Comprehensive functional characterization of complement factor I rare variant genotypes identified in the SCOPE geographic atrophy cohort.

Rare variants (RVs) in the gene encoding the regulatory enzyme complement factor I (CFI; FI) that reduce protein function or levels increase age-related macular degeneration risk. A total of 3357 subjects underwent screening in the SCOPE natural history study for geographic atrophy secondary to age-related macular degeneration, including CFI sequencing and serum FI measurement. Eleven CFI RV genotypes that were challenging to categorize as type I (low serum level) or type II (normal serum level, reduced enzymatic function) were characterized in the context of pure FI protein in C3b and C4b fluid phase cleavage assays and a novel bead-based functional assay (BBFA) of C3b cleavage.

Effect of aerobic exercise training on pulse wave velocity in adults with and without long-term conditions: a systematic review and meta-analysis.

Rationale: There is conflicting evidence whether aerobic exercise training (AET) reduces pulse wave velocity (PWV) in adults with and without long-term conditions (LTCs).

Objective: To explore whether PWV improves with AET in adults with and without LTC, to quantify the magnitude of any effect and understand the influence of the exercise prescription.

Data Sources: CENTRAL, MEDLINE and EMBASE were among the databases searched.

Understanding the effectiveness of different exercise training programme designs on V̇O in COPD: a component network meta-analysis.

Pulmonary rehabilitation programmes including aerobic training improve cardiorespiratory fitness in patients with COPD, but the optimal programme design is unclear. We used random effects additive component network meta-analysis to investigate the relative effectiveness of different programme components on fitness measured by V̇O in COPD. The included 59 studies involving 2191 participants demonstrated that V̇O increased after aerobic training of at least moderate intensity with the greatest improvement seen following high intensity training.

Exercise rehabilitation in COPD and heart failure: comparison of two national audits.

Background: Pulmonary (PR) and cardiac rehabilitation (CR) are recommended in the management of chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF); the impact of coexisting COPD and CHF on completion and outcomes of rehabilitation programmes is unknown. We examined enrolment, completion and clinical outcomes of CR and PR in adults with COPD, CHF and coexisting COPD and CHF.

Methods: The National Audit of CR and National COPD Audit Programme: clinical audits of PR were analysed (211 PR and 237 CR programmes); adults with a diagnosis of CHF, COPD or coexisting COPD and CHF were identified (COPD+CHF or CHF+COPD according to database).

An assessment of prevalence of Type 1 CFI rare variants in European AMD, and why lack of broader genetic data hinders development of new treatments and healthcare access.

Purpose: Advanced age-related macular degeneration (AAMD) risk is associated with rare complement Factor I (FI) genetic variants associated with low FI protein levels (termed 'Type 1'), but it is unclear how variant prevalences differ between AMD patients from different ethnicities.

Methods: Collective prevalence of Type 1 CFI rare variant genotypes were examined in four European AAMD datasets. Collective minor allele frequencies (MAFs) were sourced from the natural history study SCOPE, the UK Biobank, the International AMD Genomics Consortium (IAMDGC), and the Finnish Biobank Cooperative (FINBB), and compared to paired control MAFs or background population prevalence rates from the Genome Aggregation Database (gnomAD).

Evaluating a Causal Relationship between Complement Factor I Protein Level and Advanced Age-Related Macular Degeneration Using Mendelian Randomization.

Importance: Risk of advanced age-related macular degeneration (AAMD) is associated with rare genetic variants in the gene encoding Complement factor I (), which is associated with lower circulating CFI protein levels, but the nature of the relationship is unclear.

Objective: Can genetic factors be used to infer whether low circulating CFI is associated with AAMD risk?

Design: Two-sample inverse variance weighted Mendelian Randomisation (MR) was used to evaluate evidence for a relationship between CFI levels and AAMD risk, comparing CFI levels from genetically predefined subsets in AAMD and control cohorts.

Setting: Published genetic and proteomic data was combined with data from cohorts of Geographic Atrophy (GA) patients in a series of MR analyses.

Developing Appropriate Pulmonary Rehabilitation Services in Sri Lanka: Assessment of People Living with COPD and Healthcare Providers in Urban and Semi Urban Areas in Sri Lanka.

Introduction: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide, corresponding to 5% of all deaths globally, with more than 90% occurring in low- and middle-income countries (LMIC). Pulmonary Rehabilitation (PR) is a routine clinical service for COPD management, often used in western countries. At present, there is no formal PR in Sri Lanka; a culturally appropriate programme is required that considers the views of adults living with COPD and healthcare providers (HCPs) who would be involved in the referral or delivery of PR.

Culturally adapted pulmonary rehabilitation for adults living with post-tuberculosis lung disease in Kyrgyzstan: protocol for a randomised controlled trial with blinded outcome measures.

Introduction: Pulmonary rehabilitation (PR) is a programme of individually prescribed physical exercise, education and self-management activities. PR is recommended in international guidelines for managing chronic obstructive pulmonary disease (COPD) and other chronic respiratory diseases. PR is still under-recognised in tuberculosis (TB) guidelines and PR is not available in many low and middle-income countries and for people with post-TB lung disease (PTBLD).

What should pulmonary rehabilitation look like for people living with post-tuberculosis lung disease in the Bishkek and Chui region of the Kyrgyz Republic? A qualitative exploration.

Objective: After experiencing tuberculosis (TB), many people develop post-tuberculosis lung disease (PTBLD). Pulmonary rehabilitation (PR) centrally comprising of education and exercise is recommended internationally for people living with chronic respiratory diseases. However, no such service exists in Kyrgyzstan.

Potential for integrating yoga within pulmonary rehabilitation and recommendations of reporting framework.

There is a rising burden of chronic obstructive pulmonary disease (COPD) in India. Pulmonary rehabilitation (PR), is a universally recommended multidisciplinary therapeutic strategy for the management of COPD; however, its needs are unmet. The diversity in the healthcare systems, availability of PR specialists and sociocultural multiformity requires contextualised and innovative PR models.

Identifying Appropriate Delivery of and Referral to Pulmonary Rehabilitation in Uganda: A Survey Study of People Living with Chronic Respiratory Disease and Health Care Workers.

Introduction: Pulmonary rehabilitation (PR) is a low cost, high impact intervention that ameliorates the disability associated with chronic respiratory diseases (CRD). PR is becoming increasingly recognized in low resource settings where the burden of CRD is rapidly increasing. To aid the implementation of PR in Uganda, we conducted a study to assess the attitudes and opinions towards PR among patients with CRD in Uganda and explore barriers faced by health care workers (HCWs) in referring to PR.

Protocol for the cultural adaptation of pulmonary rehabilitation and subsequent testing in a randomised controlled feasibility trial for adults with chronic obstructive pulmonary disease in Sri Lanka.

Introduction: International guidelines recommend pulmonary rehabilitation (PR) should be offered to adults living with chronic obstructive pulmonary disease (COPD), but PR availability is limited in Sri Lanka. Culturally appropriate PR needs to be designed and implemented in Sri Lanka. The study aims to adapt PR to the Sri Lankan context and determine the feasibility of conducting a future trial of the adapted PR in Sri Lanka.

Change in V˙O in Response to Aerobic Exercise Training and the Relationship With Exercise Prescription in People With COPD: A Systematic Review and Meta-analysis.

Background: Despite the wide-ranging benefits of pulmonary rehabilitation, conflicting results remain regarding whether people with COPD can improve their peak oxygen uptake (V˙O with aerobic training.

Research Question: The goal of this study was to investigate the effect of aerobic training and exercise prescription on V˙O in COPD.

Study Design And Methods: A systematic review was performed by using MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, and Cochrane databases for all studies measuring V˙O prior to and following supervised lower-limb aerobic training in COPD.

Outcome measures in a combined exercise rehabilitation programme for adults with COPD and chronic heart failure: A preliminary stakeholder consensus event.

Combined exercise rehabilitation for chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) is potentially attractive. Uncertainty remains as to the baseline profiling assessments and outcome measures that should be collected within a programme. Current evidence surrounding outcome measures in cardiac and pulmonary rehabilitation were presented by experts at a stakeholder consensus event and all stakeholders ( = 18) were asked to (1) rank in order of importance a list of categories, (2) prioritise outcome measures and (3) prioritise baseline patient evaluation measures that should be assessed in a combined COPD and CHF rehabilitation programme.

Protocol for a feasibility trial to inform the development of a breathlessness rehabilitation programme for chronic obstructive pulmonary disease and chronic heart failure (the COHERE trial).

Introduction: Adults with chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) commonly suffer from exertional dyspnoea and fatigue. Exercise training is recommended in the management of both diseases, yet many of the outcome measures traditionally reported are disease specific and may not fully acknowledge the multimorbid older adult. Based on our previous research, a breathlessness rehabilitation programme for patients with COPD/CHF or combined disease has been introduced as a service improvement within University Hospital Leicester National Health Service Trust and has amalgamated aspects of cardiac and pulmonary rehabilitation.

A Novel t(1;9)(p36;p24.1) JAK2 Translocation and Review of the Literature.

The JAK2V617F point mutation has been implicated in the pathogenesis of the vast majority of myeloproliferative neoplasms (MPNs), but translocations involving JAK2 have increasingly been identified in patients with JAK2V617F-negativeMPNs. Here, we present a case of a patient diagnosed with JAK2V617F-negativepolycythemia vera (PV) that transformed to the MPN-blast phase. Cytogenetic and FISH analysis revealed a novel translocation of t(1;9)(p36;p24.

Obesity and metabolic syndrome in COPD: Is exercise the answer?

Approximately half of all patients with chronic obstructive pulmonary disease (COPD) attending pulmonary rehabilitation (PR) programmes are overweight or obese which negatively impacts upon dyspnoea and exercise tolerance particularly when walking. Within the obese population (without COPD), the observed heterogeneity in prognosis is in part explained by the variability in the risk of developing cardiovascular disease or diabetes (cardiometabolic risk) leading to the description of metabolic syndrome. In obesity alone, high-intensity aerobic training can support healthy weight loss and improve the constituent components of metabolic syndrome.

GWAS of self-reported mosquito bite size, itch intensity and attractiveness to mosquitoes implicates immune-related predisposition loci.

Understanding the interaction between humans and mosquitoes is a critical area of study due to the phenomenal burdens on public health from mosquito-transmitted diseases. In this study, we conducted the first genome-wide association studies (GWAS) of self-reported mosquito bite reaction size (n = 84,724), itchiness caused by bites (n = 69,057), and perceived attractiveness to mosquitoes (n = 16,576). In total, 15 independent significant (P < 5×10-8) associations were identified.

Genome-wide association analysis of pain severity in dysmenorrhea identifies association at chromosome 1p13.2, near the nerve growth factor locus.

Dysmenorrhea is a common chronic pelvic pain syndrome affecting women of childbearing potential. Family studies suggest that genetic background influences the severity of dysmenorrhea, but genetic predisposition and molecular mechanisms underlying dysmenorrhea are not understood. In this study, we conduct the first genome-wide association study to identify genetic factors associated with dysmenorrhea pain severity.

Genetic and Environmental Risk for Chronic Pain and the Contribution of Risk Variants for Major Depressive Disorder: A Family-Based Mixed-Model Analysis.

Background: Chronic pain is highly prevalent and a significant source of disability, yet its genetic and environmental risk factors are poorly understood. Its relationship with major depressive disorder (MDD) is of particular importance. We sought to test the contribution of genetic factors and shared and unique environment to risk of chronic pain and its correlation with MDD in Generation Scotland: Scottish Family Health Study (GS:SFHS).

Genetic variation at MECOM, TERT, JAK2 and HBS1L-MYB predisposes to myeloproliferative neoplasms.

Clonal proliferation in myeloproliferative neoplasms (MPN) is driven by somatic mutations in JAK2, CALR or MPL, but the contribution of inherited factors is poorly characterized. Using a three-stage genome-wide association study of 3,437 MPN cases and 10,083 controls, we identify two SNPs with genome-wide significance in JAK2(V617F)-negative MPN: rs12339666 (JAK2; meta-analysis P=1.27 × 10(-10)) and rs2201862 (MECOM; meta-analysis P=1.