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Differential connection between estradiol about neural and mental tension response in postmenopausal girls together with remitted Significant Depressive Disorder.
We investigated if long-term household air pollution (HAP) is associated with asthma and lung function decline in middle-aged adults, and whether these associations were modified by glutathione
-transferase (GST) gene variants, ventilation and atopy.

Prospective data on HAP (heating, cooking, mould and smoking) and asthma were collected in the Tasmanian Longitudinal Health Study (TAHS) at mean ages 43 and 53 years (n=3314). Subsamples had data on lung function (n=897) and GST gene polymorphisms (n=928). Latent class analysis was used to characterise longitudinal patterns of exposure. Regression models assessed associations and interactions.

We identified seven longitudinal HAP profiles. Of these, three were associated with persistent asthma, greater lung function decline and % reversibility by age 53 years compared with the "Least exposed" reference profile for those who used reverse-cycle air conditioning, electric cooking and no smoking. The "All gas" (OR 2.64, 95% CI 1.22-5.70), "Wood heating/smoking" (OR 2.71, 95% CI 1.21-6.05) and "Wood heating/gas cooking" (OR 2.60, 95% CI 1.11-6.11) profiles were associated with persistent asthma, as well as greater lung function decline and % reversibility. Participants with the
Ile/Ile genotype were at a higher risk of asthma or greater lung function decline when exposed compared with other genotypes. Exhaust fan use and opening windows frequently may reduce the adverse effects of HAP produced by combustion heating and cooking on current asthma, presumably through increasing ventilation.

Exposures to wood heating, gas cooking and heating, and tobacco smoke over 10 years increased the risks of persistent asthma, lung function decline and % reversibility, with evidence of interaction by GST genes and ventilation.
Exposures to wood heating, gas cooking and heating, and tobacco smoke over 10 years increased the risks of persistent asthma, lung function decline and % reversibility, with evidence of interaction by GST genes and ventilation.Pulmonary fibrosis is a devastating, progressive disease and carries a prognosis worse than most cancers. Despite ongoing research, the mechanisms that underlie disease pathogenesis remain only partially understood. However, the self-perpetuating nature of pulmonary fibrosis has led several researchers to propose the existence of pathological signalling loops. According to this hypothesis, the normal wound-healing process becomes corrupted and results in the progressive accumulation of scar tissue in the lung. In addition, several negative regulators of pulmonary fibrosis are downregulated and, therefore, are no longer capable of inhibiting these feed-forward loops. The combination of pathological signalling loops and loss of a checks and balances system ultimately culminates in a process of unregulated scar formation. This review details specific signalling pathways demonstrated to play a role in the pathogenesis of pulmonary fibrosis. learn more The evidence of detrimental signalling loops is elucidated with regard to epithelial cell injury, cellular senescence and the activation of developmental and ageing pathways. We demonstrate where these loops intersect each other, as well as common mediators that may drive these responses and how the loss of pro-resolving mediators may contribute to the propagation of disease. By focusing on the overlapping signalling mediators among the many pro-fibrotic pathways, it is our hope that the pulmonary fibrosis community will be better equipped to design future trials that incorporate the redundant nature of these pathways as we move towards finding a cure for this unrelenting disease.
There are no determined treatment agents for severe COVID-19. It is suggested that methylprednisolone, as an immunosuppressive treatment, can reduce the inflammation of the respiratory system in COVID-19 patients.

We conducted a single-blind, randomised controlled clinical trial involving severe hospitalised patients with confirmed COVID-19 at the early pulmonary phase of the illness in Iran. The patients were randomly allocated in a 11 ratio by the block randomisation method to receive standard care with methylprednisolone pulse (intravenous injection, 250 mg·day
for 3 days) or standard care alone. The study end-point was the time of clinical improvement or death, whichever came first. Primary and safety analysis was done in the intention-to-treat (ITT) population.

68 eligible patients underwent randomisation (34 patients in each group) from April 20, 2020 to June 20, 2020. In the standard care group, six patients received corticosteroids by the attending physician before the treatment and were excluded from the overall analysis. The percentage of improved patients was higher in the methylprednisolone group than in the standard care group (94.1%
57.1%) and the mortality rate was significantly lower in the methylprednisolone group (5.9%
42.9%; p<0.001). We demonstrated that patients in the methylprednisolone group had a significantly increased survival time compared with patients in the standard care group (log-rank test p<0.001; hazard ratio 0.293, 95% CI 0.154-0.556). Two patients (5.8%) in the methylprednisolone group and two patients (7.1%) in the standard care group showed severe adverse events between initiation of treatment and the end of the study.

Our results suggest that methylprednisolone pulse could be an efficient therapeutic agent for hospitalised severe COVID-19 patients at the pulmonary phase.
Our results suggest that methylprednisolone pulse could be an efficient therapeutic agent for hospitalised severe COVID-19 patients at the pulmonary phase.Conventional molecular tests for detecting Mycobacterium tuberculosis complex (MTBC) drug resistance on clinical samples cover a limited set of mutations. Whole-genome sequencing (WGS) typically requires culture.Here, we evaluated the Deeplex Myc-TB targeted deep-sequencing assay for prediction of resistance to 13 anti-tuberculous drugs/drug classes, directly applicable on sputum.With MTBC DNA tests, the limit of detection was 100-1000 genome copies for fixed resistance mutations. Deeplex Myc-TB captured in silico 97.1-99.3% of resistance phenotypes correctly predicted by WGS from 3651 MTBC genomes. On 429 isolates, the assay predicted 92.2% of 2369 first- and second-line phenotypes, with a sensitivity of 95.3% and a specificity of 97.4%. 56 out of 69 (81.2%) residual discrepancies with phenotypic results involved pyrazinamide, ethambutol and ethionamide, and low-level rifampicin or isoniazid resistance mutations, all notoriously prone to phenotypic testing variability. Only two out of 91 (2.2%) resistance phenotypes undetected by Deeplex Myc-TB had known resistance-associated mutations by WGS analysis outside Deeplex Myc-TB targets. Phenotype predictions from Deeplex Myc-TB analysis directly on 109 sputa from a Djibouti survey matched those of MTBSeq/PhyResSE/Mykrobe, fed with WGS data from subsequent cultures, with a sensitivity of 93.5/98.5/93.1% and a specificity of 98.5/97.2/95.3%, respectively. Most residual discordances involved gene deletions/indels and 3-12% heteroresistant calls undetected by WGS analysis or natural pyrazinamide resistance of globally rare "Mycobacterium canettii" strains then unreported by Deeplex Myc-TB. On 1494 arduous sputa from a Democratic Republic of the Congo survey, 14 902 out of 19 422 (76.7%) possible susceptible or resistance phenotypes could be predicted culture-free.Deeplex Myc-TB may enable fast, tailored tuberculosis treatment.
Sarcoidosis and tuberculosis are granulomatous pulmonary diseases characterised by heightened immune reactivity to
antigens. We hypothesised that an unsupervised analysis comparing the molecular characteristics of granulomas formed in response to
antigens in patients with sarcoidosis or latent tuberculosis infection (LTBI) would provide novel insights into the pathogenesis of sarcoidosis.

A genomic analysis identified differentially expressed genes in granuloma-like cell aggregates formed by sarcoidosis (n=12) or LTBI patients (n=5) in an established
human granuloma model wherein peripheral blood mononuclear cells were exposed to
antigens (beads coated with purified protein derivative) and cultured for 7 days. Pathway analysis of differentially expressed genes identified canonical pathways, most notably antigen processing and presentation
phagolysosomes, as a prominent pathway in sarcoidosis granuloma formation. The phagolysosomal pathway promoted mechanistic target of rapamycin complex 1 (bly and acidification are required to support mTORc1 signalling to promote sarcoidosis granuloma formation.
Obesity is a common comorbidity in asthma and associated with poorer asthma control, more frequent/severe exacerbations, and reduced response to asthma pharmacotherapy.

This review aims to compare use of all classes of asthma medications in obese (body mass index (BMI) ≤30 kg·m
)
healthy-weight (BMI <25 kg·m
) subjects with asthma.

Databases including CINAHL (Cumulative Index to Nursing and Allied Health Literature), Cochrane, Embase and MEDLINE were searched up to July 2019 for English-language studies that recorded medication use or dose in obese and healthy-weight adults with asthma. A critical appraisal checklist was utilised for scrutinising methodological quality of eligible studies. Meta-analysis was performed and heterogeneity was examined with the use of the Chi-squared test. This review was conducted based on a published protocol (www.crd.york.ac.uk/PROSPERO CRD42020148671).

Meta-analysis showed that obese subjects are more likely to use asthma medications, including short-acting β
a medication classes and higher ICS doses than healthy-weight asthma subjects, despite lower FEV1 and a similar FEV1/FVC %. A better understanding of the factors driving increased medication use is required to improve outcomes in this subgroup of asthmatics.
Weight estimation of both adult and paediatric patients is often necessary in emergency or low-resource settings when it is not possible to weigh the patient. There are many methods for paediatric weight estimation, but no standard methods for adults. PAWPER and Mercy tapes are used in children, but have not been assessed in adults. The primary aim of this study was to assess weight estimation methods in patients of all ages.

Patients were prospectively recruited from emergency and outpatient departments in Kigali, Rwanda. Participants (or guardians) were asked to estimate weight. Investigators collected weight, height, mid-arm circumference (MAC) and humeral-length data. In all participants, estimates of weight were calculated from height and MAC (PAWPER methods), MAC and humeral length (Mercy method). In children, Broselow measurements and age-based formulae were also used. The primary outcome measure was the proportion of estimates within 20% of actual weight (p20).

We recruited 947 participants 307 eir use in this setting.
Coronavirus disease 2019 is spreading rapidly across the world. This study aimed to assess the characteristics of kidney injury and its association with disease progression and death of patients with coronavirus disease 2019.

This is a retrospective study. Two representative cohorts were included. Cohort 1 involved severe and critical patients with coronavirus disease 2019 from Wuhan, China. Cohort 2 was all patients with coronavirus disease 2019 in Shenzhen city (Guangdong province, China). Any kidney injury was defined as the presence of any of the following hematuria, proteinuria, in-hospital AKI, or prehospital AKI. AKI was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) creatinine criteria. The primary outcome was death at the end of follow-up. The secondary outcome was progression to critical illness during the study period.

A total of 555 patients were enrolled; 42% of the cases (229 of 549) were detected with any kidney injury, 33% of the cases (174 of 520) were detected with proteinuria, 22% of the cases (112 of 520) were detected with hematuria, and 6% of the cases (29 of 520) were detected with AKI.
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