Multiple Prior Live Births Are Associated With Cardiac Remodeling and Heart Failure Risk in Women.

OBJECTIVE: Greater parity has been associated with cardiovascular disease risk. We sought to find whether the effects on cardiac remodeling and heart failure risk are clear. METHODS: We examined the association of number of live births with echocardiographic measures of cardiac structure and function in participants of the Framingham Heart Study (FHS) using multivariable linear regression. We next examined the association of parity with incident heart failure with preserved (HFpEF) or reduced (HFrEF) ejection fraction using a Fine-Gray subdistribution hazards model in a pooled analysis of n = 12,635 participants in the FHS, the Cardiovascular Health Study, the Multi-Ethnic Study of Atherosclerosis, and Prevention of Renal and Vascular Endstage Disease. Secondary analyses included major cardiovascular disease, myocardia infarction and stroke. RESULTS: Among n = 3931 FHS participants (mean age 48 ± 13 years), higher numbers of live births were associated with worse left ventricular fractional shortening (multivariable ß -1.11 (0.31); P = 0.0005 in ≥ 5 live births vs nulliparous women) and worse cardiac mechanics, including global circumferential strain and longitudinal and radial dyssynchrony (P < 0.01 for all comparing ≥ 5 live births vs nulliparity). When examining HF subtypes, women with ≥ 5 live births were at higher risk of developing future HFrEF compared with nulliparous women (HR 1.93, 95% CI 1.19-3.12; P = 0.008); by contrast, a lower risk of HFpEF was observed (HR 0.58, 95% CI 0.37-0.91; P = 0.02). CONCLUSIONS: Greater numbers of live births are associated with worse cardiac structure and function. There was no association with overall HF, but a higher number of live births was associated with greater risk for incident HFrEF.

Longitudinal changes in glucose during pregnancy in women with gestational diabetes risk factors.

AIMS/HYPOTHESIS: Despite recommendations to screen women with diabetes risk factors for hyperglycaemia in the first trimester, criteria for normal glucose values in early pregnancy have not been firmly established. We aimed to compare glucose levels in early pregnancy with those later in gestation and outside of pregnancy in women with diabetes risk factors. METHODS: In pregnant women (N = 123) followed longitudinally through the postpartum period, and a separate cohort of non-pregnant women (N = 65), we performed 75 g oral glucose tolerance tests. All participants had one or more risk factors for diabetes. Using linear regression, we tested for differences in glucose levels between non-pregnant and pregnant women at early (7-15 weeks) and mid-late (24-32 weeks) gestation as well as postpartum, with adjustment for maternal age, parity, marital status and BMI. In a longitudinal analysis using mixed-effects models, we tested for differences in glucose levels across early and mid-late pregnancy compared with postpartum. Differences are expressed as ß (95% CI). RESULTS: Fasting glucose was lower in pregnant compared with non-pregnant women by 0.34 (0.18, 0.51) mmol/l (p < 0.0001) in early pregnancy and by 0.45 (0.29, 0.61) mmol/l (p < 0.0001) in mid-late pregnancy. In longitudinal models, fasting glucose was lower by 0.13 (0.04, 0.21) mmol/l (p = 0.003) in early pregnancy and by 0.16 (0.08, 0.25) mmol/l (p = 0.0003) in mid-late pregnancy compared with the same women postpartum. Early pregnancy post-load glucose levels did not differ from those in non-pregnant women or the same women postpartum. In mid-late pregnancy, compared with non-pregnant women, elevations in 1 h post-load glucose level (0.60 [-0.12, 1.33] mmol/l, p = 0.10) and 2 h post-load glucose (0.49 [-0.21, 1.19] mmol/l, p = 0.17) were not statistically significant. However, in longitudinal analyses, 1 h and 2 h post-load glucose levels were higher in mid-late pregnancy (by 0.78 [0.35, 1.21] mmol/l, p = 0.0004, and 0.67 [0.30, 1.04] mmol/l, p = 0.0005, respectively) when compared with postpartum. CONCLUSIONS/INTERPRETATION: In women with diabetes risk factors, fasting glucose declines in the first trimester. Post-load glucose increases later in pregnancy. These findings may inform criteria for diagnosing hyperglycaemia early in pregnancy.

The Use of Non-insulin Agents in Gestational Diabetes: Clinical Considerations in Tailoring Therapy.

PURPOSE OF REVIEW: To assess evidence to date for use of non-insulin agents in treatment of gestational diabetes mellitus. RECENT FINDINGS: There has been increasing interest in the use of non-insulin agents, primarily metformin and glyburide (which both cross the placenta). Metformin has been associated with less maternal weight gain; however, recent studies have shown a trend toward increased weight in offspring exposed to metformin in utero. Glyburide has been associated with increased neonatal hypoglycemia. Glycemic control during pregnancy is essential to optimize both maternal and fetal outcomes. There are a myriad of factors to consider when designing treatment programs including patient preference, phenotype, and glucose patterns. While insulin is typically recommended as first-line, some women refuse or cannot afford insulin and in those cases, non-insulin agents may be used. Further studies are needed to assess treatment in pregnancy, perinatal outcomes, and particularly long-term metabolic profiles in mothers and offspring.

Category-specific neural oscillations predict recall organization during memory search.

Retrieved-context models of human memory propose that as material is studied, retrieval cues are constructed that allow one to target particular aspects of past experience. We examined the neural predictions of these models by using electrocorticographic/depth recordings and scalp electroencephalography (EEG) to characterize category-specific oscillatory activity, while participants studied and recalled items from distinct, neurally discriminable categories. During study, these category-specific patterns predict whether a studied item will be recalled. In the scalp EEG experiment, category-specific activity during study also predicts whether a given item will be recalled adjacent to other same-category items, consistent with the proposal that a category-specific retrieval cue is used to guide memory search. Retrieved-context models suggest that integrative neural circuitry is involved in the construction and maintenance of the retrieval cue. Consistent with this hypothesis, we observe category-specific patterns that rise in strength as multiple same-category items are studied sequentially, and find that individual differences in this category-specific neural integration during study predict the degree to which a participant will use category information to organize memory search. Finally, we track the deployment of this retrieval cue during memory search: Category-specific patterns are stronger when participants organize their responses according to the category of the studied material.

Long-term Cardiovascular Disease After Adverse Pregnancy Outcomes.

Cardiovascular disease (CVD) is the leading cause of death among women. Adverse pregnancy outcomes (APOs) are cardiovascular risk factors that are unique to women and include gestational diabetes (GDM) and preeclampsia. While these risk factors emerge during the reproductive years and allow for early risk reduction counseling, they are often overlooked and not elicited by providers. This mini-review focuses primarily on GDM and preeclampsia, their relationship with CVD, mechanisms by which these conditions lead to CVD, and management, pharmacological and nonpharmacological, for the clinician who is caring for a woman with a history of an APO.

Spontaneously reactivated patterns in frontal and temporal lobe predict semantic clustering during memory search.

Although it is well established that remembering an item will bring to mind memories of other semantically related items (Bousfield, 1953), the neural basis of this phenomenon is poorly understood. We studied how the similarity relations among items influence their retrieval by analyzing electrocorticographic recordings taken as 46 human neurosurgical patients studied and freely recalled lists of words. We first identified semantic components of neural activity that varied systematically with the meanings of each studied word, as defined by latent semantic analysis (Landauer and Dumais, 1997). We then examined the dynamics of these semantic components as participants attempted to recall the previously studied words. Our analyses revealed that the semantic components of neural activity were spontaneously reactivated during memory search, just before recall of the studied words. Further, the degree to which neural activity correlated with semantic similarity during recall predicted participants' tendencies to organize the sequences of their responses on the basis of semantic similarity. Thus, our work shows that differences in the neural correlates of semantic information, and how they are reactivated before recall, reveal how individuals organize and retrieve memories of words.

A digitally enhanced home-based physical activity intervention for high-risk middle school youth during COVID-19.

COVID-19 significantly impacted physical activity among high-risk youth. Camp from Home, a digitally enhanced home-based intervention, was developed to address physical activity disparities among middle school youth during COVID-19. Camp from Home enrolled 62 youth in 54 families from five schools in Philadelphia during the summer of 2020. The 6-week intervention comprised of (1) three home deliveries of "activity kits" including exercise equipment and activity booklets, (2) asynchronous sport and exercise videos posted to a private YouTube channel, and (3) supportive text-messages from health coaches. YouTube analytics and self-report surveys completed by parents and youth at baseline and at the end of programming were used to assess engagement, acceptability, and preliminary efficacy. Youth participants were 12.4 (1.2) years, 38.7% female and 90.3% Black/African American. At follow-up, 41 parents (75.9%) and 34 youth (54.8%) completed measures. Youth self-reported increases in self-efficacy (ΔM(sd) = 0.4(1.0), p = .03) and physical activity (ΔM(sd) = 4.2(7.9), p = .004), despite suboptimal engagement in digital program components. Overall, participants highly rated the program. Activity kits and text-messages from health coaches were rated as most helpful. Most parents (95.1%) and youth (83.8%) expressed interested in participating again in the future. A 6-week digitally enhanced, home-based physical activity intervention was acceptable and feasible among parents and youth during the summer of 2020, with youth reporting improvements in self-efficacy and physical activity. Summer programs are critical for reducing disparities in physical activity and hold potential for addressing key barriers for high-risk youth even outside the context of COVID-19.

Carbohydrate Intake and Oral Glucose Tolerance Test Results in the Postpartum Period.

CONTEXT: The American Diabetes Association (ADA) recommends a 3-day preparatory diet prior to a diagnostic oral glucose tolerance test (OGTT), a test often recommended in postpartum individuals with a history of gestational diabetes (GDM). OBJECTIVE: Evaluate the relationship between carbohydrate intake and OGTT glucose in 2 cohorts of postpartum individuals. METHODS: We performed analyses of postpartum individuals from 2 prospective studies with recent GDM (Balance after Baby Intervention, BABI, n = 177) or risk factors for GDM (Study of Pregnancy Regulation of INsulin and Glucose, SPRING, n = 104) .We measured carbohydrate intake using 24-hour dietary recalls (SPRING) or Food Frequency Questionnaire (BABI) and performed 2-hour 75-g OGTTs. The main outcome measure was 120-minute post-OGTT glucose. RESULTS: There was no relationship between carbohydrate intake and 120-minute post-OGTT glucose level in either study population (SPRING: ß = 0.03, [-5.5, 5.5] mg/dL, P = .99; BABI: ß = -3.1, [-9.5, 3.4] mg/dL, P = .35). Adding breastfeeding status to the model did not change results (SPRING ß = -0.14, [-5.7, 5.5] mg/dL, P = .95; BABI ß = -3.9, [-10.4, 2.7] mg/dL, P = .25). There was, however, an inverse relationship between glycemic index and 120-minute post OGTT glucose (BABI: ß = -1.1, [-2.2, -0.03] mg/dL, P = .04). CONCLUSION: Carbohydrate intake is not associated with post-OGTT glucose levels among postpartum individuals. Dietary preparation prior to the OGTT may not be necessary in this population.

Report of Prolonged Neonatal Hypoglycemia in Three Infants of Mothers With Variants in HNF1A.

Background/Objective: Genetic variants in hepatic nuclear factor 1α (HNF1A) cause maturity-onset diabetes of the young (MODY). We sought to examine whether HNF1A MODY variants also cause neonatal hypoglycemia. Case Report: We present 3 infants with variants in HNF1A shared with their mothers. The infants experienced neonatal hypoglycemia, 2 extending beyond 1 year and the third resolving by 28 days, and all were large for gestational age (birth weights of >99th percentile). In 2 cases, genetic testing for neonatal hypoglycemia revealed pathogenic variants in HNF1A; 1 mother was previously diagnosed with HNF1A MODY, and the other's genetic testing and ultimate MODY diagnosis were prompted by her child's hypoglycemia workup. In the third case, the infant's persistent hypoglycemia prompted genetic testing, revealing an HNF1A variant of uncertain significance, which was then identified in the mother. Discussion: Genetic variants causing HNF1A MODY have not been definitively linked to neonatal hypoglycemia or fetal overgrowth in utero. MODY caused by HNF1A is clinically similar to that caused by HNF4A, for which a causal relationship with neonatal hypoglycemia is more certain. Case reports have previously implicated variants in HNF1A in congenital hyperinsulinism; however, these cases have generally not been in families with MODY. The cases presented here suggest that HNF1A variants causing MODY may also cause neonatal hypoglycemia. Conclusion: Although confounding factors make the assessment of neonatal hypoglycemia challenging, these cases offer potential support for single genetic variants in HNF1A causing both MODY and neonatal hypoglycemia, with associated fetal overgrowth in utero.

Circulating Androgen Concentrations and Risk of Incident Heart Failure in Older Men: The Cardiovascular Health Study.

Background Circulating androgen concentrations in men decline with age and have been linked to diabetes and atherosclerotic cardiovascular disease (ASCVD). A similar relationship has been reported for low total testosterone and incident heart failure (HF) but remains unstudied for free testosterone or the more potent androgen dihydrotestosterone (DHT). We hypothesized that total/free testosterone are inversely related, sex hormone-binding globulin is positively related, and total/free DHT bear a U-shaped relationship with incident HF. Methods and Results In a sample of men from the CHS (Cardiovascular Health Study) without atherosclerotic cardiovascular disease or HF, serum testosterone and DHT concentrations were measured by liquid chromatography-tandem mass spectrometry, and sex hormone-binding globulin by immunoassay. Free testosterone or DHT was calculated from total testosterone or total DHT, sex hormone-binding globulin, and albumin. We used Cox regression to estimate relative risks of HF after adjustment for potential confounders. In 1061 men (aged 76±5 years) followed for a median of 9.6 years, there were 368 HF events. After adjustment, lower calculated free testosterone was significantly associated with higher risk of HF (hazard ratio [HR], 1.14 [95% CI, 1.01-1.28]). Risk estimates for total testosterone (HR, 1.12 [95% CI, 0.99-1.26]), total DHT (HR, 1.10 [95% CI, 0.97-1.24]), calculated free dihydrotestosterone (HR, 1.09 [95% CI, 0.97-1.23]), and sex hormone-binding globulin (HR, 1.07 [95% CI, 0.95-1.21]) were directionally similar but not statistically significant. Conclusions Calculated free testosterone was inversely associated with incident HF, suggesting a contribution of testosterone deficiency to HF incidence among older men. Additional research is necessary to determine whether testosterone replacement therapy might be an effective strategy to lower HF risk in older men.

Testosterone, dihydrotestosterone, bone density, and hip fracture risk among older men: The Cardiovascular Health Study.

BACKGROUND: Little is known about the relationships of dihydrotestosterone (DHT), a more potent androgen than testosterone (T), with bone mineral density (BMD) and fracture risk. Our objectives were to evaluate the relationships of T, DHT and sex hormone binding globulin (SHBG) with BMD, fracture risk, and lean body mass (LBM). METHODS: We evaluated 1128 older men free of cardiovascular disease in a prospective cohort study using data from the Cardiovascular Health Study. T and DHT were measured by liquid chromatography-tandem mass spectrometry and SHBG by fluoroimmunoassay. Our outcomes included incident hip fracture (n = 106) over a median of 10.2 years and BMD and LBM by dual-energy x-ray absorptiometry (n = 439). RESULTS: In Cox regression models mutually adjusted for T, SHBG, and covariates, each standard deviation increment in DHT (0.23 ng/ml) was associated with a 26% lower risk of hip fracture (adjusted hazard ratio [aHR] 0.74, 95% confidence interval (CI) 0.55-1.00, p = 0.049). Similarly, SHBG was associated with fracture in mutually adjusted models (aHR HR 1.26, 95% CI, 1.01-1.58, p = 0.045). In contrast, T (aHR, 1.16, 95% CI, 0.86-1.56, p = 0.324) was not significantly associated with fracture in mutually adjusted models. T, DHT and SHBG were not associated with BMD. T and DHT were both positively associated with LBM in individual models. CONCLUSIONS: In older men, DHT was inversely associated with hip fracture risk and SHBG was positively associated with hip fracture risk, while T was not. Future studies should elucidate the mechanisms by which DHT affects bone health.

Relationship between carbohydrate intake and oral glucose tolerance test results among pregnant women.

AIMS: Evaluate the relationship between self-reported carbohydrate intake and oral glucose tolerance test (OGTT) results in pregnancy. METHODS: We measured carbohydrate intake using 24-hour dietary recall and performed a 2-hour 75-gram OGTT in 95 pregnant women with risk factors for gestational diabetes (GDM) at a median of 26 weeks' gestation. We tested for associations between carbohydrate intake in the 24 hours preceding the OGTT and 60-minute OGTT glucose, glucose at other timepoints, and glucose area under the curve (AUC) using linear regression, with adjustment for potential confounders. RESULTS: We observed an inverse linear relationship between carbohydrate intake (median 237 grams [interquartile range: 196, 303]) and 60-minute OGTT glucose. For every 50 gram reduction in carbohydrate intake, there was an 8.9 mg/dl increase in 60-minute OGTT glucose (P < 0.01) in an adjusted model. Lower carbohydrate intake was also associated with higher 30-minute (adjusted ß = -6.5 mg/dl, P < 0.01) and 120-minute OGTT glucose (adjusted ß = -8.1 mg/dl, P = 0.01) and AUC (adjusted ß = -767, P < 0.01). CONCLUSIONS: Carbohydrate intake in the day preceding an OGTT in pregnancy is associated with post-load glucose values, with lower carbohydrate intake predicting higher glucose levels and higher carbohydrate intake predicting lower glucose levels. Carbohydrate restriction or excess before an OGTT may affect GDM diagnosis.

Cervical Spine pain as a presenting complaint in metastatic pancreatic cancer: a case report.

A 48 year-old female presented to her primary care physician with a two-month history of neck pain with negative cervical spine x-rays. During that office visit, the patient was noted to be tachycardic with EKG revealing ST depressions, which led to hospital admission. Acute coronary syndrome was ruled out, however, persistent neck pain warranted inpatient MRI of the cervical spine, which revealed a cervical spine lesion. Extensive investigation and biopsy ultimately confirmed stage IV pancreatic adenocarcinoma with metastases to the bone, liver, and likely lung. In the literature, the findings of a primary metastatic site being bone is rare with only a few case reports showing vertebral or sternal metastasis as the first clinical manifestation of pancreatic cancer. The uniqueness of this case lies in the only presenting complaint being cervical spine pain in the setting of extensive metastases to the liver, bone, and likely lung.

Medical student psychiatry examination performance at VA and non-VA Clerkship Sites.

OBJECTIVE: The authors examined the effects of medical student assignment to U.S. Department of Veterans Affairs (VA) Medical Center inpatient and outpatient psychiatry clerkship sites versus other university and community sites on the performance outcome measure of National Board of Medical Examiners (NBME) subject examination scores. METHODS: NBME psychiatry scores were compared for stratified random samples of 70 students each for inpatient and outpatient VA and non-VA sites, controlling for baseline clinical knowledge as reflected by second year Human Behavior course scores. RESULTS: No significant differences were demonstrated in NBME scores between VA and non-VA sites for either inpatient or outpatient programs. CONCLUSION: Assessed students rotating through several VA clinical sites were as well prepared for NBME subject examinations as those assigned to other sites. Additional measures of educational outcome for VA sites are recommended to assess and enhance clinical education provided by the VA and to strengthen collaboration with university-based medical student teaching programs.