Retinal arterial Aß40 deposition is linked with tight junction loss and cerebral amyloid angiopathy in MCI and AD patients.

INTRODUCTION: Vascular amyloid beta (Aß) protein deposits were detected in retinas of mild cognitively impaired (MCI) and Alzheimer's disease (AD) patients. We tested the hypothesis that the retinal vascular tight junctions (TJs) were compromised and linked to disease status. METHODS: TJ components and Aß expression in capillaries and larger blood vessels were determined in post mortem retinas from 34 MCI or AD patients and 27 cognitively normal controls and correlated with neuropathology. RESULTS: Severe decreases in retinal vascular zonula occludens-1 (ZO-1) and claudin-5 correlating with abundant arteriolar Aß40 deposition were identified in MCI and AD patients. Retinal claudin-5 deficiency was closely associated with cerebral amyloid angiopathy, whereas ZO-1 defects correlated with cerebral pathology and cognitive deficits. DISCUSSION: We uncovered deficiencies in blood-retinal barrier markers for potential retinal imaging targets of AD screening and monitoring. Intense retinal arteriolar Aß40 deposition suggests a common pathogenic mechanism of failed Aß clearance via intramural periarterial drainage.

Identification of retinal tau oligomers, citrullinated tau, and other tau isoforms in early and advanced AD and relations to disease status.

Importance: This study identifies and quantifies diverse pathological tau isoforms in the retina of both early and advanced-stage Alzheimer's disease (AD) and determines their relationship with disease status. Objective: A case-control study was conducted to investigate the accumulation of retinal neurofibrillary tangles (NFTs), paired helical filament (PHF)-tau, oligomeric tau (oligo-tau), hyperphosphorylated tau (p-tau), and citrullinated tau (Cit-tau) in relation to the respective brain pathology and cognitive dysfunction in mild cognitively impaired (MCI) and AD dementia patients versus normal cognition (NC) controls. Design setting and participants: Eyes and brains from donors diagnosed with AD, MCI (due to AD), and NC were collected (n=75 in total), along with clinical and neuropathological data. Brain and retinal cross-sections-in predefined superior-temporal and inferior-temporal (ST/IT) subregions-were subjected to histopathology analysis or Nanostring GeoMx digital spatial profiling. Main outcomes and measure: Retinal burden of NFTs (pretangles and mature tangles), PHF-tau, p-tau, oligo-tau, and Cit-tau was assessed in MCI and AD versus NC retinas. Pairwise correlations revealed associations between retinal and brain parameters and cognitive status. Results: Increased retinal NFTs (1.8-fold, p=0.0494), PHF-tau (2.3-fold, p<0.0001), oligo-tau (9.1-fold, p<0.0001), CitR 209 -tau (4.3-fold, p<0.0001), pSer202/Thr205-tau (AT8; 4.1-fold, p<0.0001), and pSer396-tau (2.8-fold, p=0.0015) were detected in AD patients. Retinas from MCI patients showed significant increases in NFTs (2.0-fold, p=0.0444), CitR 209 -tau (3.5-fold, p=0.0201), pSer396-tau (2.6-fold, p=0.0409), and, moreover, oligo-tau (5.8-fold, p=0.0045). Nanostring GeoMx quantification demonstrated upregulated retinal p-tau levels in MCI patients at phosphorylation sites of Ser214 (2.3-fold, p=0.0060), Ser396 (1.8-fold, p=0.0052), Ser404 (2.4-fold, p=0.0018), and Thr231 (3.3-fold, p=0.0028). Strong correlations were found between retinal tau forms to paired-brain pathology and cognitive status: a) retinal oligo-tau vs. Braak stage (r=0.60, P=0.0002), b) retinal PHF-tau vs. ABC average score (r=0.64, P=0.0043), c) retinal pSer396-tau vs. brain NFTs (r=0.68, P<0.0001), and d) retinal pSer202/Thr205-tau vs. MMSE scores (r= -0.77, P=0.0089). Conclusions and Relevance: This study reveals increases in immature and mature retinal tau isoforms in MCI and AD patients, highlighting their relationship with brain pathology and cognition. The data provide strong incentive to further explore retinal tauopathy markers that may be useful for early detection and monitoring of AD staging through noninvasive retinal imaging.

Alzheimer's disease pathophysiology in the Retina.

The retina is an emerging CNS target for potential noninvasive diagnosis and tracking of Alzheimer's disease (AD). Studies have identified the pathological hallmarks of AD, including amyloid ß-protein (Aß) deposits and abnormal tau protein isoforms, in the retinas of AD patients and animal models. Moreover, structural and functional vascular abnormalities such as reduced blood flow, vascular Aß deposition, and blood-retinal barrier damage, along with inflammation and neurodegeneration, have been described in retinas of patients with mild cognitive impairment and AD dementia. Histological, biochemical, and clinical studies have demonstrated that the nature and severity of AD pathologies in the retina and brain correspond. Proteomics analysis revealed a similar pattern of dysregulated proteins and biological pathways in the retina and brain of AD patients, with enhanced inflammatory and neurodegenerative processes, impaired oxidative-phosphorylation, and mitochondrial dysfunction. Notably, investigational imaging technologies can now detect AD-specific amyloid deposits, as well as vasculopathy and neurodegeneration in the retina of living AD patients, suggesting alterations at different disease stages and links to brain pathology. Current and exploratory ophthalmic imaging modalities, such as optical coherence tomography (OCT), OCT-angiography, confocal scanning laser ophthalmoscopy, and hyperspectral imaging, may offer promise in the clinical assessment of AD. However, further research is needed to deepen our understanding of AD's impact on the retina and its progression. To advance this field, future studies require replication in larger and diverse cohorts with confirmed AD biomarkers and standardized retinal imaging techniques. This will validate potential retinal biomarkers for AD, aiding in early screening and monitoring.

Exploring Natural Immune Responses to Shigella Exposure Using Multiplex Bead Assays on Dried Blood Spots in High-Burden Countries: Protocol From a Multisite Diarrhea Surveillance Study.

Background: Molecular diagnostics on human fecal samples have identified a larger burden of shigellosis than previously appreciated by culture. Evidence of fold changes in immunoglobulin G (IgG) to conserved and type-specific Shigella antigens could be used to validate the molecular assignment of type-specific Shigella as the etiology of acute diarrhea and support polymerase chain reaction (PCR)-based microbiologic end points for vaccine trials. Methods: We will test dried blood spots collected at enrollment and 4 weeks later using bead-based immunoassays for IgG to invasion plasmid antigen B and type-specific lipopolysaccharide O-antigen for Shigella flexneri 1b, 2a, 3a, and 6 and Shigella sonnei in Shigella-positive cases and age-, site-, and season-matched test-negative controls from all sites in the Enterics for Global Health (EFGH) Shigella surveillance study. Fold antibody responses will be compared between culture-positive, culture-negative but PCR-attributable, and PCR-positive but not attributable cases and test-negative controls. Age- and site-specific seroprevalence distributions will be identified, and the association between baseline antibodies and Shigella attribution will be estimated. Conclusions: The integration of these assays into the EFGH study will help support PCR-based attribution of acute diarrhea to type-specific Shigella, describe the baseline seroprevalence of conserved and type-specific Shigella antibodies, and support correlates of protection for immunity to Shigella diarrhea. These insights can help support the development and evaluation of Shigella vaccine candidates.

Nurses' Awareness and Practices of Unintentional Perioperative Hypothermia Prevention: A Cross-Sectional Study.

Unintentional perioperative hypothermia can cause potentially life-threatening complications. The aim of this study was to determine the awareness and practices of nurses regarding unintentional perioperative hypothermia prevention. The study was conducted at a teaching hospital in Gambia with descriptive cross-sectional design. A total of 53 nurses voluntarily participated in this study. The questionnaire used in this study was developed based on the American periOperative Registered Nurses (AORN) and National Institute for Health and Care Excellence perioperative hypothermia guidelines. Descriptive statistics, Pearson correlation, Student t-test, and one-way ANOVA were used in the analysis of data. The result of the study showed that nurses had high level of awareness of unintentional perioperative hypothermia prevention; however, practice levels were found to be low. Based on the results of the study, development of policies, implementation of the unintentional perioperative hypothermia prevention guidelines, and continuous education to improve nurses' knowledge and practices were recommended.

Comparison of Outcomes Between Cage Materials Used for Patients Undergoing Anterior Cervical Discectomy and Fusion with Standalone Cages: A Systematic Review and Meta-Analysis.

INTRODUCTION: Interbody cages are currently being used to address diseases of the vertebra requiring surgical stabilization. Titanium cages were first introduced in 1988. Polyetheretherketone (PEEK) cages are used frequently as one of the alternatives to titanium cages in current practice. This study aimed to compare available cage materials by reviewing the surgical and radiographic outcomes following anterior cervical discectomy and fusion. METHODS: A comprehensive search of several electronic databases was conducted following the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. Baseline characteristics, operative outcomes, arthrodesis rates, subsidence rates, and complications were collected from included studies. Collected outcomes were further stratified according to the procedure type, the number of levels operated, and graft used to compare cage materials. RESULTS: Following the screening for inclusion criteria, a total of 37 studies with 2363 patients were included. The median age was 49.5 years and the median follow-up was 26 months. Overall, no significant differences were found between PEEK and titanium cages regarding fusion, neurologic deficit, subsidence rates, or "good and excellent" outcome according to Odom criteria. However, the standalone comparison between PEEK, titanium, and poly-methyl-methacrylate (PMMA) cages showed a significantly lower fusion rate for PMMA (PEEK: 94%, PMMA: 56%, titanium: 95%, P < 0.01). CONCLUSIONS: In the present systematic review and meta-analysis, a comparison of the long-term patient-reported and the radiographic outcomes associated with the use of titanium and PEEK, intervertebral body cages showed similar findings. However, there were significantly lower fusion rates for PMMA cages when using a standalone cage without graft material.

Bumsters, big black organs and old white gold: Embodied racial myths in sexual relationships of Gambian beach boys.

Sexuality is a platform upon which ideologies are enacted. Based on ethnographic fieldwork in The Gambia, this paper discusses the embodiment of racial myths about male Black bodies and Western affluence. Methods utilized included participant observation, focus group discussions and in-depth interviews. Beach-boys, locally called bumsters, are a common feature of the country's tourism. Societal attitudes to bumsters are ambivalent. Bumsters variously indulge in a complex web of sexual activity ranging from commercial to non-commercial, voluntary to socially-imposed, individual to peer-driven, heterosexual to homosexual, casual to regular, particularly with foreign tourists. Narratives about their sexuality reveal an enactment of myths about the male Black body and superior sexual performance on one hand, and images of plundered wealth sitting in 'the West'--a dream destination flowing with milk and honey, and physically represented by the toubab--a local label for White foreigners-on the other. This highly fantasized wealth forms the core of youth aspirations to travel abroad. Sexual activity with a toubab is the ticket out of Africa's inherent scarcity. Metaphors and idioms of unlimited virility and dynamic manhood are reinforced through sex tourism and form part of the identity of Gambian bumsters. These self-images reinstate and reinforce racial stereotypes.