Faculty Bibliography

Background: Autism spectrum disorder (ASD) is a highly prevalent developmental disorder. There is notable disparity in occurrence rates between males and females, with males being 4.5 times as likely as their female counterparts to be diagnosed with the disease. A major objective for improving functional outcomes in ASD is to isolate biomarkers for earlier detection; an area as yet unexplored is whether biomarkers of future ASD symptomology may be observable in the fetal brain. Here, we focus on the amygdala, which shows sex-differential patterns of development and has been implicated in the neurobiology of ASD.
Method(s): We obtained resting-state MRI data in 109 healthy human fetuses (24-39 weeks) and Brief Infant Toddler Social Emotional Assessment (BITSEA) and Child Behavior Checklist (CBCL) measures at child age 3. The average number of frames obtained after scrubbing high-motion frames was N=169, or 5.6 minutes of resting state data (TR=2) with mean XYZ motion 0.9mm (SD=0.3). Subject-specific amygdala connectivity maps were computed and tested in a full factorial model, that included sex, age at scan, and ASD outcome.
Result(s): ASD outcomes were associated with increased amygdala connectivity to prefrontal and sensorimotor cortices, decreased connectivity to anterior insula and cerebellum, and sex interactions were observed in inferior prefrontal and striatal regions (p<0.005 and k min=25).
Conclusion(s): These observations raise exciting new ideas about the advent of risk and the ontogeny of early sex differences. Further analyses will be conducted to examine sex-differential risk and postnatal environmental effects within a multifactorial liability model framework. Supported By: NIMH R01 MH110793 NIDA R34 DA050287 NIMH R01 MH122447 NARSAD Foundation Keywords: Fetal, Autism, Resting-State, Sex Differences
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Membrane-bound angiotensin-converting enzyme 2 is important in regulation of the renin-angiotensin-aldosterone system, but the association of cleaved soluble ACE2 (sACE2) with cardiovascular disease (CVD) is unclear. We evaluated the association of sACE2 with cardiac biomarkers, structure, and function and cardiovascular events in the Atherosclerosis Risk in Communities Study. sACE2 was measured in a subset of 497 participants (mean age 78±5.4 years, 53% men, 27% black); Cox regression analyses assessed prospective associations of sACE2 with time to first CVD event at median 6.1-year follow-up. sACE2 was higher in men, blacks, and participants with prevalent CVD, diabetes, or hypertension. Higher sACE2 levels were associated with significantly higher biomarkers of cardiac injury (high-sensitivity cardiac troponin I and T, N-terminal pro-B-type natriuretic peptide), greater left ventricular mass index, and impaired diastolic function in linear regression analyses, and with increased risk for heart failure hospitalization (adjusted hazard ratio per natural log unit increase [HR] 1.32, 95% confidence interval [CI] 1.10 to 1.58), CVD events (HR 1.34, 95% CI 1.13 to 1.60), and all-cause death (HR 1.26, 95% CI 1.01 to 1.57). In an elderly biracial cohort, sACE2 was positively associated with biomarkers reflecting myocardial injury and neurohormonal activation, left ventricular mass index, impaired diastolic function, CVD, events and all-cause death.

Patient-centered care, defined as "providing care that is respectful of, and responsive to, individual patient preferences, needs and values, and ensuring that patient values guide all clinical decisions," is advocated by clinicians and professional organizations and is part of a composite criterion for augmented reimbursement for various health care settings, including patient-centered medical homes. Despite general agreement that patient-centered care is a good idea and worthy of incentivization, patient-centered care is difficult to assess accurately, scalably, and feasibly. In this commentary, we suggest that assessment of patient-centered care may be improved by identifying circumstances that indicate its probable absence-in particular, by flagging probable discordance between a patient's preferences and their treatment care plan. One potential marker of this discordance is persistent lack of control of a comorbid condition that is easily controllable by existing therapies and where existing therapies are sufficiently diverse to be compatible with a wide range of patient preferences (eg, stage 1 hypertension, type 2 diabetes with glycated hemoglobin < 8.5%). We outline how this approach may be tested, validated, and harmonized with existing quality improvement activities.

STUDY OBJECTIVES/OBJECTIVE:Obstructive sleep apnea (OSA) prevalence increases with age, but whether OSA-related sleep disruption could interrupt the processing of previously encoded wake information thought to normally occur during sleep in cognitively normal older adults remains unknown. METHODS:Fifty-two older (age = 66.9 ± 7.7 years, 56 % female), community-dwelling, cognitively normal adults explored a 3D maze environment and then performed 3 timed trials before (evening) and after (morning) sleep recorded with polysomnography (PSG) with a 20-minute morning psychomotor vigilance test (PVT). RESULTS:Twenty-two (22) subjects had untreated OSA (Apnea Hypopnea Index (AHI4%) ≥ 5/hour) where severity was mild on average [median (interquartile range (IQR))] AHI4% = 11.0 (20.7)/hour) and 30 subjects had an AHI4% < 5/hour. No significant differences were observed in overnight percent change in completion time or in the pattern of evening pre-sleep maze performance. However, during the morning post-sleep trials, there was a significant interaction between OSA group and morning trial number such that participants with OSA performed worse on average with each subsequent morning trial, whereas those without OSA showed improvements. There were no significant differences in morning PVT performance suggesting that vigilance is unlikely to account for this difference in morning maze performance. Increasing relative frontal slow wave activity (SWA) was associated with better overnight maze performance improvement in participants with OSA (r= 0.51, p = 0.02) but not in those without OSA, and no differences in slow wave activity were observed between groups. CONCLUSIONS:OSA alters morning performance in spatial navigation independent of a deleterious effect on morning vigilance or evening navigation performance. Relative frontal slow wave activity is associated with overnight performance change in older subjects with OSA, but not those without.

Problem/UNASSIGNED:The coronavirus disease 2019 (COVID-19) pandemic has disrupted health systems worldwide and threatened the supply of essential medicines. Especially affected are vulnerable patients in low- and middle-income countries who can only afford access to public health systems. Approach/UNASSIGNED:Soon after physical distancing and curfew orders began on 15 March 2020 in Kenya, we rapidly implemented three supply-chain strategies to ensure a continuous supply of essential medicines while minimizing patients' COVID-19 exposure risks. We redistributed central stocks of medicines to peripheral health facilities to ensure local availability for several months. We equipped smaller, remote health facilities with medicine tackle boxes. We also made deliveries of medicines to patients with difficulty reaching facilities. Local setting/UNASSIGNED:Τo implement these strategies we leveraged our 30-year partnership with local health authorities in rural western Kenya and the existing revolving fund pharmacy scheme serving 85 peripheral health centres. Relevant changes/UNASSIGNED:In April 2020, stocks of essential chronic and non-chronic disease medicines redistributed to peripheral health facilities increased to 835 140 units, as compared with 316 330 units in April 2019. We provided medicine tackle boxes to an additional 46 health facilities. Our team successfully delivered medications to 264 out of 311 patients (84.9%) with noncommunicable diseases whom we were able to reach. Lessons learnt/UNASSIGNED:Our revolving fund pharmacy model has ensured that patients' access to essential medicines has not been interrupted during the pandemic. Success was built on a community approach to extend pharmaceutical services, adapting our current supply-chain infrastructure and working quickly in partnership with local health authorities.

OBJECTIVE:To determine the role of race and gender in the career experience of Black/AA academic surgeons and to quantify the prevalence of experience with racial and gender bias stratified by gender. SUMMARY OF BACKGROUND DATA/BACKGROUND:Compared to their male counterparts, Black/African American (AA) women remain significantly underrepresented among senior surgical faculty and department leadership. The impact of racial and gender bias on the academic and professional trajectory of Black/AA women surgeons has not been well-studied. METHODS:A cross-sectional survey regarding demographics, employment, and perceived barriers to career advancement was distributed via email to faculty surgeon members of the Society of Black American Surgeons (SBAS) in September 2019. RESULTS:Of 181 faculty members, 53 responded (29%), including 31 women (58%) and 22 men (42%). Academic positions as a first job were common (men 95% vs women 77%, p = 0.06). Men were more likely to attain the rank of full professor (men 45% vs women 7%, p = 0.01). Reports of racial bias in the workplace were similar (women 84% vs men 86%, NS); however, reports of gender bias (women 97% vs men 27%, p < 0.001) and perception of salary inequities (women 89% vs 63%, p = 0.02) were more common among women. CONCLUSIONS AND RELEVANCE/CONCLUSIONS:Despite efforts to increase diversity, high rates of racial bias persist in the workplace. Black/AA women also report experiencing a high rate of gender bias and challenges in academic promotion.

OBJECTIVE:To assess the contemporary incidence of cancers using American Samoa as a learning set for insights into similar populations. METHODS:A retrospective observational analysis of de-identified data held in public-access databases (2004-2014) and data on uterine cancer from a hospital, both in American Samoa (2015-2016). RESULTS:There were 341 new cases of cancer in 2004-2014 (111 per 100 000 women/year), including breast (20.2%), uterine (19.4%), and cervical (5.0%); and 287 in 2011-2015 (103 per 100 000 women/year), including uterine (24.0%), breast (18.5%), and cervical (5.2%). Uterine cancer increased from 21.4 to 60.3 per 100 000 women/year, becoming the most common cancer in American Samoa. In 2011-2015, the incidence-rate ratio of uterine cancer to other cancers in American Samoa was 1.3-, 3.8-, 4.6-, 7.7-, and 23-fold higher than breast, colon, cervical, ovarian, and lung cancer, respectively. Among the most recent cases (n=33), median age was 55 years (10 [30.3%] <50 years), median BMI was 38.2; and 11 (33.3%) cases had grade 3 histology. CONCLUSION/CONCLUSIONS:The pattern of cancers in American Samoa differs from that in the US mainland. The findings reflect significant changes in cancer incidence. Cancer control programs should evaluate the potential of uterine screening in accordance with their community's needs and characteristics.

The plasma proteomic changes that precede the onset of dementia could yield insights into disease biology and highlight new biomarkers and avenues for intervention. We quantified 4,877 plasma proteins in nondemented older adults in the Atherosclerosis Risk in Communities cohort and performed a proteome-wide association study of dementia risk over five years (n = 4,110; 428 incident cases). Thirty-eight proteins were associated with incident dementia after Bonferroni correction. Of these, 16 were also associated with late-life dementia risk when measured in plasma collected nearly 20 years earlier, during mid-life. Two-sample Mendelian randomization causally implicated two dementia-associated proteins (SVEP1 and angiostatin) in Alzheimer's disease. SVEP1, an immunologically relevant cellular adhesion protein, was found to be part of larger dementia-associated protein networks, and circulating levels were associated with atrophy in brain regions vulnerable to Alzheimer's pathology. Pathway analyses for the broader set of dementia-associated proteins implicated immune, lipid, metabolic signaling and hemostasis pathways in dementia pathogenesis.

BACKGROUND AND AIMS/OBJECTIVE:Three to ten minutes of smoking cessation advice by physicians is effective to increase quit rates but not routinely practised. We examined the effectiveness of physicians' very brief (about 30 seconds) smoking cessation intervention on quit rates among Chinese outpatient smokers. DESIGN/METHODS:A pragmatic, open-label, individually randomized controlled trial. SETTING/METHODS:Seventy-two medical outpatient departments of hospitals and/or community health centers in Guangdong, China. PARTICIPANTS/METHODS:Chinese adults who were daily cigarette smokers (N = 13,671, 99% males) were invited by their physician to participate during outpatient consultation. Smokers who were receiving smoking cessation treatment or were judged to needed specialist treatment for cessation were excluded. INTERVENTIONS/METHODS:The intervention group (n = 7,015) received a 30-second intervention including physician's very brief advice, a leaflet with graphic warnings, and a card with contact information of available cessation services. The control group (n = 6,656) received a very brief intervention on consuming vegetables and fruits. A total of 3,466 participants in the intervention group were further randomized to receive a brief booster advice from trained study personnel through telephone one month following their doctor visit. MEASUREMENTS/METHODS:The primary outcome was self-reported 7-day point prevalence abstinence in the intervention and control group at the 12-month follow-up. Secondary outcomes included self-reported 30-day abstinence and biochemically validated abstinence at 12-month follow-up. FINDINGS/RESULTS:By intention-to-treat, the intervention (vs. control) group had greater self-reported 7-day abstinence (9.1% vs. 7.8%; odds ratio (OR) 1.14; 95% Confidence Interval (CI) 1.03-1.26; P = .008) and 30-day abstinence (8.0% vs. 6.9%; OR 1.14 95% CI 1.03-1.27; P=0.01) at 12-month follow-up. The effect size increased when only participants who received the intervention from compliant physicians were included (7-day PPA OR = 1.42; 1.11-1.74). The group difference in biochemically validated abstinence was small (0.8% vs. 0.8%; OR 1.00 95% CI 0.71-1.42; P=0.99). CONCLUSION/CONCLUSIONS:A 30-second smoking cessation intervention increased self-reported abstinence among mainly male smokers in China at 12-month follow-up (risk difference = 1.3%) and should be feasible to provide in most settings and delivered by all healthcare professionals.

BACKGROUND:Adults age ≥ 50 are among the fastest growing populations in correctional supervision and are medically underserved while experiencing unique health disparities. Community-living older adults, referred to as "justice-involved," are people who have been recently arrested, or are on probation or parole. Although medical complexity is common among incarcerated older adults, the occurrence of medical morbidity, substance use disorder (SUD), and mental illness among justice-involved older adults living in US communities is poorly understood. OBJECTIVE:To estimate the prevalence of medical multimorbidity (≥ 2 chronic medical diseases), SUDs, and mental illness among justice-involved adults age ≥ 50, and the co-occurrence of these conditions. DESIGN/METHODS:Cross-sectional analysis. PARTICIPANTS/METHODS:A total of 34,898 adults age ≥ 50 from the 2015 to 2018 administrations of the US National Survey on Drug Use and Health. MAIN MEASURES/METHODS:Demographic characteristics of justice-involved adults age ≥ 50 were compared with those not justice-involved. We estimated prevalence of mental illness, chronic medical diseases, and SUD among adults age ≥ 50 reporting past-year criminal justice system involvement. Logistic regression was used to estimate the odds of these conditions and co-occurrence of conditions, comparing justice-involved to non-justice-involved adults. KEY RESULTS/RESULTS:An estimated 1.2% (95% confidence interval [CI] = 1.1-1.3) of adults age > 50 experienced criminal justice involvement in the past year. Compared with non-justice-involved adults, justice-involved adults were at increased odds for mental illness (adjusted odds ratio [aOR] = 3.04, 95% CI = 2.09-4.41) and SUD (aOR = 8.10, 95% CI = 6.12-10.73), but not medical multimorbidity (aOR = 1.15, 95% CI = 0.85-1.56). Justice-involved adults were also at increased odds for all combinations of the three outcomes, including having all three simultaneously (aOR = 8.56, 95% CI = 4.10-17.86). CONCLUSIONS:Community-based middle-aged and older adults involved in the criminal justice system are at high risk for experiencing co-occurring medical multimorbidity, mental illness, and SUD. Interventions that address all three social and medical risk factors are needed for this population.