Gastro-intestinal helminths of pigeons (Columba livia) in Gujarat, India

A study was conducted to assess the prevalence of helmith parasites of domestic wild and zoo pigeons in Gujarat, India by faecal sampling and postmortem examination. Qualitative examination of 78 faecal samples revealed 71 (91%) with parasitic infections of nematodes (85%), cestodes (31%) and Eimeria sp (77%). There were 200-1600 nematode eggs per gram during the monsoon season, which was high compared to the 200-1000 eggs per gram in winter and summer. In post-mortems 85% had parasitic infections, of nematodes (75%), cestodes (69%) and Eimeria sp (58%). Two species of nematodes (Ascaridia columbae and Capillaria obsignata) and five species of three genera of cestodes (Raillietina echinobothridia, R. tetragona, R. cesticillus, Cotugnia digonophora and Hymenolepis sp) were identified. Despite their parasitic infections, not a single pigeon revealed any alarming clinical signs

Characteristics of ischaemic stroke associated with COVID-19

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is associated with coagulopathy causing venous and arterial thrombosis.1 2 Recent data from the pandemic epicentre in Wuhan, China, reported neurological complications in 36% of 214 patients with COVID-19; acute cerebrovascular disease (mainly ischaemic stroke) was more common among 88 patients with severe COVID-19 than those with non-severe disease (5.7% vs 0.8%).3 However, the mechanisms, phenotype and optimal management of ischaemic stroke associated with COVID-19 remain uncertain. We describe the demographic, clinical, radiological and laboratory characteristics of six consecutive patients assessed between 1st and 16th April 2020 at the National Hospital for Neurology and Neurosurgery, Queen Square, London, UK, with acute ischaemic stroke and COVID-19 (confirmed by reverse-transcriptase PCR (RT-PCR)) (table 1). All six patients had large vessel occlusion with markedly elevated D-dimer levels (≥1000μg/L). Three patients had multiterritory infarcts, two had concurrent venous thrombosis, and, in two, ischaemic strokes occurred despite therapeutic anticoagulation

Design and rationale of a multi-center, pragmatic, open-label randomized trial of antimicrobial therapy - the study of clinical efficacy of antimicrobial therapy strategy using pragmatic design in Idiopathic Pulmonary Fibrosis (CleanUP-IPF) clinical trial

Compelling data have linked disease progression in patients with idiopathic pulmonary fibrosis (IPF) with lung dysbiosis and the resulting dysregulated local and systemic immune response. Moreover, prior therapeutic trials have suggested improved outcomes in these patients treated with either sulfamethoxazole/ trimethoprim or doxycycline. These trials have been limited by methodological concerns. This trial addresses the primary hypothesis that long-term treatment with antimicrobial therapy increases the time-to-event endpoint of respiratory hospitalization or all-cause mortality compared to usual care treatment in patients with IPF. We invoke numerous innovative features to achieve this goal, including: 1) utilizing a pragmatic randomized trial design; 2) collecting targeted biological samples to allow future exploration of 'personalized' therapy; and 3) developing a strong partnership between the NHLBI, a broad range of investigators, industry, and philanthropic organizations. The trial will randomize approximately 500 individuals in a 1:1 ratio to either antimicrobial therapy or usual care. The site principal investigator will declare their preferred initial antimicrobial treatment strategy (trimethoprim 160 mg/ sulfamethoxazole 800 mg twice a day plus folic acid 5 mg daily or doxycycline 100 mg once daily if body weight is < 50 kg or 100 mg twice daily if ≥50 kg) for the participant prior to randomization. Participants randomized to antimicrobial therapy will receive a voucher to help cover the additional prescription drug costs. Additionally, those participants will have 4-5 scheduled blood draws over the initial 24 months of therapy for safety monitoring. Blood sampling for DNA sequencing and genome wide transcriptomics will be collected before therapy. Blood sampling for transcriptomics and oral and fecal swabs for determination of the microbiome communities will be collected before and after study completion. As a pragmatic study, participants in both treatment arms will have limited in-person visits with the enrolling clinical center. Visits are limited to assessments of lung function and other clinical parameters at time points prior to randomization and at months 12, 24, and 36. All participants will be followed until the study completion for the assessment of clinical endpoints related to hospitalization and mortality events. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02759120

Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials

Rationale Clinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities. Methods The Connective Tissue Disease associated Interstitial Lung Disease (CTD-ILD) working group of Outcome Measures in Rheumatology—a non-profit international organisation dedicated to consensus methodology in identification of outcome measures—conducted a series of investigations which included a Delphi process including >248 ILD medical experts as well as patient focus groups culminating in a nominal group panel of ILD experts and patients. The goal was to define and develop a consensus on the status of outcome measure candidates for use in randomised controlled trials in CTD-ILD and idiopathic pulmonary fibrosis (IPF). Results A core set comprising specific measures in the domains of lung physiology, lung imaging, survival, dyspnoea, cough and health-related quality of life is proposed as appropriate for consideration for use in a hypothetical 1-year multicentre clinical trial for either CTD-ILD or IPF. As many widely used instruments were found to lack full validation, an agenda for future research is proposed. Conclusion Identification of consensus preliminary domains and instruments to measure them was attained and is a major advance anticipated to facilitate multicentre RCTs in the field

Plasma neurofilament light chain and amyloid-β are associated with the kynurenine pathway metabolites in preclinical Alzheimer's disease

BACKGROUND: Blood markers indicative of neurodegeneration (neurofilament light chain; NFL), Alzheimer's disease amyloid pathology (amyloid-β; Aβ), and neuroinflammation (kynurenine pathway; KP metabolites) have been investigated independently in neurodegenerative diseases. However, the association of these markers of neurodegeneration and AD pathology with neuroinflammation has not been investigated previously. Therefore, the current study examined whether NFL and Aβ correlate with KP metabolites in elderly individuals to provide insight on the association between blood indicators of neurodegeneration and neuroinflammation. METHODS: Correlations between KP metabolites, measured using liquid chromatography and gas chromatography coupled with mass spectrometry, and plasma NFL and Aβ concentrations, measured using single molecule array (Simoa) assays, were investigated in elderly individuals aged 65-90 years, with normal global cognition (Mini-Mental State Examination Score ≥ 26) from the Kerr Anglican Retirement Village Initiative in Ageing Health cohort. RESULTS: A positive correlation between NFL and the kynurenine to tryptophan ratio (K/T) reflecting indoleamine 2,3-dioxygenase activity was observed (r = .451, p < .0001). Positive correlations were also observed between NFL and kynurenine (r = .364, p < .0005), kynurenic acid (r = .384, p < .0001), 3-hydroxykynurenine (r = .246, p = .014), anthranilic acid (r = .311, p = .002), and quinolinic acid (r = .296, p = .003). Further, significant associations were observed between plasma Aβ40 and the K/T (r = .375, p < .0005), kynurenine (r = .374, p < .0005), kynurenic acid (r = .352, p < .0005), anthranilic acid (r = .381, p < .0005), and quinolinic acid (r = .352, p < .0005). Significant associations were also observed between plasma Aβ42 and the K/T ratio (r = .215, p = .034), kynurenic acid (r = .214, p = .035), anthranilic acid (r = .278, p = .006), and quinolinic acid (r = .224, p = .027) in the cohort. On stratifying participants based on their neocortical Aβ load (NAL) status, NFL correlated with KP metabolites irrespective of NAL status; however, associations between plasma Aβ and KP metabolites were only pronounced in individuals with high NAL while associations in individuals with low NAL were nearly absent. CONCLUSIONS: The current study shows that KP metabolite changes are associated with biomarker evidence of neurodegeneration. Additionally, the association between KP metabolites and plasma Aβ seems to be NAL status dependent. Finally, the current study suggests that an association between neurodegeneration and neuroinflammation manifests in the periphery, suggesting that preventing cytoskeleton cytotoxicity by KP metabolites may have therapeutic potential

Risk Factors for Ocular Chlamydia after Three Mass Azithromycin Distributions

Trachoma, which is the leading infectious cause of blindness worldwide, is caused by repeated ocular infection with Chlamydia trachomatis. Treatment for trachoma includes mass azithromycin treatments to the entire community. The World Health Organization recommends at least 3 rounds of annual mass antibiotic distributions in areas with trachoma, with further mass treatments based on the prevalence of trachoma. However, there are other options for communities that have received several rounds of treatment. For example, programs could continue antibiotic treatments only in those households most likely to have infected individuals. In this study, we performed trachoma monitoring on children from 12 Ethiopian communities one year after a third mass azithromycin treatment, and conducted a household survey at the same time. We found that children were more likely to be infected with ocular chlamydia if they had ocular inflammatory signs or ocular discharge, or if they had missed the preceding antibiotic treatment, had an infected sibling, or came from a larger community. These risk factors suggest that after mass azithromycin treatments, trachoma programs could consider continuing antibiotic distributions to households that have missed prior antibiotic distributions, in households with children who have the clinical signs of trachoma, and in larger communities

Early impacts of the COVID-19 pandemic on mental health care and on people with mental health conditions: framework synthesis of international experiences and responses

PURPOSE: The COVID-19 pandemic has many potential impacts on people with mental health conditions and on mental health care, including direct consequences of infection, effects of infection control measures and subsequent societal changes. We aimed to map early impacts of the pandemic on people with pre-existing mental health conditions and services they use, and to identify individual and service-level strategies adopted to manage these. METHODS: We searched for relevant material in the public domain published before 30 April 2020, including papers in scientific and professional journals, published first person accounts, media articles, and publications by governments, charities and professional associations. Search languages were English, French, German, Italian, Spanish, and Mandarin Chinese. Relevant content was retrieved and summarised via a rapid qualitative framework synthesis approach. RESULTS: We found 872 eligible sources from 28 countries. Most documented observations and experiences rather than reporting research data. We found many reports of deteriorations in symptoms, and of impacts of loneliness and social isolation and of lack of access to services and resources, but sometimes also of resilience, effective self-management and peer support. Immediate service challenges related to controlling infection, especially in inpatient and residential settings, and establishing remote working, especially in the community. We summarise reports of swiftly implemented adaptations and innovations, but also of pressing ethical challenges and concerns for the future. CONCLUSION: Our analysis captures the range of stakeholder perspectives and experiences publicly reported in the early stages of the COVID-19 pandemic in several countries. We identify potential foci for service planning and research

Validation of a 22-Gene Genomic Classifier in Patients With Recurrent Prostate Cancer An Ancillary Study of the NRG/RTOG 9601 Randomized Clinical Trial

IMPORTANCE: Decipher (Decipher Biosciences Inc) is a genomic classifier (GC) developed to estimate the risk of distant metastasis (DM) after radical prostatectomy (RP) in patients with prostate cancer. OBJECTIVE: To validate the GC in the context of a randomized phase 3 trial. DESIGN, SETTING, AND PARTICIPANTS: This ancillary study used RP specimens from the phase 3 placebo-controlled NRG/RTOG 9601 randomized clinical trial conducted from March 1998 to March 2003. The specimens were centrally reviewed, and RNA was extracted from the highest-grade tumor available in 2019 with a median follow-up of 13 years. Clinical-grade whole transcriptomes from samples passing quality control were assigned GC scores (scale, 0-1). A National Clinical Trials Network–approved prespecified statistical plan included the primary objective of validating the independent prognostic ability of GC for DM, with secondary end points of prostate cancer–specific mortality (PCSM) and overall survival (OS). Data were analyzed from September 2019 to December 2019. INTERVENTIONS: Salvage radiotherapy (sRT) with or without 2 years of bicalutamide. MAIN OUTCOMES AND MEASURES: The preplanned primary end point of this study was the independent association of the GC with the development of DM. RESULTS: In this ancillary study of specimens from a phase 3 randomized clinical trial, GC scores were generated from 486 of 760 randomized patients with a median follow-up of 13 years; samples from a total of 352 men (median [interquartile range] age, 64.5 (60-70) years; 314 White [89.2%] participants) passed microarray quality control and comprised the final cohort for analysis. On multivariable analysis, the GC (continuous variable, per 0.1 unit) was independently associated with DM (hazard ratio [HR], 1.17; 95% CI, 1.05-1.32; P = .006), PCSM (HR, 1.39; 95% CI, 1.20-1.63; P < .001), and OS (HR, 1.17; 95% CI, 1.06-1.29; P = .002) after adjusting for age, race/ethnicity, Gleason score, T stage, margin status, entry prostate-specific antigen, and treatment arm. Although the original planned analysis was not powered to detect a treatment effect interaction by GC score, the estimated absolute effect of bicalutamide on 12-year OS was less when comparing patients with lower vs higher GC scores (2.4% vs 8.9%), which was further demonstrated in men receiving early sRT at a prostate-specific antigen level lower than 0.7 ng/mL (−7.8% vs 4.6%). CONCLUSIONS AND RELEVANCE: This ancillary validation study of the Decipher GC in a randomized trial cohort demonstrated association of the GC with DM, PCSM, and OS independent of standard clinicopathologic variables. These results suggest that not all men with biochemically recurrent prostate cancer after surgery benefit equally from the addition of hormone therapy to sRT. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT0000287

Azimuthal Anisotropy of Photon and Charged Particle Emission in Pb+Pb Collisions at 158 A GeV/c

The azimuthal distributions of photons and charged particles with respect to the event plane are investigated as a function of centrality in Pb + Pb collisions at 158 A GeV/c in the WA98 experiment at the CERN SPS. The anisotropy of the azimuthal distributions is characterized using a Fourier analysis. For both the photon and charged particle distributions the first two Fourier coefficients are observed to decrease with increasing centrality. The observed anisotropies of the photon distributions compare well with the expectations from the charged particle measurements for all centralities.Comment: 8 pages and 6 figures. The manuscript has undergone a major revision. The unwanted correlations were enhanced in the random subdivision method used in the earlier version. The present version uses the more established method of division into subevents separated in rapidity to minimise short range correlations. The observed results for charged particles are in agreement with results from the other experiments. The observed anisotropy in photons is explained using flow results of pions and the correlations arising due to the decay of the neutral pion

Current use of smokeless tobacco among adolescents in the Republic of Congo

<p>Abstract</p> <p>Background</p> <p>Tobacco use is a leading cause of global morbidity and mortality. Much of the epidemiologic research on tobacco focuses on smoking, especially cigarette smoking, but little attention on smokeless tobacco (SLT).</p> <p>Methods</p> <p>Using data from the Republic of Congo Global Youth Tobacco Survey (GYTS) of 2006, we estimated the prevalence of SLT use among in-school adolescents. We also assessed the association between SLT use and cigarette smoking as well as the traditional factors which are associated with cigarette smoking among adolescents (e.g. age, sex, parental or peer smoking). Unadjusted odds ratios (OR) and adjusted odds ratios (AOR) together with their 95% confidence intervals (CI) were used to measure magnitudes of associations.</p> <p>Results</p> <p>Of the 3,034 respondents, 18.0% (18.0% males and 18.1% females) reported having used smokeless tobacco (chewing tobacco, sniff or dip) in the last 30 days. In multivariate analysis, no significant associations were observed between age and sex on one hand and current smokeless tobacco use on the other. Cigarette smokers were more than six times likely to report current use of smokeless tobacco (AOR = 6.65; 95% CI [4.84, 9.14]). Having parents or friends smokers was positively associated with using smokeless tobacco (AOR = 1.98; 95% CI [1.51, 2.59] for parents who smoked cigarettes, AOR = 1.82; 95% CI [1.41, 2.69] for some friends who smoked cigarettes, and AOR = 2.02; 95% CI [1.49, 2.47] for most or all friends who smoked cigarettes). Respondents who reported have seen tobacco advertisement on TV, billboards and in newspapers/magazines were 1.95 times more likely to report current use of smokeless tobacco (AOR = 1.95; 95% CI [1.34, 3.08]). Perception that smoking was harmful to health was negatively associated with current use of smokeless tobacco (AOR = 0.60; 95% CI [0.46, 0.78]).</p> <p>Conclusions</p> <p>Prevention programs aimed to reduce teen [cigarette] smoking must also be designed to reduce other forms of tobacco use. The teenagers environment at home, at school and at leisure must also be factored in order to prevent their uptake or maintenance of tobacco use.</p