Impact of Environment and Social Gradient on Leptospira Infection in Urban Slums

Leptospirosis, a life-threatening zoonotic disease, has become an important urban slum health problem. Epidemics of leptospirosis now occur in cities throughout the developing world, as the growth of slum settlements has produced conditions for rat-borne transmission of this disease. In this prevalence survey of more than 3,000 residents from a favela slum community in Brazil, Geographical Information System (GIS) and modeling approaches identified specific deficiencies in the sanitation infrastructure of slum environments—open sewers, refuse, and inadequate floodwater drainage—that serve as sources for Leptospira transmission. In addition to the environmental attributes of the slum environment, low socioeconomic status was found to independently contribute to the risk of infection. These findings indicate that effective prevention of leptospirosis will need to address the social factors that produce unequal health outcomes among slum residents, in addition to improving sanitation

10-Year Follow-Up After Revascularization in Elderly Patients With Complex Coronary Artery Disease

BACKGROUND The optimal revascularization strategy for the elderly with complex coronary artery disease remains unclear. OBJECTIVES The goal of this study was to investigate 10-year all-cause mortality, life expectancy, 5-year major adverse cardiac or cerebrovascular events (MACCE), and 5-year quality of life (QOL) after percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) in elderly individuals (>70 years old) with 3-vessel disease (3VD) and/or left main disease (LMD). METHODS In the present pre-specified analysis on age of the SYNTAX Extended Survival study, 10-year all-cause death and 5-year MACCE were compared with Kaplan-Meier estimates and Cox proportional hazards models among elderly or nonelderly patients. Life expectancy was estimated by restricted mean survival time within 10 years, and QOL status according to the Seattle Angina Questionnaire up to 5 years was assessed by linear mixed-effects models. RESULTS Among 1,800 randomized patients, 575 patients (31.9%) were elderly. Ten-year mortality did not differ significantly between PCI and CABG in elderly (44.1% vs. 41.1%; hazard ratio [HR]: 1.08; 95% confidence interval [CI]: 0.84 to 1.40) and nonelderly patients (21.1% vs. 16.6%; HR: 1.30; 95% CI: 1.00 to 1.69; p(interaction) = 0.332). Among elderly patients, 5-year MACCE was comparable between PCI and CABG (39.4% vs. 35.1%; HR: 1.18; 95% CI: 0.90 to 1.56), whereas it was significantly higher in PCI over CABG among nonelderly patients (36.3% vs. 23.0%; HR: 1.69; 95% CI: 1.36 to 2.10; p(interaction) = 0.043). There were no significant difference in life expectancy (mean difference: 0.2 years in favor of CABG; 95% CI: -0.4 to 0.7) and 5-year QOL status between PCI and CABG among elderly patients. CONCLUSIONS Elderly patients with 3VD and/or LMD had comparable 10-year all-cause death, life expectancy, 5-year MACCE, and 5-year QOL status irrespective of revascularization mode. (C) 2021 by the American College of Cardiology Foundation

Application of mesenchymal stem cells for therapeutic agent delivery in anti-tumor treatment

Mesenchymal stem cells (MSCs) are non-hematopoietic progenitor cells, which can be isolated from different types of tissues including bone marrow, adipose tissue, tooth pulp, and placenta/umbilical cord blood. There isolation from adult tissues circumvents the ethical concerns of working with embryonic or fetal stem cells, whilst still providing cells capable of differentiating into various cell lineages, such as adipocytes, osteocytes and chondrocytes. An important feature of MSCs is the low immunogenicity due to the lack of co-stimulatory molecules expression, meaning there is no need for immunosuppression during allogenic transplantation. The tropism of MSCs to damaged tissues and tumor sites makes them a promising vector for therapeutic agent delivery to tumors and metastatic niches. MSCs can be genetically modified by virus vectors to encode tumor suppressor genes, immunomodulating cytokines and their combinations,other therapeutic approaches include MSCs priming/loading with chemotherapeutic drugs or nanoparticles. MSCs derived membrane microvesicles (MVs), which play an important role in intercellular communication, are also considered as a new therapeutic agent and drug delivery vector. Recruited by the tumor, MSCs can exhibit both pro and anti-oncogenic properties. In this regard, for the development of new methods for cancer therapy using MSCs, a deeper understanding of the molecular and cellular interactions between MSCs and the tumor microenvironment is necessary. In this review, we discuss MSC and tumor interaction mechanisms and review the new therapeutic strategies using MSCs and MSCs derived MVs for cancer treatment

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

Serum 25-hydroxyvitamin D and risk of breast cancer

Globally, a wide range of epidemiological studies have linked low levels of sunlight, ultraviolet B (UVB) irradiance, or serum 25-hydroxyvitamin D [25(OH)], with increased risk of breast cancer. Three studies of different design were employed to assess the relationship between serum 25(OH)D and breast cancer risk. The first study is an ecological analysis of the relationship between UVB irradiance and age-standardized breast cancer mortality rates worldwide. In the regression model, UVB irradiance was inversely associated with mortality rates (p = 0.04), after controlling for covariates. The overall model was statistically significant (R² = 0.34, p < 0.0001). The second study was a case-control analysis of 600 incident cases of female breast cancer and their matched controls that investigated the inverse association between pre-diagnostic serum levels of 25(OH)D and risk of breast cancer in active-duty U.S. military personnel. Conditional logistic regression was used to assess the relationship between serum 25(OH)D concentration and breast cancer risk, while controlling for race and age. In this study, there was an inverse trend between serum 25(OH)D and odds of breast cancer that did not reach statistical significance. However, in 123 pairs for whom serum was collected 90 days or fewer before case diagnosis, women in the highest quintile of serum 25(OH)D had a 70% lower estimated risk of breast cancer (odds ratio 0.30, 95% confidence interval 0.12-0.74, p <̲ 0.01) compared to those in the lowest quintile. The third study was a pooled analysis of published data from 11 ordinary and nested case-control studies. Data from all 11 studies were combined in order to calculate the pooled odds ratio of the highest vs lowest quintile of 25(OH)D. The pooled odds ratio summarizing the estimated risk in the highest compared to the lowest quintile across all studies was 0.63 (95% confidence interval 0.47, 0.80). These three studies provide compelling evidence that supports a strong inverse relationship between vitamin D status and breast cancer risk. More studies, including randomized controlled trials of higher doses of vitamin D₃ (4,000 IU - 6,000 IU/ day), and serum levels of 25(OH)D (60-80 ng/ml), should be performed without dela

Serum 25-hydroxyvitamin D and risk of breast cancer

Globally, a wide range of epidemiological studies have linked low levels of sunlight, ultraviolet B (UVB) irradiance, or serum 25-hydroxyvitamin D [25(OH)], with increased risk of breast cancer. Three studies of different design were employed to assess the relationship between serum 25(OH)D and breast cancer risk. The first study is an ecological analysis of the relationship between UVB irradiance and age-standardized breast cancer mortality rates worldwide. In the regression model, UVB irradiance was inversely associated with mortality rates (p = 0.04), after controlling for covariates. The overall model was statistically significant (R² = 0.34, p < 0.0001). The second study was a case-control analysis of 600 incident cases of female breast cancer and their matched controls that investigated the inverse association between pre-diagnostic serum levels of 25(OH)D and risk of breast cancer in active-duty U.S. military personnel. Conditional logistic regression was used to assess the relationship between serum 25(OH)D concentration and breast cancer risk, while controlling for race and age. In this study, there was an inverse trend between serum 25(OH)D and odds of breast cancer that did not reach statistical significance. However, in 123 pairs for whom serum was collected 90 days or fewer before case diagnosis, women in the highest quintile of serum 25(OH)D had a 70% lower estimated risk of breast cancer (odds ratio 0.30, 95% confidence interval 0.12-0.74, p <̲ 0.01) compared to those in the lowest quintile. The third study was a pooled analysis of published data from 11 ordinary and nested case-control studies. Data from all 11 studies were combined in order to calculate the pooled odds ratio of the highest vs lowest quintile of 25(OH)D. The pooled odds ratio summarizing the estimated risk in the highest compared to the lowest quintile across all studies was 0.63 (95% confidence interval 0.47, 0.80). These three studies provide compelling evidence that supports a strong inverse relationship between vitamin D status and breast cancer risk. More studies, including randomized controlled trials of higher doses of vitamin D₃ (4,000 IU - 6,000 IU/ day), and serum levels of 25(OH)D (60-80 ng/ml), should be performed without dela

Low Cloud Cover-Adjusted Ultraviolet B Irradiance Is Associated with High Incidence Rates of Leukemia: Study of 172 Countries.

There are 52,380 cases of leukemia and 24,090 deaths from it in the US annually. Its causes are unknown and no preventive strategies have been implemented. We hypothesized that leukemia is due mainly to vitamin D deficiency, which is due mainly to low solar ultraviolet B (UVB) irradiance. To test this hypothesis, we estimated age-standardized cloud-cover-adjusted winter UVB irradiance using cloud cover data from the International Satellite Cloud Climatology Project, latitudes of population centroids, and standard astronomical calculations. Incidence rates for 172 countries, available from the International Agency for Cancer Research, were plotted according to cloud-adjusted UVB irradiance. We used multiple regression to account for national differences in elevation and average life expectancy. Leukemia incidence rates were inversely associated with cloud-adjusted UVB irradiance in males (p ≤ 0.01) and females (p ≤ 0.01) in both hemispheres. There were few departures from the trend line, which was parabolic when plotted with the equator at the center of the display, northern hemisphere countries on the right side and southern hemisphere countries on the left. The bivariate association displayed by the polynomial trend line indicated that populations at higher latitudes had at least two times the risk of leukemia compared to equatorial populations. The association persisted in males (p ≤ 0.05) and females (p ≤ 0.01) after controlling for elevation and life expectancy. Incidence rates of leukemia were inversely associated with solar UVB irradiance. It is plausible that the association is due to vitamin D deficiency. This would be consistent with laboratory studies and a previous epidemiological study. Consideration should be given to prudent use of vitamin D for prevention of leukemia