A GMP-compliant manufacturing method for Wharton's jelly-derived mesenchymal stromal cells.

BACKGROUND: Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) hold great therapeutic potential in regenerative medicine. Therefore, it is crucial to establish a Good Manufacturing Practice (GMP)-compliant methodology for the isolation and culture of WJ-MSCs. Through comprehensive research, encompassing laboratory-scale experiments to pilot-scale studies, we aimed to develop standardized protocols ensuring the high yield and quality of WJ-MSCs manufacturing. METHODS: Firstly, optimization of parameters for the enzymatic digestion method used to isolate WJ-MSCs was conducted. These parameters included enzyme concentrations, digestion times, seeding densities, and culture media. Additionally, a comparative analysis between the explant method and the enzymatic digestion method was performed. Subsequently, the consecutive passaging of WJ-MSCs, specifically up to passage 9, was evaluated using the optimized method. Finally, manufacturing processes were developed and scaled up, starting from laboratory-scale flask-based production and progressing to pilot-scale cell factory-based production. Furthermore, a stability study was carried out to assess the storage and use of drug products (DPs). RESULTS: The optimal parameters for the enzymatic digestion method were a concentration of 0.4 PZ U/mL Collagenase NB6 and a digestion time of 3 h, resulting in a higher yield of P0 WJ-MSCs. In addition, a positive correlation between the weight of umbilical cord tissue and the quantities of P0 WJ-MSCs has been observed. Evaluation of different concentrations of human platelet lysate revealed that 2% and 5% concentrations resulted in similar levels of cell expansion. Comparative analysis revealed that the enzymatic digestion method exhibited faster outgrowth of WJ-MSCs compared to the explant method during the initial passage. Passages 2 to 5 exhibited higher viability and proliferation ability throughout consecutive passaging. Moreover, scalable manufacturing processes from the laboratory scale to the pilot scale were successfully developed, ensuring the production of high-quality WJ-MSCs. Multiple freeze-thaw cycles of the DPs led to reduced cell viability and viable cell concentration. Subsequent thawing and dilution of the DPs resulted in a significant decrease in both metrics, especially when stored at 20-27 °C. CONCLUSION: This study offers valuable insights into optimizing the isolation and culture of WJ-MSCs. Our scalable manufacturing processes facilitate the large-scale production of high-quality WJ-MSCs. These findings contribute to the advancement of WJ-MSCs-based therapies in regenerative medicine.

ZIP Code-Level Estimates from a Local Health Survey: Added Value and Limitations.

We assessed the added value and limitations of generating directly estimated ZIP Code-level estimates by aggregating 5 years of data from an annual cross-sectional survey, the New York City Community Health Survey (n = 44,886) from 2009 to 2013, that were designed to provide reliable estimates only of larger geographies. Survey weights generated directly-observed ZIP Code (n = 128) level estimates. We assessed the heterogeneity of ZIP Code-level estimates within coarser United Hospital Fund (UHF) neighborhood areas (n = 34) by using the Rao-Scott Chi-Square test and one-way ANOVA. Orthogonal linear contrasts assessed whether there were linear trends at the UHF level from 2009 to 2013. 22 of 37 health indicators were reliable in over 50% of ZIP Codes. 14 of the 22 variables showed heterogeneity in ≥4 UHFs. Variables for drinking, nutrition, and HIV testing showed heterogeneity in the most UHFs (9-24 UHFs). In half of the 32 UHFs, >20% variables had within-UHF heterogeneity. Flu vaccination and sugary beverage consumption showed significant time trends in the largest number of UHFs (12 or more UHFs). Overall, heterogeneity of ZIP Code-level estimates suggests that there is value in aggregating 5 years of data to make direct small area estimates.

Deaths, Hospitalizations, and Emergency Department Visits From Food-Related Anaphylaxis, New York City, 2000-2014: Implications for Fatality Prevention.

CONTEXT: Food-induced anaphylaxis is potentially fatal but preventable by allergen avoidance and manageable through immediate treatment. Considerable effort has been invested in preventing fatalities from nut exposure among school-aged children, but few population-based studies exist to guide additional prevention efforts. OBJECTIVES: To describe the epidemiology and trends of food-related anaphylaxis requiring emergency treatment during a 15-year span in New York City when public health initiatives to prevent deaths were implemented and to understand the situational circumstances of food-related deaths. DESIGN/SETTING/PARTICIPANTS: Retrospective death record review and analysis of inpatient hospital discharges and emergency department (ED) visits in New York City residents, 2000-2014. MAIN OUTCOME: Vital statistics data, medical examiner reports, ED, and hospital discharge data were used to examine risk for death and incidence trends in medically attended food-related anaphylaxis. Potentially preventable deaths were those among persons with a known allergy to the implicated food or occurring in public settings. RESULTS: There were 24 deaths, (1.6 deaths/year; range: 0-5), 3049 hospitalizations, and 4014 ED visits, including 7 deaths from crustacean, 4 from peanut, and 2 each from tree nut or seeds and fish exposures. Risk for death among those hospitalized or treated in the ED was highest for persons older than 65 years and for those treated for crustacean reactions (relative risk 6.5 compared with those treated for peanuts, 95% confidence interval = 1.9-22.1). Eleven of 16 deaths with medical examiner data were potentially preventable. Hospitalizations (2000-2014) and ED visit rates (2005-2014) were highest for children and those with peanut exposure and increased across periods. CONCLUSIONS: Deaths from food-related anaphylaxis were rare; however, rates of hospitalization and ED visits increased. Prevention efforts related to peanut allergies among children should continue, and additional attention is needed to prevent and treat anaphylaxis among adults, particularly those with known crustacean allergies where case fatality is highest.

A Comparison of Common Health Indicators From Two Surveys of Latinos in the Bronx, New York.

INTRODUCTION: Population health surveys inform and demonstrate the impact of public health policies. However, the performance of such surveys in specific groups of interest (e.g., Hispanics/Latinos in a neighborhood of New York City) is rarely studied. METHOD: We compared measures for obesity, hypertension, diabetes, and current smoking based on the New York City Community Health Survey (CHS, a telephone survey of New York City adults) with the Hispanic Community Health Survey/Study of Latinos (HCHS/SOL), an in-person survey of Hispanic/Latino adults in four communities in the United States (2008-2011), including the Bronx. CHS data were limited to Hispanic/Latinos living in the HCHS/SOL Bronx catchment area. RESULTS: Compared with CHS, HCHS/SOL estimated higher prevalence of obesity (in HCHS/SOL, PHCHS/SOL = 45.0% vs. in CHS, PCHS = 30.6%, p < .01) and current smoking (PHCHS/SOL = 21.2% vs. PCHS = 16.2%, p < .01) but similar for hypertension (PHCHS/SOL = 33.1% vs. PCHS = 33.8%, p > .05) and diabetes (PHCHS/SOL = 15.2% vs. PCHS = 15.7%, p > .05). Stratified estimates (by age, sex, education, and Hispanic/Latino heritage) followed similar trends. CONCLUSION: Our study emphasizes the importance of assessing potential bias in population-based surveys of Hispanics/Latinos and other populations of interest and highlights the complex nature of measuring health outcomes via population-based surveys.

Study on the Infection Mechanism of Penicillium Digitatum on Postharvest Citrus (Citrus Reticulata Blanco) Based on Transcriptomics.

Penicillium digitatum is one of the most important pathogens known widely to cause postharvest losses of citrus. It is significant to explore its infection mechanism to improve the control technology of postharvest diseases of citrus. This research aimed to study the changes in gene expression of P. digitatum at its early stages of citrus infection by transcriptomics sequencing and bioinformatics analysis in order to explore the molecular mechanism of its infection. The results showed that genes associated with pathogenic factors, such as cell wall degrading enzymes, ethylene, organic acids, and effectors, were significantly up-regulated. Concurrently, genes related to anti-oxidation and iron transport were equally up-regulated at varying degrees. From this study, we demonstrated a simple blueprint for the infection mechanism of P. digitatum in Citrus reticulata Blanco, which provided a new direction for subsequent pathological research and paves the way for developing new control strategies.

Temporal and Spatial Patterns in Utilization of Mental Health Services During and After Hurricane Sandy: Emergency Department and Inpatient Hospitalizations in New York City.

OBJECTIVE: Hurricane Sandy made landfall on October 29, 2012, causing a coastal storm surge and extensive flooding, which led to the closure of several health care facilities in New York City (NYC) and prolonged interruptions in service delivery. The impact on mental health-related emergency department (ED) and inpatient hospital service utilization was studied. METHODS: Data came from the New York Statewide Planning and Research Cooperative System. We obtained mental health-related data among NYC residents from 2010 to 2013. Patients were grouped into 5 geographic areas, including service areas of closed hospitals, the Hurricane Sandy evaluation zone, and all of NYC. The Farrington method was used to detect increases in ED visits and hospitalizations for the post-Sandy period. RESULTS: Open hospitals experienced a substantial increase in psychiatric ED visits from patients living in the service areas of closed hospitals. This surge in psychiatric ED visits persisted for 4 to 6 months after Hurricane Sandy. However, the increase in psychiatric hospitalizations was observed for 1 to 3 months. CONCLUSIONS: Several NYC hospitals received a substantially larger number of ED patients from service areas of closed hospitals after Hurricane Sandy, unlike other hospitals that experienced a decrease. Because of potential surges in the number of psychiatric ED visits, resource allocation to hospitals should be considered. (Disaster Med Public Health Preparedness. 2016;10:512-517).

Spatial Shift in the Utilization of Mental Health Services After Hurricane Sandy Among New York City Residents Enrolled in Medicaid.

OBJECTIVE: Closure of several New York City (NYC) hospitals after Hurricane Sandy caused an unanticipated, extended surge in patient demand at open hospitals. This study identified hospitals with a significant increase in mental-health-related emergency department, inpatient, and outpatient visits from Medicaid patients displaced by Hurricane Sandy. METHODS: NYC Medicaid patients were classified into non-mutually-exclusive geographic categories corresponding to residence in areas served by Bellevue Hospital Center and Coney Island Hospital, the hurricane impact area, and all of NYC. For each geographic region, we compared the observed to the expected number of service visits in the 6 months after the storm. The expected number of visits was calculated from 2-year trends in mental health claims. RESULTS: Twenty-four facilities in all 5 NYC boroughs experienced patient redistribution from storm-affected areas. Eighteen facilities had a concurrent surge in total Medicaid patients, which suggested that redistribution had a greater impact on resource use at these locations. CONCLUSIONS: The redistribution of Medicaid patients after Hurricane Sandy increased mental health service utilization at facilities not near flooded areas. Our findings can aid in surge capacity planning and thereby improve the continuity of mental health care after a natural disaster. (Disaster Med Public Health Preparedness. 2016;10:420-427).