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Persistence of rubella live vaccine has been associated with chronic skin granuloma in 3 children with primary immunodeficiency. We describe 6 additional children with these findings, including 1 with visceral extension to the spleen.

In recent years, a number of chronic diseases have been linked, in some cases definitively, to an infectious etiology: peptic ulcer disease with Helicobacter pylori, cervical cancer with several human papillomaviruses, Lyme arthritis and neuroborreliosis with Borrelia burgdorferi, AIDS with the human immunodeficiency virus, liver cancer and cirrhosis with hepatitis B and C viruses, to name a few. The proven and suspected roles of microbes does not stop with physical ailments; infections are increasingly being examined as associated causes of or possible contributors to a variety of serious, chronic neuropsychiatric disorders and to developmental problems, especially in children.The Infectious Etiology of Chronic Diseases: Defining the Relationship, Enhancing the Research, and Mitigating the Effects, summarizes a two-day workshop held by the Institute of Medicines Forum on Microbial Threats to address this rapidly evolving field. Participants explored factors driving infectious etiologies of chronic diseases of prominence, identified difficulties in linking infectious agents with chronic outcomes, and discussed broad-based strategies and research programs to advance the field.

ObjectiveOur purpose with this study is to examine the socioeconomic outcomes associated with chronic kidney disease not related to well-known risk factors (CKDnt) in four communities in Chichigalpa, Nicaragua that are home to a substantial number of sugarcane workers.MethodsWe employed a cluster-based systematic sampling design to identify differences in outcomes between those households affected directly by CKDnt and those that are not.ResultsOverall, we find that approximately one-third of households surveyed had a household member diagnosed with CKDnt. 86% of CKDnt households reported that the head of the household had been without work for the last 6 months or more, compared with 53% of non-CKDnt households. Non-CKDnt households took in more than double the earnings income on average than CKDnt households ($C52 835 and $C3120, respectively). Nonetheless, on average, CKDnt households’ total income exceeded that of non-CKDnt households due to Nicaragua’s national Instituto Nicaraguense de Seguridad Social Social Security payments to CKDnt households, suggestive of a substantial economic burden on the state resulting from the disease. Households headed by widows or widowers who are widowed as a result of CKDnt demonstrate distinct deficits in total income when compared with either non-widowed households or to households widowed by causes other than CKDnt.ConclusionsDespite strong similarities in terms of demographic characteristics and despite residing in the same communities with similar access to the available resources, households experiencing CKDnt exhibit distinct and statistically significant differences in important socioeconomic outcomes when compared to non-CKDnt households.

In China, where air pollution has become a major threat to public health, public awareness of the detrimental effects of air pollution on respiratory health is increasing—particularly in relation to haze days. Air pollutant emission levels in China remain substantially higher than are those in developed countries. Moreover, industry, traffic, and household biomass combustion have become major sources of air pollutant emissions, with substantial spatial and temporal variations. In this Review, we focus on the major constituents of air pollutants and their impacts on chronic respiratory diseases. We highlight targets for interventions and recommendations for pollution reduction through industrial upgrading, vehicle and fuel renovation, improvements in public transportation, lowering of personal exposure, mitigation of the direct effects of air pollution through healthy city development, intervention at population-based level (systematic health education, intensive and individualised intervention, pre-emptive measures, and rehabilitation), and improvement in air quality. The implementation of a national environmental protection policy has become urgent.

Dupilumab, a fully human monoclonal antibody that blocks the shared receptor component for interleukin-4 and interleukin-13, key and central drivers of type 2 inflammation, has shown efficacy and safety in a phase 3 trial involving patients with chronic obstructive pulmonary disease (COPD) and type 2 inflammation and an elevated risk of exacerbation. Whether the findings would be confirmed in a second phase 3 trial was unclear. In a phase 3, double-blind, randomized trial, we assigned patients with COPD who had a blood eosinophil count of 300 cells per microliter or higher to receive subcutaneous dupilumab (300 mg) or placebo every 2 weeks. The primary end point was the annualized rate of moderate or severe exacerbations. Key secondary end points, analyzed in a hierarchical manner to adjust for multiplicity, included the changes from baseline in the prebronchodilator forced expiratory volume in 1 second (FEV ) at weeks 12 and 52 and in the St. George's Respiratory Questionnaire (SGRQ; scores range from 0 to 100, with lower scores indicating better quality of life) total score at week 52. A total of 935 patients underwent randomization: 470 were assigned to the dupilumab group and 465 to the placebo group. As prespecified, the primary analysis was performed after a positive interim analysis and included all available data for the 935 participants, 721 of whom were included in the analysis at week 52. The annualized rate of moderate or severe exacerbations was 0.86 (95% confidence interval [CI], 0.70 to 1.06) with dupilumab and 1.30 (95% CI, 1.05 to 1.60) with placebo; the rate ratio as compared with placebo was 0.66 (95% CI, 0.54 to 0.82; P<0.001). The prebronchodilator FEV increased from baseline to week 12 with dupilumab (least-squares mean change, 139 ml [95% CI, 105 to 173]) as compared with placebo (least-squares mean change, 57 ml [95% CI, 23 to 91]), with a significant least-squares mean difference at week 12 of 82 ml (P<0.001) and at week 52 of 62 ml (P = 0.02). No significant between-group difference was observed in the change in SGRQ scores from baseline to 52 weeks. The incidence of adverse events was similar in the two groups and consistent with the established profile of dupilumab. In patients with COPD and type 2 inflammation as indicated by elevated blood eosinophil counts, dupilumab was associated with fewer exacerbations and better lung function than placebo. (Funded by Sanofi and Regeneron Pharmaceuticals; NOTUS ClinicalTrials.gov number, NCT04456673.).

A pair of review articles examines our current understanding of the biology, diagnosis, and treatment of chronic obstructive pulmonary disease. This article focuses on the pathogenesis of COPD.

It had been thought that most people with chronic obstructive pulmonary disease had normal lung function in mid-adult life and then lost it rapidly. In this study, many people with COPD already had low lung function in mid-adult life, before COPD developed. Chronic obstructive pulmonary disease (COPD) is a major cause of illness and death worldwide. 1 Since the research by Fletcher and colleagues in the 1970s, 2 , 3 the prevailing paradigm of COPD pathogenesis has been that, in susceptible persons, exposure to particulate matter — especially tobacco smoke — leads to clinical disease through acceleration of the age-related decline in lung function, as assessed by the forced expiratory volume in 1 second (FEV 1 ). Subsequent population studies supported this paradigm and led to therapeutic trials aimed at reducing the rapid decline in FEV 1 . 4 – 11 Surprisingly, the observed declines in FEV . . .

ObjectiveChronic obstructive pulmonary disease (COPD) is a global disease characterised by chronic obstruction of lung airflow interfering with normal breathing. Although the microbiota of respiratory tract is established to be associated with COPD, the causality of gut microbiota in COPD development is not yet established. We aimed to address the connection between gut microbiota composition and lung COPD development, and characterise bacteria and their derived active components for COPD amelioration.DesignA murine cigarette smoking (CS)-based model of COPD and strategies evaluating causal effects of microbiota were performed. Gut microbiota structure was analysed, followed by isolation of target bacterium. Single cell RNA sequencing, together with sera metabolomics analyses were performed to identify host responsive molecules. Bacteria derived active component was isolated, followed by functional assays.ResultsGut microbiota composition significantly affects CS-induced COPD development, and faecal microbiota transplantation restores COPD pathogenesis. A commensal bacterium Parabacteroides goldsteinii was isolated and shown to ameliorate COPD. Reduction of intestinal inflammation and enhancement of cellular mitochondrial and ribosomal activities in colon, systematic restoration of aberrant host amino acids metabolism in sera, and inhibition of lung inflammations act as the important COPD ameliorative mechanisms. Besides, the lipopolysaccharide derived from P. goldsteinii is anti-inflammatory, and significantly ameliorates COPD by acting as an antagonist of toll-like receptor 4 signalling pathway.ConclusionThe gut microbiota–lung COPD axis was connected. A potentially benefial bacterial strain and its functional component may be developed and used as alternative agents for COPD prevention or treatment.

Chronic wasting disease (CWD) is a fatal neurodegenerative disease of deer, elk, moose, and reindeer (cervids) caused by misfolded prion proteins. The disease has been reported across North America and recently discovered in northern Europe. Transmission of CWD in wild cervid populations can occur through environmental routes, but limited ability to detect prions in environmental samples has prevented the identification of potential transmission \"hot spots\". We establish widespread CWD prion contamination of mineral licks used by free-ranging cervids in an enzootic area in Wisconsin, USA. We show mineral licks can serve as reservoirs of CWD prions and thus facilitate disease transmission. Furthermore, mineral licks attract livestock and other wildlife that also obtain mineral nutrients via soil and water consumption. Exposure to CWD prions at mineral licks provides potential for cross-species transmission to wildlife, domestic animals, and humans. Managing deer use of mineral licks warrants further consideration to help control outbreaks of CWD.