Brain Differences in the Prefrontal Cortex, Amygdala, and Hippocampus in Youth with Congenital Adrenal Hyperplasia

Context: Classical Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency results in hormone imbalances present both prenatally and postnatally that may impact the developing brain. Objective: To characterize gray matter morphology in the prefrontal cortex and subregion volumes of the amygdala and hippocampus in youth with CAH, compared to controls. Design: A cross-sectional study of 27 CAH youth (16 female; 12.6 ± 3.4 year) and 35 typically developing, healthy controls (20 female; 13.0 ± 2.8 year) with 3-T magnetic resonance imaging scans. Brain volumes of interest included bilateral prefrontal cortex, and nine amygdala and six hippocampal subregions. Between-subject effects of group (CAH vs control) and sex, and their interaction (group-by-sex) on brain volumes were studied, while controlling for intracranial volume (ICV) and group differences in body mass index and bone age. Results: CAH youth had smaller ICV and increased cerebrospinal fluid volume compared to controls. In fully-adjusted models, CAH youth had smaller bilateral, superior and caudal middle frontal volumes, and smaller left lateral orbito-frontal volumes compared to controls. Medial temporal lobe analyses revealed the left hippocampus was smaller in fully-adjusted models. CAH youth also had significantly smaller lateral nucleus of the amygdala and hippocampal subiculum and CA1 subregions. Conclusions: This study replicates previous findings of smaller medial temporal lobe volumes in CAH patients, and suggests that lateral nucleus of the amygdala, as well as subiculum and subfield CA1 of the hippocampus are particularly affected within the medial temporal lobes in CAH youth

Brain Differences in the Prefrontal Cortex, Amygdala, and Hippocampus in Youth with Congenital Adrenal Hyperplasia

Context: Classical Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency results in hormone imbalances present both prenatally and postnatally that may impact the developing brain. Objective: To characterize gray matter morphology in the prefrontal cortex and subregion volumes of the amygdala and hippocampus in youth with CAH, compared to controls. Design: A cross-sectional study of 27 CAH youth (16 female; 12.6 ± 3.4 year) and 35 typically developing, healthy controls (20 female; 13.0 ± 2.8 year) with 3-T magnetic resonance imaging scans. Brain volumes of interest included bilateral prefrontal cortex, and nine amygdala and six hippocampal subregions. Between-subject effects of group (CAH vs control) and sex, and their interaction (group-by-sex) on brain volumes were studied, while controlling for intracranial volume (ICV) and group differences in body mass index and bone age. Results: CAH youth had smaller ICV and increased cerebrospinal fluid volume compared to controls. In fully-adjusted models, CAH youth had smaller bilateral, superior and caudal middle frontal volumes, and smaller left lateral orbito-frontal volumes compared to controls. Medial temporal lobe analyses revealed the left hippocampus was smaller in fully-adjusted models. CAH youth also had significantly smaller lateral nucleus of the amygdala and hippocampal subiculum and CA1 subregions. Conclusions: This study replicates previous findings of smaller medial temporal lobe volumes in CAH patients, and suggests that lateral nucleus of the amygdala, as well as subiculum and subfield CA1 of the hippocampus are particularly affected within the medial temporal lobes in CAH youth

Comparison of Surface Area across the Allograft-Host Junction Site Using Conventional and Navigated Osteotomy Technique.

Bulk allograft reconstruction plays an important role in limb-salvage surgery; however, non-union has been reported in up to 27% of cases. The purpose of this study is to quantify average surface contact areas across simulated intraoperative osteotomies using both free-hand and computer-assisted navigation techniques. Pressure-sensitive paper was positioned between two cut ends of a validated composite sawbone and compression was applied using an eight-hole large fragment dynamic compression plate. Thirty-two samples were analyzed for surface area contact to determine osteotomy congruity. Mean contact area using the free-hand osteotomy technique was equal to 0.21 square inches. Compared with a control of 0.69 square inches, average contact area was found to be 30.5% of optimal surface contact. Mean contact area using computer-assisted navigation was equal to 0.33 square inches. Compared with a control of 0.76 square inches, average contact area was found to be 43.7% of optimal surface contact. Limited contact achieved using standard techniques may play a role in the high rate of observed non-union, and an increase in contact area using computer-assisted navigation may improve rates of bone healing. The development of an oncology software package and navigation hardware may serve an important role in decreasing non-union rates in limb salvage surgery

DNA Methylation as a Biomarker for Cardiovascular Disease Risk

Elevated serum homocysteine is associated with an increased risk of cardiovascular disease (CVD). This may reflect a reduced systemic remethylation capacity, which would be expected to cause decreased genomic DNA methylation in peripheral blood leukocytes (PBL).We examined the association between prevalence of CVD (myocardial infarction, stroke) and its predisposing conditions (hypertension, diabetes) and PBL global genomic DNA methylation as represented by ALU and Satellite 2 (AS) repetitive element DNA methylation in 286 participants of the Singapore Chinese Health Study, a population-based prospective investigation of 63,257 men and women aged 45-74 years recruited during 1993-1998. Men exhibited significantly higher global DNA methylation [geometric mean (95% confidence interval (CI)): 159 (143, 178)] than women [133 (121, 147)] (P = 0.01). Global DNA methylation was significantly elevated in men with a history of CVD or its predisposing conditions at baseline (P = 0.03) but not in women (P = 0.53). Fifty-two subjects (22 men, 30 women) who were negative for these CVD/predisposing conditions at baseline acquired one or more of these conditions by the time of their follow-up I interviews, which took place on average about 5.8 years post-enrollment. Global DNA methylation levels of the 22 incident cases in men were intermediate (AS, 177) relative to the 56 male subjects who remained free of CVD/predisposing conditions at follow-up (lowest AS, 132) and the 51 male subjects with a diagnosis of CVD or predisposing conditions reported at baseline (highest AS 184) (P for trend = 0.0008) No such association was observed in women (P = 0.91). Baseline body mass index was positively associated with AS in both men and women (P = 0.007).Our findings indicate that elevated, not decreased, PBL DNA methylation is positively associated with prevalence of CVD/predisposing conditions and obesity in Singapore Chinese

Predicting Medication Use in an Elderly Hypertensive Sample: Revisiting the Established Populations for Epidemiologic Studies of the Elderly Study

Though some research has begun to examine specific factors related to race that should be targeted in the design of interventions to improve medication adherence, there remains an underreporting of factors that contribute to the use of hypertensive medications by race

Developmental changes in food perception and preference

Food choices are a key determinant of dietary intake, with brain regions, such as the mesolimbic and prefrontal cortex maturing at differential rates into adulthood. More needs to be understood about developmental changes in healthy and unhealthy food perceptions and preference. We investigated how food perceptions and preference vary as a function of age and how food attributes (taste and health) impact age-related changes. One hundred thirty-nine participants (8–23 years, 60 females) completed computerized tasks to rate high-calorie and low-calorie food cues for taste, health, and liking (preference), followed by 100 binary food choices based on each participant’s ratings. Dietary self-control was considered successful when the healthier (vs. tastier) food was chosen. Self-control success ratio was the proportion of success trials over total number of choices. Beta-weights for health (β-health) and taste (β-taste) were calculated as each attribute’s influence on food preference. Adiposity measurements included BMI z-score and waist-to-height ratio (WHtR). High-calorie foods were rated more tasty and less healthy with increasing age. Older participants liked high-calorie foods more (vs. younger participants), and β-taste was associated with age. Significant age-by-WHtR interactions were observed for health and taste ratings of high-calorie foods, β-taste, and marginally for preference of high-calorie foods. Stratifying by WHtR (high, low), we found age-related increases in taste and preference ratings of high-calorie foods in the high WHtR group alone. In contrast, age-related decreases in health ratings of high-calorie foods were significant in the low WHtR group alone. Age and β-taste were significantly associated in the high WHtR group and only marginally significant with low WHtR. Although participants rated low-calorie foods as less tasty and less healthy with increasing age, there was no association between age and preference for low-calorie foods. Participants made faster food choices with increasing age regardless of WHtR, with a significant age-by-WHtR interaction on reaction time (RT). There were no age-related effects in self-control success ratio and β-health. These results suggest that individual differences in age and central adiposity play an important role in preference for high-calorie foods, and a higher importance of food tastiness in food choice may contribute to greater preference for high-calorie foods with increasing age

Understanding the Personal and Clinical Utility of Psychiatric Advance Directives: A Qualitative Perspective

Psychiatric advance directives (PADs) are legal tools that allow competent individuals to declare preferences for future mental health treatment when they may not be capable of doing so as a result of a psychiatric crisis. PADs allow individuals to maintain self–determination during times when they are most vulnerable to loss of autonomy and in need of assistance to make their preferences known and honored. This article describes the content of twenty–eight open–ended, semi–structured qualitative interviews of adults with PADs who have experienced psychiatric crises. The qualitative analysis revealed three major themes from the interviews: (1) PADs as tools for empowerment and self–determination, (2) limited knowledge of PADs among service providers; and (3) difficulties communicating PADs to inpatient staff. In general, many participants expressed enthusiasm of the implementation of PADs but concern regarding clinicians’ general lack of awareness about them. Additionally, some consumers discussed discomfort in even mentioning that they had a PADto clinicians for fear of a negative response from them, or some type of involuntary treatment during their hospitalization. However, participants consistently viewed PADs as a positive tool to promote autonomy with the potential to facilitate stronger patient–provider relationships. Therefore, when working with individuals in psychiatric crisis who have a PAD, and who have never before experienced a sense of control over their own treatment, clinicians must recognize the potential troubling disequilibrium this sense of control may engender. In sum, though the most significant challenges facing the implementation of PADs involve clinicians’ familiarity with and education about PADs, much promise for the future growth of PADs lies in the benefits perceived by the patients

Sex-Specific Prediction Models for Sleep Apnea From the Hispanic Community Health Study/Study of Latinos

OBJECTIVE: We developed and validated the first-ever sleep apnea (SA) risk calculator in a large population-based cohort of Hispanic/Latino subjects. METHODS: Cross-sectional data on adults from the Hispanic Community Health Study/Study of Latinos (2008-2011) were analyzed. Subjective and objective sleep measurements were obtained. Clinically significant SA was defined as an apnea-hypopnea index ≥ 15 events per hour. Using logistic regression, four prediction models were created: three sex-specific models (female-only, male-only, and a sex × covariate interaction model to allow differential predictor effects), and one overall model with sex included as a main effect only. Models underwent 10-fold cross-validation and were assessed by using the C statistic. SA and its predictive variables; a total of 17 variables were considered. RESULTS: A total of 12,158 participants had complete sleep data available; 7,363 (61%) were women. The population-weighted prevalence of SA (apnea-hypopnea index ≥ 15 events per hour) was 6.1% in female subjects and 13.5% in male subjects. Male-only (C statistic, 0.808) and female-only (C statistic, 0.836) prediction models had the same predictor variables (ie, age, BMI, self-reported snoring). The sex-interaction model (C statistic, 0.836) contained sex, age, age × sex, BMI, BMI × sex, and self-reported snoring. The final overall model (C statistic, 0.832) contained age, BMI, snoring, and sex. We developed two websites for our SA risk calculator: one in English (https://www.montefiore.org/sleepapneariskcalc.html) and another in Spanish (http://www.montefiore.org/sleepapneariskcalc-es.html). CONCLUSIONS: We created an internally validated, highly discriminating, well-calibrated, and parsimonious prediction model for SA. Contrary to the study hypothesis, the variables did not have different predictive magnitudes in male and female subjects

PneuMum: Impact from a randomised controlled trial of maternal 23-valent pneumococcal polysaccharide vaccination on middle ear disease amongst Indigenous infants, Northern Territory, Australia

BackgroundWe assessed maternal 23-valent pneumococcal polysaccharide (23vPPV) vaccine efficacy (VE) against middle ear disease and pneumococcal carriage amongst Australian Indigenous infants.MethodsIn an open label, allocation concealed, outcome-assessor blinded, community stratified, randomised controlled trial, healthy pregnant Indigenous women aged 17–39 years in the Northern Territory of Australia received the 23vPPV (1:1:1) at: 30–36 weeks gestation, birth, or were unvaccinated (ClinicalTrials.gov NCT00714064). Co-primary outcomes were the point prevalences of infant middle ear disease and 23vPPV-type carriage at age 7 months.ResultsThe consent rate was 50% (313/632). Among 227 eligible participants randomised, retention rates were 86% (66/77) controls; 89% (67/75) pregnancy vaccinees; 88% (66/75) birth vaccinees. At infant age 7 months, ear disease prevalence was: 71% (47/66) controls, 63% (42/67) pregnancy vaccinees, 76% (50/66) birth vaccinees; and 23vPPV-type carriage was: 26% (17/66) controls, 18% (12/67) pregnancy vaccinees, 18% (12/66) birth vaccinees. For pregnancy vaccinees, VE was 12% (95% CI −12% to 31%) against infant ear disease and 30% (95% CI −34% to 64%) against 23vPPV-type carriage. In a post-hoc analysis, VE against infant ear disease concurrent with carriage of 23vPPV or related types was 51% (95% CI −2% to 76%). There were no serious adverse effects following receipt of the 23vPPV in pregnancy or at birth.ConclusionsIn a high risk population, our study was unable to demonstrate efficacy of 23vPPV in pregnancy against the co-primary outcomes of either all-cause infant ear disease or 23vPPV-type nasopharyngeal carriage at age 7 months. Efficacy against ear disease concurrent with carriage of vaccine-related serotypes (a more specific outcome) suggests 23vPPV in pregnancy may complement childhood pneumococcal vaccination programs