The Added Value of Water, Sanitation, and Hygiene Interventions to Mass Drug Administration for Reducing the Prevalence of Trachoma: A Systematic Review Examining

Trachoma is the leading cause of infectious blindness worldwide. The SAFE strategy, the World Health Organization-recommended method to eliminate blinding trachoma, combines developments in water, sanitation, surgery, and antibiotic treatment. Current literature does not focus on the comprehensive effect these components have on one another. The present systematic review analyzes the added benefit of water, sanitation, and hygiene education interventions to preventive mass drug administration of azithromycin for trachoma. Trials were identified from the PubMed database using a series of search terms. Three studies met the complete criteria for inclusion. Though all studies found a significant change in reduction of active trachoma prevalence, the research is still too limited to suggest the impact of the “F” and “E” components on trachoma prevalence and ultimately its effects on blindness

Ethical Approaches to Mandating Influenza Vaccinations for Local Health Department Workforce in Georgia

Background: The seasonal influenza illness occurs every year in the United States during the cooler months from October to April, sometimes lasting longer. Although certain populations are more susceptible to this condition, data have shown that otherwise healthy individuals have experienced alarming rates of morbidity and mortality associated with these infections. Despite the CDC’s recommendation for influenza vaccination for all HCWs, compliance have been lagging among local health departments’ workforce. This practice arguably exposes a wide cross section of the U.S. population to the flu, while being served in these facilities. The utilitarian approach provides a framework to examine the ethical implications to the public of mandating influenza vaccination for these employees. Methods: A systematic review of peer-reviewed literature was conducted to address the following research questions: 1) Do local public health departments in Georgia mandate annual influenza vaccinations?  2) What are the ethical considerations for mandating influenza vaccinations for public health employees? and 3) What are the ethical considerations for mandating influenza vaccinations for the community? Twenty-five articles were included in the review. Results: Descriptive analysis shows that there is no mandatory vaccination policy in place for state or local departments in health in the state of Georgia. Most of the literature available relates to policy implementation within acute or long-term care facilities. A systematic review of mandatory influenza vaccination for public health workers focused on four areas: theoretical approaches to increase influenza vaccination coverage and support of, opposition to, and alternative strategies for influenza vaccinations. Conclusions: The utilitarian approach is sufficient for the influenza vaccination policy- making strategies and in the ethical approaches of mandating influenza vaccinations for local health department workforce in Georgia if need be, for vaccination targets are to be achieved

Cardiolipin Prevents Membrane Translocation and Permeabilization by Daptomycin

This research was originally published in Journal of Biological Chemistry. Zhang, T., Muraih, J. K., Tishbi, N., Herskowitz, J., Victor, R. L., Silverman, J., … Mintzer, E. (2014). Cardiolipin Prevents Membrane Translocation and Permeabilization by Daptomycin. Journal of Biological Chemistry, 289(17), 11584–11591. © the American Society for Biochemistry and Molecular Biology." Available here: https://doi.org/10.1074/jbc.M114.554444Daptomycin is an acidic lipopeptide antibiotic that, in the presence of calcium, forms oligomeric pores on membranes containing phosphatidylglycerol. It is clinically used against various Gram-positive bacteria such as Staphylococcus aureus and Enterococcus species. Genetic studies have indicated that an increased content of cardiolipin in the bacterial membrane may contribute to bacterial resistance against the drug. Here, we used a liposome model to demonstrate that cardiolipin directly inhibits membrane permeabilization by daptomycin. When cardiolipin is added at molar fractions of 10 or 20% to membranes containing phosphatidylglycerol, daptomycin no longer forms pores or translocates to the inner membrane leaflet. Under the same conditions, daptomycin continues to form oligomers; however, these oligomers contain only close to four subunits, which is approximately half as many as observed on membranes without cardiolipin. The collective findings lead us to propose that a daptomycin pore consists of two aligned tetramers in opposite leaflets and that cardiolipin prevents the translocation of tetramers to the inner leaflet, thereby forestalling the formation of complete, octameric pores. Our findings suggest a possible mechanism by which cardiolipin may mediate resistance to daptomycin, and they provide new insights into the action mode of this important antibiotic

Estimated sweat loss, fluid and CHO intake, and sodium balance of male major junior, AHL, and NHL players during on-ice practices

Several previous studies have reported performance decrements in team sport athletes who dehydrated approximately 1.5–2% of their body mass (BM) through sweating. This study measured on-ice sweat loss, fluid intake, sodium balance, and carbohydrate (CHO) intake of 77 major junior (JR; 19 ± 1 years), 60 American Hockey League (AHL; 24 ± 4 years), and 77 National Hockey League (NHL; 27 ± 5 years) players. Sweat loss was calculated from pre- to post-exercise BM plus fluid intake minus urine loss. AHL (2.03 ± 0.62 L/hr) and NHL (2.02 ± 0.74 L/hr) players had higher sweat rates (p  .05). Sodium deficits (sodium loss − intake) were greater (p 2% BM) during 60 min of practice. However, ∼15%, 41%, and 48% of the JR, AHL, and NHL players, respectively, may have reached mild dehydration and increased risk of performance decrements in a 90-min practice

Lentiviral-mediated gene transfer to the sheep brain: Implications for gene therapy in batten disease

The neuronal ceroid lipofuscinoses (NCLs; Batten disease) are inherited neurodegenerative lysosomal storage diseases with common clinical features of blindness and seizures culminating in premature death. Gene-therapy strategies for these diseases depend on whether the missing activity is a secreted lysosomal protein taken up by neighboring cells, or an intramembrane protein that requires careful targeting. Therapies are best developed in animal models with large complex human-like brains. Lentiviral-mediated gene delivery to neural cell cultures from normal sheep and sheep affected with an NCL resulted in green fluorescent protein (GFP) expression in neurons and neuroblasts, more efficiently than in astrocytes. Similar transgene expression was obtained from two constitutive promoters, the viral MND promoter and the human EF1α promoter. In vivo studies showed stable and persistent GFP expression throughout the cell bodies, axons, and dendrites from intracortical injections and indicated ependymal and subependymal transduction. The sheep showed no ill effects from the injections. These data support continuing gene-therapy trials in the sheep models of Batten disease

Relationship of Race/Ethnicity and Survival after Single Umbilical Cord Blood Transplantation for Adults and Children with Leukemia and Myelodysplastic Syndromes

The relationship of race/ethnicity with outcomes of umbilical cord blood transplantation (UCBT) is not well known. We analyzed the association between race/ethnicity and outcomes of unrelated single UCBT for leukemia and myelodysplastic syndromes. Our retrospective cohort study consisted of 885 adults and children (612 whites, 145 blacks, and 128 Hispanics) who received unrelated single UCBT for leukemia and myelodysplastic syndromes between 1995 and 2006 and were reported to the Center for International Blood and Marrow Transplant Research. A 5-6/6 HLA-matched unit with a total nucleated cell count infused of ≥2.5 × 107/kg was given to 40% white and 42% Hispanic, but only 21% black patients. Overall survival at 2 years was 44% for whites, 34% for blacks, and 46% for Hispanics (P = .008). In multivariate analysis adjusting for patient, disease, and treatment factors (including HLA match and cell dose), blacks had inferior overall survival (relative risk of death, 1.31; P = .02), whereas overall survival of Hispanics was similar (relative risk, 1.03; P = .81) to that of whites. For all patients, younger age, early-stage disease, use of units with higher cell dose, and performance status ≥80 were independent predictors of improved survival. Black patients and white patients infused with well-matched cords had comparable survival; similarly, black and white patients receiving units with adequate cell dose had similar survival. These results suggest that blacks have inferior survival to whites after single UCBT, but outcomes are improved when units with a higher cell dose are used

A Randomized Phase II Crossover Study of Imatinib or Rituximab for Cutaneous Sclerosis after Hematopoietic Cell Transplantation

Cutaneous sclerosis (CS) occurs in 20% of patients with chronic graft-versus-host disease (GVHD) and can compromise mobility and quality of life

Cancer health disparities in racial/ethnic minorities in the United States

There are well-established disparities in cancer incidence and outcomes by race/ethnicity that result from the interplay between structural, socioeconomic, socio-environmental, behavioural and biological factors. However, large research studies designed to investigate factors contributing to cancer aetiology and progression have mainly focused on populations of European origin. The limitations in clinicopathological and genetic data, as well as the reduced availability of biospecimens from diverse populations, contribute to the knowledge gap and have the potential to widen cancer health disparities. In this review, we summarise reported disparities and associated factors in the United States of America (USA) for the most common cancers (breast, prostate, lung and colon), and for a subset of other cancers that highlight the complexity of disparities (gastric, liver, pancreas and leukaemia). We focus on populations commonly identified and referred to as racial/ethnic minorities in the USA—African Americans/Blacks, American Indians and Alaska Natives, Asians, Native Hawaiians/other Pacific Islanders and Hispanics/Latinos. We conclude that even though substantial progress has been made in understanding the factors underlying cancer health disparities, marked inequities persist. Additional efforts are needed to include participants from diverse populations in the research of cancer aetiology, biology and treatment. Furthermore, to eliminate cancer health disparities, it will be necessary to facilitate access to, and utilisation of, health services to all individuals, and to address structural inequities, including racism, that disproportionally affect racial/ethnic minorities in the USA.Fil: Zavala, Valentina A.. University of California; Estados UnidosFil: Bracci, Paige M.. University of California; Estados UnidosFil: Carethers, John M.. University of Michigan; Estados UnidosFil: Carvajal Carmona, Luis. University of California at Davis; Estados UnidosFil: Coggins, Nicole B.. University of California at Davis; Estados UnidosFil: Cruz Correa, Marcia R.. Universidad de Puerto Rico; Puerto RicoFil: Davis, Melissa. No especifíca;Fil: de Smith, Adam J.. University of California; Estados UnidosFil: Dutil, Julie. Ponce Research Institute; Puerto RicoFil: Figueiredo, Jane C.. Cedars Sinai Medical Center; Estados UnidosFil: Fox, Rena. University of California; Estados UnidosFil: Graves, Kristi D.. University Of Georgetown; Estados UnidosFil: Gomez, Scarlett Lin. University of California; Estados UnidosFil: Llera, Andrea Sabina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Neuhausen, Susan L.. No especifíca;Fil: Newman, Lisa. No especifíca;Fil: Nguyen, Tung. University of California; Estados UnidosFil: Palmer, Julie R.. National Institutes of Health; Estados UnidosFil: Palmer, Nynikka R.. University of California; Estados UnidosFil: Pérez Stable, Eliseo J.. National Institutes of Health; Estados UnidosFil: Piawah, Sorbarikor. University of California; Estados UnidosFil: Rodriquez, Erik J.. National Institutes of Health; Estados UnidosFil: Sanabria Salas, María Carolina. Instituto Nacional de Cancerología; ColombiaFil: Schmit, Stephanie L.. University of Southern California; Estados UnidosFil: Serrano Gomez, Silvia J.. Instituto Nacional de Cancerología; ColombiaFil: Stern, Mariana Carla. University of Southern California; Estados UnidosFil: Weitzel, Jeffrey. No especifíca;Fil: Yang, Jun J.. St. Jude Children’s Research Hospital; Estados UnidosFil: Zabaleta, Jovanny. No especifíca;Fil: Ziv, Elad. University of California; Estados UnidosFil: Fejerman, Laura. University of California; Estados Unido

Performance of Three-Biomarker Immunohistochemistry for Intrinsic Breast Cancer Subtyping in the AMBER Consortium

Classification of breast cancer into intrinsic subtypes has clinical and epidemiologic importance. To examine accuracy of immunohistochemistry (IHC)-based methods for identifying intrinsic subtypes, a three-biomarker IHC panel was compared to the clinical record and RNA-based intrinsic (PAM50) subtypes

Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function.

BACKGROUND: Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function. METHODS: We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis. RESULTS: The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 × 10(-7)). In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 × 10(-8)) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively. CONCLUSIONS: In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function