Human herpesvirus infections and dementia or mild cognitive impairment: a systematic review and meta-analysis

Interest is growing in the role of infectious agents in the pathogenesis of dementia, but current evidence is limited. We conducted a systematic review and meta-analysis to investigate the effect of any of eight human herpesviruses on development of dementia or mild cognitive impairment (MCI). We searched the Cochrane Library, Embase, Global Health, Medline, PsycINFO, Scopus, Web of Science, clinical trials registers and grey literature sources from inception to December 2017 for observational studies with cohort, case control or self-controlled designs, or randomised controlled trials of interventions against herpesviruses. Pooled effect estimates and 95% confidence intervals (CIs) were generated through random effects meta-analyses across studies with the same design, outcome, and virus type, method and site of measurement. We included 57 studies across various geographic settings. Past infection with herpesviruses, measured by IgG seropositivity, was generally not associated with dementia risk. A single cohort study rated moderate quality showed an association between varicella zoster virus reactivation (ophthalmic zoster) and incident dementia (HR 2.97; 95%CI, 1.89 to 4.66). Recent infection with, or reactivation of, herpes simplex virus type 1 or type 1/2 unspecified, cytomegalovirus and human herpes virus-6 measured by serum IgM, high titre IgG or clinical disease may be associated with dementia or MCI, though results were inconsistent across studies and overall evidence rated very low quality. Longitudinal population studies with robust repeated virus measurements taken sufficiently proximal to dementia onset are needed to establish whether, when and among whom herpesviruses affect dementia risk

Regulation of Transforming Growth Factor-β1–driven Lung Fibrosis by Galectin-3

Rationale: Idiopathic pulmonary fibrosis (IPF) is a chronic dysregulated response to alveolar epithelial injury with differentiation of epithelial cells and fibroblasts into matrix-secreting myofibroblasts resulting in lung scaring. The prognosis is poor and there are no effective therapies or reliable biomarkers. Galectin-3 is a beta-galactoside binding lectin that is highly expressed in fibrotic tissue of diverse etiologies. Objectives: To examine the role of galectin-3 in pulmonary fibrosis. Methods: We used genetic deletion and pharmacologic inhibition in well-characterized murine models of lung fibrosis. Further mechanistic studies were performed in vitro and on samples from patients with IPF. Measurements and Main Results: Transforming growth factor (TGF)-beta and bleomycin-induced lung fibrosis was dramatically reduced in mice deficient in galectin-3, manifest by reduced TGF-beta 1 induced EMT and myofibroblast activation and collagen production. Galectin-3 reduced phosphorylation and nuclear translocation of beta-catenin but had no effect on Smad2/3 phosphorylation. A novel inhibitor of galectin -3, TD139, blocked TGF-beta-induced beta-catenin activation in vitro and in vivo and attenuated the late-stage progression of lung fibrosis after bleomycin. There was increased expression of galectin-3 in the bronchoalveolar lavage fluid and serum from patients with stable IPF compared with nonspecific interstitial pneumonitis and controls, which rose sharply during an acute exacerbation suggesting that. galectin-3 may be a marker of active fibrosis in IPF and that strategies that block galectin-3 may be effective in treating acute fibrotic exacerbations of IPF. Conclusions: This study identifies galectin-3 as an important regulator of lung fibrosis and provides a proof of principle for galectin-3 inhibition as a potential novel therapeutic strategy for IPF

Health surveillance of deployed military personnel occasionally leads to unexpected findings

Post-traumatic stress disorder (PTSD) can be caused by life threatening illness, such as cancer and coronary events. The study by Forbes et al. made the unexpected finding that military personnel evacuation with medical illness have similar rates of PTSD to those evacuated with combat injuries. It may be that the illness acts as a nonspecific stressor that interacts with combat exposures to increase the risk of PTSD. Conversely, the inflammatory consequence of systemic illness may augment the effects to traumatic stress and facilitate the immunological abnormalities that are now being associated with PTSD and depression. The impact of the stress on cytokine systems and their role in the onset of PTSD demands further investigation. Military personnel evacuated due to physical illness require similar screening and monitoring for the risk of PTSD to those injured who are already known to be at high risk.Alexander C McFarlan

Magnetic resonance imaging protocols for paediatric neuroradiology

Increasingly, radiologists are encouraged to have protocols for all imaging studies and to include imaging guidelines in care pathways set up by the referring clinicians. This is particularly advantageous in MRI where magnet time is limited and a radiologist’s review of each patient’s images often results in additional sequences and longer scanning times without the advantage of improvement in diagnostic ability. The difficulties of imaging small children and the challenges presented to the radiologist as the brain develops are discussed. We present our protocols for imaging the brain and spine of children based on 20 years experience of paediatric neurological MRI. The protocols are adapted to suit children under the age of 2 years, small body parts and paediatric clinical scenarios

Incidence of diabetes after SARS-CoV-2 infection in England and the implications of COVID-19 vaccination: a retrospective cohort study of 16 million people

Background: Some studies have shown that the incidence of type 2 diabetes increases after a diagnosis of COVID-19, although the evidence is not conclusive. However, the effects of the COVID-19 vaccine on this association, or the effect on other diabetes subtypes, are not clear. We aimed to investigate the association between COVID-19 and incidence of type 2, type 1, gestational and non-specific diabetes, and the effect of COVID- 19 vaccination, up to 52 weeks after diagnosis. Methods: In this retrospective cohort study, we investigated the diagnoses of incident diabetes following COVID-19 diagnosis in England in a pre-vaccination, vaccinated, and unvaccinated cohort using linked electronic health records. People alive and aged between 18 years and 110 years, registered with a general practitioner for at least 6 months before baseline, and with available data for sex, region, and area deprivation were included. Those with a previous COVID-19 diagnosis were excluded. We estimated adjusted hazard ratios (aHRs) comparing diabetes incidence after COVID-19 diagnosis with diabetes incidence before or in the absence of COVID-19 up to 102 weeks after diagnosis. Results were stratified by COVID-19 severity (categorised as hospitalised or non-hospitalised) and diabetes type. Findings: 16 669 943 people were included in the pre-vaccination cohort (Jan 1, 2020–Dec 14, 2021), 12 279 669 in the vaccinated cohort, and 3 076 953 in the unvaccinated cohort (both June 1–Dec 14, 2021). In the pre-vaccination cohort, aHRs for the incidence of type 2 diabetes after COVID-19 (compared with before or in the absence of diagnosis) declined from 4·30 (95% CI 4·06–4·55) in weeks 1–4 to 1·24 (1·14–1.35) in weeks 53–102. aHRs were higher in unvaccinated people (8·76 [7·49–10·25]) than in vaccinated people (1·66 [1·50–1·84]) in weeks 1–4 and in patients hospitalised with COVID-19 (pre-vaccination cohort 28·3 [26·2–30·5]) in weeks 1–4 declining to 2·04 [1·72–2·42] in weeks 53–102) than in those who were not hospitalised (1·95 [1·78–2·13] in weeks 1–4 declining to 1·11 [1·01–1·22] in weeks 53–102). Type 2 diabetes persisted for 4 months after COVID-19 in around 60% of those diagnosed. Patterns were similar for type 1 diabetes, although excess incidence did not persist beyond 1 year after a COVID-19 diagnosis. Interpretation: Elevated incidence of type 2 diabetes after COVID-19 is greater, and persists for longer, in people who were hospitalised with COVID-19 than in those who were not, and is markedly less apparent in people who have been vaccinated against COVID-19. Testing for type 2 diabetes after severe COVID-19 and the promotion of vaccination are important tools in addressing this public health problem. Funding: UK National Institute for Health and Care Research, UK Research and Innovation (UKRI) Medical Research Council, UKRI Engineering and Physical Sciences Research Council, Health Data Research UK, Diabetes UK, British Heart Foundation, and the Stroke Association

Physical activity for people living with dementia: carer outcomes and side effects from the perspectives of professionals and family carers

Adherence to physical activity is challenging for people living with dementia, and largely dependent on carers' involvement. Carers are likely to support physical activity based on their perceived balance between benefits and potential side effects of such intervention for both patients and themselves. Professionals also have a role in terms of optimising such interventions not only for people with dementia but also their carers.publishe

COVID-19 and Mental Illnesses in Vaccinated and Unvaccinated People

IMPORTANCE: Associations have been found between COVID-19 and subsequent mental illness in both hospital- and population-based studies. However, evidence regarding which mental illnesses are associated with COVID-19 by vaccination status in these populations is limited. OBJECTIVE: To determine which mental illnesses are associated with diagnosed COVID-19 by vaccination status in both hospitalized patients and the general population. DESIGN, SETTING, AND PARTICIPANTS: This study was conducted in 3 cohorts, 1 before vaccine availability followed during the wild-type/Alpha variant eras (January 2020-June 2021) and 2 (vaccinated and unvaccinated) during the Delta variant era (June-December 2021). With National Health Service England approval, OpenSAFELY-TPP was used to access linked data from 24 million people registered with general practices in England using TPP SystmOne. People registered with a GP in England for at least 6 months and alive with known age between 18 and 110 years, sex, deprivation index information, and region at baseline were included. People were excluded if they had COVID-19 before baseline. Data were analyzed from July 2022 to June 2024. EXPOSURE: Confirmed COVID-19 diagnosis recorded in primary care secondary care, testing data, or the death registry. MAIN OUTCOMES AND MEASURES: Adjusted hazard ratios (aHRs) comparing the incidence of mental illnesses after diagnosis of COVID-19 with the incidence before or without COVID-19 for depression, serious mental illness, general anxiety, posttraumatic stress disorder, eating disorders, addiction, self-harm, and suicide. RESULTS: The largest cohort, the pre-vaccine availability cohort, included 18 648 606 people (9 363 710 [50.2%] female and 9 284 896 [49.8%] male) with a median (IQR) age of 49 (34-64) years. The vaccinated cohort included 14 035 286 individuals (7 308 556 [52.1%] female and 6 726 730 [47.9%] male) with a median (IQR) age of 53 (38-67) years. The unvaccinated cohort included 3 242 215 individuals (1 363 401 [42.1%] female and 1 878 814 [57.9%] male) with a median (IQR) age of 35 (27-46) years. Incidence of most outcomes was elevated during weeks 1 through 4 after COVID-19 diagnosis, compared with before or without COVID-19, in each cohort. Incidence of mental illnesses was lower in the vaccinated cohort compared with the pre-vaccine availability and unvaccinated cohorts: aHRs for depression and serious mental illness during weeks 1 through 4 after COVID-19 were 1.93 (95% CI, 1.88-1.98) and 1.49 (95% CI, 1.41-1.57) in the pre-vaccine availability cohort and 1.79 (95% CI, 1.68-1.90) and 1.45 (95% CI, 1.27-1.65) in the unvaccinated cohort compared with 1.16 (95% CI, 1.12-1.20) and 0.91 (95% CI, 0.85-0.98) in the vaccinated cohort. Elevation in incidence was higher and persisted longer after hospitalization for COVID-19. CONCLUSIONS AND RELEVANCE: In this study, incidence of mental illnesses was elevated for up to a year following severe COVID-19 in unvaccinated people. These findings suggest that vaccination may mitigate the adverse effects of COVID-19 on mental health

A constructive approach for discovering new drug leads: Using a kernel methodology for the inverse-QSAR problem

<p>Abstract</p> <p>Background</p> <p>The inverse-QSAR problem seeks to find a new molecular descriptor from which one can recover the structure of a molecule that possess a desired activity or property. Surprisingly, there are very few papers providing solutions to this problem. It is a difficult problem because the molecular descriptors involved with the inverse-QSAR algorithm must adequately address the forward QSAR problem for a given biological activity if the subsequent recovery phase is to be meaningful. In addition, one should be able to construct a feasible molecule from such a descriptor. The difficulty of recovering the molecule from its descriptor is the major limitation of most inverse-QSAR methods.</p> <p>Results</p> <p>In this paper, we describe the reversibility of our previously reported descriptor, the vector space model molecular descriptor (VSMMD) based on a vector space model that is suitable for kernel studies in QSAR modeling. Our inverse-QSAR approach can be described using five steps: (1) generate the VSMMD for the compounds in the training set; (2) map the VSMMD in the input space to the kernel feature space using an appropriate kernel function; (3) design or generate a new point in the kernel feature space using a kernel feature space algorithm; (4) map the feature space point back to the input space of descriptors using a pre-image approximation algorithm; (5) build the molecular structure template using our VSMMD molecule recovery algorithm.</p> <p>Conclusion</p> <p>The empirical results reported in this paper show that our strategy of using kernel methodology for an inverse-Quantitative Structure-Activity Relationship is sufficiently powerful to find a meaningful solution for practical problems.</p