Effects of exercise training on airway responsiveness and airway cells in healthy subjects

J Appl Physiol. 2010 Aug;109(2):288-94. Epub 2010 Jun 10. Effects of exercise training on airway responsiveness and airway cells in healthy subjects. Scichilone N, Morici G, Zangla D, Chimenti L, Dav\uec E, Reitano S, Patern\uf2 A, Santagata R, Togias A, Bellia V, Bonsignore MR. SourceDept. of Internal Medicine, Div. of Pulmonology (DIBIMIS Univ. of Palermo, "Villa Sofia-Cervello" Hospital, Via Trabucco 180, 90146 Palermo, Italy. [email protected] Abstract Airway responsiveness to methacholine (Mch) in the absence of deep inspirations (DIs) is lower in athletes compared with sedentary individuals. In this prospective study, we tested the hypothesis that a training exercise program reduces the bronchoconstrictive effect of Mch. Ten healthy sedentary subjects (M/F: 3/7; mean + or - SD age: 22 + or - 3 yr) entered a 10-wk indoor rowing exercise program on rowing ergometer and underwent Mch bronchoprovocation in the absence of DIs at baseline, at weeks 5 and 10, as well as 4-6 wk after the training program was completed. Exercise-induced changes on airway cells and markers of airway inflammation were also assessed by sputum induction and venous blood samples. Mean power output during the 1,000 m test was 169 + or - 49 W/stroke at baseline, 174 + or - 49 W/stroke at 5 wk, and 200 + or - 60 W/stroke at 10 wk of training (P < 0.05). The median Mch dose used at baseline was 50 mg/ml (range 25-75 mg/ml) and remained constant per study design. At the pretraining evaluation, the percent reduction in the primary outcome, the inspiratory vital capacity (IVC) after inhalation of Mch in the absence of DIs was 31 +/- 13%; at week 5, the Mch-induced reduction in IVC was 22 + or - 19%, P = 0.01, and it further decreased to 15 + or - 11% at week 10 (P = 0.0008). The percent fall in IVC 4-6 wk after the end of training was 15 + or - 11% (P = 0.87 vs. end of training). Changes in airway cells were not associated with changes in airway responsiveness. Our data show that a course of exercise training can attenuate airway responsiveness against Mch inhaled in the absence of DIs in healthy subjects and suggest that a sedentary lifestyle may favor development of airways hyperresponsiveness. Comment in J Appl Physiol. 2010 Aug;109(2):267-8. PMID:20538849[PubMed - in process

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p&lt;0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p&lt;0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p&lt;0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP &gt;5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

A search for novel cancer susceptibility genes

The overriding aim of this research was to identify novel cancer susceptibility genes by investigating rare families with potentially new cancer susceptibility syndromes. In selecting families suitable for the research, a number of families with an unusual clustering of different cancer types were identified that did not have a coding mutation in any plausible candidate cancer genes. In additon to these families, a large Australian family with a new Gastric Adenocarcinoma and Proximal Polyposis Syndrome (GAPPS) was identified and investigated. To investigate families with multiple different cancer types, the genetic analysis of tumour and germline DNA samples was conducted in order to determine whether a common inherited mutation exisited for each individual family. Methods for this analysis involved the analysis of multiple tumours within each family using a SNP-based arrayCGH (SNP-CGH) approach to assess the tumours for common regions of chromosome copy number loss and gain, and linkage analysis in sufficiently informative families. The SNP-CGH approach was largely uninformative due to the technical difficulties associated with analysing formalin-fixed paraffin embedded tumours. However, linkage analysis in two families identified regions with LOD scores of 2 or greater that, after additional haplotype analysis in these families, were prioritised for further investigation. The most signifanct result of the research is the description of the novel cancer syndrome, GAPPS, and mapping the causal GAPPS locus to chromosome 5q13-21 by linkage analysis of the large Australian kindred. A number of approaches were used to pinpoint the GAPPS locus and included expression analysis of gastric polyps and blood samples from the Australian family, SNP-CGH to assess fresh-frozen polyp samples for chromosome copy number changes, and targeted next generation sequencing of GAPPS cases (one case from the Australian family, one case from an additional GAPPS family identified in North American family). These approaches did not result in a clear candidate gene responsible for GAPPS that was shared by both cases but a number of candidate genes from the Australian case have been prioritised for further investigation. Furthermore, the SNP-CGH approach identified a copy number loss covering the 5q13-21 linkage region in three of eight polyps investigated, suggesting that a loss of function of a tumour suppressor gene may be the mechanism of cancer pathogenesis that underpins GAPPS progression. Overall, this research used a range of contemporary and traditional methods coupled with novel research aims to identify new cancer susceptibility genes. This work demonstrates the value of family-based studies for identifying cancer genes and in furthering our understanding of cancer development

U.K. support network for maternity acupuncture : survey of acupuncturists on the Acupuncture (for Conception to) Childbirth Team

Objective: In the United Kingdom, a professional acupuncture network, the Acupuncture (for Conception to) Childbirth Team (ACT), provides education and support for practitioners using maternity acupuncture. However, the nature of treatments their members provide has been unknown. The aim of this survey was to explore how ACT members used acupuncture for maternity care within their women's health practices. Materials and Methods: An anonymous self-completion questionnaire, hosted by Survey Monkey, was completed by practitioners from 10 ACT branches. Questions covered demographic information, type and frequency of treatment provided in the previous year, and referral networks. Descriptive statistics were used to report the data. Results: Of 114 survey forms sent, 99 replies were received, a response rate of 86.8%. In addition to fertility and menstrual conditions, the majority of the practitioners (87 [87.8%]) had treated at least 1 pregnant woman each. The most-common maternity situations encountered were: birth preparation (84 [96.5%]); nausea & vomiting (82 [94.2%]); and inducing labor (79 [90.8%]). More than 50% of the practitioners were also treating lower-back and pelvic pain (77 [88.5%]), breech presentations (74 [85.0%]), threatened miscarriages (55 [63.2%]), and headaches/migraines (46 [52.8%]). Only a minority (8 [9.1%]) attended births. A greater number of referrals were received from medical health professionals for pregnancy (54 [65.8%]) than for fertility (16 [19.5%]) or menstrual conditions (8 [9.7%]). Conclusions: ACT practitioners were treating a wide range of maternity conditions. Referrals from Western medical practitioners were more common for maternity acupuncture than for fertility or menstrual health. It may be that this professional network approach would be beneficial in other countries to support practitioners interested in providing maternity acupuncture

Who am I? A qualitative exploration of the identities of spouses/partners of UK Armed Forces Veterans

Introduction: Events such as frequent separation, relocation, and the inherent risks of military service may negatively affect partner health/well-being and sense of identity. While research has attempted to understand how the identities of personnel change after transitioning out of the military community, there is little focus on partner identities. Methods: Qualitative interviews with 37 current and former partners (31 female, 6 male) participating in the UK Veterans Family Study (UKVFS) explored the lived experiences of partners of military Veterans and their mental health/well-being. Data were analyzed using thematic analysis. Results: Three themes were created: military identity and culture, role-based identities, and loss of personal identity. Participants described ascribed and adopted identities including wife of, parent, employee, and member of the armed forces community. These identities interacted and changed but were underpinned by military life and culture both during and after service. Participants highlighted long-term impacts on self-esteem and confidence but also pride and resilience. Employment post-transition allowed restoration of personal identity but could come at the cost of belonging provided by the military community. Discussion: Findings demonstrate the challenges some military and Veteran partners experienced in maintaining personal identity and highlight both positive and negative long-term effects of military life on self-perceptions of identity. Many identities discussed were in service to others — often at the expense of partners’ well-being and autonomy. Future research should concentrate on short- and long-term effects of identity loss/change on military and Veteran partners to inform and improve current and future strategies aiming to support partners