Kitchen Concentrations of Fine Particulate Matter and Particle Number Concentration in Households Using Biomass Cookstoves in Rural Honduras

Cooking and heating with solid fuels results in high levels of household air pollutants, including particulate matter (PM); however, limited data exist for size fractions smaller than PM2.5 (diameter less than 2.5 μm). We collected 24-h time-resolved measurements of PM2.5 (n = 27) and particle number concentrations (PNC, average diameter 10–700 nm) (n = 44; 24 with paired PM2.5 and PNC) in homes with wood-burning traditional and Justa (i.e., with an engineered combustion chamber and chimney) cookstoves in rural Honduras. The median 24-h PM2.5 concentration (n = 27) was 79 μg/m3 (interquartile range [IQR]: 44–174 μg/m3); traditional (n = 15): 130 μg/m3 (IQR: 48–250 μg/m3); Justa (n = 12): 66 μg/m3 (IQR: 44–97 μg/m3). The median 24-h PNC (n = 44) was 8.5 × 104 particles (pt)/cm3 (IQR: 3.8 × 104–1.8 × 105 pt/cm3); traditional (n = 27): 1.3 × 105 pt/cm3 (IQR: 3.3 × 104–2.0 × 105 pt/cm3); Justa (n = 17): 6.3 × 104 pt/cm3 (IQR: 4.0 × 104–1.2 × 105 pt/cm3). The 24-h average PM2.5 and particle number concentrations were correlated for the full sample of cookstoves (n = 24, Spearman ρ: 0.83); correlations between PM2.5 and PNC were higher in traditional stove kitchens (n = 12, ρ: 0.93) than in Justa stove kitchens (n = 12, ρ: 0.67). The 24-h average concentrations of PM2.5 and PNC were also correlated with the maximum average concentrations during shorter-term averaging windows of one-, five-, 15-, and 60-min, respectively (Spearman ρ: PM2.5 [0.65, 0.85, 0.82, 0.71], PNC [0.74, 0.86, 0.88, 0.86]). Given the moderate correlations observed between 24-h PM2.5 and PNC and between 24-h and the shorter-term averaging windows within size fractions, investigators may need to consider cost-effectiveness and information gained by measuring both size fractions for the study objective. Further evaluations of other stove and fuel combinations are needed

Multi-ancestry genome-wide association meta-analysis of Parkinson’s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations

Author Correction: Discovery of 42 genome-wide significant loci associated with dyslexia

Correction to: Nature Genetics https://doi.org/10.1038/s41588-022-01192-y. Published online 20 October 2022. In the version of this article originally published, a paragraph was omitted in the Methods section, reading “Genomic control. Top SNPs are reported from the more conservative GWAS results adjusted for genomic control (Fig. 1, Extended Data Figs. 1–4, and Supplementary Tables 1, 2, 9 and 10), whereas downstream analyses (including gene-set analysis, enrichment and heritability partitioning, genetic correlations, polygenic prediction, candidate gene replication) are based on GWAS results without genomic control.” The paragraph has now been included in the HTML and PDF versions of the article

Real-world experience of nintedanib for progressive fibrosing interstitial lung disease in the UK

Background Nintedanib slows progression of lung function decline in patients with progressive fibrosing (PF) interstitial lung disease (ILD) and was recommended for this indication within the United Kingdom (UK) National Health Service in Scotland in June 2021 and in England, Wales and Northern Ireland in November 2021. To date, there has been no national evaluation of the use of nintedanib for PF-ILD in a real-world setting.Methods 26 UK centres were invited to take part in a national service evaluation between 17 November 2021 and 30 September 2022. Summary data regarding underlying diagnosis, pulmonary function tests, diagnostic criteria, radiological appearance, concurrent immunosuppressive therapy and drug tolerability were collected via electronic survey.Results 24 UK prescribing centres responded to the service evaluation invitation. Between 17 November 2021 and 30 September 2022, 1120 patients received a multidisciplinary team recommendation to commence nintedanib for PF-ILD. The most common underlying diagnoses were hypersensitivity pneumonitis (298 out of 1120, 26.6%), connective tissue disease associated ILD (197 out of 1120, 17.6%), rheumatoid arthritis associated ILD (180 out of 1120, 16.0%), idiopathic nonspecific interstitial pneumonia (125 out of 1120, 11.1%) and unclassifiable ILD (100 out of 1120, 8.9%). Of these, 54.4% (609 out of 1120) were receiving concomitant corticosteroids, 355 (31.7%) out of 1120 were receiving concomitant mycophenolate mofetil and 340 (30.3%) out of 1120 were receiving another immunosuppressive/modulatory therapy. Radiological progression of ILD combined with worsening respiratory symptoms was the most common reason for the diagnosis of PF-ILD.Conclusion We have demonstrated the use of nintedanib for the treatment of PF-ILD across a broad range of underlying conditions. Nintedanib is frequently co-prescribed alongside immunosuppressive and immunomodulatory therapy. The use of nintedanib for the treatment of PF-ILD has demonstrated acceptable tolerability in a real-world setting

Genome-wide association study of {REM} sleep behavior disorder identifies polygenic risk and brain expression effects

AbstractRapid-eye movement (REM) sleep behavior disorder (RBD), enactment of dreams during REM sleep, is an early clinical symptom of alpha-synucleinopathies and defines a more severe subtype. The genetic background of RBD and its underlying mechanisms are not well understood. Here, we perform a genome-wide association study of RBD, identifying five RBD risk loci near SNCA, GBA, TMEM175, INPP5F, and SCARB2. Expression analyses highlight SNCA-AS1 and potentially SCARB2 differential expression in different brain regions in RBD, with SNCA-AS1 further supported by colocalization analyses. Polygenic risk score, pathway analysis, and genetic correlations provide further insights into RBD genetics, highlighting RBD as a unique alpha-synucleinopathy subpopulation that will allow future early intervention

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Multi-ancestry genome-wide association meta-analysis of Parkinson?s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations

Rating scale item assessment of self-harm in postpartum women: a cross-sectional analysis

We examined the utility of screening instruments to identify risk factors for suicidal ideation (SI) in a population of women with neuropsychiatric illnesses at high risk for postpartum depression. Pregnant women with neuropsychiatric illness enrolled prior to 20 weeks of gestation. Follow-up visits at 4-8-week intervals through 13 weeks postpartum included assessment of depressive symptoms with both clinician and self-rated scales. A total of 842 women were included in the study. Up to 22.3% of postpartum women admitted SI on rating scales, despite the majority (79%) receiving active pharmacological treatment for psychiatric illness. Postpartum women admitting self-harm/SI were more likely to meet criteria for current major depressive episode (MDE), less than college education, an unplanned pregnancy, a history of past suicide attempt, and a higher score on the Childhood Trauma Questionnaire. In women with a history of neuropsychiatric illness, over 20% admitted SI during the postpartum period despite ongoing psychiatric treatment. Patient-rated depression scales are more sensitive screening tools than a clinician-rated depression scale for +SI in the postpartum period