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A 74-year-old man with chronic obstructive pulmonary disease, glaucoma, and Stage IIIB squamous cell lung cancer experienced several minutes of flashing lights in his right visual hemifield, followed by onset of a right visual field defect. On examination, the patient had a right homonymous hemianopsia that was most dense inferiorly by confrontation testing. Emergent CT scan of the head revealed a 2.5 · 3 cm hypodensity in the left occipital lobe, which was interpreted as an acute stroke. Continuous EEG monitoring captured left posterior quadrant seizures that were temporally correlated to the positive visual phenomena. Subsequent MRI of the brain with and without contrast revealed a conglomerate of centrally necrotic and peripherally enhancing mass lesions. On biopsy, a thick purulent material was drained and Gram stain of the sample revealed gram-positive beaded rods, which speciated to Nocardia farcinica. The patient was treated with a six-week course of intravenous meropenem and a one-year course of oral trimethroprim–sulfamethoxazole. On follow-up, the patient experienced resolution of the right visual field deficit. [ABSTRACT FROM AUTHOR]

In spite of the tremendous achievements in the quality and quantity of health services attained globally, healthcare provision in developing countries remains a serious problem. Accessibility issues have been noted in peri-urban areas and measures to improve physical access to health services continue. This paper offers a comprehensive and analytical methodology of analysing geographical accessibility of healthcare facilities using geospatial techniques. The study employed ArcGIS Network Analyst to build a road network dataset and measure the shortest network-distance and travel-time to the closest healthcare via road networks. Walking speed was also assigned as 3km/hr throughout the whole network. Public transport speed limits of 30km/hr were assigned based on the roads speed limits of Mbeya City, without considering road condition and topography. A total of 70 healthcare facilities and 95 households' settlement points (incidents) were loaded as input in the ArcGIS analyst tool. The findings show that most health facilities are not easily accessible by walking; and that there is a poor spatial accessibility to health facilities and wellbeing among residents in the peri-urban area. Thus, the local government authority is advised to improve the road infrastructure to enhance accessibility to sparsely distributed healthcare facilities. [ABSTRACT FROM AUTHOR]

This study examines the implication of fire on tree species diversity in northwest Uluguru Nature Forest Reserve (UNFR). The study compared tree species diversity between burned and unburned areas, and determined whether burned and unburned areas depicted any variation in stages of succession. Tree species samples were drawn from eighteen stands, and tree species data were ordinate using Nonmetric Multidimensional Scaling (NMS or NMDS) (PC-ORD version 5.10) to describe relationships (similarity and dissimilarities) between tree species, forest succession, and the effect of fire on tree species. Species richness did not vary significantly between burned and unburned plots. However, species composition was high in burned stands, which contributed to a high basal area in burned stands. Unburned stands had low species composition and low basal area. Fire intolerant tree species dominated unburned areas while species in the burned areas were fire adapted. A few species existed in burned and unburned stands. Trees in burned areas are still at a young succession stage while in unburned stands vegetation development has reached a succession stage that the vegetation is stable with hardwood forest formation. A sustainable management plan for the UNFR must base on empirical data on fire regime variation over space and time. [ABSTRACT FROM AUTHOR]

Amyloid-β (Aβ)-induced changes in synaptic function in experimental models of Alzheimer's disease (AD) suggest that A generation and accumulation may affect fundamental mechanisms of synaptic plasticity. To test this hypothesis, we examined the effect of APP overexpression on a well characterized, in vivo, developmental model of systems-level plasticity, ocular dominance plasticity. Following monocular visual deprivation during the critical period, mice that express mutant alleles of amyloid precursor protein (APPswe) and Presenilin1 (PS1dE9), as well as mice that express APPswe alone, lack ocular dominance plasticity in visual cortex. Defects in the spatial extent and magnitude of the plastic response are evident using two complementary approaches, Arc induction and optical imaging of intrinsic signals in awake mice. This defect in a classic paradigm of systems level synaptic plasticity shows that A overexpression, even early in postnatal life, can perturb plasticity in cerebral cortex, and supports the idea that decreased synaptic plasticity due to elevatedAβ exposure contributes to cognitive impairment in AD. [ABSTRACT FROM AUTHOR]

Anti-amyloid-beta immunization leads to amyloid clearance in patients with Alzheimer's disease, but the effect of vaccination on amyloid-beta-induced neuronal pathology has not been quantitatively examined. The objectives of this study were to address the effects of anti-amyloid-beta active immunization on neurite trajectories and the pathological hallmarks of Alzheimer's disease in the human hippocampus. Hippocampal sections from five patients with Alzheimer's disease enrolled in the AN1792 Phase 2a trial were compared with those from 13 non-immunized Braak-stage and age-matched patients with Alzheimer's disease, and eight age-matched non-demented controls. Analyses included neurite curvature ratio as a quantitative measure of neuritic abnormalities, amyloid and tau loads, and a quantitative characterization of plaque-associated neuritic dystrophy and astrocytosis. Amyloid load and density of dense-core plaques were decreased in the immunized group compared to non-immunized patients (P < 0.01 and P < 0.001, respectively). The curvature ratio in non-immunized patients with Alzheimer's disease was elevated compared to non-demented controls (P < 0.0001). In immunized patients, however, the curvature ratio was normalized when compared to non-immunized patients (P < 0.0001), and not different from non-demented controls. In the non-immunized patients, neurites close to dense-core plaques (within 50 microm) were more abnormal than those far from plaques (i.e. beyond 50 microm) (P < 0.0001). By contrast, in the immunized group neurites close to and far from the remaining dense-core plaques did not differ, and both were straighter compared to the non-immunized patients (P < 0.0001). Compared to non-immunized patients, dense-core plaques remaining after immunization had similar degree of astrocytosis (P = 0.6060), more embedded dystrophic neurites (P < 0.0001) and were more likely to have mitochondrial accumulation (P < 0.001). In addition, there was a significant decrease in the density of paired helical filament-1-positive neurons in the immunized group as compared to the non-immunized (P < 0.05), but not in the density of Alz50 or thioflavin-S positive tangles, suggesting a modest effect of anti-amyloid-beta immunization on tangle pathology. Clearance of amyloid plaques upon immunization with AN1792 effectively improves a morphological measure of neurite abnormality in the hippocampus. This improvement is not just attributable to the decrease in plaque load, but also occurs within the halo of the remaining dense-core plaques. However, these remaining plaques still retain some of their toxic potential. Anti-amyloid-beta immunization might also ameliorate the hippocampal tau pathology through a decrease in tau phosphorylation. These data agree with preclinical animal studies and further demonstrate that human anti-amyloid-beta immunization does not merely clear amyloid from the Alzheimer's disease brain, but reduces some of the neuronal alterations that characterize Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Cancer of unknown primary (CUP) constitutes between 2% and 5% of human malignancies and is among the most common causes of cancer death in the United States. Brain metastases are often the first clinical presentation of CUP; despite extensive pathological and imaging studies, 20%-45% of CUP are never assigned a primary site. DNA methylation array profiling is a reliable method for tumor classification but tumor-type-specific classifier development requires many reference samples. This is difficult to accomplish for CUP as many cases are never assigned a specific diagnosis. Recent studies identified subsets of methylation quantitative trait loci (mQTLs) unique to specific organs, which could help increase classifier accuracy while requiring fewer samples. We performed a retrospective genome-wide methylation analysis of 759 carcinoma samples from formalin-fixed paraffin-embedded tissue samples using Illumina EPIC array. Utilizing mQTL specific for breast, lung, ovarian/gynecologic, colon, kidney, or testis (BLOCKT) (185k total probes), we developed a deep learning-based methylation classifier that achieved 93.12% average accuracy and 93.04% average F1-score across a 10-fold validation for BLOCKT organs. Our findings indicate that our organ-based DNA methylation classifier can assist pathologists in identifying the site of origin, providing oncologists insight on a diagnosis to administer appropriate therapy, improving patient outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc.)