Effects of Paecilomyces lilacinus protease and chitinase on the eggshell structures and hatching of Meloidogyne javanica juveniles

A serine protease and an enzyme preparation consisting of six chitinases, previously semi-purified from a liquid culture of Paecilomyces lilacinus strain 251, were applied to Meloidogyne javanica eggs to study the effect of the enzymes on eggshell structures. Transmission electron microscopic studies revealed that the protease and chitinases drastically altered the eggshell structures when applied individually or in combination. In the protease-treated eggs, the lipid layer disappeared and the chitin layer was thinner than in the control. The eggs treated with chitinases displayed large vacuoles in the chitin layer, and the vitelline layer was split and had lost its integrity. The major changes in the eggshell structures occurred by the combined effect of P. lilacinus protease and chitinases. The lipid layer was destroyed; the chitin layer hydrolyzed and the vitelline layer had lost integrity. The effect of P. lilacinus protease and chitinase enzymes on the hatching of M. javanica juveniles was also compared with a commercially available bacterial chitinase. The P. lilacinus protease and chitinase enzymes, either individually or in combination, reduced hatching of M. javanica juveniles whereas a commercial bacterial chitinase had an enhancing effect. Some juveniles hatched when the eggs were exposed to a fungal protease and chitinase mixture. We also established that P. lilacinus chitinases retained their activity in the presence of endogenous protease activity. © 2004 Elsevier Inc. All rights reserved

Does antiretroviral treatment increase the infectiousness of smear-positive pulmonary tuberculosis?

BACKGROUND: Understanding of the effects of human immunodeficiency virus (HIV) infection and antiretroviral treatment (ART) on Mycobacterium tuberculosis transmission dynamics remains limited. We undertook a cross-sectional study among household contacts of smear-positive pulmonary tuberculosis (TB) cases to assess the effect of established ART on the infectiousness of TB. METHOD: Prevalence of tuberculin skin test (TST) positivity was compared between contacts of index cases aged 2-10 years who were HIV-negative, HIV-positive but not on ART, on ART for <1 year and on ART for 1 year. Random-effects logistic regression was used to take into account clustering within households. RESULTS: Prevalence of M. tuberculosis infection in contacts of HIV-negative patients, HIV-positive patients on ART 1 year and HIV-positive patients not on ART/on ART <1 year index cases was respectively 44%, 21% and 22%. Compared to contacts of HIV-positive index cases not on ART or recently started on ART, the odds of TST positivity was similar in contacts of HIV-positive index cases on ART 1 year (adjusted OR [aOR] 1.0, 95%CI 0.3-3.7). The odds were 2.9 times higher in child contacts of HIV-negative index cases (aOR 2.9, 95%CI 1.0-8.2). CONCLUSIONS: We found no evidence that established ART increased the infectiousness of smear-positive, HIV-positive index cases

Risk factors for Mycobacterium tuberculosis infection in 2-4 year olds in a rural HIV-prevalent setting.

BACKGROUND: Mycobacterium tuberculosis infection in children acts as a sentinel for infectious tuberculosis. OBJECTIVE: To assess risk factors associated with tuberculous infection in pre-school children. METHOD: We conducted a population-wide tuberculin skin test (TST) survey from January to December 2012 in Malawi. All children aged 2-4 years residing in a demographic surveillance area were eligible. Detailed demographic data, including adult human immunodeficiency virus (HIV) status, and clinical and sociodemographic data on all diagnosed tuberculosis (TB) patients were available. RESULTS: The prevalence of M. tuberculosis infection was 1.1% using a TST induration cut-off of 15 mm (estimated annual risk of infection of 0.3%). The main identifiable risk factors were maternal HIV infection at birth (adjusted OR [aOR] 3.6, 95%CI 1.1-12.2), having three or more adult members in the household over a lifetime (aOR 2.4, 95%CI 1.2-4.8) and living in close proximity to a known case of infectious TB (aOR 1.6, 95%CI 1.1-2.4), modelled as a linear variable across categories (>200 m, 100-200 m, <100 m, within household). Less than 20% of the infected children lived within 200 m of a known diagnosed case. CONCLUSION: Household and community risk factors identified do not explain the majority of M. tuberculosis infections in children in our setting

Variance in multiplex suspension array assays: A distribution generation machine for multiplex counts

<p>Abstract</p> <p>Background</p> <p>This study attempted to replicate Luminex experimental results for large numbers of beads per classifier using multiplexed assays and routine instrument use conditions.</p> <p>Conclusion</p> <p>Using larger numbers of microspheres per classifier highlights a fundamental stochastic distribution of bead counts issue complicated by other factors. The more classifiers and the higher the count required per classifier there are, the more apparent the distribution of counts per classifier will be, and the more microspheres are required. Additional problems have been identified. Alternate methods of improving precision and reliability are recommended such as intraplexing and multi-well sample replicates to improve precision and confidence.</p

The validity and reliability of observational assessment tools available to measure fundamental movement skills in school-age children: A systematic review

Background Fundamental Movement Skills (FMS) play a critical role in ontogenesis. Many children have insufficient FMS, highlighting the need for universal screening in schools. There are many observational FMS assessment tools, but their psychometric properties are not readily accessible. A systematic review was therefore undertaken to compile evidence of the validity and reliability of observational FMS assessments, to evaluate their suitability for screening. Methods A pre-search of ‘fundamental movement skills’ OR ‘fundamental motor skills’ in seven online databases (PubMed, Ovid MEDLINE, Ovid Embase, EBSCO CINAHL, EBSCO SPORTDiscus, Ovid PsycINFO and Web of Science) identified 24 assessment tools for school-aged children that: (i) assess FMS; (ii) measure actual motor competence and (iii) evaluate performance on a standard battery of tasks. Studies were subsequently identified that: (a) used these tools; (b) quantified validity or reliability and (c) sampled school-aged children. Study quality was assessed using COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklists. Results Ninety studies were included following the screening of 1863 articles. Twenty-one assessment tools had limited or no evidence to support their psychometric properties. The Test of Gross Motor Development (TGMD, n = 34) and the Movement Assessment Battery for Children (MABC, n = 37) were the most researched tools. Studies consistently reported good evidence for validity, reliability for the TGMD, whilst only 64% of studies reported similarly promising results for the MABC. Twelve studies found good evidence for the reliability and validity of the Bruininks-Oseretsky Test of Motor Proficiency but poor study quality appeared to inflate results. Considering all assessment tools, those with promising psychometric properties often measured limited aspects of validity/reliability, and/or had limited feasibility for large scale deployment in a school-setting. Conclusion There is insufficient evidence to justify the use of any observational FMS assessment tools for universal screening in schools, in their current form

Herpes encephalitis presenting as mild aphasia: Case report

BACKGROUND: Encephalitis presenting as a change in mental status can be challenging to recognize in the primary care setting. However, early detection via a low threshold of suspicion can be useful, leading in turn to early treatment and improved survival. CASE PRESENTATION: We present a case which we consider relevant to primary care practitioners. The patient in question presented with relatively mild mental status changes, progressing to confusion, dysnomia and delirium over a period of three days. While infection did not appear to be the leading cause on her differential diagnosis, she was found on extensive workup to have encephalitis caused by Herpes Simplex Virus type 1. CONCLUSION: The case is instructive for general practitioners and other clinicians to maintain vigilance for central nervous system (CNS) infections which may present atypically

Monoclonal antibody levels and protection from COVID-19

Multiple monoclonal antibodies have been shown to be effective for both prophylaxis and therapy for SARS-CoV-2 infection. Here we aggregate data from randomized controlled trials assessing the use of monoclonal antibodies (mAb) in preventing symptomatic SARS-CoV-2 infection. We use data on the in vivo concentration of mAb and the associated protection from COVID-19 over time to model the dose-response relationship of mAb for prophylaxis. We estimate that 50% protection from COVID-19 is achieved with a mAb concentration of 96-fold of the in vitro IC50 (95% CI: 32—285). This relationship provides a tool for predicting the prophylactic efficacy of new mAb and against SARS-CoV-2 variants. Finally, we compare the relationship between neutralization titer and protection from COVID-19 after either mAb treatment or vaccination. We find no significant difference between the 50% protective titer for mAb and vaccination, although sample sizes limited the power to detect a difference

Effect of Cyclooxygenase(COX)-1 and COX-2 inhibition on furosemide-induced renal responses and isoform immunolocalization in the healthy cat kidney

BACKGROUND: The role of cyclooxygenase(COX)-1 and COX-2 in the saluretic and renin-angiotensin responses to loop diuretics in the cat is unknown. We propose in vivo characterisation of isoform roles in a furosemide model by administering non-steroidal anti-inflammatory drugs (NSAIDs) with differing selectivity profiles: robenacoxib (COX-2 selective) and ketoprofen (COX-1 selective). RESULTS: In this four period crossover study, we compared the effect of four treatments: placebo, robenacoxib once or twice daily and ketoprofen once daily concomitantly with furosemide in seven healthy cats. For each period, urine and blood samples were collected at baseline and within 48 h of treatment starting. Plasma renin activity (PRA), plasma and urinary aldosterone concentrations, glomerular filtration rate (GFR) and 24 h urinary volumes, electrolytes and eicosanoids (PGE(2), 6-keto-PGF1(α,) TxB(2)), renal injury biomarker excretions [N-acetyl-beta-D-glucosaminidase (NAG) and Gamma-Glutamyltransferase] were measured. Urine volume (24 h) and urinary sodium, chloride and calcium excretions increased from baseline with all treatments. Plasma creatinine increased with all treatments except placebo, whereas GFR was significantly decreased from baseline only with ketoprofen. PRA increased significantly with placebo and once daily robenacoxib and the increase was significantly higher with placebo compared to ketoprofen (10.5 ± 4.4 vs 4.9 ± 5.0 ng ml(−1) h(−1)). Urinary aldosterone excretion increased with all treatments but this increase was inhibited by 75 % with ketoprofen and 65 % with once daily robenacoxib compared to placebo. Urinary PGE(2) excretion decreased with all treatments and excretion was significantly lower with ketoprofen compared to placebo. Urinary TxB(2) excretion was significantly increased from baseline only with placebo. NAG increased from baseline with all treatments. Immunohistochemistry on post-mortem renal specimens, obtained from a different group of cats that died naturally of non-renal causes, suggested constitutive COX-1 and COX-2 co-localization in many renal structures including the macula densa (MD). CONCLUSIONS: These data suggest that both COX-1 and COX-2 could generate the signal from the MD to the renin secreting cells in cats exposed to furosemide. Co-localization of COX isoenzymes in MD cells supports the functional data reported here. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0598-z) contains supplementary material, which is available to authorized users

A self-report comorbidity questionnaire for haemodialysis patients

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise statedBackground: Patients with end-stage renal disease (ESRD) have multiple comorbid conditions. Obtaining comorbidity data from medical records is cumbersome. A self-report comorbidity questionnaire is a useful alternative. Our aim in this study was to examine the predictive value of a self-report comorbidity questionnaire in terms of survival in ESRD patients. Methods. We studied a prospective cross-sectional cohort of 282 haemodialysis (HD) patients in a single centre. Participants were administered the self-report questionnaire during an HD session. Information on their comorbidities was subsequently obtained from an examination of the patient's medical records. Levels of agreement between parameters derived from the questionnaire, and from the medical records, were examined. Participants were followed-up for 18 months to collect survival data. The influence on survival of comorbidity scores derived from the self-report data (the Composite Self-report Comorbidity Score [CSCS]) and from medical records data - the Charlson Comorbidity Index [CCI] were compared. Results: The level of agreement between the self-report items and those obtained from medical records was almost perfect with respect the presence of diabetes (Kappa score κ 0.97), substantial for heart disease and cancer (κ 0.62 and κ 0.72 respectively), moderate for liver disease (κ 0.51), only fair for lung disease, arthritis, cerebrovascular disease, and depression (κ 0.34, 0.35, 0.34 and 0.29 respectively). The CSCS was strongly predictive of survival in regression models (Nagelkerke R2value 0.202), with a predictive power similar to that of the CCI (Nagelkerke R2value 0.211). The influences of these two parameters were additive in the models - suggesting that these parameters make different contributions to the assessment of comorbidity. Conclusion: This self-report comorbidity questionnaire is a viable tool to collect comorbidity data and may have a role in the prediction of short-term survival in patients with end-stage renal disease on haemodialysis. Further work is required in this setting to refine the tool and define its role.Peer reviewe

Determinants of passive antibody efficacy in SARS-CoV-2 infection: a systematic review and meta-analysis

Background: Randomised controlled trials of passive antibodies as treatment and prophylaxis for COVID-19 have reported variable efficacy. However, the determinants of efficacy have not been identified. We aimed to assess how the dose and timing of administration affect treatment outcome. Methods: In this systematic review and meta-analysis, we extracted data from published studies of passive antibody treatment from Jan 1, 2019, to Jan 31, 2023, that were identified by searching multiple databases, including MEDLINE, PubMed, and ClinicalTrials.gov. We included only randomised controlled trials of passive antibody administration for the prevention or treatment of COVID-19. To compare administered antibody dose between different treatments, we used data on in-vitro neutralisation titres to normalise dose by antibody potency. We used mixed-effects regression and model fitting to analyse the relationship between timing, dose and efficacy. Findings: We found 58 randomised controlled trials that investigated passive antibody therapies for the treatment or prevention of COVID-19. Earlier clinical stage at treatment initiation was highly predictive of the efficacy of both monoclonal antibodies (p<0·0001) and convalescent plasma therapy (p=0·030) in preventing progression to subsequent stages, with either prophylaxis or treatment in outpatients showing the greatest effects. For the treatment of outpatients with COVID-19, we found a significant association between the dose administered and efficacy in preventing hospitalisation (relative risk 0·77; p<0·0001). Using this relationship, we predicted that no approved monoclonal antibody was expected to provide more than 30% efficacy against some omicron (B.1.1.529) subvariants, such as BQ.1.1. Interpretation: Early administration before hospitalisation and sufficient doses of passive antibody therapy are crucial to achieving high efficacy in preventing clinical progression. The relationship between dose and efficacy provides a framework for the rational assessment of future passive antibody prophylaxis and treatment strategies for COVID-19. Funding: The Australian Government Department of Health, Medical Research Future Fund, National Health and Medical Research Council, the University of New South Wales, Monash University, Haematology Society of Australia and New Zealand, Leukaemia Foundation, and the Victorian Government