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The nervous system is rich in miRNAs, indicating an important role of these molecules in regulating processes associated with cognition, memory, and others. Therefore, qualitative and quantitative imbalances involving such miRNAs may be involved in dementia contexts, including Late-Onset Alzheimer's Disease (LOAD). To test the viability of circulating miRNAs (c-miRNAs) as biomarkers for LOAD, we proceed accordingly to the following reasoning. The first stage was to discover and identify profile of c-miRNAs by RNA sequencing (RNA-Seq). For this purpose, blood serum samples were used from LOAD patients (n = 5) and cognitively healthy elderly control group (CTRL_CH) (n = 5), all over 70 years old. We identified seven c-miRNAs differentially expressed (p ≤ 0.05) in the serum of LOAD patients compared to CTRL_CH (miR-10a-5p; miR-29b-2-5p; miR-125a-5p; miR-342-3p, miR-708-5p, miR-380-5p and miR-340-3p). Of these, five (p ≤ 0.01) were selected for in silico analysis (miR-10a-5p; miR-29b-2-5p; miR-125a-5p; miR-342-3p, miR-708-5p), for which 44 relevant target genes were found regulated by these c-miRNAs and related to LOAD. Through the analysis of these target genes in databases, it was possible to observe that they have functions related to the development and progress of LOAD, directly or indirectly connecting the different Alzheimer's pathways. Thus, this work found five promising serum c-miRNAs as options for biomarkers contributing to LOAD diagnosis. Our study shows the complex network between these molecules and LOAD, supporting the relevance of studies using c-miRNAs in dementia contexts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

No accurate and rapid diagnostic test exists for tuberculous meningitis (TBM), leading to delayed diagnosis. We leveraged data from multiple studies to improve the predictive performance of diagnostic models across different populations, settings, and subgroups to develop a new predictive tool for TBM diagnosis. We conducted a systematic review to analyze eligible datasets with individual-level participant data (IPD). We imputed missing data and explored three approaches: stepwise logistic regression, classification and regression tree (CART), and random forest regression. We evaluated performance using calibration plots and C-statistics via internal-external cross-validation. We included 3,761 individual participants from 14 studies and nine countries. A total of 1,240 (33%) participants had "definite" (30%) or "probable" (3%) TBM by case definition. Important predictive variables included cerebrospinal fluid (CSF) glucose, blood glucose, CSF white cell count, CSF differential, cryptococcal antigen, HIV status, and fever presence. Internal validation showed that performance varied considerably between IPD datasets with C-statistic values between 0.60 and 0.89. In external validation, CART performed the worst (C = 0.82), and logistic regression and random forest had the same accuracy (C = 0.91). We developed a mobile app for TBM clinical prediction that accounted for heterogeneity and improved diagnostic performance (https://tbmcalc.github.io/tbmcalc). Further external validation is needed.

Although monocyte chemoattractant protein (MCP-1)/CCL2 is believed to mediate trafficking of HIV-activated leukocytes into the CNS, its role has not been studied directly in humans. To evaluate MCP-1's effects on CNS leukocyte infiltration, we measured CSF leukocytes and MCP-1 levels in serial plasma and cerebrospinal fluid (CSF) samples from subjects who experienced large increases in viral load after interrupting antiretrovirals. Following large increases in CSF MCP-1, CSF leukocytosis (15-166 cells/microL) developed in 4 of 6 subjects. Both initial MCP-1 levels and subsequent changes were 3-fold larger in CSF than plasma. The magnitude and timing of changes suggested that MCP-1 triggers the development of CSF pleocytosis.

Background: Increased expression of monocyte chemoattractant protein type 1 (MCP-1) is associated with HIV CNS disease. This study evaluated the temporal relationships between MCP-1 expression and HIV replication in the CNS., Methods: MCP-1 and HIV viral load (VL) were measured in serially obtained samples of plasma and cerebrospinal fluid (CSF) in subjects either interrupting (TI) or starting (TS) antiretroviral therapy., Results: Following TI, plasma VL rebounded first, followed by increases in CSF MCP-1, which immediately preceded or coincided with a rebound of CSF VL., Conclusion: The close temporal relationship of the increase of MCP-1 and CSF VL suggests that they are co-regulated, or that one is a stimulus for the other.

Aims: To report the case of a 26 year old white man, who developed chronic meningitis and intracerebral granulomata 15 days after an episode of near drowning in a swamp., Methods: Aspergillus fumigatus was isolated from cerebrospinal fluid cultures., Results: The patient died 70 days after the symptoms were first noticed, and seven days after a subarachnoid haemorrhage. Aspergillus has never been reported before as a cause of intracranial infection after near drowning., Conclusions: Physicians must be aware of this possibility when confronted with such a situation, because there are now effective therapeutic options for systemic aspergillosis.

This report describes a fatal case of central nervous system pseudallescheriasis. A 32 year old white man presented with headache and meningismus 15 days after nearly drowning in a swine sewage reservoir. Computerised tomography and magnetic resonance imaging of the head revealed multiple brain granulomata, which vanished when steroid and broad spectrum antimicrobial and antifungal agents, in addition to dexamethasone, were started. Cerebrospinal fluid analysis disclosed a neutrophilic meningitis. Treatment with antibiotics and amphotericin B, together with fluconazole and later itraconazole, was ineffective. Miconazole was added through an Ommaya reservoir, but was insufficient to halt the infection. Pseudallescheria boydii was finally isolated and identified in cerebrospinal fluid cultures, a few days before death, three and a half months after the symptoms began. Diagnosis was delayed because of a reduction in the lesions after partial treatment, which prevented a stereotactic biopsy. Physicians should be aware of this condition, and provide prompt stereotactic biopsy. Confirmed cases should perhaps be treated with voriconazole, probably the most effective, currently available treatment for this agent.

A group of neurologists and clinical neurochemists representing twelve countries worked towards a consensus on laboratory techniques to improve the quality of analysis and interpretation of cerebrospinal fluid (CSF) proteins. Consensus was approached via a virtual Lotus Notes-based TeamRoom. This new approach respecting multicultural differences, common views, and minority opinions, is available in http://www.teamspace.net/ CSF, presenting the implicit, complementary version of this explicit, printed consensus. Three key recommendations were made: CSF and (appropriately diluted) serum samples should be analyzed together in one analytical run, i.e., with reference to the same calibration curve. Results are evaluated as CSF/serum quotients, taking into account the non-linear, hyperbolic relation between immunoglobulin (Ig)- and albumin-quotients rather than using the linear IgG index or IgG synthesis rate. Controls should include materials with values within the reference ranges (IgM: 0.5-1.5 mg/l; IgA: 1-3 mg/l; IgG: 10-30 mg/l and albumin: 100-300 mg/l). The physiological, methodological and clinical significance of CSF/serum quotients is reviewed. We confirmed the previous consensus on oligoclonal IgG, in particular the usefulness of the five typical interpretation patterns. The group compared current external and internal quality assurance schemes and encouraged all members to maintain national or local traditions. Values for acceptable imprecision in the CSF quality assurance are proposed.