Faculty Bibliography

BACKGROUND AND OBJECTIVE/OBJECTIVE:Systemic chronic inflammation is linked to metabolic syndrome, type-2 diabetes, and heart disease. Lipopolysaccharide (LPS), a Gram negative microbial product, triggers inflammation through toll-like-receptor-4 (TLR-4) signaling. It has been reported that dietary fatty acids also modulate inflammation through TLR-4. We investigated whether fish oil (FO) rich diet in comparison to saturated fat (SF) rich diet would confer protection from pathologies induced by LPS. METHODS:Twenty C57BL/6 mice were divided into two groups. One group received FO-diet and other received SF-diet ad libitum for 60 days. Diets were isocaloric containing 45% energy from fat. After 60-days of feeding, blood was collected after overnight fast. Mice were allowed to recover for 4-days, fasted for 5-hours, challenged with 100 ng/mL of LPS intraperitonially, and bled after 2-hours. After 7-days of recuperation, mice were challenged with 500 ng/mL of LPS intraperitonially and observed for physical health. RESULTS:Food intake was similar in FO- and SF-fed mice. FO-fed mice compared to SF-fed mice had significantly less body weight gain (P = 0.005), epididymal fat weight (P = 0.005), fasting blood glucose (70.8 vs 83.3 ng/dL; P < 0.05), HOMA-IR (5.0 vs 13.6; P < 0.019), and serum cholesterol (167 vs 94 mg/dL; P < 0.05). When challenged with LPS, FO-fed mice had significantly lower serum IL-1β compared to SF-fed mice (2.0 vs 30.0 pg/mL; P < 0.001). After LPS-challenge, SF-fed mice had higher mortality, lost more body weight, and had greater decrease in blood glucose compared to FO-fed mice. CONCLUSION/CONCLUSIONS:Overall, FO-diet compared to SF-diet offered protection against deleterious effects of LPS in mice.

BACKGROUND:Patients with tuberculosis require retreatment if they fail or default from initial treatment or if they relapse following initial treatment success. Outcomes among patients receiving a standard World Health Organization Category II retreatment regimen are suboptimal, resulting in increased risk of morbidity, drug resistance, and transmission.. In this study, we evaluated the risk factors for initial treatment failure, default, or early relapse leading to the need for tuberculosis retreatment in Morocco. We also assessed retreatment outcomes and drug susceptibility testing use for retreatment patients in urban centers in Morocco, where tuberculosis incidence is stubbornly high. METHODS:Patients with smear- or culture-positive pulmonary tuberculosis presenting for retreatment were identified using clinic registries in nine urban public clinics in Morocco. Demographic and outcomes data were collected from clinical charts and reference laboratories. To identify factors that had put these individuals at risk for failure, default, or early relapse in the first place, initial treatment records were also abstracted (if retreatment began within two years of initial treatment), and patient characteristics were compared with controls who successfully completed initial treatment without early relapse. RESULTS:291 patients presenting for retreatment were included; 93% received a standard Category II regimen. Retreatment was successful in 74% of relapse patients, 48% of failure patients, and 41% of default patients. 25% of retreatment patients defaulted, higher than previous estimates. Retreatment failure was most common among patients who had failed initial treatment (24%), and default from retreatment was most frequent among patients with initial treatment default (57%). Drug susceptibility testing was performed in only 10% of retreatment patients. Independent risk factors for failure, default, or early relapse after initial treatment included male gender (aOR = 2.29, 95% CI 1.10-4.77), positive sputum smear after 3 months of treatment (OR 7.14, 95% CI 4.04-13.2), and hospitalization (OR 2.09, 95% CI 1.01-4.34). Higher weight at treatment initiation was protective. Male sex, substance use, missed doses, and hospitalization appeared to be risk factors for default, but subgroup analyses were limited by small numbers. CONCLUSIONS:Outcomes of retreatment with a Category II regimen are suboptimal and vary by subgroup. Default among patients receiving tuberculosis retreatment is unacceptably high in urban areas in Morocco, and patients who fail initial tuberculosis treatment are at especially high risk of retreatment failure. Strategies to address risk factors for initial treatment default and to identify patients at risk for failure (including expanded use of drug susceptibility testing) are important given suboptimal retreatment outcomes in these groups.

Human pluripotent stem cells (hPSC) hold great promise as models for understanding disease and as a source of cells for transplantation therapies. However, the lack of simple, robust and efficient culture methods remains a significant obstacle for realizing the utility of hPSCs. Here we describe a platform for the culture of hPSCs that 1) allows for dissociation and replating of single cells, 2) significantly increases viability and replating efficiency, 3) improves freeze/thaw viability 4) improves cloning efficiency and 5) colony size variation. When combined with standard methodologies for genetic manipulation, we found that the enhanced culture platform allowed for lentiviral transduction rates of up to 95% and electroporation efficiencies of up to 25%, with a significant increase in the total number of antibiotic-selected colonies for screening for homologous recombination. We further demonstrated the utility of the enhanced culture platform by successfully targeting the ISL1 locus. We conclude that many of the difficulties associated with culturing and genetic manipulation of hPSCs can be addressed with optimized culture conditions, and we suggest that the use of the enhanced culture platform could greatly improve the ease of handling and general utility of hPSCs.

Background: Food insecurity, a disruption in a household's eating habits due to insufficient resources for food, is a growing problem in the U.S., where 17.4 million households are food insecure. It is especially detrimental to oncology patients. No studies have yet assessed levels of food insecurity among oncology patients in major population centers. This study aims to estimate the prevalence and predictors of food insecurity among a cohort of medically underserved oncology patients. Methods: Demographic background, diagnosis and treatment information, and responses to the USDA Household Food Security Survey Module were collected and analyzed for a sample of 411 patients with a clinical cancer diagnosis who were in care at 10 hospitals in New York, NY. Food insecurity status was defined according to USDA guidelines, by the number of reported food insecure conditions and behaviors in the USDA Household Food Security Survey Module. Results: The prevalence of food insecurity was 55%, with low and very low food security rates of 45% and 10%, respectively. Food insecure patients were more likely to be younger than food secure patients, and have worse access to health care. Conclusions: This cohort of predominantly immigrant and minority cancer patients had rates of food insecurity nearly 5 times higher than the state average. More research is needed to better understand the causes and impact of food insecurity among cancer and other patients with severe and chronic illnesses. Food insecurity screening should be considered as a component of the standard of care for all cancer and chronic disease patients

Orbital fractures in children are uncommon. The pattern of orbital fractures changes as children age. Although the management of pediatric orbital fractures is evolving, a thorough clinical assessment with computed tomographic scan imaging is essential. Urgent surgical intervention is indicated in cases of entrapment or acute enophthalmos. Entrapment with oculocardiac reflex is common in the white-eyed blow-out or trapdoor fractures. Otherwise, pediatric fractures may be treated conservatively with surveillance. A variety of autogenous and allogenic materials may be used to repair the fractured orbit. Resorbable plating systems are an alternative to rigid metallic fixation and may be used on the developing craniofacial skeleton.