An experimental model for calcium carbonate urolithiasis in goats

This article is also available at the journal website: https://onlinelibrary.wiley.com/doi/full/10.1111/jvim.15061Background: Calcium carbonate is a common urolith type in small ruminants with no high-yield experimental model to evaluate animal susceptibility or preventative measure response. Hypothesis: That novel plastic winged implants would allow accumulation and quantification of calcium carbonate calculus formation in goats on a high-calcium diet and identify individual variation between goats in the mass of calculi produced. Animals: Eight nonpregnant 3- and 4-year-old Boer-cross does, weighing 22.3–39.5 kg, determined to be healthy based on physical examination, were used in these experiments. Methods: Prospective cohort study for in vivo experimental model development. Implants were placed into the urinary bladder lumen in 8 goats over 2 evaluation periods. The alfalfa-based ration had a total ration Ca : P of 3.29 and 3.84 : 1, respectively. Urine was collected at 0, 28, 56, and 84 days in the 1st experiment; blood and urine at those timepoints in the 2nd experiment. For each evaluation period, the implants were removed 84 days after implantation and weighed. Accumulated calculi mass was calculated and compared between goats and was analyzed for composition. Results: Implant retention was 100% and 86% in the 2 studies. All goats with retained implants accumulated calcium carbonate at a mean implant gain per day across studies ranging from 0.44 to 57.45 mg. Two goats accumulated (0.44–7.65 mg/day and 33.64 & 57.45 mg/day) significantly more urolith material than the cohort across both studies (P5.047). No routine analytes on blood or urine were found to be explanatory for the difference observed. Conclusions and Clinical Importance: These findings form a basis for implant and diet selection for use in future studies of urolithiasis development and for studies regarding individual susceptibility to urolithiasis. KEYWORDS 3D printing, calculogenesis, urinary calculi, urolithFunding information: Department of Large Animal Clinical Sciences, Texas A&M University College of Veterinary Medicin

Tau as a diagnostic instrument in clinical trials to predict amyloid in Alzheimer's disease

Abstract INTRODUCTION Alzheimer's disease (AD) is characterized by the presence of both amyloid and tau pathology. In vivo diagnosis can be made with amyloid and tau positron emission tomography (PET) imaging. Emergent evidence supports that amyloid and tau accumulation are associated and that amyloid accumulation may precede that of tau. This report further investigates the relationship between amyloid and tau to assess whether elevated cortical tau can predict elevated amyloid in participants with early symptomatic AD. METHODS Florbetapir F18 and flortaucipir F18 uptake were evaluated from baseline PET scans collected in three multi‐center studies with cognitively impaired participants, including A05 (N = 306; NCT02016560), TB (N = 310; TRAILBLAZER‐ALZ; NCT03367403), and TB2 (N = 1165; TRAILBLAZER‐ALZ 2; NCT04437511). Images were assessed using visual and quantitative approaches to establish amyloid (A+) and tau (T+) positivity, as well as a combination method (tauVQ) to establish T+. Associations between global amyloid and tau were evaluated with positive and negative predictive values (PPV, NPV) and likelihood ratios (LR+, LR–). Predictive values within subgroups according to ethnicity, race, cognitive score, age, and sex were also evaluated. The relationship between regional tau (four target and two reference regions were tested) and global amyloid was investigated in A05 participant scans using receiver‐operating characteristic (ROC) curves. RESULTS PPV for amyloid positivity was ≥93% for all three trials using various A+ and T+ definitions, including visual, quantitative, and combination methods. Population characteristics did not have an impact on A+ predictability. Regional analyses (early tau (Eτ) volume of interest (VOI), temporal, parietal, frontal) revealed significant area under the ROC curve in Eτ VOI compared to frontal region, regardless of reference region and consistent among visual and quantitative A+ definitions (p < 0.001). DISCUSSION These findings suggest that a positive tau PET scan is associated (≥93%) with amyloid positivity in individuals with early symptomatic AD, with the potential benefits of reducing clinical trial and health care expenses, radiation exposure, and participant time. Highlights Positron emission tomography (PET) evaluates candidates for Alzheimer's disease (AD) research. A positive tau PET scan is associated (≥93%) with amyloid positivity. A positive amyloid PET is not necessarily associated with tau positivity. Tau PET could be the sole diagnostic tool to confirm candidates for AD trials

Positive Behavioural Support in the UK: A State of the Nation Report

Background: Early Positive Approaches to Support (E-PAtS) is a co-produced and co-facilitated group programme that aims to provide early years support to family caregivers of children with Intellectual and Developmental Disabilities. Method: Thirty-five caregivers who had attended E-PAtS groups took part in individual interviews or focus groups. Caregiver experiences concerning attendance of E-PAtS were explored, in relation to process variables and perceived outcomes. Interviews were thematically analysed. Results: Three major themes were identified: Our Group, Evolving Emotions, and Positive Approaches. Being with and being supported by other families was very important to caregivers. Families reported increased confidence and greater realisation of the need for self-care. Children were reported to show fewer behaviours that challenge and increases in adaptive skills. Findings corresponded to mechanisms and outcomes in the E-PAtS logic model. Conclusion: E-PAtS shows promise as one way families and children with Intellectual and Developmental Disabilities can access early years suppor

Impact of pre-existing chronic viral infection and reactivation on the development of long COVID

BACKGROUNDThe presence and reactivation of chronic viral infections, such as EBV, CMV, and HIV, have been proposed as potential contributors to long COVID (LC), but studies in well-characterized postacute cohorts of individuals with COVID-19 over a longer time course consistent with current case definitions of LC are limited.METHODSIn a cohort of 280 adults with prior SARS-CoV-2 infection, we assessed the presence and types of LC symptoms and prior medical history (including COVID-19 history and HIV status) and performed serological testing for EBV and CMV using a commercial laboratory. We used covariate-adjusted binary logistic regression models to identify independent associations between variables and LC symptoms.RESULTSWe observed that LC symptoms, such as fatigue and neurocognitive dysfunction, at a median of 4 months following initial diagnosis were independently associated with serological evidence suggesting recent EBV reactivation (early antigen-diffuse IgG positivity) or high nuclear antigen (EBNA) IgG levels but not with ongoing EBV viremia. Serological evidence suggesting recent EBV reactivation (early antigen-diffuse IgG positivity) was most strongly associated with fatigue (OR = 2.12). Underlying HIV infection was also independently associated with neurocognitive LC (OR = 2.5). Interestingly, participants who had serologic evidence of prior CMV infection were less likely to develop neurocognitive LC (OR = 0.52).CONCLUSIONOverall, these findings suggest differential effects of chronic viral coinfections on the likelihood of developing LC and association with distinct syndromic patterns. Further assessment during the acute phase of COVID-19 is warranted.TRIAL REGISTRATIONLong-term Impact of Infection with Novel Coronavirus; ClinicalTrials.gov NCT04362150.FUNDINGThis work was supported by NIH/National Institute of Allergy and Infectious Diseases grants (3R01AI141003-03S1, R01AI158013, and K24AI145806); the Zuckerberg San Francisco General Hospital Department of Medicine and Division of HIV, Infectious Diseases, and Global Medicine; and the UCSF-Bay Area Center for AIDS Research (P30-AI027763)