Challenges Faced by Rural Health Care Providers Caring for Parkinson's Disease Patients in Neighbor Islands of Hawai'i.

When compared to their urban counterparts, rural regions have worse health outcomes and more challenges in health care access. As the only island state in the US, Hawai'i's unique geographic layout may magnify these disparities. However, there are limited publications on the impact of urban-rural disparities in health care in Hawai'i. The study team aimed to identify the challenges rural health care providers face when managing treatment of Parkinson's disease (PD), a complex disease. A self-administered survey was sent to 247 eligible providers who practiced in Hawai'i and prescribed PD medications from 2017-2019. The survey assessed: provider's comfort level in PD management; utilization and accessibility of health care services; perspective on barriers to PD care; and perspective on telemedicine. Providers were categorized into O'ahu providers (OP, urban) and neighbor island (Hawai'i, Kaua'i, and Maui) providers (NIP, rural). The final sample size was 44 providers (18% response rate). NIP were significantly less likely than OP to report access to social workers (P=.025), geriatric services (P=.001), and psychologist/psychiatrist/mental health professionals (P=.009). There were no statistical differences in: criteria used for PD diagnosis, resources utilized for PD education, and comfort in prescribing PD medications. The findings show that NIP are just as engaged and capable in providing PD care as OP. However, NIP encounter more limitations to accessibility, which can affect the quality of PD care that their rural patients receive. Further research is needed to understand how these limitations affect health-related outcomes in PD as well as other chronic diseases.

Assessing Racial Disparities in Access, Use, and Outcomes for Pregnant and Postpartum Veterans and Their Infants in Veterans Health Administration.

Objective: Limited population-based data examines racial disparities among pregnant and postpartum Veterans. Our objective was to determine whether Black/white racial disparities in health care access, use, and Veteran and infant outcomes are present among pregnant and postpartum Veterans and their infants using Veterans Health Administration (VA) care. Methods: The VA National Veteran Pregnancy and Maternity Care Survey included all Veterans with a VA paid live birth between June 2018 and December 2019. Participants could complete the survey online or by telephone. The independent variable was self-reported race. Outcomes included timely initiation of prenatal care, perceived access to timely prenatal care, attendance at a postpartum check-up, receipt of needed mental health care, cesarean section, postpartum rehospitalization, low birthweight, preterm birth, admission to a neonatal intensive care unit, and breastfeeding. Nonresponse weighted general linear models with a log-link were used to examine associations of race with outcomes. Cox regression was used to examine the association of race with duration of breastfeeding. Models adjusted for age, ethnicity, urban versus rural residence, and parity. Results: The analytic sample consisted of 1,220 Veterans (Black n = 916; white n = 304) representing 3,439 weighted responses (Black n = 1,027; white n = 2,412). No racial disparities were detected for health care access or use. Black Veterans were more likely than white Veterans to have a postpartum rehospitalization (RR 1.67, 95% CI: 1.04-2.68) and a low-birthweight infant (RR 1.67, 95% CI: 1.20-2.33). Conclusion: While no racial disparities were detected for health care access and use, we identified disparities in postpartum rehospitalization and low birthweight, underscoring that access is not sufficient for ensuring health equity.

Gender differences in social support for diabetes self-management: A qualitative study among veterans.

OBJECTIVE: Describe the role of social support in veterans' diabetes self-management and examine gender differences. METHODS: We conducted semi-structured interviews among veterans with diabetes from one Veterans Health Administration Health Care System. Participants described how support persons influenced their diabetes self-management and perspectives on a proposed self-management program incorporating a support person. We used thematic analysis to identify salient themes and examine gender differences. RESULTS: Among 18 women and 18 men, we identified four themes: 1) women felt responsible for their health and the care of others; 2) men shared responsibility for managing their diabetes, with support persons often attempting to correct behaviors (social control); 3) whereas both men and women described receiving instrumental and informational social support, primarily women described emotional support; and 4) some women's self-management efforts were hindered by support persons. Regarding programs incorporating a support person, some participants endorsed including family/friends and some preferred programs including other individuals with diabetes. CONCLUSIONS: Notable gender differences in social support for self-management were observed, with women assuming responsibility for their diabetes and their family's needs and experiencing interpersonal barriers. PRACTICE IMPLICATIONS: Gender differences in the role of support persons in diabetes self-management should inform support-based self-management programs.

Using an antimalarial in mosquitoes overcomes Anopheles and Plasmodium resistance to malaria control strategies.

The spread of insecticide resistance in Anopheles mosquitoes and drug resistance in Plasmodium parasites is contributing to a global resurgence of malaria, making the generation of control tools that can overcome these roadblocks an urgent public health priority. We recently showed that the transmission of Plasmodium falciparum parasites can be efficiently blocked when exposing Anopheles gambiae females to antimalarials deposited on a treated surface, with no negative consequences on major components of mosquito fitness. Here, we demonstrate this approach can overcome the hurdles of insecticide resistance in mosquitoes and drug resistant in parasites. We show that the transmission-blocking efficacy of mosquito-targeted antimalarials is maintained when field-derived, insecticide resistant Anopheles are exposed to the potent cytochrome b inhibitor atovaquone, demonstrating that this drug escapes insecticide resistance mechanisms that could potentially interfere with its function. Moreover, this approach prevents transmission of field-derived, artemisinin resistant P. falciparum parasites (Kelch13 C580Y mutant), proving that this strategy could be used to prevent the spread of parasite mutations that induce resistance to front-line antimalarials. Atovaquone is also highly effective at limiting parasite development when ingested by mosquitoes in sugar solutions, including in ongoing infections. These data support the use of mosquito-targeted antimalarials as a promising tool to complement and extend the efficacy of current malaria control interventions.

Long-term association between diet quality and characteristics of the gut microbiome in the multiethnic cohort study.

As past usual diet quality may affect gut microbiome (GM) composition, we examined the association of the Healthy Eating Index (HEI)-2015 assessed 21 and 9 years before stool collection with measures of fecal microbial composition in a subset of the Multiethnic Cohort. A total of 5936 participants completed a validated quantitative FFQ (QFFQ) at cohort entry (Q1, 1993-1996), 5280 at follow-up (Q3, 2003-2008) and 1685 also at a second follow-up (Adiposity Phenotype Study (APS), 2013-2016). All participants provided a stool sample in 2013-2016. Fecal microbial composition was obtained from 16S rRNA gene sequencing (V1-V3 regions). HEI-2015 scores were computed based on each QFFQ. Using linear regression adjusted for relevant covariates, we calculated associations of HEI-2015 scores with gut microbial diversity and 152 individual genera. The mean HEI-2015 scores increased from Q1 (67 (sd 10)) to Q3 (71 (sd 11)) and APS (72 (sd 10)). Alpha diversity assessed by the Shannon Index was significantly higher with increasing tertiles of HEI-2015. Of the 152 bacterial genera tested, seven (Anaerostipes, Coprococcus_2, Eubacterium eligens, Lachnospira, Lachnospiraceae_ND3007, Ruminococcaceae_UCG-013 and Ruminococcus_1) were positively and five (Collinsella, Parabacteroides, Ruminiclostridium_5, Ruminococcus gnavus and Tyzzerella) were inversely associated with HEI-2015 assessed in Q1, Q3 and APS. The estimates of change per unit of the HEI-2015 score associated with the abundance of these twelve genera were consistent across the three questionnaires. The quality of past diet, assessed as far as ∼20 years before stool collection, is equally predictive of GM composition as concurrently assessed diet, indicative of the long-term consistency of this relation.

AMPA Receptor Surface Expression Is Regulated by S-Nitrosylation of Thorase and Transnitrosylation of NSF.

The regulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) trafficking affects multiple brain functions, such as learning and memory. We have previously shown that Thorase plays an important role in the internalization of AMPARs from the synaptic membrane. Here, we show that N-methyl-d-aspartate receptor (NMDAR) activation leads to increased S-nitrosylation of Thorase and N-ethylmaleimide-sensitive factor (NSF). S-nitrosylation of Thorase stabilizes Thorase-AMPAR complexes and enhances the internalization of AMPAR and interaction with protein-interacting C kinase 1 (PICK1). S-nitrosylated NSF is dependent on the S-nitrosylation of Thorase via trans-nitrosylation, which modulates the surface insertion of AMPARs. In the presence of the S-nitrosylation-deficient C137L Thorase mutant, AMPAR trafficking, long-term potentiation, and long-term depression are impaired. Overall, our data suggest that both S-nitrosylation and interactions of Thorase and NSF/PICK1 are required to modulate AMPAR-mediated synaptic plasticity. This study provides critical information that elucidates the mechanism underlying Thorase and NSF-mediated trafficking of AMPAR complexes.

Concomitant Bilateral Salpingo-Oophorectomy at Hysterectomy: Differences by Race and Menopausal Status in the Veterans Affairs Health Care System, 2007-2014.

Background: Hysterectomy can be performed with concomitant bilateral salpingo-oophorectomy (BSO) to treat symptomatic pathology of the ovary (e.g., endometriosis) or to prevent ovarian cancer. Our objective was to examine the relationship between race and concomitant BSO by menopausal status in the Veterans Affairs (VA) health care system. Methods: This is a longitudinal study utilizing VA administrative data to identify hysterectomies provided or paid for by VA (i.e., source of care) between 2007 and 2014. We defined BSO as removal of both ovaries and fallopian tubes at the time of hysterectomy, identified by International Classification of Diseases-Ninth Revision codes. Covariates included demographic (e.g., ethnicity) and gynecological diagnoses (e.g., endometriosis). We used generalized linear models with a log-link and binomial distribution to estimate associations of race with BSO by menopausal status and source of care. Results: We identified 6,785 Veterans with hysterectomies, including 2,320 with concomitant BSO. Overall, Black Veterans were more likely to be single, obese, and undergo abdominal hysterectomy. After adjustment, premenopausal Black Veterans had a 41% lower odds of BSO than their White counterparts (odds ratio [OR]: 0.59, 95% confidence interval [CI]: 0.51-0.68). Stratifying on source of care, these results remained unchanged (provided: OR: 0.61, 95% CI: 0.52-0.72; paid: OR: 0.58, 95% CI: 0.48-0.71). There was insufficient evidence of an association among postmenopausal Veterans. Conclusions: Premenopausal Black Veterans are less likely to undergo BSO even after adjustment for salient characteristics. Our findings may have implications for equitable gynecological care for Veterans. Additional research is needed to better understand the role of differential preferences or cancer risk in these racial differences.

Association of Depression and Post-Traumatic Stress Disorder with Receipt of Minimally Invasive Hysterectomy for Uterine Fibroids: Findings from the U.S. Department of Veterans Affairs.

BACKGROUND: When hysterectomy is used to treat uterine fibroids, a minimally invasive versus open abdominal approach is preferred. Depression and post-traumatic stress disorder (PTSD) may be associated with surgical mode. We sought to examine whether depression and PTSD are associated with minimally invasive hysterectomy (MIH). METHODS: This was a cross-sectional study of veterans with uterine fibroids undergoing hysterectomy in the Department of Veterans Affairs between 2012 and 2014. Diagnoses and procedures were identified by International Classification of Disease, Ninth Revision, codes. MIH was defined as laparoscopic, vaginal, or robotic-assisted versus open abdominal. A dichotomous variable indicated presence of depression or PTSD. Clinical variables, including uterine size, were abstracted from the medical record. We employed generalized linear models to estimate adjusted percentages and 95% confidence intervals (CIs) of MIH by presence of depression or PTSD and sequentially adjusted for sociodemographic variables and health indicators (model 1), and then gynecologic and reproductive history variables, including uterine size (model 2). RESULTS: We included 770 veterans in our analytic sample. Veterans with depression or PTSD were more likely than those without such diagnoses to have a MIH (49% vs. 42%). Differences were attenuated in model 1 (47% [95% CI, 37%-57%] vs. 43% [95% CI, 34%-52%]) and no longer detectable in model 2 (45% [95% CI, 36%-54%] vs. 44% [95% CI, 36%-52%]). CONCLUSIONS: Veterans with depression or PTSD were more likely that those without to have a MIH, possibly owing to smaller uterine size, suggesting that they may be undergoing hysterectomy earlier in the disease process. Further research is needed to understand whether this reflects high-quality, patient-centered care.

Understanding Variation in Availability and Provision of Minimally Invasive Hysterectomy: A Qualitative Study of Department of Veterans Affairs Gynecologists.

BACKGROUND: Approximately one-half of women undergoing hysterectomy in the Department of Veterans Affairs health care system receive minimally invasive hysterectomies (MIH), with Black women less likely than White women to receive MIH. We sought to characterize gynecologists' perspectives on factors contributing to the availability and provision of MIH and on the role of race/ethnicity in decision making. METHODS: Between October 2017 and January 2018, we conducted 16 in-depth semistructured telephone interviews with Department of Veterans Affairs gynecologists exploring practice characteristics and barriers and facilitators to providing MIH, including clinical and nonclinical characteristics of patients impacting surgical decision making. We identified key themes using simultaneous deductive and inductive thematic analysis. RESULTS: Gynecologists identified provider-, facility-, and patient-level barriers and facilitators to MIH. Provider-level factors included gynecologists' skills and training in MIH, and facility factors included access to qualified surgical assistants, availability of surgical equipment, and operating room resources, particularly time. On the patient level, clinical characteristics, including uterine size, were the most common determinants of surgical approach, but nonclinical factors such as patients' attitudes toward surgery also contributed. Race/ethnicity was identified by a minority of respondents as influencing hysterectomy route through clinical presentation and surgical attitudes. CONCLUSIONS: Given the range of factors identified, efforts to promote MIH in the Department of Veterans Affairs will likely require a multipronged approach that includes support for MIH training, increased access to surgical assistants with MIH skills, and reduced barriers to obtaining equipment. Patient perspectives are needed to more fully capture nonclinical patient-level contributors to MIH and differences in MIH between Black and White Veterans.

The COSMIC Bubble Helmet: A Non-Invasive Positive Pressure Ventilation System for COVID-19.

Goal: COSMIC Medical, a Vancouver-based open-source volunteer initiative, has designed an accessible, affordable, and aerosol-confining non-invasive positive-pressure ventilator (NIPPV) device, known as the COSMIC Bubble Helmet (CBH). This device is intended for COVID-19 patients with mild-to-moderate acute respiratory distress syndrome. System Design: CBH is composed of thermoplastic polyurethane, which creates a flexible neck seal and transparent hood. This device can be connected to wall oxygen, NIPPVs including Continuous Positive Airway Pressure and Bi-level Positive Airway Pressure, and mechanical ventilators. Discussion: Justification of CBH design components relied on several factors, predominantly the safety and comfort of patients and healthcare providers. Conclusion: CBH has implications within and outside of the pandemic, as an alternative to invasive mechanical ventilation methods. We have experimentally verified that CBH is effective in minimizing aerosolization risks and performs at specified clinical requirements.

Contributors to Racial Disparities in Minimally Invasive Hysterectomy in the US Department of Veterans Affairs.

BACKGROUND: Minimally invasive hysterectomy for fibroids decreases recovery time and risk of postoperative complications compared with abdominal hysterectomy. Within Veterans Affair (VA), black women with uterine fibroids are less likely to receive a minimally invasive hysterectomy than white women. OBJECTIVE: To quantify the contributions of patient, facility, temporal and geographic factors to VA black-white disparity in minimally invasive hysterectomy. RESEARCH DESIGN: A cross-sectional study. SUBJECTS: Veterans with fibroids and hysterectomy performed in VA between October 1, 2012 and September 30, 2015. MEASURES: Hysterectomy mode was defined using ICD-9 codes as minimally invasive (laparoscopic, vaginal, or robotic-assisted) versus abdominal. The authors estimated a logistic regression model with minimally invasive hysterectomy modeled as a function of 4 sets of factors: sociodemographic characteristics other than race, health risk factors, facility, and temporal and geographic factors. Using decomposition techniques, systematically substituting each white woman's characteristics for each black woman's characteristics, then recalculating the predicted probability of minimally invasive hysterectomy for black women for each possible combination of factors, we quantified the contribution of each set of factors to observed disparities in minimally invasive hysterectomy. RESULTS: Among 1255 veterans with fibroids who had a hysterectomy at a VA, 61% of black women and 39% of white women had an abdominal hysterectomy. Our models indicated there were 99 excess abdominal hysterectomies among black women. The majority (n=77) of excess abdominal hysterectomies were unexplained by measured sociodemographic factors beyond race, health risk factors, facility, and temporal or geographic trends. CONCLUSION: Closer examination of the equity of VA gynecology care and ways in which the VA can work to ensure equitable care for all women veterans is necessary.

Non-classical B Cell Memory of Allergic IgE Responses.

The long-term effectiveness of antibody responses relies on the development of humoral immune memory. Humoral immunity is maintained by long-lived plasma cells that secrete antigen-specific antibodies, and memory B cells that rapidly respond to antigen re-exposure by generating new plasma cells and memory B cells. Developing effective immunological memory is essential for protection against pathogens, and is the basis of successful vaccinations. IgE responses have evolved for protection against helminth parasites infections and against toxins, but IgE is also a potent mediator of allergic diseases. There has been a dramatic increase in the incidence of allergic diseases in recent decades and this has provided the impetus to study the nature of IgE antibody responses. As will be discussed in depth in this review, the IgE memory response has unique features that distinguish it from classical B cell memory.

Women Veterans' Experiences with Department of Veterans Affairs Maternity Care: Current Successes and Targets for Improvement.

INTRODUCTION: Little is known about women veterans' experiences accessing and using Department of Veterans Affairs (VA) maternity care, which is nearly all purchased from non-VA providers. OBJECTIVE: To understand women veterans' experiences, preferences, and challenges using VA maternity care. METHODS: We conducted 27 semistructured interviews with women veterans who used VA maternity care during fiscal year 2016. To capture a wide variety of experiences, we randomly sampled veterans from urban and rural VA facilities with higher and lower volumes of VA paid deliveries. All interviews were recorded and transcribed verbatim. Transcripts were analyzed using inductive and deductive content analysis. RESULTS: Themes included experiences initiating prenatal care, obtaining prenatal and lactation classes, the role of maternity care coordinators, mental health care, and satisfaction with care. Women described challenges obtaining authorization for care and establishing care with non-VA providers. First-time mothers appreciated the availability of prenatal and lactation classes. VA maternity care coordinators helped women veterans to navigate the challenges related to VA maternity care, ranging from finding non-VA providers to billing. The majority of participants were engaged with mental health care before pregnancy and continued this care during pregnancy. Women's satisfaction with VA maternity care was impacted by access to supportive, knowledgeable providers; care coordinators; woman-centered labor and delivery experiences; and billing issues. CONCLUSIONS: Our findings provide a portrait of the current state of VA maternity care from the perspectives of women veterans and highlight areas, such as care coordination and woman-centered models for labor and delivery, that can improve satisfaction with care.

Preconception Health Risk Factors in Women with and without a History of Military Service.

INTRODUCTION: Given the increasing number of women service members and veterans of childbearing age, it is important to understand the preconception risks in this potentially vulnerable population. This study compared the prevalence of modifiable preconception risk factors among women with and without a history of service. METHODS: Analyses included data from the 2013 and 2014 Centers for Disease Control and Prevention Behavioral Risk Factor Surveillance System. Preconception risk factors included health behaviors, chronic conditions, and mental health among women of childbearing age. Multivariate logistic regressions were used to compare the adjusted prevalence of each outcome among women with and without a history of service. Interaction terms assessed variation by age and history of service. RESULTS: Compared with women without a history of service, women with a history of service reported higher prevalence of insufficient sleep (49.6% vs. 36.3%; p < .001) and diagnosed depression (26.5% vs. 21.6%; p < .01). Women with a history of service were overall less likely to have obesity (19.8% vs. 26.5%; p < .001). Age-stratified results suggested that, compared with women without a history of service, women with a history of service were more likely to smoke in the 25 to 34 age group and reported comparable levels of obesity in the 35 to 44 age group. CONCLUSIONS: Women with a history of service demonstrated a preconception health profile that differs from women without a history of service. It is critical that providers are aware of their patients' military status and potential associated risks.

Reproductive Health of Women Veterans: A Systematic Review of the Literature from 2008 to 2017.

The literature on the reproductive health and healthcare of women Veterans has increased dramatically, though there are important gaps. This article aims to synthesize recent literature on reproductive health and healthcare of women Veterans. We updated a literature search to identify manuscripts published between 2008 and July 1, 2017. We excluded studies that were not original research, only included active-duty women, or had few women Veterans in their sample. Manuscripts were reviewed using a standardized abstraction form. We identified 52 manuscripts. Nearly half (48%) of the new manuscripts addressed contraception and preconception care (n = 15) or pregnancy (n = 10). The pregnancy and family planning literature showed that (1) contraceptive use and unintended pregnancy among women Veterans using VA healthcare is similar to that of the general population; (2) demand for VA maternity care is increasing; and (3) women Veterans using VA maternity care are a high-risk population for adverse pregnancy outcomes. A recurrent finding across topics was that history of lifetime sexual assault and mental health conditions were highly prevalent among women Veterans and associated with a wide variety of adverse reproductive health outcomes across the life course. The literature on women Veterans' reproductive health is rapidly expanding, but remains largely observational. Knowledge gaps persist in the areas of sexually transmitted infections, infertility, and menopause.

Thorase variants are associated with defects in glutamatergic neurotransmission that can be rescued by Perampanel.

The AAA+ adenosine triphosphatase (ATPase) Thorase plays a critical role in controlling synaptic plasticity by regulating the expression of surface α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Bidirectional sequencing of exons of ATAD1, the gene encoding Thorase, in a cohort of patients with schizophrenia and healthy controls revealed rare Thorase variants. These variants caused defects in glutamatergic signaling by impairing AMPAR internalization and recycling in mouse primary cortical neurons. This contributed to increased surface expression of the AMPAR subunit GluA2 and enhanced synaptic transmission. Heterozygous Thorase-deficient mice engineered to express these Thorase variants showed altered synaptic transmission and several behavioral deficits compared to heterozygous Thorase-deficient mice expressing wild-type Thorase. These behavioral impairments were rescued by the competitive AMPAR antagonist Perampanel, a U.S. Food and Drug Administration-approved drug. These findings suggest that Perampanel may be useful for treating disorders involving compromised AMPAR-mediated glutamatergic neurotransmission.

Trends in hysterectomy rates among women veterans in the US Department of Veterans Affairs.

BACKGROUND: Prior studies demonstrate a higher prevalence of hysterectomy among veterans compared with nonveterans. While studies identify overall decreasing hysterectomy rates in the United States, none report rates of hysterectomy among women veterans. Given the increasing numbers of women veterans using Veterans Affairs health care, there is an ongoing need to ensure high-quality gynecology care. Therefore, it is important to examine current hysterectomy trends, including proportion of minimally invasive surgeries, among veterans using Veterans Affairs health care. OBJECTIVE: Our objective was to describe hysterectomy trends and utilization of minimally invasive hysterectomy in the Veterans Affairs healthcare system. STUDY DESIGN: This longitudinal study used Veterans Affairs clinical and administrative data from fiscal year 2008 to 2014 to identify hysterectomies provided or paid for by Veterans Affairs. Crude and age-adjusted hysterectomy rates were calculated by indication (benign or malignant), mode (abdominal, laparoscopic, vaginal, robotic assisted, unspecified), and source of care (provided vs paid for by Veterans Affairs). Mode and indication for hysterectomy were classified using International Classification of Diseases, ninth revision, codes. The distribution of hysterectomy mode in each year was calculated by indication and source of care. RESULTS: Between fiscal year 2008 and fiscal year 2014, the total hysterectomy rate decreased from 4.0 per 1000 to 2.6 per 1000 unique women veteran Veterans Affairs users. Age-adjusted rates of abdominal hysterectomy for benign indications decreased over the study period from 1.54 per 1000 (95% confidence interval, 1.40-1.69) to 0.77 per 1000 (95% confidence interval, 0.69-0.85) for procedures provided by Veterans Affairs and 0.77 per 1,000 (95% confidence interval, 0.69-0.85) to 0.29 per 1,000 (95% confidence interval, 0.23-0.34) for those paid for by Veterans Affairs. Among hysterectomies for benign indications provided by (n = 5296) or paid for (n = 2610) by Veterans Affairs, the percentage of hysterectomies performed abdominally decreased from 67.2% to 46.8% and from 68.9% to 57.6%, respectively. CONCLUSION: These findings suggest that gynecology care provided within Veterans Affairs has kept pace with national trends in reducing hysterectomy rates and increasing utilization of minimally invasive surgical techniques.

Precision therapy for a new disorder of AMPA receptor recycling due to mutations in ATAD1.

OBJECTIVE: ATAD1 encodes Thorase, a mediator of α-amino-3-hydroxy-5-methylisoxazole-4-proprionate (AMPA) receptor recycling; in this work, we characterized the phenotype resulting from ATAD1 mutations and developed a targeted therapy in both mice and humans. METHODS: Using exome sequencing, we identified a novel ATAD1 mutation (p.E276X) as the etiology of a devastating neurologic disorder characterized by hypertonia, seizures, and death in a consanguineous family. We postulated that pathogenesis was a result of excessive AMPA receptor activity and designed a targeted therapeutic approach using perampanel, an AMPA-receptor antagonist. RESULTS: Perampanel therapy in ATAD1 knockout mice reversed behavioral defects, normalized brain MRI abnormalities, prevented seizures, and prolonged survival. The ATAD1 patients treated with perampanel showed improvement in hypertonicity and resolution of seizures. CONCLUSIONS: This work demonstrates that identification of novel monogenic neurologic disorders and observation of response to targeted therapeutics can provide important insights into human nervous system functioning.

Preconception care and reproductive planning in primary care.

Preconception care is designed to identify and reduce biomedical, behavioral, and social risks to the health of a woman or her baby before pregnancy occurs. Few women present requesting preconception care; however, 1 in 10 US women of childbearing age will become pregnant each year. As primary care physicians (PCPs) care for reproductive-aged women before, between, and after their pregnancies, they are ideally positioned to help women address health risks before conception, including optimizing chronic conditions, to prevent adverse pregnancy and longer-term health outcomes. PCPs can help women make informed decisions both about preparing for pregnancy and about using effective contraception when pregnancy is not desired.