Management of severe gastrointestinal tuberculosis with injectable antituberculous drugs

Abstract: Abdominal tuberculosis (TB) is generally responsive to medical treatment, and early diagnosis and management can prevent unnecessary surgical intervention. However, intravenous therapy is needed for severe forms of tuberculosis with extensive gastrointestinal involvement. The authors report an immunocompetent patient with gastrointestinal TB who was successfully managed with a combination of surgical intervention and anti-TB medications, and discuss the importance of injectable anti-TB medications in the management of severe gastrointestinal TB. The present case report provides a model for assessment and intervention in severe forms of gastrointestinal TB

Changes in Body Mass Index and Atherosclerotic Disease Risk Score After Switching From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide.

Background: Switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF)-containing antiretroviral therapy (ART) can improve renal function and bone mineral density in people with human immunodeficiency virus (PWH). The switch can also negatively influence cholesterol, but changes in body mass index (BMI) and atherosclerotic cardiovascular disease (ASCVD) risk are unknown. Methods: This retrospective observational study evaluated BMI and ASCVD risk score changes in virologically suppressed PWH who switched from TDF to TAF without switching other ART regimen components. Adults on TDF for ≥1 year with 2 consecutive HIV ribonucleic acid values/mL before a TAF switch were included. Body weight, BMI, cholesterol, and ASCVD risk score were collected for the year before and after the switch. Pre- and postswitch values were compared with the Wilcoxon signed-rank test. Changes in BMI and ASCVD scores were modeled using generalized estimating equations regression. Results: One hundred ten patients were included. In unadjusted analyses, there were significant increases in weight, BMI, total cholesterol, LDL, HDL, and ASCVD risk score in the year after switching from TDF to TAF (each P ≤ .01). In regression models, switching from TDF to TAF was associated with a 0.45 kg/m2 increase in BMI (95% confidence interval [CI], 0.14-0.76) and a 13% increase in ASCVD risk score (95% CI, 4%-23%). Conclusions: We observed significant BMI and ASCVD score increases in PWH 1 year after switching from TDF to TAF. The mechanism of changes is unclear and requires additional study

Roles of the ocean mesoscale in the horizontal supply of mass, heat, carbon and nutrients to the Northern Hemisphere subtropical gyres

Horizontal transport at the boundaries of the subtropical gyres plays a crucial role in providing the nutrients that fuel gyre primary productivity, the heat that helps restratify the surface mixed layer, and the dissolved inorganic carbon (DIC) that influences air‐sea carbon exchange. Mesoscale eddies may be an important component of these horizontal transports; however, previous studies have not quantified the horizontal tracer transport due to eddies across the subtropical gyre boundaries. Here we assess the physical mechanisms that control the horizontal transport of mass, heat, nutrients and carbon across the North Pacific and North Atlantic subtropical gyre boundaries using the eddy‐rich ocean component of a climate model (GFDL's CM2.6) coupled to a simple biogeochemical model (mini‐BLING). Our results suggest that horizontal transport across the gyre boundaries supplies a substantial amount of mass and tracers to the ventilated layer of both Northern Hemisphere subtropical gyres, with the Kuroshio and Gulf Stream acting as main exchange gateways. Mass, heat, and DIC supply is principally driven by the time‐mean circulation, whereas nutrient transport differs markedly from the other tracers, as nutrients are mainly supplied to both subtropical gyres by down‐gradient eddy mixing across gyre boundaries. A budget analysis further reveals that the horizontal nutrient transport, combining the roles of both mean and eddy components, is responsible for more than three quarters of the total nutrient supply into the subtropical gyres, surpassing a recent estimate based on a coarse resolution model and thus further highlighting the importance of horizontal nutrient transport

A quantitative risk assessment of waterborne infectious disease in the inundation area of a tropical monsoon region

Flooding and inundation are annual events that occur during the rainy season in Cambodia, and inundation has a strong relationship with human health. This study simulated the coliform bacteria distribution using a hydraulic model and estimated the impact of inundation on public health using a dose–response model. The model parameters were calibrated using field survey data from Cambodia and obtained good agreement with the coliform group count distribution. The results suggest that the impact of inundation on human health is most noticeable in residential areas. The annual average risk of infection during medium-sized flood events is 0.21. The risk due to groundwater use ranges from 0.12 to 0.17 in inundation areas and reaches as high as 0.23 outside the inundation areas. The risk attributed to groundwater use is therefore higher than that for surface water use (0.02–0.06), except in densely populated areas at the city center. There is a high risk for infection with waterborne disease in residential areas, and the annual average risk during small flood events is 0.94. An assessment of possible countermeasures to reduce the risk shows that the control of inundation may bring more risk to public health in Cambodia. Shallower inundation water (<0.3 m) leads to a higher risk of infection, but if the depth is greater than 2 m, the risk is low in residential areas.The simulated results explain the spatial distributions of infection risk, which are vitally important for determining the highest priority places with relatively high risk and will be helpful for decision makers when considering the implementation of countermeasures

Induction of tumor-specific acquired immunity against already established tumors by selective stimulation of innate DEC-205+ dendritic cells

Two major distinct subsets of dendritic cells (DCs) are arranged to regulate our immune responses in vivo; 33D1+ and DEC-205+ DCs. Using anti-33D1-specific monoclonal antibody, 33D1+ DCs were successfully depleted from C57BL/6 mice. When 33D1+ DC-depleted mice were stimulated with LPS, serum IL-12, but not IL-10 secretion that may be mediated by the remaining DEC-205+ DCs was markedly enhanced, which may induce Th1 dominancy upon TLR signaling. The 33D1+ DC-depleted mice, implanted with syngeneic Hepa1-6 hepatoma or B16-F10 melanoma cells into the dermis, showed apparent inhibition of already established tumor growth in vivo when they were subcutaneously (sc) injected once or twice with LPS after tumor implantation. Moreover, the development of lung metastasis of B16-F10 melanoma cells injected intravenously was also suppressed when 33D1+ DC-deleted mice were stimulated twice with LPS in a similar manner, in which the actual cell number of NK1.1+CD3− NK cells in lung tissues was markedly increased. Furthermore, intraperitoneal (ip) administration of a very small amount of melphalan (l-phenylalanine mustard; l-PAM) (0.25 mg/kg) in LPS-stimulated 33D1+ DC-deleted mice helped to induce H-2Kb-restricted epitope-specific CD8+ cytotoxic T lymphocytes (CTLs) among tumor-infiltrating lymphocytes against already established syngeneic E.G7-OVA lymphoma. These findings indicate the importance and effectiveness of selective targeting of a specific subset of DCs, such as DEC-205+ DCs alone or with a very small amount of anticancer drugs to activate both CD8+ CTLs and NK effectors without externally added tumor antigen stimulation in vivo and provide a new direction for tumor immunotherapy

PMIP4-CMIP6: the contribution of the Paleoclimate Modelling Intercomparison Project to CMIP6

The goal of the Palaeoclimate Modelling Intercomparison Project (PMIP) is to understand the response of the climate system to changes in different climate forcings and to feedbacks. Through comparison with observations of the environmental impacts of these climate changes, or with climate reconstructions based on physical, chemical or biological records, PMIP also addresses the issue of how well state-of-the-art models simulate climate changes. Palaeoclimate states are radically different from those of the recent past documented by the instrumental record and thus provide an out-of-sample test of the models used for future climate projections and a way to assess whether they have the correct sensitivity to forcings and feedbacks. Five distinctly different periods have been selected as focus for the core palaeoclimate experiments that are designed to contribute to the objectives of the sixth phase of the Coupled Model Intercomparison Project (CMIP6). This manuscript describes the motivation for the choice of these periods and the design of the numerical experiments, with a focus upon their novel features compared to the experiments performed in previous phases of PMIP and CMIP as well as the benefits of common analyses of the models across multiple climate states. It also describes the information needed to document each experiment and the model outputs required for analysis and benchmarking