Global burden of disease due to rifampicin-resistant tuberculosis: a mathematical modeling analysis.

In 2020, almost half a million individuals developed rifampicin-resistant tuberculosis (RR-TB). We estimated the global burden of RR-TB over the lifetime of affected individuals. We synthesized data on incidence, case detection, and treatment outcomes in 192 countries (99.99% of global tuberculosis). Using a mathematical model, we projected disability-adjusted life years (DALYs) over the lifetime for individuals developing tuberculosis in 2020 stratified by country, age, sex, HIV, and rifampicin resistance. Here we show that incident RR-TB in 2020 was responsible for an estimated 6.9 (95% uncertainty interval: 5.5, 8.5) million DALYs, 44% (31, 54) of which accrued among TB survivors. We estimated an average of 17 (14, 21) DALYs per person developing RR-TB, 34% (12, 56) greater than for rifampicin-susceptible tuberculosis. RR-TB burden per 100,000 was highest in former Soviet Union countries and southern African countries. While RR-TB causes substantial short-term morbidity and mortality, nearly half of the overall disease burden of RR-TB accrues among tuberculosis survivors. The substantial long-term health impacts among those surviving RR-TB disease suggest the need for improved post-treatment care and further justify increased health expenditures to prevent RR-TB transmission.

Employing Smartphone Health Apps in Weight Management for Adolescents: Analysis on Experiences and Perspectives From Pediatric Providers.

The rising popularity of smartphone health applications (apps) offers great potential for facilitating pediatric weight management. Pediatric providers can determine health interventions for young patients with excess weight. We surveyed 51 pediatric providers at a Midwest academic medical institution and found that 78% thought currently available resources were not sufficient for pediatric weight management. In all, 76% of respondents reported use of at least one smartphone health app for their personal health. The quality of pediatric providers' experiences with their favorite app was strongly associated with their willingness to recommend the app to their patients (P < .001), but few of them have made such a recommendation in practice, mainly due to the lack of either personal knowledge about health apps or about evidence-based health apps for pediatric weight management. Moreover, respondents shared ideas about qualities for an effective health app, which shed new light on developing apps specifically for adolescents with excess weight.

Periodic Exposure of Plasma-Activated Medium Alters Fibroblast Cellular Homoeostasis.

Excess amounts of redox stress and failure to regulate homeostatic levels of reactive species are associated with several skin pathophysiologic conditions. Nonmalignant cells are assumed to cope better with higher reactive oxygen and nitrogen species (RONS) levels. However, the effect of periodic stress on this balance has not been investigated in fibroblasts in the field of plasma medicine. In this study, we aimed to investigate intrinsic changes with respect to cellular proliferation, cell cycle, and ability to neutralize the redox stress inside fibroblast cells following periodic redox stress in vitro. Soft jet plasma with air as feeding gas was used to generate plasma-activated medium (PAM) for inducing redox stress conditions. We assessed cellular viability, energetics, and cell cycle machinery under oxidative stress conditions at weeks 3, 6, 9, and 12. Fibroblasts retained their usual physiological properties until 6 weeks. Fibroblasts failed to overcome the redox stress induced by periodic PAM exposure after 6 weeks, indicating its threshold potential. Periodic stress above the threshold level led to alterations in fibroblast cellular processes. These include consistent increases in apoptosis, while RONS accumulation and cell cycle arrest were observed at the final stages. Currently, the use of NTP in clinical settings is limited due to a lack of knowledge about fibroblasts' behavior in wound healing, scar formation, and other fibrotic disorders. Understanding fibroblasts' physiology could help to utilize nonthermal plasma in redox-related skin diseases. Furthermore, these results provide new information about the threshold capacity of fibroblasts and an insight into the adaptation mechanism against periodic oxidative stress conditions in fibroblasts.

Influence of Redox Stress on Crosstalk between Fibroblasts and Keratinocytes.

Although the skin is constantly subjected to endogenous and exogenous stress, it maintains a homeostatic state through wound repair and regeneration pathways. Treatment for skin diseases and injury requires a significant understanding of the various mechanisms and interactions that occur within skin cells. Keratinocytes and fibroblasts interact with each other and act as key players in the repair process. Although fibroblasts and keratinocytes are widely studied in wound healing and skin remodeling under different conditions, the influence of redox stress on keratinocyte-fibroblast crosstalk has not been thoroughly investigated. In this study, we used cold atmospheric plasma (CAP) to generate and deliver oxidative stress to keratinocytes and fibroblasts and to assess its impact on their interactions. To this end, we used a well-established in vitro 3D co-culture model imitating a realistic scenario. Our study shows that low CAP exposure is biocompatible and does not affect the viability or energetics of fibroblasts and keratinocytes. Exposure to low doses of CAP enhanced the proliferation rate of cells and stimulated the expression of key genes (KGF, MMP2, GMCSF, IL-6, and IL-8) in fibroblasts, indicating the activation and initiation of the skin repair process. Additionally, enhanced migration was observed under co-culture conditions under the given redox stress conditions, and expression of the upstream regulator and the effectors of the Hippo pathway (YAP and CYR61, respectively), which are associated with enhanced migration, were elevated. Overall, this study reinforces the application of CAP and redox stress in skin repair physiology.

Community-wide Screening for Tuberculosis in a High-Prevalence Setting.

BACKGROUND: The World Health Organization has set ambitious targets for the global elimination of tuberculosis. However, these targets will not be achieved at the current rate of progress. METHODS: We performed a cluster-randomized, controlled trial in Ca Mau Province, Vietnam, to evaluate the effectiveness of active community-wide screening, as compared with standard passive case detection alone, for reducing the prevalence of tuberculosis. Persons 15 years of age or older who resided in 60 intervention clusters (subcommunes) were screened for pulmonary tuberculosis, regardless of symptoms, annually for 3 years, beginning in 2014, by means of rapid nucleic acid amplification testing of spontaneously expectorated sputum samples. Active screening was not performed in the 60 control clusters in the first 3 years. The primary outcome, measured in the fourth year, was the prevalence of microbiologically confirmed pulmonary tuberculosis among persons 15 years of age or older. The secondary outcome was the prevalence of tuberculosis infection, as assessed by an interferon gamma release assay in the fourth year, among children born in 2012. RESULTS: In the fourth-year prevalence survey, we tested 42,150 participants in the intervention group and 41,680 participants in the control group. A total of 53 participants in the intervention group (126 per 100,000 population) and 94 participants in the control group (226 per 100,000) had pulmonary tuberculosis, as confirmed by a positive nucleic acid amplification test for Mycobacterium tuberculosis (prevalence ratio, 0.56; 95% confidence interval [CI], 0.40 to 0.78; P<0.001). The prevalence of tuberculosis infection in children born in 2012 was 3.3% in the intervention group and 2.6% in the control group (prevalence ratio, 1.29; 95% CI, 0.70 to 2.36; P = 0.42). CONCLUSIONS: Three years of community-wide screening in persons 15 years of age or older who resided in Ca Mau Province, Vietnam, resulted in a lower prevalence of pulmonary tuberculosis in the fourth year than standard passive case detection alone. (Funded by the Australian National Health and Medical Research Council; ACT3 Australian New Zealand Clinical Trials Registry number, ACTRN12614000372684.).

Electrodeposited Amorphous Tungsten-doped Cobalt Oxide as an Efficient Catalyst for the Oxygen Evolution Reaction.

Thin film of amorphous tungsten-doped cobalt oxide (W:CoO) was successfully grown on a conducting electrode via an electrochemical oxidation process employing a [Co(WS4 )2 ]2- deposition bath. The W:CoO catalyst displays an attractive performance for the oxygen evolution reaction in an alkaline solution. In an NaOH solution of pH 13, W:CoO operates with a moderate onset overpotential of 230 mV and requires 320 mV overpotential to generate a catalytic current density of 10 mA cm-2 . A low Tafel slope of 45 mV decade-1 was determined, indicating a rapid O2 -evolving kinetics. The as-prepared W:CoO belongs to the best cobalt oxide-based catalysts ever reported for the oxygen evolution (OER) reaction.

Molecular epidemiology of tuberculosis and recent developments in understanding the epidemiology of tuberculosis.

The development of molecular typing techniques during the last decade has led to remarkable improvements in epidemiological studies of tuberculosis (TB) and other infectious disease. In this paper, the burden of TB disease, current issues about disease control in developed countries including Australia and the contribution of molecular typing to improved understanding of TB epidemiology are reviewed.

Radiotherapy for cancer of the head and neck: altered fractionation regimens.

A greater understanding of radiobiology led to the development of two classes of radiation fractionation schedules for the treatment of head and neck cancers. The aim of accelerated fractionation is to reduce tumour proliferation, which is a major cause of relapse, by shortening the total duration of radiotherapy. By contrast, hyperfractionation exploits the differential sensitivity of tumour cells and normal tissues to radiation, to increase the therapeutic gain. The results of clinical trials of various types of altered fractionation schedules in head and neck carcinomas are examined in this review. Acceleration of radiation by 1 week without dose reduction and hyperfractionation are consistently better than standard fractionation for locoregional control of intermediate to advanced carcinomas without an increase in late toxic effects. However, improvement in survival of patients has not been consistent. Clinical investigations show that improvement in locoregional disease control and consistent gain in survival have been achieved with combinations of radiotherapy and concurrent chemotherapy in patients with mostly stage IV carcinomas. However, these benefits have been at the expense of increased late morbidity. Consequently, concurrent radiochemotherapy is now preferred for non-surgical treatment of patients with locally advanced carcinomas, whereas altered fractionation is generally selected for patients with intermediate-stage tumours or who are medically unfit to receive chemotherapy. Further data is needed before the combination of altered fractionation with chemotherapy can be recommended outside of a study setting.