Understanding Traumatic Brain Injury in Females: A State-of-the-Art Summary and Future Directions.

In this report, we identify existing issues and challenges related to research on traumatic brain injury (TBI) in females and provide future directions for research. In 2017, the National Institutes of Health, in partnership with the Center for Neuroscience and Regenerative Medicine and the Defense and Veterans Brain Injury Center, hosted a workshop that focused on the unique challenges facing researchers, clinicians, patients, and other stakeholders regarding TBI in women. The goal of this "Understanding TBI in Women" workshop was to bring together researchers and clinicians to identify knowledge gaps, best practices, and target populations in research on females and/or sex differences within the field of TBI. The workshop, and the current literature, clearly highlighted that females have been underrepresented in TBI studies and clinical trials and have often been excluded (or ovariectomized) in preclinical studies. Such an absence in research on females has led to an incomplete, and perhaps inaccurate, understanding of TBI in females. The presentations and discussions centered on the existing knowledge regarding sex differences in TBI research and how these differences could be incorporated in preclinical and clinical efforts going forward. Now, a little over 2 years later, we summarize the issues and state of the science that emerged from the "Understanding TBI in Women" workshop while incorporating updates where they exist. Overall, despite some progress, there remains an abundance of research focused on males and relatively little explicitly on females.

A Report of the 24th Annual Congress on Women's Health-Workshop on Transforming Women's Health: From Research to Practice.

Sex and gender are critical contributors to overall health and disease, and considering both in research informs the development of prevention strategies and treatment interventions for both men and women. The National Institutes of Health (NIH) Office of Research on Women's Health sponsored a preconference workshop on this topic at the 24th Annual Women's Health Congress, which was held in Crystal City, VA, in April 2016. The workshop featured presentations by NIH intramural and extramural scientists who presented data on a variety of topics including polycystic kidney disease, vaccine protection, depression, drug addiction, and cardiovascular disease. In this publication, we discuss the major points of each presentation and demonstrate the importance of considering sex and gender in biomedical research.

National Institutes of Health Research Plan on Rehabilitation: NIH Medical Rehabilitation Coordinating Committee.

One in five Americans experiences disability that affects their daily function because of impairments in mobility, cognitive function, sensory impairment, or communication impairment. The need for rehabilitation strategies to optimize function and reduce disability is a clear priority for research to address this public health challenge. The National Institutes of Health (NIH) recently published a Research Plan on Rehabilitation that provides a set of priorities to guide the field over the next 5 years. The plan was developed with input from multiple Institutes and Centers within the NIH, the National Advisory Board for Medical Rehabilitation Research, and the public. This article provides an overview of the need for this research plan, an outline of its development, and a listing of six priority areas for research. The NIH is committed to working with all stakeholder communities engaged in rehabilitation research to track progress made on these priorities and to work to advance the science of medical rehabilitation.This article is being published almost simultaneously in the following six journals: American Journal of Occupational Therapy, American Journal of Physical Medicine and Rehabilitation, Archives of Physical Medicine and Rehabilitation, Neurorehabilitation and Neural Repair, Physical Therapy, and Rehabilitation Psychology. Citation information is as follows: NIH Medical Rehabilitation Coordinating Committee. Am J Phys Med Rehabil. 2017;97(4):404-407.

Understanding the Intersection of Young Age, Mucosal Injury, and HIV Susceptibility.

Adolescent boys and girls are disproportionately affected in the current HIV epidemic. Numerous sociobehavioral studies have addressed the indirect drivers surrounding this vulnerability-for example, socioeconomic, geographical locale, and all forms of violence. However, the direct factors that may influence infection, such as the anatomical and physiological maturation of the anogenital tracts of adolescents or the trauma and wound-healing processes of injured mucosal tissue, are understudied and represent a gap within the HIV prevention field. This article reviews the epidemiology of HIV infection and violence in adolescents and the available basic science knowledge attending this research area. More importantly, this review highlights the most critical gaps that need to be addressed to design preventive interventions that are safe and effective for this population, which is key to ending the HIV pandemic.

The science of sex and gender in human health: online courses to create a foundation for sex and gender accountability in biomedical research and treatment.

BACKGROUND: Sex and gender differences play a significant role in the course and outcome of conditions that affect specific organ systems in the human body. Research on differences in the effects of medical intervention has helped scientists develop a number of sex- and gender-specific guidelines on the treatment and management of these conditions. An online series of courses, "The Science of Sex and Gender in Human Health," developed by the National Institutes of Health Office of Research on Women's Health and the U.S. Food and Drug Administration Office of Women's Health, examines sex and gender differences and their implications. Thus far, three online courses have been generated. The first course offers an overview of the scientific and biological basis for sex- and gender-related differences. The second course is focused on disease-specific sex and gender differences in health and behavior and their implications. Finally, the third course covers the influence of sex and gender on disease manifestation, treatment, and outcome. METHODS: Data were obtained using website analytics and post-course surveys. RESULTS: To date, over 1000 individuals have completed at least one course. Additionally, 600 users have received continuing education credit for completing a course in the series. Finally, the majority of respondents to the online course survey have indicated that the courses considerably enhanced their professional effectiveness. CONCLUSIONS: "The Science of Sex and Gender in Human Health" online courses are freely available sources of information that provide healthcare providers and researchers with the resources to successfully account for sex and gender in their medical practice and research programs.

Programmatic Efforts at the National Institutes of Health to Promote and Support the Careers of Women in Biomedical Science.

Although women have reached parity at the training level in the biological sciences and medicine, they are still significantly underrepresented in the professoriate and in mid- and senior-level life science positions. Considerable effort has been devoted by individuals and organizations across science sectors to understanding this disparity and to developing interventions in support of women's career development. The National Institutes of Health (NIH) formed the Office of Research on Women's Health (ORWH) in 1990 with the goals of supporting initiatives to improve women's health and providing opportunities and support for the recruitment, retention, reentry, and sustained advancement of women in biomedical careers. Here, the authors review several accomplishments and flagship activities initiated by the NIH and ORWH in support of women's career development during this time. These include programming to support researchers returning to the workforce after a period away (Research Supplements to Promote Reentry into Biomedical and Behavioral Research Careers), career development awards made through the Building Interdisciplinary Research Careers in Women's Health program, and trans-NIH involvement and activities stemming from the NIH Working Group on Women in Biomedical Careers. These innovative programs have contributed to advancement of women by supporting the professional and personal needs of women in science. The authors discuss the unique opportunities that accompany NIH partnerships with the scientific community, and conclude with a summary of the impact of these programs on women in science.

A Report of the Women's Health Congress Workshop on The Health of Women of Color: A Critical Intersection at the Corner of Sex/Gender and Race/Ethnicity.

Women of color face unique health challenges that differ significantly from those of other women and men of color. To bring these issues to light, the National Institutes of Health (NIH) Office of Research on Women's Health sponsored a preconference workshop at the 23rd Annual Women's Health Congress, which was held in Washington, DC, in April 2015. The workshop featured presentations by NIH intramural and extramural scientists who provided insight on the disparities of a wide range of conditions, including cancer, cardiovascular disease, the risk of HIV infection, and disability in an aging population. In this study, we highlight the major points of each presentation and the ensuing discussion.

Fetal pulse oximetry for fetal assessment in labour.

BACKGROUND: The use of conventional cardiotocographic (CTG) monitoring of fetal well-being during labour is associated with an increased caesarean section rate, compared with intermittent auscultation of the fetal heart rate, resulting in a reduction in neonatal seizures, although no differences in other neonatal outcomes. To improve the sensitivity of this test and therefore reduce the number of caesarean sections performed for nonreassuring fetal status, several additional measures of evaluating fetal well-being have been considered. These have demonstrated some effect on reducing caesarean section rates, for example, fetal scalp blood sampling for pH estimation/lactate measurement. The adaptation of pulse oximetry for use in the unborn fetus could potentially contribute to improved evaluation during labour and therefore lead to a reduction in caesarean sections for nonreassuring fetal status, without any change in neonatal outcomes. OBJECTIVES: To compare the effectiveness and safety of fetal intrapartum pulse oximetry with other surveillance techniques. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2014), contacted experts in the field and searched reference lists of retrieved studies. In previous versions of this review, we performed additional searches of MEDLINE, Embase and Current Contents. These searches were discontinued for this review update, as they consistently failed to identify any trials that were not shown in the Cochrane Pregnancy and Childbirth Group's Trials Register. SELECTION CRITERIA: All published and unpublished randomised controlled trials that compared maternal and fetal outcomes when fetal pulse oximetry was used in labour, (i) with or without concurrent use of conventional fetal surveillance, that is, cardiotocography (CTG), compared with using CTG alone or (ii) with or without concurrent use of both CTG and other method(s) of fetal surveillance, such as fetal electrocardiography (ECG) plus CTG. DATA COLLECTION AND ANALYSIS: At least two independent review authors performed data extraction. We sought additional information from the investigators of three of the reported trials. MAIN RESULTS: We included seven published trials: six comparing fetal pulse oximetry and CTG with CTG alone (or when fetal pulse oximetry values were blinded) and one comparing fetal pulse oximetry plus CTG with fetal ECG plus CTG. The published trials, with some unpublished data, were at high risk of bias in terms of the impractical nature of blinding participants and clinicians, as well as high risk or unclear risk of bias for outcome assessor for all but one report. Selection bias, attrition bias, reporting bias and other sources of bias were of low or unclear risk. The trials reported on a total of 8013 pregnancies. Differing entry criteria necessitated separate analyses, rather than meta-analysis of all trials.Systematic review of four trials from 34 weeks not requiring fetal blood sampling (FBS) prior to study entry showed no evidence of differences in the overall caesarean section rate between those monitored with fetal oximetry and those not monitored with fetal pulse oximetry or for whom the fetal pulse oximetry results were masked (average risk ratio (RR) 0.99 using random-effects, 95% confidence intervals (CI) 0.86 to 1.13, n = 4008, I² = 45%). There was evidence of a higher risk of caesarean section in the group with fetal oximetry plus CTG than in the group with fetal ECG plus CTG (one study, n = 180, RR 1.56, 95% CI 1.06 to 2.29). Neonatal seizures and neonatal encephalopathy were rare in both groups. No studies reported details of long-term disability.There was evidence of a decrease in caesarean section for nonreassuring fetal status in the fetal pulse oximetry plus CTG group compared to the CTG group, gestation from 34 weeks (average RR (random-effects) 0.65, 95% CI 0.46 to 0.90, n = 4008, I² = 63%). There was no evidence of differences between groups in caesarean section for dystocia, although the overall incidence rates varied between the trials. AUTHORS' CONCLUSIONS: The addition of fetal pulse oximetry does not reduce overall caesarean section rates. One study found a higher caesarean section rate in the group monitored with fetal pulse oximetry plus CTG, compared with fetal ECG plus CTG. The data provide limited support for the use of fetal pulse oximetry when used in the presence of a nonreassuring CTG, to reduce caesarean section for nonreassuring fetal status. A better method than pulse oximetry is required to enhance the overall evaluation of fetal well-being in labour.

Local cooling for relieving pain from perineal trauma sustained during childbirth.

BACKGROUND: Perineal trauma is common during childbirth and may be painful. Contemporary maternity practice includes offering women numerous forms of pain relief, including the local application of cooling treatments. OBJECTIVES: To evaluate the effectiveness and side effects of localised cooling treatments compared with no treatment, other forms of cooling treatments and non-cooling treatments. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (10 January 2012), CINAHL (1982 to 10 January 2012), the Australian New Zealand Clinical Trials Register (10 January 2012) and contacted experts in the field. SELECTION CRITERIA: Published and unpublished randomised and quasi-randomised trials (RCTs) that compared localised cooling treatment applied to the perineum with no treatment or other treatments applied to relieve pain related to perineal trauma sustained during childbirth. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed trials for inclusion, assessed trial quality and extracted data. A sub-set of data were double checked for accuracy. Analyses were performed on an intention-to-treat basis where data allowed. We sought additional information from the authors of three trials. MAIN RESULTS: Ten published RCTs were included (involving 1825 women). Comparisons were local cooling treatments (ice packs, cold gel pads (with or without compression) or cold/iced baths) with no treatment, gel pads with compression, hamamelis water (witch hazel), pulsed electromagnetic energy (PET), hydrocortisone/pramoxine foam (Epifoam), oral paracetamol or warm baths. Ice packs provided improved pain relief 24 to 72 hours after birth compared with no treatment (risk ratio (RR) 0.61; 95% confidence interval (CI) 0.41 to 0.91; one study, n = 208). Women preferred the utility of the gel pads compared with ice packs or no treatment (RR 0.82; 95% CI 0.73, 0.92). Differences detected in a composite of perineal oedema and bruising and overall wound healing were noted in one small study, favouring cold gel pads (n = 37) over ice (n = 35, mean difference (MD) 0.63 on a scale of 0 to 15; 95% CI 0.20 to 1.06) or no treatment (n = 39, MD -2.10; 95% CI -3.80 to -0.40) three to 14 days after giving birth. Women reported more pain (RR 5.60; 95% CI 2.35 to 13.33; one study, 100 women) and used more additional analgesia (RR 4.00; 95% CI 1.44 to 11.13; one study, 100 women) following the application of ice packs compared with PET. AUTHORS' CONCLUSIONS: There is only limited evidence to support the effectiveness of local cooling treatments (ice packs, cold gel pads, cold/iced baths) applied to the perineum following childbirth to relieve pain.

Childbearing, child-rearing, cardiovascular risk factors, and progression of carotid intima-media thickness: the Cardiovascular Risk in Young Finns study.

BACKGROUND AND PURPOSE: Parity is associated with the risk of clinical cardiovascular events and the severity of preclinical atherosclerosis in older subjects. We sought to determine whether childbearing is associated with concurrent changes in cardiovascular risk factors and the progression of carotid intima-media thickness. METHODS: We examined the association between the number of children born during a 6-year period and concurrent changes in cardiovascular risk factors and progression of carotid intima-media thickness in men and women of reproductive age from the Cardiovascular Risk in Young Finns study. Complete data for parity and carotid intima-media thickness were available for 1786 subjects (1005 females, 781 males). RESULTS: For females, childbirth during the 6-year follow-up was associated with concurrent reductions in high-density lipoprotein cholesterol (P(trend)<0.0001), apolipoprotein A-I (P(trend)<0.0001), and apolipoprotein B (P(trend)=0.01); a redistribution of adiposity to abdominal deposits; and increased progression of carotid intima-media thickness (7.5+/-3.2 mum/birth [mean+/-SEM], P=0.02). The association of childbirth with carotid intima-media thickness progression was not greatly modified by adjustment for concurrent changes in cardiovascular risk factors (fully adjusted: P=0.05). This association was significantly stronger in females than males (P(heterogeneity)=0.001), who served as a control group exposed to the social and lifestyle influences of child-rearing but not the biological influences of childbearing. CONCLUSIONS: The progression of carotid atherosclerosis over a 6-year period is increased in females who gave birth during the same period, independent of traditional risk factors. Mechanisms that underlie this observation possibly include parity-induced changes in nontraditional risk factors or an acute influence of pregnancy itself.

The NIH Human Microbiome Project.

The Human Microbiome Project (HMP), funded as an initiative of the NIH Roadmap for Biomedical Research (http://nihroadmap.nih.gov), is a multi-component community resource. The goals of the HMP are: (1) to take advantage of new, high-throughput technologies to characterize the human microbiome more fully by studying samples from multiple body sites from each of at least 250 "normal" volunteers; (2) to determine whether there are associations between changes in the microbiome and health/disease by studying several different medical conditions; and (3) to provide both a standardized data resource and new technological approaches to enable such studies to be undertaken broadly in the scientific community. The ethical, legal, and social implications of such research are being systematically studied as well. The ultimate objective of the HMP is to demonstrate that there are opportunities to improve human health through monitoring or manipulation of the human microbiome. The history and implementation of this new program are described here.

Parity and carotid atherosclerosis in men and women: insights into the roles of childbearing and child-rearing.

BACKGROUND AND PURPOSE: Parity appears to be associated with carotid atherosclerosis in women aged 45 years and older. Studying this association among younger women and men may provide insight into whether this association relates predominantly to childbearing or child-rearing. METHODS: The association between parity and carotid atherosclerosis (intima-media thickness and presence of plaques) was assessed in a cohort consisting of 750 women and 1164 men, all with at least one traditional cardiovascular risk factor, aged 18 to 80 years of age. Traditional cardiovascular risk factors were also assessed, and the Framingham Risk Score calculated. RESULTS: In age-adjusted analyses, the number of children was associated with adiposity, fasting glucose, 2-hour glucose, Framingham risk score, and carotid atherosclerosis in women, but not in men. Multivariate linear regression models indicate that the prevalence of plaques was increased by 15% (95% CI, 2 to 29) per child among women, and 0% (95% CI, -10 to 11) among men, after adjustment for age, socioeconomic and lifestyle factors (including waist circumference). The association between parity and carotid intima-media thickness was similar in younger and older women (P(Heterogeneity)=0.20). CONCLUSIONS: A higher number of children is associated with increased carotid atherosclerosis in both younger and older women, but not among men. These findings indicate that childbearing, but not child-rearing, may be a risk factor for atherosclerosis, and suggest the potential importance of considering the number of children when assessing the level of cardiovascular risk in women.

Update on intrapartum fetal pulse oximetry.

This article examines the current status of fetal pulse oximetry (FPO) as a means of intrapartum assessment of fetal wellbeing. FPO has been developed to a stage where it is a safe and accurate indicator of intrapartum fetal oxygenation. In general, sliding the FPO sensor along the examiner's fingers and through the cervix, to lie alongside the fetal cheek or temple is easy The recent publication of a randomised controlled trial (RCT) of FPO versus conventional intrapartum monitoring has validated its use to reduce caesarean section rates for nonreassuring fetal status. An Australian multicentre RCT is currently underway. Maternal satisfaction rates with FPO are high. FPO may be used during labour when the electronic fetal heart rate trace is nonreassuring or when conventional monitoring is unreliable, such as with fetal arrhythmias. If the fetal oxygen saturation (FSpO2) values are < 30%, prompt obstetric intervention is indicated, such as fetal scalp blood sampling or delivery FSpO2 monitoring should not form the sole basis of intrapartum fetal welfare assessment. Rather, the whole clinical picture should be considered.

Audit of maternal and fetal outcomes in women treated for glucose intolerance during pregnancy.

OBJECTIVE: To determine whether one should aim for glycaemia that is statistically 'normal' or for levels of glycaemia low enough to prevent macrosomia (if such a threshold exists) when glucose intolerance is detected during pregnancy. DESIGN: An audit of pregnancy outcomes in women with impaired glucose tolerance in pregnancy as compared to a local age-matched reference group with normal glucose tolerance. RESULTS: Our study suggests that for most patients, more intensive therapy would not have been justified. Maternal smoking appeared to convey some 'advantages' in terms of neonatal outcomes, with reduction in large-for-gestational-age (LGA) infants and jaundice in babies of impaired glucose tolerance (IGT) mothers. CONCLUSIONS: These observations demonstrate the importance of considering risk factors other than GTT results in analysing pregnancy outcomes, while emphasising that 'normalisation' of fetal size should not be our only therapeutic endpoint. Our detailed outcome review allows us to reassure patients with GDM that with current treatment protocols, they should have every expectation of a positive pregnancy outcome.