Cerebrovascular Complications Associated With Iatrogenic Fungal Meningitis Following Surgical Procedures in Mexico.

BACKGROUND: The current fungal meningitis outbreak caused by contaminated epidural anesthesia with Fusarium solani among patients who underwent surgical procedures in Matamoros, Mexico remains a cause of concern. Its association with an increased susceptibility for cerebrovascular complications (CVC) has not been reported. This single-center study describes 3 patients with a unique pattern of CVC attributed to fungal meningitis. METHODS: A retrospective case series of patients diagnosed with fungal meningitis following surgical procedures under contaminated epidural anesthesia who developed a unique pattern of CVC during their hospitalization. RESULTS: Three female patients (mean age, 35 years) with CVC due to iatrogenic fungal meningitis were included. Positive Fungitell ß-D-glucan assay in cerebrospinal fluid was documented in all cases, and F. solani was confirmed by polymerase chain reaction in case 3. All cases were complicated by severe vertebrobasilar circulation vasculopathy and arterial dissections with resultant subarachnoid hemorrhage and intraventricular hemorrhage, ultimately leading to patients' death. CONCLUSIONS: The death toll from the ongoing fungal meningitis outbreak keeps rising, underscoring the need for early recognition and aggressive treatment. We highlight the risk for vertebrobasilar circulation CVC among these patients. The angioinvasive nature of F. solani is yet to be clarified; however, a clear pattern has been observed. Public health awareness should be raised and a strong response should be pursued.

Machine learning-based placental clusters and their associations with adverse pregnancy outcomes.

BACKGROUND: Placental abnormalities have been described in clinical convenience samples, with predominately adverse outcomes. Few studies have described placental patterns in unselected samples. OBJECTIVE: We aimed to investigate associations between co-occurring placental features and adverse pregnancy outcomes in a prospective cohort of singletons. METHODS: Data were from the Safe Passage study (U.S. and South Africa, 2007-2015). Before 24 weeks' gestation, participants were randomly invited to donate placental tissue at delivery for blinded, standardised pathological examination. We used hierarchical clustering to construct statistically derived groups using 60 placental features. We estimated associations between the placental clusters and select adverse pregnancy outcomes, expressed as unadjusted and adjusted risk ratios (RRs) and robust 95% confidence intervals (CI). RESULTS: We selected a 7-cluster model. After collapsing 2 clusters to form the reference group, we labelled the resulting 6 analytic clusters according to the overarching category of their most predominant feature(s): severe maternal vascular malperfusion (n = 117), fetal vascular malperfusion (n = 222), other vascular malperfusion (n = 516), inflammation 1 (n = 269), inflammation 2 (n = 175), and normal (n = 706). Risks for all outcomes were elevated in the severe maternal vascular malperfusion cluster. For instance, in unadjusted analyses, this cluster had 12 times the risk of stillbirth (RR 12.07, 95% CI 4.20, 34.68) and an almost doubling in the risk of preterm delivery (RR 1.93, 95% CI 1.27, 2.93) compared with the normal cluster. Small infant size was more common among the abnormal clusters, with the highest unadjusted RRs observed in the fetal vascular malperfusion cluster (small for gestational age birth RR 2.99, 95% CI 2.24, 3.98, head circumference <10th percentile RR 2.86, 95% CI 1.60, 5.12). Upon adjustment for known risk factors, most RRs attenuated but remained >1. CONCLUSION: Our study adds to the growing body of epidemiologic research, finding adverse pregnancy outcomes may occur through etiologic mechanisms involving co-occurring placental abnormalities.

Bias analyses to investigate the impact of differential participation: Application to a birth defects case-control study.

BACKGROUND: Certain associations observed in the National Birth Defects Prevention Study (NBDPS) contrasted with other research or were from areas with mixed findings, including no decrease in odds of spina bifida with periconceptional folic acid supplementation, moderately increased cleft palate odds with ondansetron use and reduced hypospadias odds with maternal smoking. OBJECTIVES: To investigate the plausibility and extent of differential participation to produce effect estimates observed in NBDPS. METHODS: We searched the literature for factors related to these exposures and participation and conducted deterministic quantitative bias analyses. We estimated case-control participation and expected exposure prevalence based on internal and external reports, respectively. For the folic acid-spina bifida and ondansetron-cleft palate analyses, we hypothesized the true odds ratio (OR) based on prior studies and quantified the degree of exposure over- (or under-) representation to produce the crude OR (cOR) in NBDPS. For the smoking-hypospadias analysis, we estimated the extent of selection bias needed to nullify the association as well as the maximum potential harmful OR. RESULTS: Under our assumptions (participation, exposure prevalence, true OR), there was overrepresentation of folic acid use and underrepresentation of ondansetron use and smoking among participants. Folic acid-exposed spina bifida cases would need to have been ≥1.2× more likely to participate than exposed controls to yield the observed null cOR. Ondansetron-exposed cleft palate cases would need to have been 1.6× more likely to participate than exposed controls if the true OR is null. Smoking-exposed hypospadias cases would need to have been ≥1.2 times less likely to participate than exposed controls for the association to falsely appear protective (upper bound of selection bias adjusted smoking-hypospadias OR = 2.02). CONCLUSIONS: Differential participation could partly explain certain associations observed in NBDPS, but questions remain about why. Potential impacts of other systematic errors (e.g. exposure misclassification) could be informed by additional research.

Exploring the relationship between oculomotor preparation and gaze-cued covert shifts in attention.

Eye gaze plays dual perceptual and social roles in everyday life. Gaze allows us to select information, while also indicating to others where we are attending. There are situations, however, where revealing the locus of our attention is not adaptive, such as when playing competitive sports or confronting an aggressor. It is in these circumstances that covert shifts in attention are assumed to play an essential role. Despite this assumption, few studies have explored the relationship between covert shifts in attention and eye movements within social contexts. In the present study, we explore this relationship using the saccadic dual-task in combination with the gaze-cueing paradigm. Across two experiments, participants prepared an eye movement or fixated centrally. At the same time, spatial attention was cued with a social (gaze) or non-social (arrow) cue. We used an evidence accumulation model to quantify the contributions of both spatial attention and eye movement preparation to performance on a Landolt gap detection task. Importantly, this computational approach allowed us to extract a measure of performance that could unambiguously compare covert and overt orienting in social and non-social cueing tasks for the first time. Our results revealed that covert and overt orienting make separable contributions to perception during gaze-cueing, and that the relationship between these two types of orienting was similar for both social and non-social cueing. Therefore, our results suggest that covert and overt shifts in attention may be mediated by independent underlying mechanisms that are invariant to social context.

An observational, prospective, multicenter, natural history study of patients with mucopolysaccharidosis type IIIA.

Mucopolysaccharidosis type IIIA (MPS IIIA, also known as Sanfilippo syndrome) is a rare genetic lysosomal storage disease characterized by early and progressive neurodegeneration resulting in a rapid decline in cognitive function affecting speech and language, adaptive behavior, and motor skills. We carried out a prospective observational study to assess the natural history of patients with MPS IIIA, using both standardized tests and patient-centric measures to determine the course of disease progression over a 2-year period. A cohort of 23 patients (7 girls, 16 boys; mean age 28-105 months at baseline) with a confirmed diagnosis of MPS IIIA were assessed and followed up at intervals of 3-6 months; cognitive function was measured using Bayley Scales of Infant and Toddler Development 3rd edition (BSID-III) to derive cognitive development quotients (DQ). Daily living, speech/language development and motor skills were measured using the Vineland Adaptive Behavior Scale (VABS-II). Sleep-wake patterns, behavior and quality-of-life questionnaires were also reported at each visit using parent/caregiver reported outcome tools. All patients had early onset severe MPS IIIA, were diagnosed before 74 months of age, and had cognitive scores below normal developmental levels at baseline. Patients less than 40 months of age at baseline were more likely to continue developing new skills over the first 6-12 months of follow-up. There was a high variability in cognitive developmental age (DA) in patients between 40 and 70 months of age; two-thirds of these patients already had profound cognitive decline, with a DA ≤10 months. The highest cognitive DA achieved in the full study cohort was 34 months. Post hoc, patients were divided into two groups based on baseline cognitive DQ (DQ ≥50 or <50). Cognitive DQ decreased linearly over time, with a decrease from baseline of 30.1 and 9.0 points in patients with cognitive DQ ≥50 at baseline and cognitive DQ <50 at baseline, respectively. Over the 2-year study, VABS-II language scores declined progressively. Motor skills, including walking, declined over time, although significantly later than cognitive decline. No clear pattern of sleep disturbance was observed, but night waking was common in younger patients. Pain scores, as measured on the quality-of-life questionnaire, increased over the study period. The findings of this study strengthen the natural history data on cognitive decline in MPS IIIA and importantly provide additional data on endpoints, validated by the patient community as important to treat, that may form the basis of a multidomain endpoint capturing the disease complexity.

Relational Factors and HIV Testing Practices: Qualitative Insights from Urban Refugee Youth in Kampala, Uganda.

Despite the global phenomenon of refugee urbanization, little is known of relational contexts that shape HIV testing among urban refugee youth. We explored perspectives, experiences, and preferences for social support in HIV testing among refugee youth aged 16-24 in Kampala, Uganda. We conducted five focus groups with refugee youth (n = 44) and five in-depth key informant interviews. Participant narratives signaled relational contexts shaping HIV testing included informal sources (intimate partners and family members) and formal sources (peer educators and professionals). There was heterogeneity in perspectives based on relationship dynamics. While some felt empowered to test with partners, others feared negative relationship consequences. Participant narratives reflected kinship ties that could facilitate testing with family, while others feared coercion and judgment. Peer support was widely accepted. Professional support was key for HIV testing as well as conflict-related trauma. Findings emphasize bonding and bridging social capital as salient components of enabling HIV testing environments.

Inequities in Adverse Maternal and Perinatal Outcomes: The Effect of Maternal Race and Nativity.

OBJECTIVES: To evaluate the effect of race and ethnicity on differences in maternal and perinatal outcomes among U.S.-born and foreign-born women, as well as racial and ethnic disparities in outcomes within these groups. METHODS: This retrospective study analyzed singleton pregnancies (n = 11,518) among women delivering at Boston Medical Center from January 2010-March 2015. Outcomes of interest included preterm birth, early preterm birth, cesarean delivery, hypertensive disorders, diabetes, low birth weight at term (LBW, < 2500 g), NICU admission and intrauterine fetal demise (IUFD). Prevalence ratios and 95% confidence intervals comparing outcomes between U.S.- and foreign-born women were calculated and stratified by race. Obstetric outcomes among Black and Hispanic women were compared to those of white women within both U.S.- and foreign-born groups. RESULTS: Preterm birth, hypertensive disorders, LBW and NICU admission were more likely to occur among U.S.-born women and their neonates compared to foreign-born women. Controlling for sociodemographic characteristics did not significantly impact these disparities. Among foreign-born women, Black women had a higher prevalence of many maternal and neonatal complications, while Hispanic women had a lower prevalence of some complications compared to white women. Black woman and infants consistently exhibit worse outcomes regardless of their nativity, while Hispanic women foreign-born women experience less disparate outcomes. CONCLUSIONS FOR PRACTICE: Overall, women born in the United States are at higher risk of several adverse perinatal outcomes compared to foreign-born women. Racial and ethnic disparities in birth outcomes exist in both groups. However, the complex interplay between biopsychosocial influences that mediate these inequities appear to have different effects among U.S- and foreign- born women. A better understanding of these factors can be used to combat disparities and improve outcomes for all women.

Trends in first-trimester nausea and vomiting of pregnancy and use of select treatments: Findings from the National Birth Defects Prevention Study.

BACKGROUND: Although nausea and vomiting of pregnancy (NVP) is common, the secular and demographic trends of NVP and its treatments are not well-studied. OBJECTIVES: To describe the prevalence and patterns of first-trimester NVP and selected treatments among controls in the National Birth Defects Prevention Study (NBDPS). METHODS: National Birth Defects Prevention Study is a population-based case-control study of birth defects in the United States (1997-2011). We collected self-reported data about NVP and use of commonly reported pharmacological and herbal/natural treatments (ondansetron, promethazine, pyridoxine, metoclopramide, doxylamine succinate, ginger, phosphorated carbohydrate solution, and prochlorperazine) from mothers of non-malformed control infants. We estimated the prevalence of NVP and selected treatments and examined secular and demographic trends (education, race/ethnicity, and maternal age) for such use, adjusting for study centre. RESULTS: Among 10 540 mothers of controls, 7393 women (70.1%) reported first-trimester NVP, and 12.2% of those used one or more of the commonly reported treatments. Specific treatment use varied after adjustment for study centre (ondansetron: 3.4%; promethazine: 4.2%; pyridoxine: 3.2%; metoclopramide: 0.7%; doxylamine succinate: 1.7%; ginger: 1.0%; phosphorated carbohydrate solution: 0.4%; and prochlorperazine: 0.3%). Treatment use increased for each agent over the study period. Women with more years of education reported more NVP and treatment use. White (72%), Hispanic (71%), and other race (73%) women reported more NVP than Black women (67%); White women used selected NVP treatments most frequently, and Black women used them more than Hispanic women. Though women aged 25-34 years reported more NVP (72%) than younger (69%) or older (67%) women, the frequency of medication use was similar among women aged 25-34 and ≥35, and lower among women aged <25 years. CONCLUSIONS: National Birth Defects Prevention Study controls reported NVP at frequencies similar to those previously reported. Of note, we observed an increase in use of selected treatments over time, and variations in NVP and treatments by study site and demographic factors.

Sexual and reproductive health self-care interventions in the Eastern Mediterranean Region: findings from a cross-sectional values and preferences survey to inform WHO normative guidance on self-care interventions.

BACKGROUND: Self-care strategies for sexual and reproductive health (SRH) include practices, tools, and strategies for people to manage their health. Access to SRH services has increased in the Eastern Mediterranean Region (EMR) in the past decade. The objective of this manuscript is to provide a preliminary assessment of self-care SRH interventions focusing on access, knowledge, perceived challenges, and recommendations for the future. We aim to contribute to the evidence base on knowledge and uptake of self-care SRH strategies in the EMR. METHODS: We conducted an online cross-sectional Global Values and Preferences Survey (GVPS) to inform WHO guideline development on self-care interventions for SRH. Recruitment was web-based and included hosting the survey on the WHO Department of Reproductive Health and Research website, and sharing the survey link to diverse SRH websites. Analyses included the subsample of respondents living in EMR countries. We first conducted descriptive statistics of sociodemographic and self-care intervention responses. We then conducted bivariate analyses to examine statistically significant differences in knowledge for each intervention between EMR and non-EMR regions. We extracted open-text responses and applied thematic analysis techniques. RESULTS: There were 53 respondents from the EMR spanning 14 countries, including16 health care providers (HCP) and 37 laypersons. Qualitative responses (n = 16) suggest that (a) perceived benefits of self-care SRH strategies include enhanced SRH access, knowledge, and improved SRH outcomes; (b) perceived concerns include misuse and safety; (c) linkage to care following self-care SRH interventions can consider mobile phone apps, hotlines, health care liaisons, and community outreach; (d) HCP want additional training on strengthening therapeutic alliances with patients and practical information on interventions; and (e) future research can focus on reproductive health, condom use, service barriers, and implementation. EMR respondents reported lower knowledge levels than non-EMR respondents on the following strategies: diaphragm/cervical cap, contraceptive patch, web-based SRH information, post-exposure prophylaxis, re-exposure prophylaxis, and HIV treatment. CONCLUSIONS: Knowledge of self-care SRH strategies varies by intervention type in the EMR. Future research with larger and more representative samples can inform regional self-care SRH implementation. Knowledge dissemination, stigma reduction, accessibility, and training of health care professionals are key domains for advancing access to self-care SRH strategies in the EMR.

International Cooperation to Enable the Diagnosis of All Rare Genetic Diseases.

Provision of a molecularly confirmed diagnosis in a timely manner for children and adults with rare genetic diseases shortens their "diagnostic odyssey," improves disease management, and fosters genetic counseling with respect to recurrence risks while assuring reproductive choices. In a general clinical genetics setting, the current diagnostic rate is approximately 50%, but for those who do not receive a molecular diagnosis after the initial genetics evaluation, that rate is much lower. Diagnostic success for these more challenging affected individuals depends to a large extent on progress in the discovery of genes associated with, and mechanisms underlying, rare diseases. Thus, continued research is required for moving toward a more complete catalog of disease-related genes and variants. The International Rare Diseases Research Consortium (IRDiRC) was established in 2011 to bring together researchers and organizations invested in rare disease research to develop a means of achieving molecular diagnosis for all rare diseases. Here, we review the current and future bottlenecks to gene discovery and suggest strategies for enabling progress in this regard. Each successful discovery will define potential diagnostic, preventive, and therapeutic opportunities for the corresponding rare disease, enabling precision medicine for this patient population.

Characteristics of the vaginal microbiome in women with and without clinically confirmed vulvodynia.

BACKGROUND: Vulvodynia (idiopathic vulvar pain) affects up to 8% of women by age 40 years, has a poorly understood etiology, and has variable treatment efficacy. Several risk factors are associated with vulvodynia from a history of yeast infections to depression and allergies. Recent work suggests an altered immune inflammatory mechanism plays a role in vulvodynia pathophysiology. Because the vaginal microbiome plays an important role in local immune-inflammatory responses, we evaluated the vaginal microbiome among women with vulvodynia compared with controls as 1 component of the immune system. OBJECTIVE: The objective of the study was to characterize the vaginal microbiome in women with clinically confirmed vulvodynia and age-matched controls and assess its overall association with vulvodynia and how it may serve to modify other factors that are associated with vulvodynia as well. STUDY DESIGN: We conducted a case-control study of 234 Minneapolis/Saint Paul-area women with clinically confirmed vulvodynia and 234 age-matched controls clinically confirmed with no history of vulvar pain. All participants provided vulvovaginal swab samples for culture-based and non-culture (sequencing)-based microbiological assessments, background and medical history questionnaires on demographic characteristics, sexual and reproductive history, and history of psychosocial factors. Vaginal microbiome diversity was assessed using the Shannon alpha diversity Index. Data were analyzed using logistic regression. RESULTS: Culture and molecular-based analyses of the vaginal microbiome showed few differences between cases and controls. However, among women with alpha diversity below the median (low), there was a strong association between increasing numbers of yeast infections and vulvodynia onset, relative to comparable time periods among controls (age-adjusted odds ratio, 8.1, 95% confidence interval, 2.9-22.7 in those with 5 or more yeast infections). Also among women with low-diversity microbiomes, we observed a strong association between moderate to severe childhood abuse, antecedent anxiety, depression, and high levels of rumination and vulvodynia with odds ratios from 1.83 to 2.81. These associations were not observed in women with high-diversity microbiomes. CONCLUSION: Although there were no overall differences in microbiome profiles between cases and controls, vaginal microbiome diversity influenced associations between environmental and psychosocial risk factors and vulvodynia. However, it is unclear whether vaginal diversity modifies the association between the risk factors and vulvodynia or is altered as a consequence of the associations.

Maternal acetaminophen use during pregnancy and childhood behavioural problems: Discrepancies between mother- and teacher-reported outcomes.

BACKGROUND: Maternal acetaminophen use during pregnancy is common and has been associated with childhood behavioural problems among offspring, specifically hyperactivity and conduct problems. OBJECTIVE: Assessments of child behaviour in many previous studies have relied on maternal or parent report. Acknowledging that results of behavioural assessments vary between informants, we examined the association between maternal acetaminophen use during pregnancy and behaviour problems in childhood based on mother- and teacher-report. METHODS: A longitudinal study of 560 mother-child pairs with data on illnesses and medication use during pregnancy and neurodevelopmental assessments during childhood was conducted. Acetaminophen use during pregnancy was captured using a standardised maternal interview, completed 1 year after delivery on average. Measures of childhood (6-12 years of age) behaviour were obtained via mother- and teacher-report, using the Child Behaviour Checklist and Teacher Report Form. Linear and log-binomial models were used to calculate adjusted mean differences (MD) and risk ratios (RR), respectively and 95% confidence intervals (CI) for internalising, externalising, and total behaviour problems comparing acetaminophen users to non-users. Stabilized inverse probability weights were used to account for loss to follow-up, and adjustments for indication were made. RESULTS: Approximately 60% (n = 354) of women reported use of acetaminophen during pregnancy. Acetaminophen use during pregnancy was associated with an increase in total behaviour problem score and risk of clinical behaviour problems according to mother report (MD 2.2, 95% CI 0.3, 4.1 and RR 1.93, 95% CI 0.99, 3.76) but not according to teacher report. Weighting to account for participation did not alter results, while adjustment for indications of acetaminophen use greatly attenuated the associations with mother-reported total behaviour problem score and risk of clinical behaviour problems (MD 0.1, 95% CI -2.1, 2.3 and RR 1.31, 95% CI 0.67, 2.58). CONCLUSIONS: Acetaminophen use during pregnancy was weakly associated with mother-reported behaviour problems and not associated with teacher-reported problems.

Outcomes and prognostic factors of pediatric patients with a Glasgow Coma Score of 3 after blunt head trauma.

PURPOSE: This study aims to assess outcomes of pediatric patients with blunt traumatic brain injury (TBI) with a presenting Glasgow Coma Score (GCS) of 3. METHODS: After local institutional review board approval, we identified patients ages 0 to15 years with blunt TBI and a reported GCS of 3 between 2007 and 2017 from a pediatric level 1 trauma center prospective registry. Exclusion criteria were cardiac death on arrival and penetrating injury. We recorded clinical variables from patients with a non-pharmacologic GCS of 3 and pupillary exam documented by a neurosurgical attending or resident. The original Glasgow Outcome Scale (GOS) was used to compare with other studies. Importance of variables to survival was calculated. RESULTS: A total of 88 patients (mean age 6.9 years) were included with a mortality rate of 68%. Twelve percent had a poor long-term outcome (GOS 2 or 3) while 20% had a good long-term outcome (GOS 4 or 5). Median follow-up was 1.8 years. Initial group comparison revealed patients in group 1 (survivors) had less hypotension on arrival (14% SBP < 90 mmHg vs. 66%, p < 0.0001), higher temperatures on arrival (36.3 °C vs 34.9 °C, p = 0.0002), lower ISS (29.7 vs 39.5, p = 0.003), less serious injury to other major organs (34% vs 61%, p = 0.02), more epidural hematomas (24% vs 7%, p = 0.04), and less evidence of brain ischemia on CT (7% vs 39%, p = 0.002) or brainstem infarct, hemorrhage, or herniation (0% vs 27%, p = 0.002). Differences between the 2 groups in age, sex, race, MOI, AIS score, presence of midline shift > 5 mm, or time from injury to hospital arrival or time to surgery were not statistically significant. Classification tree analysis showed that the most important variable for survival was pupillary exam; mortality was 92% in presence of bilateral, fixed dilated pupils. The relative importance of initial temperature, MOI, and hypotension to survivability was 0.79, 0.75, and 0.47, respectively. CONCLUSION: Twenty percent of our pediatric non-pharmacologic GCS 3 cohort had a good functional outcome. Lack of bilaterally fixed and dilated pupils was the most important factor for survival. Temperature, MOI, and hypotension also correlated with survival. The data support selective aggressive management for these patients.

One-Carbon Cofactor Intake and Risk of Neural Tube Defects Among Women Who Meet Folic Acid Recommendations: A Multicenter Case-Control Study.

We aimed to investigate associations between individual and concurrent (≥2) intakes of one-carbon cofactors vitamins B6 and B12, choline, betaine, and methionine and neural tube defect (NTD) outcomes among mothers meeting the folic acid recommendations. In the Slone Birth Defects Study (case-control design; North America, 1998-2015), mothers of 164 NTD cases and 2,831 nonmalformed controls completed food frequency questionnaires and structured interviews. Estimated intakes of one-carbon cofactors were dichotomized (high vs. low) for all except betaine (low or middle vs. high). We used logistic regression models to estimate odds ratios and 95% confidence intervals adjusted for center, age, and race. The analysis was restricted to mothers with estimated daily total folate intake of ≥400 µg during periconception. Fewer cases, compared with controls, had high intakes for each one-carbon cofactor except betaine, where the starkest contrast occurred in the middle group. Women with concurrent high intakes of B6, B12, choline, and methionine and moderate intake of betaine had approximately half the risk of an NTD-affected pregnancy (odds ratio = 0.49, 95% confidence interval: 0.23, 1.08). These findings suggest that, in the presence of folic acid, one-carbon cofactors-notably when consumed together-might reduce NTD risk. Additional research should inform any changes to clinical recommendations.

Peptoids advance multidisciplinary research and undergraduate education in parallel: Sequence effects on conformation and lipid interactions.

Peptoids are versatile peptidomimetic molecules with wide-ranging applications from drug discovery to materials science. An understanding of peptoid sequence features that contribute to both their three-dimensional structures and their interactions with lipids will expand functions of peptoids in varied fields. Furthermore, these topics capture the enthusiasm of undergraduate students who prepare and study diverse peptoids in laboratory coursework and/or in faculty led research. Here, we present the synthesis and study of 21 peptoids with varied functionality, including 19 tripeptoids and 2 longer oligomers. We observed differences in fluorescence spectral features for 10 of the tripeptoids that correlated with peptoid flexibility and relative positioning of chromophores. Interactions of representative peptoids with sonicated glycerophospholipid vesicles were also evaluated using fluorescence spectroscopy. We observed evidence of conformational changes effected by lipids for select peptoids. We also summarize our experiences engaging students in peptoid-based projects to advance both research and undergraduate educational objectives in parallel.

Exploring Hygienic Behaviors and Vulvodynia.

OBJECTIVES: Vulvodynia is common and characterized by vulvar discomfort and pain. However, few studies have assessed hygienic practices in relation to onset. We investigated whether hygienic behaviors were associated with the onset of vulvodynia. MATERIALS AND METHODS: We assessed a self-reported history of personal hygienic behaviors, including wearing tight-fitting clothing, vulva care and genital washing, pubic hair removal, douching, and powdering, a year before first reported onset of vulvar pain among 213 clinically confirmed cases and a similar time period among 221 general population controls. RESULTS: Compared with women who reported never wearing tight-fitting jeans or pants, women wearing tight-fitting jeans or pants 4 or more times per week had twice the odds of vulvodynia (95% CI = 1.14-3.95). Relative to controls, women with vulvodynia were substantially less likely to report use of soaps and gels to cleanse the vulva (95% CI = 0.17-0.63). Among women who chose to remove pubic hair, those who removed pubic hair from the mons pubis compared with bikini-area only hair removal, were 74% more likely to have vulvodynia (95% CI = 1.05-2.89). Finally, compared with women who reported bikini-area only hair removal less than monthly, those who removed hair from the mons pubis weekly or more were nearly 2 times more likely to be vulvodynia cases (95% CI = 0.83-3.49). CONCLUSIONS: Wearing tight-fitting jeans or pants and removing hair from the mons pubis area were associated with increased odds of vulvodynia. Research on how hygienic practices could influence vulvar pain in larger and more temporally addressed populations is warranted.

Gastroschisis and Cumulative Stressor Exposures.

BACKGROUND: Gastroschisis, a congenital defect of the abdominal wall, occurs disproportionately more in offspring of young mothers and has been increasing in prevalence over the past decades. A wide range of exposures have been reported in association with an increased gastroschisis risk, independent of mother's age; many have also been correlated with stress responses. METHODS: We explored cumulative exposures to such stressor exposures among 1,261 mothers of gastroschisis cases and 10,682 mothers of controls in the National Birth Defects Prevention Study (1997-2011). We considered 16 exposures as stressors in the first trimester: fever, genitourinary infection, anti-herpetic medication use, injury, bronchodilator use, cigarette smoking, alcohol intake, illicit drug use, prescription opioid use, oral contraceptive use, interpregnancy interval < 12 months, residential move, aspirin use, ibuprofen use, venlafaxine use, and paroxetine use. RESULTS: Mothers of cases reported more stressor exposures than controls. For 1, 2, 3, and ≥ 4 stressor exposures compared with none, the age-adjusted odds ratios (95% confidence interval) were 1.3 (1.1, 1.6), 1.7 (1.4, 2.1), 2.5 (2.0, 3.1), and 3.6 (2.9, 4.4), respectively. When we weighted cumulative stress scores according to the magnitude of stressor-specific odds ratios, similar associations were observed. Cumulative stressor exposure did not account for the strong inverse association between age and gastroschisis risk. CONCLUSIONS: These findings show that gastroschisis risk appears to increase with accumulation of widely different types of exposures, consistent with the hypothesis that stress-induced inflammation might play an etiologic role.

Association of Clomiphene and Assisted Reproductive Technologies With the Risk of Neural Tube Defects.

Clomiphene and assisted reproductive technologies (ART) are methods used to help subfertile couples become pregnant. ART has been reported to be associated with neural tube defects (NTDs) in offspring. To evaluate these associations, we studied mothers of 219 cases and 4,262 controls from the Slone Epidemiology Center Birth Defects Study (1993-2012) who were interviewed within 6 months after delivery about pregnancy events, including use of fertility treatments. We considered exposures to clomiphene (without ART) and ART during the periconceptional period. Logistic regression models were used to calculate adjusted odds ratios and 95% confidence intervals, controlling for education and study center. We observed elevated adjusted odds ratios of 2.1 (95% confidence interval: 0.9, 4.8) and 2.0 (95% confidence interval: 1.1, 3.6) for clomiphene and ART exposure, respectively. We performed a mediation analysis to assess whether the observed elevated NTD risk was mediated through multiple births. For clomiphene exposure without ART use, the direct effect estimate of the adjusted odds ratio (aORDE) was 1.7 and the indirect effect estimate (aORIE) was 1.4. Conversely, for ART exposure, the aORDE was 0.9 and the aORIE was 2.5. Our findings suggest that relatively little of the clomiphene-NTD association is mediated through the pathway of multiple births, while the ART-NTD association was explained by the multiple-births pathway.

Maternal Antibodies to Herpes Virus Antigens and Risk of Gastroschisis in Offspring.

Gastroschisis risk is highest in offspring of young women and is increasing in prevalence, suggesting that exposures that are increasingly common among younger females may be causal. Some infections by viruses in the herpes family are more common in the earlier childbearing years and have been increasing in prevalence over time. Data from the Finnish Maternity Cohort were linked to Finnish malformation and birth registers (1987-2012) for this study, a nested case-control study of mothers of offspring with gastroschisis and age-matched controls. Maternal antibody responses in early pregnancy (mean gestational age = 11.1 weeks) to Epstein Barr virus (EBV), herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), and cytomegalovirus were measured. Conditional logistic regression models were used to estimate odds ratios (and 95% confidence intervals) for high immunoglobulin reactivity. Odds ratios for high immunoglobulin M (IgM) reactivity to EBV-viral capsid antigen and HSV-1 or HSV-2 (as indicators of recent infection) were 2.16 (95% confidence interval (CI): 0.97, 4.79) and 1.94 (95% CI: 0.74, 5.12), respectively. For higher immunoglobulin G (IgG) reactivity to EBV-viral capsid antigen and HSV-2 IgG, odds ratios were 2.16 (95% CI: 0.82, 5.70) and 2.48 (95% CI: 1.50, 4.10), respectively. Reactivities to HSV-1 IgG, cytomegalovirus IgM, or cytomegalovirus IgG did not appear to increase gastroschisis risk. Primary EBV infection was not associated with gastroschisis, but observed associations with both IgM and IgG reactivities to EBV and HSV suggest that reactivations may be risk factors for it.