Faculty Bibliography

Persistent organic pollutants (POPs) are believed to alter metabolic homeostasis during fetal development, leading to childhood obesity. However, limited studies have explored how fetal chemical exposures relate to birth and infant weight outcomes in low-income Hispanic families at the highest risk of obesity. Therefore, we sought to determine associations between neonatal POPs exposure measured in newborn dried blood spots (DBS) and prenatal diet quality, birth weight, and overweight status at 18 months old. We conducted a case-control study nested within the Starting Early Program randomized controlled trial comparing POPs concentrations in infants with healthy weight (n = 46) and overweight status (n = 52) at age 18 months. Three categories of POPs, organochlorine pesticides (OCPs), polybrominated diphenyl ethers (PBDEs) and perfluoroalkyl substances (PFASs) were measured in archived newborn DBS. We assessed correlations between prenatal diet quality and neonatal POPs concentrations. Multivariable regression analyses examined associations between POPs (dichotomized at the mean) and birth weight z-score and weight status at 18 months, controlling for confounders. Seven of eight chemicals had detectable levels in greater than 94% of the sample. Higher protein, sodium and refined grain intake during pregnancy were correlated with lower POPs in newborn DBS. We found that high concentrations of perfluorooctanesulfonate (unstandardized coefficient [B]: -0.62, 95% confidence interval [CI]: -0.96 to -0.29) and perfluorohexanesulfate (B: -0.65, 95% CI: -0.99 to -0.31) were related to lower birth weight z-scores compared to those with low concentrations. We did not find associations between PBDEs, OCPs, and the other PFASs with birth weight z-scores, or between any POPs and weight status at 18 months. In conclusion, two PFASs were associated with lower birth weight, an important indicator of child health and growth, although direct associations with infant overweight status were not found. Whether neonatal POPs exposures contribute to economic and ethnic disparities in early obesity remains unclear.

Food carts are common along streets in cities throughout the world. In North America, food cart vendors generally use propane, charcoal, or both propane and charcoal (P and C) for food preparation. Although cooking emissions are known to be a major source of indoor air pollution, there is limited knowledge on outdoor cooking's impact on the ambient environment and, in particular, the relative contribution of the different cooking fuels. This field study investigated the air pollution the public is exposed to in the micro-environment around 19 food carts classified into 3 groups: propane, charcoal, and P and C carts. Concentrations near the food carts were measured using both real-time and filter-based methods. Mean real-time concentrations of PM_2.5, BC_2.5, and particle counts were highest near the charcoal food carts: 196 μg/m³, 5.49 μg/m³, and 69,000 particles/cm³, respectively, with peak exposures of 1520 μg/m³, 67.9 μg/m³, and 235,000 particles/cm³, respectively. In order of pollution emission impacts: charcoal > P and C > propane carts. Thus, significant differences in air pollution emissions occurred in the vicinity of mobile food carts, depending on the fuel used in food preparation. Local air pollution polices should consider these emission factors in regulating food cart vendor operations.

Post-traumatic stress disorder (PTSD) impacts many veterans and active duty soldiers, but diagnosis can be problematic due to biases in self-disclosure of symptoms, stigma within military populations, and limitations identifying those at risk. Prior studies suggest that PTSD may be a systemic illness, affecting not just the brain, but the entire body. Therefore, disease signals likely span multiple biological domains, including genes, proteins, cells, tissues, and organism-level physiological changes. Identification of these signals could aid in diagnostics, treatment decision-making, and risk evaluation. In the search for PTSD diagnostic biomarkers, we ascertained over one million molecular, cellular, physiological, and clinical features from three cohorts of male veterans. In a discovery cohort of 83 warzone-related PTSD cases and 82 warzone-exposed controls, we identified a set of 343 candidate biomarkers. These candidate biomarkers were selected from an integrated approach using (1) data-driven methods, including Support Vector Machine with Recursive Feature Elimination and other standard or published methodologies, and (2) hypothesis-driven approaches, using previous genetic studies for polygenic risk, or other PTSD-related literature. After reassessment of ~30% of these participants, we refined this set of markers from 343 to 28, based on their performance and ability to track changes in phenotype over time. The final diagnostic panel of 28 features was validated in an independent cohort (26 cases, 26 controls) with good performance (AUC = 0.80, 81% accuracy, 85% sensitivity, and 77% specificity). The identification and validation of this diverse diagnostic panel represents a powerful and novel approach to improve accuracy and reduce bias in diagnosing combat-related PTSD.

CONTEXT/BACKGROUND:Telemedicine provides remote clinical support using technological tools. It may facilitate health care delivery while reducing unnecessary visits to the clinic. The coronavirus disease 2019 (COVID-19) outbreak has caused an abrupt change in our daily urological practice, converting many of us to be reliant on telehealth. OBJECTIVE:To provide practical recommendations for effective use of technological tools in telemedicine. EVIDENCE ACQUISITION/METHODS:A Medline-based and gray literature search was conducted through April 2020. We selected the most relevant articles related to "telemedicine" and "smart working" that could provide important information. EVIDENCE SYNTHESIS/RESULTS:Telemedicine refers to the use of electronic information and telecommunications tools to provide remote clinical health care support. Smart working is a model of work that uses new or existing technologies to improve performance. Telemedicine is becoming a useful invaluable tool during and even beyond the COVID-19 pandemic. It is time for us to formalize the place of telemedicine in routine urological practice, and it is our responsibility to adapt and learn about all the tools and possible strategies for their optimal implementation during the pandemic to ensure that the quality of care received by patients and the outcomes of patients and their families are of the highest standard. CONCLUSIONS:Telemedicine facilitates specialized urological clinical support at a distance, solves problems of limitations in mobility, reduces unnecessary visits to clinics, and is useful for reducing the risk of viral transmission in the current COVID-19 outbreak. Furthermore, both personal and societal considerations may favor continued use of telemedicine, even beyond the COVID-19 pandemic. PATIENT SUMMARY/UNASSIGNED:Telemedicine in urology offers specialized remote clinical support to patients, similar to face-to-face visits. It is very useful for reducing unnecessary visits to the clinic, as well as reducing the risk of contagion in the current coronavirus disease 2019 (COVID-19) pandemic.

BACKGROUND:People living with HIV are diagnosed with age-related chronic health conditions, including cardiovascular disease, at higher than expected rates. Medical management of these chronic health conditions frequently occur in HIV specialty clinics by providers trained in general internal medicine, family medicine, or infectious disease. In recent years, changes in the healthcare financing for people living with HIV in the U.S. has been dynamic due to changes in the Affordable Care Act. There is little evidence examining how healthcare financing characteristics shape primary and secondary cardiovascular disease prevention among people living with HIV. Our objective was to examine the perspectives of people living with HIV and their healthcare providers on how healthcare financing influences cardiovascular disease prevention. METHODS:As part of the EXTRA-CVD study, we conducted in-depth, semi-structured interviews with 51 people living with HIV and 34 multidisciplinary healthcare providers and at three U.S. HIV clinics in Ohio and North Carolina from October 2018 to March 2019. Thematic analysis using Template Analysis techniques was used to examine healthcare financing barriers and enablers of cardiovascular disease prevention in people living with HIV. RESULTS:Three themes emerged across sites and disciplines (1): healthcare payers substantially shape preventative cardiovascular care in HIV clinics (2); physician compensation tied to relative value units disincentivizes cardiovascular disease prevention efforts by HIV providers; and (3) grant-based services enable tailored cardiovascular disease prevention, but sustainability is limited by sponsor priorities. CONCLUSIONS:With HIV now a chronic disease, there is a growing need for HIV-specific cardiovascular disease prevention; however, healthcare financing complicates effective delivery of this preventative care. It is important to understand the effects of evolving payer models on patient and healthcare provider behavior. Additional systematic investigation of these models will help HIV specialty clinics implement cardiovascular disease prevention within a dynamic reimbursement landscape. TRIAL REGISTRATION/BACKGROUND:Clinical Trial Registration Number: NCT03643705 .

BACKGROUND:Worsening socioeconomic conditions in rural America have been fueling increases in chronic disease and poor health. The goal of this study was to identify cost-effective methods of deploying geographically targeted health surveys in rural areas, which often have limited resources. These health surveys were administered in New York's rural Sullivan County, which has some of the poorest health outcomes in the entire state. METHODS:Comparisons were made for response rates, estimated costs, respondent demographics, and prevalence estimates of a brief health survey delivered by mail and phone using address-based sampling, and in-person using convenience sampling at a sub-county level in New York's rural Sullivan County during 2017. RESULTS:Overall response rates were 27.0% by mail, 8.2% by phone, and 71.4% for convenience in-person surveys. Costs to perform phone surveys were substantially higher than mailed or convenience in-person surveys. All modalities had lower proportions of Hispanic respondents compared to Census estimates. Unadjusted and age-adjusted prevalence estimates were similar between mailed and in-person surveys, but not for phone surveys. CONCLUSIONS:These findings are consistent with declining response rates of phone surveys, which obtained an inadequate sample of rural residents. Though in-person surveys had higher response rates, convenience sampling failed to obtain a geographically distributed sample of rural residents. Of modalities tested, mailed surveys provided the best opportunity to perform geographically targeted rural health surveillance.

Background Metabolic dysfunction is highly prevalent in pulmonary arterial hypertension (PAH) and likely contributes to both pulmonary vascular disease and right ventricular (RV) failure in part because of increased oxidant stress. Currently, there is no cure for PAH and human studies of metabolic interventions, generally well tolerated in other diseases, are limited in PAH. Metformin is a commonly used oral antidiabetic that decreases gluconeogenesis, increases fatty acid oxidation, and reduces oxidant stress and thus may be relevant to PAH. Methods and Results We performed a single-center, open-label 8-week phase II trial of up to 2 g/day of metformin in patients with idiopathic or heritable PAH with the co-primary end points of safety, including development of lactic acidosis and study withdrawal, and plasma oxidant stress markers. Exploratory end points included RV function via echocardiography, plasma metabolomic analysis performed before and after metformin therapy, and RV triglyceride content by magnetic resonance spectroscopy in a subset of 9 patients. We enrolled 20 patients; 19/20 reached the target dose and all completed the study protocol. There was no clinically significant lactic acidosis or change in oxidant stress markers. Metformin did not change 6-minute walk distance but did significantly improve RV fractional area change (23±8% to 26±6%, P=0.02), though other echocardiographic parameters were unchanged. RV triglyceride content decreased in 8/9 patients (3.2±1.8% to 1.6±1.4%, P=0.015). In an exploratory metabolomic analysis, plasma metabolomic correlates of ≥50% reduction in RV lipid included dihydroxybutyrate, acetylputrescine, hydroxystearate, and glucuronate (P<0.05 for all). In the entire cohort, lipid metabolites were among the most changed by metformin. Conclusions Metformin therapy was safe and well tolerated in patients with PAH in this single-arm, open-label phase II study. Exploratory analyses suggest that metformin may be associated with improved RV fractional area change and, in a subset of patients, reduced RV triglyceride content that correlated with altered lipid and glucose metabolism markers. Registration URL: http://www.clinicaltrials.gov; Unique identifier: NCT01884051.

BACKGROUND:Eye-hand coordination (EHC) is a sophisticated act that requires interconnected processes governing synchronization of ocular and manual motor systems. Precise, timely and skillful movements such as reaching for and grasping small objects depend on the acquisition of high-quality visual information about the environment and simultaneous eye and hand control. Multiple areas in the brainstem and cerebellum, as well as some frontal and parietal structures, have critical roles in the control of eye movements and their coordination with the head. Although both cortex and cerebellum contribute critical elements to normal eye-hand function, differences in these contributions suggest that there may be separable deficits following injury. METHOD/METHODS:As a preliminary assessment for this perspective, we compared eye and hand-movement control in a patient with cortical stroke relative to a patient with cerebellar stroke. RESULT/RESULTS:We found the onset of eye and hand movements to be temporally decoupled, with significant decoupling variance in the patient with cerebellar stroke. In contrast, the patient with cortical stroke displayed increased hand spatial errors and less significant temporal decoupling variance. Increased decoupling variance in the patient with cerebellar stroke was primarily due to unstable timing of rapid eye movements, saccades. CONCLUSION/CONCLUSIONS:These findings highlight a perspective in which facets of eye-hand dyscoordination are dependent on lesion location and may or may not cooperate to varying degrees. Broadly speaking, the results corroborate the general notion that the cerebellum is instrumental to the process of temporal prediction for eye and hand movements, while the cortex is instrumental to the process of spatial prediction, both of which are critical aspects of functional movement control.

Oral cavity cancer has a low 5-y survival rate, but outcomes improve when the disease is detected early. Cytology is a less invasive method to assess oral potentially malignant disorders relative to the gold-standard scalpel biopsy and histopathology. In this report, we aimed to determine the utility of cytological signatures, including nuclear F-actin cell phenotypes, for classifying the entire spectrum of oral epithelial dysplasia and oral squamous cell carcinoma. We enrolled subjects with oral potentially malignant disorders, subjects with previously diagnosed malignant lesions, and healthy volunteers without lesions and obtained brush cytology specimens and matched scalpel biopsies from 486 subjects. Histopathological assessment of the scalpel biopsy specimens classified lesions into 6 categories. Brush cytology specimens were analyzed by machine learning classifiers trained to identify relevant cytological features. Multimodal diagnostic models were developed using cytology results, lesion characteristics, and risk factors. Squamous cells with nuclear F-actin staining were associated with early disease (i.e., lower proportions in benign lesions than in more severe lesions), whereas small round parabasal-like cells and leukocytes were associated with late disease (i.e., higher proportions in severe dysplasia and carcinoma than in less severe lesions). Lesions with the impression of oral lichen planus were unlikely to be either dysplastic or malignant. Cytological features substantially improved upon lesion appearance and risk factors in predicting squamous cell carcinoma. Diagnostic models accurately discriminated early and late disease with AUCs (95% CI) of 0.82 (0.77 to 0.87) and 0.93 (0.88 to 0.97), respectively. The cytological features identified here have the potential to improve screening and surveillance of the entire spectrum of oral potentially malignant disorders in multiple care settings.

BACKGROUND:Scabies is a neglected tropical disease. In resource-poor settings, scabies and other skin infections are often unreported to a health centre, or misdiagnosed. Dermatological expertise and training are often lacking. Little is known about patient healthcare-seeking behaviour. This study reviewed diagnosed skin infections reported to urban (Greater Accra) and rural (Oti region) study health centres in Ghana over six months in 2019. METHODS:Study staff received classroom and clinical dermatology training. Skin infection diagnoses and anonymised patient information were recorded. Descriptive statistics and spatial analysis described patient demographics, and distance travelled to clinic, noting bypassing of their nearest centre. RESULTS:Overall, 385 cases of skin infections were reported across the Greater Accra and Oti study clinics, with 45 scabies cases (11.6%). For scabies, 29 (64.4%) cases were in males. Scabies was the third most common diagnosis, behind bacterial dermatitis (102, 26.5%) and tinea (75, 19.5%). In the rural Oti region, 48.4% of patients bypassed their nearest clinic, travelling a mean 6.2 km further than they theoretically needed to. Females travelled further in comparison to males.