Hyporesponsiveness to aerosolized but not to infused methacholine in cigarette-smoking dogs.

Abstract Seven beagles were exposed via a tracheostomy to smoke from 10 cigarettes/day, 5 days/wk for 10 months; 2 other dogs were exposed for 6 months only. Four dogs served as sham-exposed control animals. Mucus was collected 2 times/wk prior to and during the exposure period by resting a cytology brush on the lower trachea for 2 to 5 min. At least once prior to and as often as 3 times during exposure, transpulmonary pressure and flow were monitored under anesthesia to determine resistance RL. Two airway responses to methacholine were determined: the infusion response delta Ri, the increment in RL 4 to 6 min after infusion of 4 micrograms/kg/min, and the aerosol response delta Ra, the increment in RL 2 min after aerosolization of 2 mg/ml, the highest common dose reached. Eight of 9 smoking dogs developed persistent mucus hypersecretion. In 5 dogs, tracheal mucus flux increased 5- to 10-fold; in 3 dogs, the increase was 2 to 3 times that of control animals. One of the sham-exposed dogs developed moderate hypersecretion. After 10 months of smoke exposure, delta Ri increased to 2.24 times that of the initial value (+/- 0.47 SE) (n = 7, p less than 0.05), whereas delta Ra decreased to 0.28 times that of the control value (+/- 0.21 SE) (n = 6, p less than 0.02). The difference between aerosol and infusion response, delta Rai = delta Ra - delta Ri, is an index of relative hyporesponsiveness to methacholine aerosol.(ABSTRACT TRUNCATED AT 250 WORDS

Postpartum depression screening in mothers and fathers at well-child visits: a feasibility study within the NASCITA cohort

Objective To assess the feasibility of the family paediatrician’s (FP) role in identifying the signs of postpartum depression in parents in time to guarantee child well-being.Design, setting and participants Data for this observational prospective study were collected within the NASCITA (NAscere e creSCere in ITAlia) cohort. During the first visit, paediatricians collected sociodemographic data regarding the parents and information about their health status, the pregnancy and the delivery. Whooley questions were administered during the first and second visits (scheduled 60–90 days after childbirth). Moreover, on the third visit (5–7 months after childbirth) the FP was asked to answer ‘yes’ or ‘no’ to a question on the parental postpartum depression, based on his knowledge and on the acquired information.Results In 2203 couples who completed the assessment, 529 mothers (19.9%), 141 fathers (6.3%) and 110 (5%) couples reported any depressive symptomatology. Of these, 141 mothers (5.3% of the total sample) and 18 fathers (0.8% of the total sample) were classified as ‘likely depressed’. An association was found between maternal postnatal depressive symptoms and having a diagnosed psychiatric disorder during pregnancy (OR 9.49, 95% CI: 3.20 to 28.17), not exclusively breastfeeding at hospital discharge (OR 1.76, 95% CI: 1.19 to 2.61) and the presence of child sleeping disorders at 3 (OR 2.46, 95% CI: 1.41 to 4.28) and 6 months (OR 2.18, 95% CI: 1.37 to 3.47). Another significant predictor of postpartum depression was being primiparous (OR 1.99, 95% CI: 1.31 to 3.02). Concerning the fathers, a significant association was reported only between likely depressed fathers and child sleeping disorders at 3 months (OR 7.64, 95% CI: 2.92 to 19.97). Moreover, having a likely depressed partner was strongly associated with depressive symptoms in fathers (OR 85.53, 95% CI 26.83 to 272.69).Conclusions The findings of this study support the feasibility of an active screening programme for parental postnatal depression during well-child visits as an integral part of postpartum care.Trial registration number NCT03894566; Pre-results

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3,4,5,6,7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease