Cytogerontology since 1881: A reappraisal of August Weismann and a review of modern progress

Cytogerontology, the science of cellular ageing, originated in 1881 with the prediction by August Weismann that the somatic cells of higher animals have limited division potential. Weismann's prediction was derived by considering the role of natural selection in regulating the duration of an organism's life. For various reasons, Weismann's ideas on ageing fell into neglect following his death in 1914, and cytogerontology has only reappeared as a major research area following the demonstration by Hayflick and Moorhead in the early 1960s that diploid human fibroblasts are restricted to a finite number of divisions in vitro. In this review we give a detailed account of Weismann's theory, and we reveal that his ideas were both more extensive in their scope and more pertinent to current research than is generally recognised. We also appraise the progress which has been made over the past hundred years in investigating the causes of ageing, with particular emphasis being given to (i) the evolution of ageing, and (ii) ageing at the cellular level. We critically assess the current state of knowledge in these areas and recommend a series of points as primary targets for future research

Genetic characterization of morphologically variant strains of Paracoccidioides brasiliensis

Molecular characterization of Paracoccidioides brasiliensis variant strains that had been preserved under mineral oil for decades was carried out by random amplified polymorphic DNA analysis (RAPD). On P. brasiliensis variants in the transitional phase and strains with typical morphology, RAPD produced reproducible polymorphic amplification products that differentiated them. A dendrogram based on the generated RAPD patterns placed the 14 P. brasiliensis strains into five groups with similarity coefficients of 72%. A high correlation between the genotypic and phenotypic characteristics of the strains was observed. A 750 bp-RAPD fragment found only in the wild-type phenotype strains was cloned and sequenced. Genetic similarity analysis using BLASTx suggested that this RAPD marker represents a putative domain of a hypothetical flavin-binding monooxygenase (FMO)-like protein of Neurospora crassa.FiocruzBritish Council Progra

Co-morbidity and polypharmacy in Parkinson's Disease:insights from a large Scottish primary care database

Background: Parkinson’s disease is complicated by comorbidity and polypharmacy, but the extent and patterns of these are unclear. We describe comorbidity and polypharmacy in patients with and without Parkinson’s disease across 31 other physical, and seven mental health conditions. Methods: We analysed primary health-care data on 510,502 adults aged 55 and over. We generated standardised prevalence rates by age-groups, gender, and neighbourhood deprivation, then calculated age, sex and deprivation adjusted odds ratios (OR) and 95% confidence intervals (95% CI) for those with PD compared to those without, for the prevalence, and number of conditions. Results: Two thousand six hundred forty (0.5%) had Parkinson’s disease, of whom only 7.4% had no other conditions compared with 22.9% of controls (adjusted OR [aOR] 0.43, 95% 0.38–0.49). The Parkinson’s group had more conditions, with the biggest difference found for seven or more conditions (PD 12.1% vs. controls 3.9%; aOR 2.08 95% CI 1.84–2.35). 12 of the 31 physical conditions and five of the seven mental health conditions were significantly more prevalent in the PD group. 44.5% with Parkinson’s disease were on five to nine repeat prescriptions compared to 24.5% of controls (aOR 1.40; 95% CI 1.28 to 1.53) and 19.2% on ten or more compared to 6.2% of controls (aOR 1.90; 95% CI 1.68 to 2.15). Conclusions: Parkinson’s disease is associated with substantial physical and mental co-morbidity. Polypharmacy is also a significant issue due to the complex nature of the disease and associated treatments

Population‐based cohort study of outcomes following cholecystectomy for benign gallbladder diseases

Background The aim was to describe the management of benign gallbladder disease and identify characteristics associated with all‐cause 30‐day readmissions and complications in a prospective population‐based cohort. Methods Data were collected on consecutive patients undergoing cholecystectomy in acute UK and Irish hospitals between 1 March and 1 May 2014. Potential explanatory variables influencing all‐cause 30‐day readmissions and complications were analysed by means of multilevel, multivariable logistic regression modelling using a two‐level hierarchical structure with patients (level 1) nested within hospitals (level 2). Results Data were collected on 8909 patients undergoing cholecystectomy from 167 hospitals. Some 1451 cholecystectomies (16·3 per cent) were performed as an emergency, 4165 (46·8 per cent) as elective operations, and 3293 patients (37·0 per cent) had had at least one previous emergency admission, but had surgery on a delayed basis. The readmission and complication rates at 30 days were 7·1 per cent (633 of 8909) and 10·8 per cent (962 of 8909) respectively. Both readmissions and complications were independently associated with increasing ASA fitness grade, duration of surgery, and increasing numbers of emergency admissions with gallbladder disease before cholecystectomy. No identifiable hospital characteristics were linked to readmissions and complications. Conclusion Readmissions and complications following cholecystectomy are common and associated with patient and disease characteristics

Self-monitoring of blood pressure following a stroke or transient ischaemic attack (TASMIN5S): a randomised controlled trial

Background: Blood pressure (BP) control following stroke is important but currently sub-optimal. This trial aimed to determine whether self-monitoring of hypertension with telemonitoring and a treatment escalation protocol, results in lower BP than usual care in people with previous stroke or transient ischaemic attack (TIA). Methods: Unblinded randomised controlled trial, comparing a BP telemonitoring-based intervention with control (usual care) for hypertension management in 12 primary care practices in England. People with previous stroke or TIA with clinic systolic BP 130–180 mmHg, taking ≤ 3 antihypertensive medications and on stable treatment for at least four weeks were randomised 1:1 using secure online system to intervention or control. The BP:Together intervention comprised self-monitoring of blood pressure with a digital behavioural intervention which supported telemonitoring of self-monitored BP with feedback to clinicians and patients regarding medication titration. The planned primary outcome was difference in clinic measured systolic BP 12 months from randomisation but was not available following early study termination due to withdrawal of funding during the COVID-19 pandemic. Instead, in addition to pre-randomised data, routinely recorded BP was extracted from electronic patient records both pre- and post-randomisation and presented descriptively only. An intention to treat approach was taken. Results: From 650 postal invitations, 129 (20%) responded, of whom 95 people had been screened for eligibility prior to the pandemic (November 2019-March 2020) and 55 (58%) were randomised. Pre-randomisation routinely recorded mean BP was 145/78 mmHg in the control (n = 26) and 145/79 mmHg in the self-monitoring (n = 21) groups. Post-randomisation mean BP was 134/73 mmHg in the control (n = 19) and 130/75 mmHg in the self-monitoring (n = 25) groups. Participants randomised to self-monitoring used the intervention for ≥ 7 months in 25/27 (93%) of cases. Conclusions: Recruitment of people with stroke/TIA to a trial comparing a BP self-monitoring and digital behavioural intervention to usual care was feasible prior to the COVID-19 pandemic and the vast majority of those randomised to intervention used it while the trial was running. Routinely recorded blood pressure control improved in both groups. Digital interventions including self-monitoring are feasible for people with stroke/TIA and should be definitively evaluated in future trials. Trail registration: ISRCTN57946500 06/09/2019 Prospective

Frequency of symptoms, determinants of severe symptoms, validity of and cut-off score for Menopause Rating Scale (MRS) as a screening tool: A cross-sectional survey among midlife Nepalese women

<p>Abstract</p> <p>Background</p> <p>Majority of Nepalese women live in remote rural areas, where health services are not easily accessible. We determined the validity of Menopause Rating Scale (MRS) as a screening tool for identification of women with severe menopausal symptoms and cut-off MRS score for referral.</p> <p>Methods</p> <p>A cross-sectional survey was carried out between February and August, 2008. Trained health workers administered MRS and a questionnaire to 729 women (40 to 65 years) attending health screening camps in Kaski district of Western Development Region of Nepal. Information about demographics, menopausal status, and use of hormone replacement therapy (HRT), chronic disease, self-perceived general health and reproductive history was also collected. Menopausal status was classified according to the Staging of Reproductive Ageing Workshop (STRAW). We calculated rates of menopausal symptoms, sensitivity, and specificity and likelihood ratios of MRS scores for referral to a gynaecologist. We also carried out multivariate analyses to identify the predictors for referral to a gynaecologist for severe symptoms.</p> <p>Results</p> <p>A total 729 women were interviewed. Mean age at menopause was 49.9 years (SD 5.6). Most frequently reported symptoms were, sleeping problems (574, 78.7%), physical and mental exhaustion (73.5%), hot flushes (508, 69.7%), joint and muscular discomfort (500, 68.6%) and dryness of vagina (449, 61.6%). Postmenopausal women (247, 33.9%) and perimenopausal (215, 29.5%) women together experienced significantly higher prevalence of all symptoms than the premenopausal (267, 36.6%) women. MRS score of ≥16 had highest ratio for (sensitivity + specificity)/2. Women who reported urogenital symptoms [OR 5.29, 95% CI 2.59, 10.78], and self perceived general health as poor [OR 1.29, 95% CI 1.11, 1.53] were more likely to be referred to a gynaecologist for severe menopausal symptoms. While women reporting somatic [OR 0.72, 95% CI 0.63, 0.82] and psychological [OR 0.86, 95% CI 0.74, 0.99] symptoms were less likely to be referred.</p> <p>Conclusion</p> <p>MRS may be used as a screening tool at a cut-off score of ≥16 with least misclassification rate. However, its utility may be limited by woman's general health status and occurrence of urogenital symptoms.</p

Treatment for Schistosoma japonicum, Reduction of Intestinal Parasite Load, and Cognitive Test Score Improvements in School-Aged Children

Parasitic worm infections are associated with cognitive impairment and lower academic achievement for infected relative to uninfected children. However, it is unclear whether curing or reducing worm infection intensity improves child cognitive function. We examined the independent associations between: (i) Schistosoma japonicum infection-free duration, (ii) declines in single helminth species, and (iii) joint declines of ≥2 soil-transmitted helminth (STH) infections and improvements in four cognitive tests during18 months of follow-up. Enrolled were schistosome-infected school-aged children among whom coinfection with STH was common. All children were treated for schistosome infection only at enrolment with praziquantel. Children cured or schistosome-free for >12 months scored higher in memory and verbal fluency tests compared to persistently infected children. Likewise, declines of single and polyparasitic STH infections predicted higher scores in three of four tests. We conclude that reducing the intensity of certain helminth species and the frequency of multi-species STH infections may have long-term benefits for affected children's cognitive performance. The rapidity of schistosome re-infection and the ubiquity of concurrent multi-species infection highlight the importance of sustained deworming for both schistosome and STH infections to enhance the learning and educational attainment of children in helminth-endemic settings