observed temperament, observational ratings of general parenting at T1, maternal report of ERSBs at T1 & T2, behavioral measures of emotion knowledge at T3, and teacher ratings of children's adjustment at T4. There were no predictors of ERSBs above prior levels. Higher executive control and lower maternal depressive symptoms predicted greater child emotion knowledge, highlighting the roles of maternal and child contributors to emotion knowledge. Greater emotion knowledge and positive affective quality in parenting predicted children's adjustment, with emotion knowledge mediating the effects of executive control on children's adjustment. In addition, lower levels of maternal supportive ERSBs predicted greater adjustment problems. This study highlights the roles of key variables in Eisenberg, Cumberland, and Spinrad's (1998) heuristic model of emotion socialization and the importance of emotion socialization and emotion knowledge in children's adjustment. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

The United States implemented mandatory fortification of cereal grains with folic acid in 1998 to prevent neural tube defects (NTDs) during pregnancy. The health benefits of folate (vitamin B9) are well documented, however, there are potential risks of exceeding the upper tolerable limit, particularly in vulnerable populations. We conducted a population-based analysis of the Food Fortification Initiative dataset to determine the strength of the evidence regarding reports of decreased NTDs at the national level in response to mandatory folic acid fortification of cereal grains. We found a very weak correlation between NTD prevalence and the level of folic acid fortification, irrespective of the cereal grain fortified (wheat, maize or rice). Stratification of the data based on socioeconomic status (SES) indicated a strong linear relationship between reduced NTDs and better SES. We conclude that national fortification with folic acid is not associated with a significant decrease in the prevalence of NTDs at the population level.

The prevalence of HIV among people in correctional facilities remains much higher than that of the general population. Numerous studies have demonstrated the effectiveness and acceptability of HIV treatment for individuals incarcerated in US prisons and jails. However, the period following incarceration is characterized by significant disruptions in HIV care. These disruptions include failure to link in a timely manner (or at all) to community care post-release, as well as not being retained in care after linking. We used a retrospective, propensity-matched cohort design to compare retention in care between HIV-positive individuals recently released from prison (releasees) who linked to care in Ryan White HIV/AIDS Program (RWHAP) clinics and RWHAP patients without a recent incarceration history (community controls). We also performed analyses comparing viral load suppression of those retained in both groups. This study shows that even for those who do successfully link to care after prison, they are 24 to 29 percentage points less likely to be retained in care than those already in community care. However, we found that for those who did retain in care, there was no disparity in rates of viral suppression. These findings provide valuable insight regarding how best to address challenges associated with ensuring that HIV-positive individuals leaving prison successfully move through the HIV care continuum to become virally suppressed.

One in three U.S. women has experienced intimate partner violence (IPV) and many seek domestic violence protective orders (DVPOs) for secondary IPV prevention. Because judges have considerable autonomy making DVPO decisions, there is a need to describe how courtroom interactions and information available to judges may influence DVPO dispositions. We conducted DVPO hearing observations and phone interviews with District Court Judges. Qualitative themes emerged that may influence judges’ decision making in DVPO hearings: case information availability, judge engagement level, and litigant credibility. Recommendations include more time for judges to review case files, IPV-related training for judges, and increased court advocate use.

Noroviruses are the leading cause of food-borne gastroenteritis outbreaks and childhood diarrhoea globally, estimated to be responsible for 200,000 deaths in children each year 1-4 . Thus, reducing norovirus-associated disease is a critical priority. Development of vaccines and therapeutics has been hindered by the limited understanding of basic norovirus pathogenesis and cell tropism. While macrophages, dendritic cells, B cells and stem-cell-derived enteroids can all support infection of certain noroviruses in vitro 5-7 , efforts to define in vivo norovirus cell tropism have generated conflicting results. Some studies detected infected intestinal immune cells 8-12 , other studies detected epithelial cells 13 , and still others detected immune and epithelial cells 14-16 . Major limitations of these studies are that they were performed on tissue sections from immunocompromised or germ-free hosts, chronically infected hosts where the timing of infection was unknown, or following non-biologically relevant inoculation routes. Here, we report that the dominant cellular targets of a murine norovirus inoculated orally into immunocompetent mice are macrophages, dendritic cells, B cells and T cells in the gut-associated lymphoid tissue. Importantly, we also demonstrate that a norovirus can infect T cells, a previously unrecognized target, in vitro. These findings represent the most extensive analyses to date of in vivo norovirus cell tropism in orally inoculated, immunocompetent hosts at the peak of acute infection and thus they significantly advance our basic understanding of norovirus pathogenesis.

Tauopathies are a group of neurodegenerative disorders, including Alzheimer’s disease, defined by the presence of brain pathological inclusions comprised of abnormally aggregated and highly phosphorylated tau protein. The abundance of brain tau aggregates correlates with disease severity and select phospho-tau epitopes increase at early stages of disease. We generated and characterized a series of novel monoclonal antibodies directed to tau phosphorylated at several of these phospho-epitopes, including Ser396/Ser404, Ser404 and Thr205. We also generated phosphorylation independent antibodies against amino acid residues 193–211. We show that most of these antibodies are highly specific for tau and strongly recognize pathological inclusions in human brains and in a transgenic mouse model of tauopathy. They also reveal epitope-specific differences in the biochemical properties of Alzheimer’s disease sarkosyl-insoluble tau. These new reagents will be useful for investigating the progression of tau pathology and further as tools to target the cellular transmission of tau pathology.

The optimal method of managing stress urinary incontinence (SUI) in women undergoing colpocleisis remains unclear, especially in a setting of urinary retention. We aim to compare postoperative retention after colpocleisis with or without concomitant midurethral sling (MUS).A retrospective chart review of all women who underwent colpocleisis with or without MUS from October 2007 to October 2017 was performed. Women with preoperative and 2-week postoperative post-void residual volume (PVR) measurements were included. Urinary retention was defined as PVR of ≥100 ml. Analysis included t tests/Wilcoxon rank, Chi-squared/Fisher's exact, and multivariate linear regression models.A total of 231 women with a mean age of 77.7 years (± 6.0 years SD) met the inclusion criteria. One hundred and thirty-eight women underwent colpocleisis alone, whereas 93 women had colpocleisis with MUS. Preoperative retention rates were high (44.9% vs 34.4%, for colpocleisis alone versus with MUS, p = 0.114). Postoperative retention rates were lower and similar between the groups (10.1% vs 11.8%, for colpocleisis alone vs with MUS, p = 0.69). Linear regression models showed the adjusted odds ratio for postoperative urinary retention in patients with concomitant MUS was 1.68 (95% confidence interval: 0.64-4.41) compared with patients with colpocleisis alone and this did not reach statistical significance (p = 0.292). Fortunately, after colpocleisis, women had high rates of resolution of retention, regardless of MUS (80.3% vs 90.6% for colpocleisis alone vs with MUS; p = 0.20). Few women required reoperation for retention (3.1%).Placement of an MUS at the time of colpocleisis is a safe and effective therapy. This appears to be unaffected by preoperative urinary retention status.

Bidirectional associations between child temperament (fear, frustration, positive affect, effortful control) and parenting behaviors (warmth, negativity, limit setting, scaffolding, responsiveness) were examined as predictors of preschool-age children's adjustment problems and social competence. Participants were a community sample of children (N = 306; 50% female, 64% European American) and their mothers. Observational measures of child temperament and parenting were obtained using laboratory tasks at two time points (children's ages 36 and 54 months). Teacher-reported adjustment measures were collected at the first and third time points (children's ages 36 and 63 months). Cross-lagged analyses were performed to examine whether child temperament and parenting predict changes in one another, whether they each contribute independently to children's adjustment, and whether these transactional relations account for adjustment outcomes. Maternal negativity at 36 months predicted increases in child frustration at 54 months. Maternal negativity and child effortful control predicted decreases in each other from 36 to 54 months. Maternal warmth predicted increases in child effortful control over time. Child frustration, child effortful control, maternal warmth, and maternal negativity at 54 months each independently predicted child adjustment problems at 63 months, controlling for problems at 36 months. Child executive control at 54 months predicted increases in child social competence at 63 months. The findings suggest that temperament and parenting have independent and additive effects on preschool-age child adjustment, with some support for a bidirectional relation.

Since 9/11, military service in the United States has been characterized by wartime deployments and reintegration challenges that contribute to a context of stress for military families. Research indicates the negative impact of wartime deployment on the well being of service members, military spouses, and children. Yet, few studies have considered how parental deployments may affect adjustment in young children and their families. Using deployment records and parent-reported measures from primary caregiving (N = 680) and military (n = 310) parents, we examined the influence of deployment on adjustment in military families with children ages 0-10 years. Greater deployment exposure was related to impaired family functioning and marital instability. Parental depressive and posttraumatic stress symptoms were associated with impairments in social emotional adjustment in young children, increased anxiety in early childhood, and adjustment problems in school-age children. Conversely, parental sensitivity was associated with improved social and emotional outcomes across childhood. These findings provide guidance to developing preventive approaches for military families with young children.

Objectives Worldwide, women face sexual and reproductive health (SRH) risks including unintended pregnancy and sexually transmitted infections (STIs) including HIV. Multipurpose prevention technologies (MPTs) combine protection against two or more SRH risks into one product. Male and female condoms are the only currently available MPT products, but several other forms of MPTs are in development. We examined the global distribution of selected SRH issues to determine where various risks have the greatest geographical overlap. Study design We examined four indicators relevant to MPTs in development: HIV prevalence, herpes simplex virus type 2 prevalence (HSV-2), human papillomavirus prevalence (HPV) and the proportion of women with unmet need for modern contraception. Using ArcGIS Desktop, we mapped these indicators individually and in combination on choropleth and graduated symbol maps. We conducted a principal components analysis to reduce data and enable visual mapping of all four indicators on one graphic to identify overlap. Results Our findings document the greatest overlapping risks in Sub-Saharan Africa, and we specify countries in greatest need by specific MPT indication. Conclusions These results can inform strategic planning for MPT introduction, market segmentation and demand generation; data limitations also highlight the need for improved (non-HIV) STI surveillance globally. Implications MPTs are products in development with the potential to empower women to prevent two or more SRH risks. Geographic analysis of overlapping SRH risks demonstrates particularly high need in Sub-Saharan Africa. This study can help to inform strategic planning for MPT introduction, market segmentation and demand generation.

Persistent postconcussion syndrome (PPCS) after mild traumatic brain injury (mTBI) is a significant public health and military problem for which there is limited treatment evidence. The aim of this study was to determine whether forty 150 kPa hyperbaric oxygen therapies (HBOTs) can improve symptoms and cognitive function in subjects with the PPCS of mTBI, using a randomized controlled crossover design with 2-month follow-up. Sixty-three civilian and military subjects with mTBI/PPCS were randomized to either 40 HBOTs at 150 kPa/60 minutes, once daily, 5 days per week in 8 weeks or an equivalent no-treatment control period. The Control Group was then crossed over to HBOT. Subjects underwent symptom, neuropsychological, and psychological testing, before and after treatment or control with retesting 2 months after the 40th HBOT. Fifty subjects completed the protocol with primary outcome testing. HBOT subjects experienced significant improvements in Neurobehavioral Symptom Inventory, Memory Index, Automated Neuropsychological Assessment Metrics, Hamilton Depression Scale, Hamilton Anxiety Scale, Post-Traumatic Stress Disorder Checklist, Pittsburgh Sleep Quality Index, and Quality Of Life after Brain Injury compared to the Control Group. After crossing over to HBOT the Control Group experienced near-identical significant improvements. Further improvements were experienced by both groups during the 2-month follow-up period. These data indicate that 40 HBOTs at 150 kPa/60 minutes demonstrated statistically significant improvements in postconcussion and Post-Traumatic Stress Disorder symptoms, memory, cognitive functions, depression, anxiety, sleep, and quality of life in civilian and military subjects with mTBI/PPCS compared to controls. Improvements persisted at least 2 months after the 40th HBOT. The study was registered on ClinicalTrials.gov (NCT02089594) on March 18, 2014 and with the U.S. Food and Drug Administration under Investigational New Drug #113823. The Institutional Review Boards of the United States Army Medical Research and Materiel Command Office of Research Protections Human Research Protection Office and the Louisiana State University School of Medicine (approval No. 7381) approved the study on May 13, 2014 and December 20, 2013, respectively.

Mechanisms underlying α-synuclein (αSyn) mediated neurodegeneration are poorly understood. Intramuscular (IM) injection of αSyn fibrils in human A53T transgenic M83+/− mice produce a rapid model of α-synucleinopathy with highly predictable onset of motor impairment. Using varying doses of αSyn seeds, we show that αSyn-induced phenotype is largely dose-independent. We utilized the synchrony of this IM model to explore the temporal sequence of αSyn pathology, neurodegeneration and neuroinflammation. Longitudinal tracking showed that while motor neuron death and αSyn pathology occur within 2 months post IM, astrogliosis appears at a later timepoint, implying neuroinflammation is a consequence, rather than a trigger, in this prionoid model of synucleinopathy. Initiating at 3 months post IM, immune activation dominates the pathologic landscape in terminal IM-seeded M83+/− mice, as revealed by unbiased transcriptomic analyses. Our findings provide insights into the role of neuroinflammation in αSyn mediated proteostasis and neurodegeneration, which will be key in designing potential therapies.

Metabotropic glutamate receptor 5 (mGluR

This study examined state-trait models of diurnal cortisol (morning level and diurnal slope), and whether income, cumulative risk and parenting behaviors predicted variance in trait and state levels of cortisol. The sample of 306 mothers and their preschool children included 29% families at or near poverty, 27% families below the median income, and the remaining families at middle and upper income. Diurnal cortisol, income, cumulative risk, and parenting were measured at 4 time points, once every 9 months, starting when children were 36-40 months. State-trait models fit the data, suggesting significant state but not trait variance in cortisol. Low income and cumulative risk were related to trait levels of diurnal cortisol with little evidence of time-varying or state effects. Stable levels of parenting predicted trait levels of diurnal cortisol and time-varying levels of parenting predicted time-varying state levels of diurnal cortisol. Findings highlight the allostatic process of adaptation to risk as well as time-specific reactivity to variability in experience.

Incarcerated people remain a priority group in efforts to control and reverse the HIV epidemic. Following release, social instability and reengagement in key transmission risk behaviors increase the risk of secondary transmission of HIV. Targeted programs have been developed to facilitate reengagement in care on reentry. Evaluation of the impact of these initiatives requires a systematic, confidential, framework for assessment of linkage to care for persons released from corrections. By linking HIV viral load surveillance data to corrections release data, the time to the first laboratory monitoring service in the community as well as the virologic status can be assessed. Using this method, we linked release data for sentenced individuals released from Massachusetts state correctional facilities in 2012 to HIV surveillance data from the Massachusetts HIV/AIDS Surveillance Program (MHASP) for the years 2012-2013. We identified 41 individuals with HIV released in 2012. Ninety-one percent had identified virologic assessments post release, 41% within 30 days. Thirty-three percent did not have a viral load assessed for more than 90 days and 31% had detectable virus at the time of their initial assessment. Persons with longer incarcerations (> 180 days) were more likely to have suppressed viral load at the time of follow-up (p = 0.05). This work demonstrates the important value of HIV laboratory surveillance data and correctional release data as a tool to assess linkage to care following release from corrections. We encourage jurisdictions to explore utilizing similar methodology to evaluate the effectiveness of the linkage to HIV care after release from incarceration.

Bioecological models of developmental psychopathology underscore the role of familial experiences of adversity and children’s individual-level characteristics in heightening risk for pediatric anxiety through direct, combined, and interactive effects. To date, much of the existing research dedicated to pediatric anxiety disorders has largely been examined in bioecological models of diathesis-stress using community samples. OBJECTIVE: This study extends our understanding of children’s differential responsiveness to familial adversity by examining the diathesis-stress interaction of cumulative risk and children’s individual-level vulnerabilities (negative affectivity and coping efficacy) within a clinic-referred treatment study for pediatric anxiety disorders. METHOD: A cumulative risk index assessing exposure to familial adversity (e.g., socioeconomic status, parent psychiatric illness), and self-reported measures of children’s negative affectivity and coping efficacy were each measured at the intake of a randomized controlled clinical trial for the treatment of pediatric anxiety disorders (N = 488; ages 7–17). Trajectories of interviewer-rated anxiety symptoms were assessed across 12-weeks of treatment at baseline, 4, 8 and 12 weeks. RESULTS: Consistent with models of temperamental risk for mental health problems, negative affectivity predicted higher anxiety symptoms at intake. A significant diathesis-stress interaction between cumulative risk and coping efficacy emerged, as high risk and perceptions of lower coping efficacy attenuated declines in anxiety across 12-weeks. These patterns did not differ across treatment conditions. CONCLUSION: The results indicate that for youth experiencing high levels of stress, additional treatment efforts targeting familial stressors and coping efficacy may be important in maximizing treatment outcomes.

Age-related changes in ligament properties may have clinical implications for injuries in the mature athlete. Previous preclinical models documented mechanical and biochemical changes in ligaments with aging. The purpose of this study was to investigate the effect of aging on ligament properties (mechanical, molecular, biochemical) by comparing medial collateral ligaments (MCLs) from 1-year-old and 3-year-old rabbits. The MCLs underwent mechanical (n=7, 1-year-old; n=7, 3-year-old), molecular (n=8, 1-year-old; n=6, 3-year-old), collagen and glycosaminoglycan (GAG) content (n=8, 1-year-old; n=6, 3-year-old) and water content (n=8, 1-year-old; n=5, 3-year-old) assessments. Mechanical assessments evaluated total creep strain, failure strain, ultimate tensile strength and modulus. Molecular assessments using RT-qPCR evaluated gene expression for collagens, proteoglycans, hormone receptors, and matrix metalloproteinases and their inhibitors. While total creep strain and ultimate tensile strength were not affected by aging, failure strain was increased and modulus was decreased comparing MCLs from 3-year-old rabbits to those from 1-year-old rabbits. The mRNA expression levels for lubricin/proteoglycan 4 (PRG4) and tissue inhibitor of metalloproteinase-3 increased with aging; whereas, the mRNA expression levels for estrogen receptor and matrix metalloproteinase-1 decreased with aging. Collagen and GAG content assays and water content assessments did not demonstrate any age-related changes. The increased failure strain and decreased modulus with aging may have implications for increased susceptibility to ligament damage/injury with aging. Lubricin/PRG4 gene expression was affected by aging and its speculated role in ligament function may be related to interfascicular lubrication, which in turn may lead to altered mechanical function with aging and increases in potential for injury.

Approximately one in three women in the United States experience intimate partner violence (IPV). IPV is associated with long-term negative health consequences; therefore, there is a need to examine potential prevention strategies. Evidence suggests that domestic violence protective orders (DVPOs), a legal intervention that prevents contact between two parties for up to 12 months, are an effective secondary prevention tool. However, because judges have relative autonomy in granting or denying DVPOs, research is needed to examine the processes they use to guide their decisions. The aim of the study was to investigate how District Court judges decide whether to issue a DVPO. Using in-depth interviews with 20 North Carolina District Court judges, the present study addressed three research questions: (a) what factors influence judges’ decisions to grant or deny a DVPO, (b) what heuristics or cognitive shortcuts potentially guide their decisions, and (c) what judges worry about when making decisions. Three themes emerged from the data analyses: (a) violent incidents must reach a certain threshold, (b) the presence of children creates competing concerns, and (c) judges worry about the negative impact their decisions may have on the lives of those involved. Recommendations for improving the DVPO issuance process are also discussed.

Environmental risk predicts disrupted basal cortisol levels in preschool children. However, little is known about the stability or variability of diurnal cortisol morning levels or slope patterns over time in young children. This study used latent profile analysis to identify patterns of the hypothalamic–pituitary–adrenal axis activity during the preschool period. Using a community sample (N = 306), this study measured income, cumulative risk, and children's diurnal cortisol (morning level and slope) four times across 2.5 years, starting when children were 36 months old. Latent profile analysis profiles indicated that there were predominantly stable patterns of diurnal cortisol level and slope over time and that these patterns were predicted by income and cumulative risk. In addition, there were curvilinear relations of income and cumulative risk to profiles of low morning cortisol level and flattened diurnal slope across time, suggesting that both lower and higher levels of income and cumulative risk were associated with a stress-sensitive physiological system. Overall, this study provides initial evidence for the role of environmental risk in predicting lower, flattened basal cortisol patterns that remain stable over time.

Exposure to environmental toxicants that target ovarian follicles can have long-lasting effects on women's reproductive health and health of the offspring. Experiments in rodents have contributed knowledge about the effects of individual toxicants on ovarian follicles. However, little is known about the effects of mixtures of toxicants on ovarian follicular health. We studied the combined effects of low, physiologically- and environmentally-relevant concentrations of toxicants on murine secondary ovarian follicles cultured in an encapsulated three-dimensional (3D) system. Exposure to lindane and 7,12-dimenthylbenz(a)anthracene (DMBA) led to decreased follicle survival, impaired development and compromised maturation in a concentration-dependent manner. DMBA showed a greater toxicity to cultured follicles compared to lindane. The mixtures of lindane and DMBA did not produce a synergistic toxic effect on follicles. Rather, ovarian follicles exposed to the mixtures showed survival and growth patterns similar to the follicles exposed to the same concentrations of individual toxicants. Our findings regarding follicle toxicity at such low concentrations help informing what might be overlooked when regulating environmental toxicants. The proposed 3D culture system allowed studying the effects of mixtures of environmental toxicants in a physiological setting, providing much needed information on how simultaneous exposure to multiple toxicants affects complex and sensitive biological structures, such as ovarian follicles.

Fish stocks can be defined by differences in their distribution, life history, and genetics. Managing fish based on stock structure is integral to successful management of a species because fishing may affect stocks disproportionately. Genetic and environmental differences can affect the shape and growth of otoliths and these differences may be indicative of stock structure. To investigate the potential for speciation or stock structure in giant grenadier, Albatrossia pectoralis, we quantified the shape of female giant grenadier otoliths and compared body growth rates for fish with three otolith shapes; shape types were classified visually by an experienced giant grenadier age reader, and were not defined by known distribution or life history differences. We found extreme variation in otolith shape among individuals; however, the shapes were a gradation and not clearly defined into three groups. The two more extreme shapes, visually defined as "hatchet" and "comb", were discernable based on principal component analyses of elliptical Fourier descriptors, and the "mixed" shape overlapped both of the extreme shapes. Fish with hatchet-shaped otoliths grew faster than fish with comb-shaped otoliths. A genetic test (cytochrome c oxidase 1 used by the Fish Barcode of Life Initiative) showed almost no variability among samples, indicating that the samples were all from one species. The lack of young specimens makes it difficult to link otolith shape and growth difference to life history. In addition, shape could not be correlated with adult movement patterns because giant grenadiers experience 100% mortality after capture and, therefore, cannot be tagged and released. Despite these limitations, the link between body growth and otolith shape indicates measurable differences that deserve more study.

To characterize neurodevelopmental outcomes after fetal aortic valvuloplasty for evolving hypoplastic left heart syndrome and determine the risk factors for adverse neurodevelopment.Questionnaires were mailed to families of children who underwent fetal aortic valvuloplasty from 2000 to 2012, and medical records were reviewed retrospectively. The primary outcome was the General Adaptive Composite score of the Adaptive Behavior Assessment System Questionnaire-Second Edition. Other questionnaires included the Behavior Assessment System for Children, Behavior Rating Inventory of Executive Function, Ages and Stages, and Pediatric Quality of Life Inventory.Among 69 eligible subjects, 52 (75%) completed questionnaires at median age of 5.5 (range 1.3-12) years; 30 (58%) had biventricular status circulation. The General Adaptive Composite mean score (92 ± 17) was lower than population norms (P .001) and similar to published reports in patients with hypoplastic left heart syndrome without fetal intervention; scores in the single ventricular versus biventricular group were 97 ± 19 vs 89 ± 14, respectively (P = .10). On multivariable analysis, independent predictors of a lower General Adaptive Composite score were total hospital duration of stay in the first year of life (P = .001) and, when forced into the model, biventricular status (P = .02). For all other neurodevelopmental questionnaires (Behavior Assessment System for Children, Behavior Rating Inventory of Executive Function, Ages and Stages, Pediatric Quality of Life Inventory), most subscale scores for patients with biventricular and single ventricular status were similar.Children who underwent fetal aortic valvuloplasty have neurodevelopmental delay, similar to patients with hypoplastic left heart syndrome without fetal intervention. Achievement of biventricular circulation was not associated with better outcomes. We infer that innate patient factors and morbidity during infancy have the greatest effect on neurodevelopmental outcomes.

A 27-year-old female with Trisomy 9 mosaicism presented to Children's Hospital Colorado for outpatient dental surgery under general anesthesia. The patient's past medical history was also significant for premature birth, gastroesophageal reflux, scoliosis and kyphosis, obesity, and developmental delay. Per her mother's report, the patient had no cardiac issues. She had undergone multiple previous general anesthetics, some of which documented respiratory complications such as laryngospasm, bronchospasm, and possible aspiration. During this anesthetic, the patient became hypotensive on induction, with sluggish response to intravenous fluids, glycopyrrolate, and ephedrine. Her electrocardiogram demonstrated what appeared to be left bundle branch block at baseline, with possible ST segment changes after induction. Due to her abnormal reaction to the induction and subsequent treatment for hypotension, an echocardiogram was performed. The patient was found to have an ejection fraction of 25%–30%. The anesthetic was uneventful for the remainder of the procedure, and following recovery, the patient was admitted by the heart failure team for further care.

The study examined growth in effortful control (executive control, delay ability) in relation to income, cumulative risk (aggregate of demographic and psychosocial risk factors), and adjustment in 306 preschool-age children (50 % girls, 50 % boys) from families representing a range of income (29 % at- or near-poverty; 28 % lower-income; 25 % middle-income; 18 % upper-income), with 4 assessments starting at 36-40 month. Income was directly related to levels of executive control and delay ability. Cumulative risk accounted for the effects of income on delay ability but not executive control. Higher initial executive control and slope of executive control and delay ability predicted academic readiness, whereas levels, but not growth, of executive control and delay ability predicted social competence and adjustment problems. Low income is a marker for lower effortful control, which demonstrates additive or mediating effects in the relation of income to children's preschool adjustment.

The authors investigate whether inner relationship focusing increases self-awareness in medical students and, in the process, to give them experience with empathic listening. Thirteen second-year medical students were randomized into experimental and control groups and surveyed pre-course and post-course about their self-awareness and perceived comfort with clinical interpersonal skills. Subjects attended a 20-h course on inner relationship focusing, followed by 5 months of weekly sessions. Pre-course and post-course survey scores were averaged by group, and mean differences were calculated and compared using the two-sample t test. The experimental group showed improvement in all areas compared to the control group. Improvement in one area (comfort talking to patients about how recurring symptoms might relate to issues in their lives) reached statistical significance (P = 0.05). Inner relationship focusing is a potential tool to increase self-awareness and empathic listening in medical students.

The aim of this investigation was to evaluate how parental anxiety predicted change in pediatric anxiety symptoms across four different interventions: cognitive-behavioral therapy (CBT), medication (sertraline; SRT), their combination (COMB), and pill placebo. Participants were 488 youths (ages 7-17) with separation anxiety disorder, generalized anxiety disorder, and/or social phobia and their primary caregivers. Latent growth curve modeling assessed how pre-treatment parental trait anxiety symptoms predicted trajectories of youth anxiety symptom change across 12 weeks of treatment at four time points. Interactions between parental anxiety and treatment condition were tested. Parental anxiety was not associated with youth’s pre-treatment anxiety symptom severity. Controlling for parental trait anxiety, youth depressive symptoms, and youth age, youths who received COMB benefitted most. Counter to expectations, parental anxiety influenced youth anxiety symptom trajectory only within the SRT condition, whereas parental anxiety was not significantly associated with youth anxiety trajectories in the other treatment conditions. Specifically, within the SRT condition, higher levels of parental anxiety predicted a faster and greater reduction in youth anxiety over the acute treatment period compared to youths in the SRT condition whose parents had lower anxiety levels. While all active treatments produced favorable outcomes, results provide insight regarding the treatment-specific influence of parental anxiety on the time course of symptom change. (ClinicalTrials.gov number NCT00052078.)

OBJECTIVE: To estimate the rate of vaginal implant exposure associated with biologic grafts and permanent mesh used for pelvic organ prolapse (POP) surgery, to describe treatments used for these complications, and to estimate response rates to these treatments. The secondary aims were to describe the operative and perioperative complications. METHODS: This was a retrospective analysis of female members of Kaiser Permanente Southern and Northern California and Hawaii who underwent POP surgeries with biologic grafts and permanent mesh between September 2008 and May 2010. Inpatient and outpatient electronic medical records were reviewed for postoperative adverse events. RESULTS: During the 21-month period, 1,282 women, mean age of 62 years (±10 standard deviation), median parity of 3 (interquartile range 2-4), and median body mass index of 28 (interquartile range 24-30) underwent prolapse repairs with 1,484 implants with a mean follow-up time of 358 days (±276 standard deviation). Vaginal exposures occurred more often with permanent mesh (53/847 [6%]) than biologic grafts (10/637 [1.6%]) (P

One in seven of the approximately 2.2 million Department of Defense active duty military personnel are women. Among active duty servicewomen, about 40% are under 26 years old, and almost half are young, lower ranking enlisted personnel. This article will include a review of the literature on military women's health topics such including contraception access, pregnancy, and pregnancy outcomes after environmental exposures. In these early adult years, contraception use may not be consistent, leading to higher rates of unintended pregnancy that is similar to their civilian counterparts, but it may affect troop readiness. Women who become pregnant after deployment must be evacuated from theater. Complications in pregnancy that require immediate intervention, such as ectopic pregnancy, may be more difficult to diagnose and manage if far away from comprehensive medical services. Environmental exposures may affect the pregnancy outcome, or may produce delayed responses for future childbearing. Women face other gynecologic choices including menstrual suppression while deployed. Many of these issues have not been fully studied, sample sizes are small or methodological flaws exist in the analysis limiting conclusions that can be drawn. Further research with greater rigor, larger sample sizes, and careful design are needed to address many of these questions.

While burden of disease (BOD) data exists for plaque psoriasis, and to a lesser extent other phenotypes of psoriasis, there is no published data on the impact of inverse (intertriginous) psoriasis. We sought to assess the overall BOD among patients with inverse psoriasis (IP). We introduce the Inverse Psoriasis Burden of Disease (IPBOD) questionnaire and compare it to the Dermatology Life Quality Index (DLQI). In this cross-sectional pilot study, we administered the IPBOD and the DLQI to 16 patients. We present the initial psychometric properties of the IPBOD survey. We used Spearman's correlation coefficients to compare the two questionnaires on overall performance and in specific domains. Our cohort had an average age of 55.6 (SD 16.6) years, was predominantly female (68.8%), and white (87.5%). 87.5% of patients had a second psoriasis subtype. A majority of patients reported some effect of IP on pain (n=14, 87.5%). Thirteen (81.3%) patients reported some effect on depressed mood or anxiety/worry. Overall, the largest effect was on body self-image (93.8% reporting an effect). The average DLQI score was 8.5/30, higher than average DLQI scores reported in patients with plaque psoriasis or psoriatic arthritis. Average IPBOD score was 4.9/10. The reliability of IPBOD was good (overall Cronbach's alpha = 0.89, individual items' range 0.88 - 0.91). Correlations between IPBOD and DLQI were: overall (Spearman'semP/em=0.650,emP/em=0.006), symptoms (emP/em=0.462,emP/em=0.072), daily activities (emP/em=0.507,emP/em=0.045), leisure (emP/em=0.633,emP/em=0.008), interpersonal function (emP/em=0.728,emP/em=0.001), and work and school (emP/em=0.427,emP/em=0.100). IP has a profound impact on patients' lives and the results of this pilot study suggest that the IPBOD questionnaire may be a useful disease-specific tool for measuring the BOD of IP.br /br /emJ Drugs Dermatol/em. 2016;15(8):1011-1016.

We thank Murakami et al for their interest in our article.1 They propose that the aortic dilatation observed in patients with connective tissue disorders is a compensatory response to increased aortic stiffness to preserve coronary blood flow. Although our study was not designed to test this interesting hypothesis, we agree that future investigations designed specifically to address this theory are warranted. Weismann et al question the use of aortic strain in our study and suggest that its relationship with adverse aortic outcomes may be driven by aortic size alone. However, their comments fail to take into account that, in addition to aortic size, several other factors …

Introduction Core data are crucial for detailing an accurate profile of the midwifery workforce in the United States. The American College of Nurse-Midwives (ACNM) and the American Midwifery Certification Board, Inc. (AMCB), at the request and with support from the US Health Resources and Services Administration (HRSA), are engaged in a collaborative effort to develop a data collection strategy (the Midwifery MasterFile) that will reflect demographic and practice characteristics of certified nurse-midwives (CNMs) and certified midwives (CMs) in the United States. Methods Two independent datasets, one collected by ACNM in 2012 and one by AMCB in 2013, were examined to determine key workforce information. ACNM data were collected from the online Core Data Survey sent to ACNM members. AMCB data were extracted from information submitted online by applicants seeking initial certification in 2013 and applicants seeking to recertify following 5 years of initial certification. Results The ACNM 2012 survey was partially or fully completed by 36% (n = 2185) of ACNM members (N = 6072). AMCB respondents included 100% of new certificants (N = 539) and those applying for recertification in 2013 (n = 1323) of the total 11,682 certificants in the AMCB database. These two datasets demonstrate that midwives remain largely white, female, and older in age, with most engaged in clinical midwifery while employed primarily by hospitals and medical centers. Differences were reported between the ACNM membership and AMCB certification datasets in the numbers of midwives holding other certifications, working full-time, attending births, and providing newborn care. Discussion The new collaboration among HRSA, ACNM, and AMCB, represented as the Midwifery MasterFile, provides the opportunity to clearly profile CNMs/CMs, distinct from advanced practice registered nurses, in government reports about the health care workforce. This information is central to identifying and marketing the role and contribution of CNMs/CMs in the provision of primary and reproductive health care services.