Burden of Illness in People with Alzheimer's Disease: A Systematic Review of Epidemiology, Comorbidities and Mortality.

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disease worldwide, and an updated quantification of its impact on morbidity, disability, and mortality is warranted. We conducted a systematic literature review, focusing on the past decade, to characterize AD and assess its impact on affected individuals. METHODS: Searches of Embase, MEDLINE, and the Cochrane Library were conducted on August 7, 2020 and updated on November 10, 2021. Observational studies from any country reporting incidence, prevalence, comorbidities, and/or outcomes related to disability and mortality/life expectancy, in people with mild cognitive impairment (MCI) due to AD, or mild, moderate, or severe AD dementia, were considered relevant. RESULTS: Data were extracted from 88 studies (46 incidence/prevalence; 44 comorbidities; 25 mortality-/disability-related outcomes), mostly from Europe, the USA, and Asia. AD dementia diagnosis was confirmed using biomarkers in only 6 studies. Estimated 5-year mortality in AD was 35%, and comorbidity prevalence estimates varied widely (hypertension: 30.2-73.9%; diabetes: 6.0-24.3%; stroke: 2.7-13.7%). Overall, people with AD dementia were more likely to have cardiovascular disease or diabetes than controls, and 5-year mortality in people with AD dementia was double that in the age- and year-matched general population (115.0 vs 60.6 per 1,000 person-years). CONCLUSIONS: AD is associated with excess morbidity and mortality. Future longitudinal studies of population aging, incorporating biomarker assessment to confirm AD diagnoses, are needed to better characterize the course of MCI due to AD and AD dementia.

The local microbiome after pediatric bladder augmentation: intestinal segments and the native urinary bladder host similar mucosal microbiota.

INTRODUCTION: Next-generation sequencing (NGS) techniques have provided novel insights into the microbiome of the urinary bladder (UB). In children after bladder augmentation using either ileum (ileocystoplasty, ICP) or colon (colocystoplasty, CCP), the fate of the mucosal microbiome introduced into the urinary tract remains unknown. OBJECTIVE: The aim was to compare the mucosal microbiome of the native UB vs the augmented intestinal segment (IS) using NGS. STUDY DESIGN: Twelve children after bladder augmentation (ICP n = 6, CCP n = 6) were included. Biopsies were taken during routine postoperative cystoscopy from the native UB and the IS. Specimens underwent whole-genome DNA extraction, 16S rRNA gene amplification, NGS, and Quantitative Insights Into Microbial Ecology (QIIME) data analysis. Downstream statistical data analyses were performed in Calypso. RESULTS: Patients' median age at the time of surgery was 11 years (6-17 years), and the median interval between augmentation and sampling was 7 years (4-13 years). α-Diversity (Shannon diversity index) was not significantly different between IS vs UB, ICP vs CCP, and male vs female. No general differences in the overall bacterial pattern (ß-diversity) were found between IS, UB, ICP, and CCP groups. The groups overlapped in principal coordinate analysis (PCoA) and non-metric multidimensional scaling (NMDS) analysis (Figure). Age at sampling had a statistically significant influence on ß-diversity at the genus level. Corynebacterium, Pseudoxanthomonas, Lactobacillus, Flavobacterium, and Micrococcus were the most dominating taxa detected over all samples. There was an obvious dominance of the genus Corynebacterium in the samples taken from the UB and IS in both ICP and CCP patients. Limitations of this study include the relatively small number of patients. CONCLUSION: After bladder augmentation, the native UB and augmented ISs (ICP and CCP) host similar microbiota despite their distinct differences of originating mucosal anatomy.

Natural history of eosinophilic esophagitis: a systematic review of epidemiology and disease course.

Eosinophilic esophagitis is a chronic immune-mediated esophageal disorder. For its timely diagnosis, clinicians must recognize common symptoms, and understand differences in symptoms across patient groups. The aim of this study is to systematically review the epidemiology and natural history of eosinophilic esophagitis. The MEDLINE, Embase, and Cochrane databases were searched from 1974 to February 2017 for studies describing the epidemiology and natural history of eosinophilic esophagitis. Congress abstracts from 2014 to 2016 were also searched. Search results were screened against predetermined inclusion/exclusion criteria by two independent reviewers, and data extraction was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Of 1376 articles identified, 47 met the inclusion criteria: 20 on epidemiology and 27 on natural history. Incidence and prevalence of eosinophilic esophagitis varied widely across North America and Europe, and increased over time. Incidence increased 131-fold in the Netherlands (1996-2010), 20-fold in Denmark (1997-2006), and 5.1-fold in Calgary, Canada (2004-2008). The most commonly reported symptoms were emesis and abdominal pain in children, and dysphagia and food impaction in adults. Age at diagnosis was 5.9-12.0 years in children, and approximately 30 years in adults. Time between symptom onset and diagnosis was 1.2-3.5 years in children and 3.0-8.0 years in adults. Diagnostic delay was associated with an increased risk of endoscopic features of fibrostenosis. Symptoms of eosinophilic esophagitis differed significantly by age and race. In conclusion, there is an increasing incidence and prevalence of eosinophilic esophagitis. The considerable delay between symptom onset and diagnosis suggests that clinicians do not readily recognize the disease, which may have important clinical ramifications.

Mineralization and Preservation of an extremotolerant Bacterium Isolated from an Early Mars Analog Environment.

The artificial mineralization of a polyresistant bacterial strain isolated from an acidic, oligotrophic lake was carried out to better understand microbial (i) early mineralization and (ii) potential for further fossilisation. Mineralization was conducted in mineral matrixes commonly found on Mars and Early-Earth, silica and gypsum, for 6 months. Samples were analyzed using microbiological (survival rates), morphological (electron microscopy), biochemical (GC-MS, Microarray immunoassay, Rock-Eval) and spectroscopic (EDX, FTIR, RAMAN spectroscopy) methods. We also investigated the impact of physiological status on mineralization and long-term fossilisation by exposing cells or not to Mars-related stresses (desiccation and radiation). Bacterial populations remained viable after 6 months although the kinetics of mineralization and cell-mineral interactions depended on the nature of minerals. Detection of biosignatures strongly depended on analytical methods, successful with FTIR and EDX but not with RAMAN and immunoassays. Neither influence of stress exposure, nor qualitative and quantitative changes of detected molecules were observed as a function of mineralization time and matrix. Rock-Eval analysis suggests that potential for preservation on geological times may be possible only with moderate diagenetic and metamorphic conditions. The implications of our results for microfossil preservation in the geological record of Earth as well as on Mars are discussed.

Evaluation of procedures for the collection, processing, and analysis of biomolecules from low-biomass surfaces.

To comprehensively assess microbial diversity and abundance via molecular-analysis-based methods, procedures for sample collection, processing, and analysis were evaluated in depth. A model microbial community (MMC) of known composition, representative of a typical low-biomass surface sample, was used to examine the effects of variables in sampling matrices, target cell density/molecule concentration, and cryogenic storage on the overall efficacy of the sampling regimen. The MMC used in this study comprised 11 distinct species of bacterial, archaeal, and fungal lineages associated with either spacecraft or clean-room surfaces. A known cellular density of MMC was deposited onto stainless steel coupons, and after drying, a variety of sampling devices were used to recover cells and biomolecules. The biomolecules and cells/spores recovered from each collection device were assessed by cultivable and microscopic enumeration, and quantitative and species-specific PCR assays. rRNA gene-based quantitative PCR analysis showed that cotton swabs were superior to nylon-flocked swabs for sampling of small surface areas, and for larger surfaces, biological sampling kits significantly outperformed polyester wipes. Species-specific PCR revealed differential recovery of certain species dependent upon the sampling device employed. The results of this study empower current and future molecular-analysis-based microbial sampling and processing methodologies.