Background:Alzheimer’s disease (AD) is currently incurable and a majority of investigational drugs have failed clinical trials. One explanation for this failure may be the invalidity of hypotheses focus-ing on amyloid to explain AD pathogenesis. Recently, hypotheses which are centered on synaptic and met-abolic dysfunction are increasingly implicated in AD.Objective:Evaluate AD hypotheses by comparing neurotransmitter and metabolite marker concentrations in normal versus AD CSF.Methods:Meta-analysis allows for statistical comparison of pooled, existing cerebrospinal fluid (CSF) marker data extracted from multiple publications, to obtain a more reliable estimate of concentrations. This method also provides a unique opportunity to rapidly validate AD hypotheses using the resulting CSF con-centration data. Hubmed, Pubmed and Google Scholar were comprehensively searched for published Eng-lish articles, without date restrictions, for the keywords “AD”, “CSF”, and “human” plus markers selected for synaptic and metabolic pathways. Synaptic markers were acetylcholine, gamma-aminobutyric acid (GABA), glutamine, and glycine. Metabolic markers were glutathione, glucose, lactate, pyruvate, and 8 other amino acids. Only studies that measured markers in AD and controls (Ctl), provided means, standard er-rors/deviation, and subject numbers were included. Data were extracted by six authors and reviewed by two others for accuracy. Data were pooled using ratio of means (RoM of AD/Ctl) and random effects meta-analysis using Cochrane Collaboration’s Review Manager software.Results:Of the 435 identified publications, after exclusion and removal of duplicates, 35 articles were in-cluded comprising a total of 605 AD patients and 585 controls. The following markers of synaptic and met-abolic pathways were significantly changed in AD/controls: acetylcholine (RoM 0.36, 95% CI 0.24-0.53, p<0.00001), GABA (0.74, 0.58-0.94, p<0.01), pyruvate (0.48, 0.24-0.94, p=0.03), glutathione (1.11, 1.01-1.21, p=0.03), alanine (1.10, 0.98-1.23, p=0.09), and lower levels of significance for lactate (1.2, 1.00-1.47, p=0.05). Of note, CSF glucose and glutamate levels in AD were not significantly different than that of the controls.Conclusion:This study provides proof of concept for the use of meta-analysis validation of AD hypothe-ses, specifically via robust evidence for the cholinergic hypothesis of AD. Our data disagree with the other synaptic hypotheses of glutamate excitotoxicity and GABAergic resistance to neurodegeneration, given ob-served unchanged glutamate levels and decreased GABA levels. With regards to metabolic hypotheses, the data supported upregulation of anaerobic glycolysis, pentose phosphate pathway (glutathione), and anaple-rosis of the tricarboxylic acid cycle using glutamate. Future applications of meta-analysis indicate the pos-sibility of further in silico evaluation and generation of novel hypotheses in the AD field.

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Introduction: Reverse total shoulder arthroplasty (rTSA) has become a popular option for the surgical management of rotator cuff arthropathy and complex fractures of the proximal humerus. However, there is a paucity of studies evaluating outcomes, especially between patients of different age groups. The purpose of this study was to compare functional outcomes and survivorship between patients older than 65 years (o65) and those 65 years and younger (y65). Methods: A retrospective review was conducted at a single academic medical center identifying a consecutive cohort of patients undergoing rTSA between 2018 and 2020. The minimum follow-up time was 2 years. Patients were stratified into two groups for comparative analyses (y65 and o65). Patient demographics, perioperative and postoperative data, and functional outcomes were collected. A Kaplan-Meier survival analysis was conducted to determine survivorship, defined as revision surgery or implant failure. Results: Forty-eight patients were included for final analysis. Nineteen patients comprised the y65 group while 29 patients comprised the o65 group. No difference was observed in Quick Disabilities of the Arm, Shoulder, and Hand scores at baseline nor at the latest follow-up between the two groups. Patients in the y65 group had significantly greater internal and external rotation (IR/ER) from 3 months to 2 years compared with patients in the o65 group ( P ≤ 0.05). Finally, there were no differences in revision surgery rates between the y65 group and the o65 group (11% vs. 14%, P = 1.0). A KM survival analysis revealed no difference in implant failure, necessitating revision surgery between the two groups at the latest follow-up ( P = 0.69). Discussion: Despite a notable difference in the number of baseline comorbidities, there were no notable differences in functional outcomes, survivorship, and revision surgery rates between each cohort. Although both groups had a similar function initially, by 3 months postoperatively, the y65 group had markedly greater range of motion in IR and ER. Longer term survivorship is needed; however, rTSA may offer a reliable option for shoulder reconstruction even in the y65 patient group.

This study assessed knowledge, attitudes and perceptions of various stakeholders in Grenada regarding genetically modified organisms and the release of genetically modified mosquitoes. The study adopted a cross sectional design with a study population that comprised of members from seven stakeholder groups of civil society in Grenada. The sample population was obtained through a snowballing strategy and data collection for the study consisted of a semi-structured interview. Data was managed through the collection and reviewing of data from transcribed interview notes, as well as observations and interpretations made during the field collection. Interview recordings were analyzed to identify emerging themes. These themes were ranked according to the frequency with which they appeared, and main concepts identified by linking related themes. Most groups supported the use of genetically modified mosquitoes against Zika, but there were several varying concerns, including environmental worries and the impact of these organisms on humans. Many questioned the characteristics of Zika itself, and some believed Zika is a man-made virus created in a lab. Others doubted the link of Zika virus to microcephaly and other birth defects, and some were unsure if Zika virus is transmitted by mosquitoes. There is a wide range of differing knowledge, attitudes, and perceptions towards genetically modifying technology in general and towards mosquitoes in response to Zika.