Evaluating the diagnostic accuracy of magnetic resonance imaging in distinguishing strictures in Crohn's disease: a systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis sought to assess the diagnostic accuracy of magnetic resonance imaging (MRI) in distinguishing fibrotic from inflammatory strictures in Crohn's disease (CD) patients. METHODS: A rigorous and systematic exploration of five key databases yielded studies that met predefined criteria. Data were extracted for a comprehensive meta-analysis using MetaDiSC and MetaDTA software, providing diagnostic accuracy measures. The Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool was utilized for evaluating the methodological quality and potential bias within the studies. RESULTS: The systematic review involved the evaluation of 7437 records, culminating in the inclusion of 22 studies. In detecting fibrotic strictures in CD patients, MRI exhibited a pooled sensitivity of 85.20% (95% CI: 76.10-91.20%) and specificity of 96.00% (95% CI: 87.80-98.70%). For differentiating fibrotic strictures from inflammatory stenosis, the sensitivity was 81.5% (95% CI: 70.2-89.20%), and the specificity was 97.2% (95% CI: 90.0-99.3%). In terms of assessing the severity of strictures, sensitivity stood at 90.4% (95% CI: 78.1-96.1%) and specificity at 89.4% (95% CI: 57.4-98.2%). The consistency of the diagnostic accuracy was observed across different geographical locations and the various reference tests applied in the studies. CONCLUSIONS: The results of this meta-analysis underscore the robust diagnostic accuracy of MRI in detecting fibrotic strictures, distinguishing between fibrotic and inflammatory strictures, and evaluating stricture severity in CD patients. These findings support the integration of MRI into standard diagnostic protocols for patients with CD. Further large-scale, multicenter trials are warranted to confirm these results and to identify any potential limitations associated with the application of MRI in this clinical setting.

Galectin-3: A Novel Marker for the Prediction of Stroke Incidence and Clinical Prognosis.

Stroke, whether ischemic or haemorrhagic, is one of the main causes of mortality and disability all over the world, which entails huge burdens in both healthcare environments as well as social and economic aspects of life. Therefore, there is a continuous search for novel reliable biomarkers that can enhance the recognition of stroke events in a timely manner and predict the clinical outcomes following a stroke event. Galectins are a group of proteins expressed by many types of cells and tissues including vasculature, certain immune cells, fibroblasts, and gastrointestinal epithelial cells. These proteins vary in their structure and configuration according to their type and have a diversity of functions according to the type of tissue they are expressed in. Among these proteins, a few studies investigated mainly the roles played by galectin-1 (Gal-1) and galectin-3 (Gal-3) in the molecular mechanisms of atherosclerosis and in brain tissue remodeling after a stroke event. In this review, we present an updated overview of the current understanding of Gal-3's functions and implications in stroke occurrence and the response of the brain tissue to stroke events, which may be a key to its utility as a predictor of stroke incidence and clinical prognosis in the future.

Tranexamic acid for patients with aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis of 2991 patients.

OBJECTIVE: We aimed to synthesize evidence from published clinical trials on the efficacy and safety of tranexamic acid (TXA) administration in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: We followed the standard methods of the Cochrane Handbook of Systematic Reviews for interventions and the PRISMA statement guidelines 2020 when conducting and reporting this study. A computer literature search of PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials was conducted from inception until 1 January 2022. We selected observational studies and clinical trials comparing TXA versus no TXA in aSAH patients. Data of all outcomes were pooled as the risk ratio (RR) with the corresponding 95% confidence intervals in the meta-analysis models. RESULTS: Thirteen studies with a total of 2991 patients were included in the analysis. TXA could significantly cut the risk of rebleeding (RR 0.56, 95% CI 0.44 to 0.72) and mortality from rebleeding (RR 0.60, 95% CI 0.39 to 0.92, p = 0.02). However, TXA did not significantly improve the overall mortality, neurological outcome, delayed cerebral ischemia, or hydrocephalus (all p > 0.05). In terms of safety, no significant adverse events were reported. No statistical heterogeneity or publication bias was found in all outcomes. CONCLUSION: In patients with aSAH, TXA significantly reduces the incidence of rebleeding and mortality from rebleeding. However, current evidence does not support any benefits in overall mortality, neurological outcome, delayed cerebral ischemia, or hydrocephalus.

Transcranial Magnetic Stimulation Versus Transcutaneous Neuromuscular Electrical Stimulation in Post Stroke Dysphagia: A Clinical Randomized Controlled Trial.

OBJECTIVES: To evaluate the efficacy of high-frequency repeated transcranial magnetic stimulation (rTMS) applied contralesionally versus transcutaneous neuromuscular electrical stimulation (TNES) in acute post-stroke dysphagic patients. MATERIALS AND METHODS: A randomized, parallel, comparative, controlled trial was conducted on patients with acute ischemic stroke who were admitted to our department. Fifteen patients received rTMS, 15 patients received TNES, and 15 patients were recruited as a control group. Between the second and tenth days after a stroke, patients were enrolled. The study and follow-up periods were completed by all patients. RESULTS: Among the screened patients, 45 (31.47%) right-handed patients were diagnosed with post-stroke dysphagia with a mean age of 60.53 ± 8.23 years. Immediately after intervention both rTMS and TNES groups significantly improve the swallowing disturbance questionnaire (SDQ) and penetration aspiration scale (PAS), compared to the control (p < 0.001 and p = 0.027), respectively. rTMS was more effective than TNES in reducing SDQ and PAS (p < 0.05). rTMS and TNES improved the Yale Pharyngeal Residue Severity Rating Scale (YPRSRS) significantly (p = 0.002); however, their efficacy was comparable (p > 0.05). A significant (p < 0.001) strong negative correlation was observed between the grade of weakness and all scores. CONCLUSION: Our findings showed that high-frequency rTMS and TNES effectively improved the clinical condition of acute post-stroke dysphagic patients in terms of swallowing disturbance assessed by SDQ, pharyngeal residue assessed by YPRSRS, and the severity of penetration and aspiration events evaluated by PAS, compared to the controls. The outcomes of high-frequency rTMS were more favorable than those of TNES in terms of SDQ and PAS.

Impact of Obstructive Sleep Apnea on Cognitive and Motor Functions in Parkinson's Disease.

INTRODUCTION: Parkinson's disease (PD) is a chronic neurodegenerative disorder that presents with motor and non-motor manifestations. Amongst the non-motor features, various forms of sleep disturbances can occur, and obstructive sleep apnea (OSA) is considered to be a common comorbidity. We conducted this systematic review and meta-analysis to assess the impact of OSA on cognitive and motor functions in PD. METHODS: The information sources of for this systematic review and meta-analysis were PubMed, SCOPUS, Web of Science, and ScienceDirect. Studies meeting the following criteria were included: (1) studies including idiopathic PD patients, (2) studies using polysomnography to categorize PD patients into PD with OSA and PD without OSA, and (3) studies with observational designs (case-control, cohort, or cross-sectional). Data analysis was performed using RevMan. RESULTS: Our meta-analysis showed that OSA was associated with significantly lower scores of Montreal Cognitive Assessments (MoCA) (mean difference (MD) = -0.70, 95% confidence interval (CI) [-1.28, -0.13], P = 0.01) and Mini-Mental State Examination (MMSE) (MD = -0.69, 95% CI [-1.17, -0.21], P = 0.005). Moreover, the score of the motor part of the Unified Parkinson's Disease Rating Scale (UPDRS III) was significantly higher in PD patients with OSA as compared with those without OSA (MD = 1.63, 95% CI [0.03, 3.23], P = 0.049). CONCLUSIONS: OSA is associated with increased severity of PD-associated cognitive dysfunction and motor symptoms. However, further studies are needed to corroborate these findings, assess the underlying mechanisms by which OSA influences the motor and cognitive functions in PD, and investigate whether OSA can accelerate the neurodegenerative process of PD. © 2020 International Parkinson and Movement Disorder Society.

Mavoglurant (AFQ056) for the treatment of levodopa-induced dyskinesia in patients with Parkinson's disease: a meta-analysis.

BACKGROUND: Mavoglurant (AFQ056), a selective metabotropic glutamate receptor 5 (mGluR5) inhibitor, was tested for t levodopa-induced dyskinesia (LID) in patients with Parkinson's Disease (PD). However, clinical trials showed inconsistent results regarding the efficacy of mavoglurant in treating LID in patients with Parkinson's disease (PD). METHODS: A computer literature search of PubMed, Scopus, Web of science, and Cochrane CENTRAL was conducted until March 2021. We selected relevant randomized controlled trials comparing mavoglurant to placebo. Study data were extracted and pooled as mean difference (MD) in the meta-analysis model. RESULTS: Six RCTs were included in this meta-analysis with a total of 485 patients. Mavoglurant was not significantly superior to placebo in terms of the "off-time" (MD -0.27 h, 95% CI -0.65 to 0.11), "on time" (MD 0.29 h, 95% CI -0.09 to 0.66), Lang-Fahn activities of daily living dyskinesia scale (MD -0.95, 95% CI -1.98 to 0.07), UPDRS-III (MD -0.51, 95% CI -1.66 to 0.65), or UPDRS-IV (MD -0.41, 95% CI -0.85 to 0.03). However, the pooled modified abnormal involuntary movement scale favored the mavoglurant group than the placebo group (MD -2.53, 95% CI -4.23 to -0.82). CONCLUSIONS: This meta-analysis provides level one evidence that mavoglurant is not effective in treating the LID in patients with PD.

Molecular Mechanisms of Astaxanthin as a Potential Neurotherapeutic Agent.

Neurological disorders are diseases of the central and peripheral nervous system that affect millions of people, and the numbers are rising gradually. In the pathogenesis of neurodegenerative diseases, the roles of many signaling pathways were elucidated; however, the exact pathophysiology of neurological disorders and possible effective therapeutics have not yet been precisely identified. This necessitates developing multi-target treatments, which would simultaneously modulate neuroinflammation, apoptosis, and oxidative stress. The present review aims to explore the potential therapeutic use of astaxanthin (ASX) in neurological and neuroinflammatory diseases. ASX, a member of the xanthophyll group, was found to be a promising therapeutic anti-inflammatory agent for many neurological disorders, including cerebral ischemia, Parkinson's disease, Alzheimer's disease, autism, and neuropathic pain. An effective drug delivery system of ASX should be developed and further tested by appropriate clinical trials.

Neural Stem Cell-Based Therapies and Glioblastoma Management: Current Evidence and Clinical Challenges.

Gliomas, which account for nearly a quarter of all primary CNS tumors, present significant contemporary therapeutic challenges, particularly the highest-grade variant (glioblastoma multiforme), which has an especially poor prognosis. These difficulties are due to the tumor's aggressiveness and the adverse effects of radio/chemotherapy on the brain. Stem cell therapy is an exciting area of research being explored for several medical issues. Neural stem cells, normally present in the subventricular zone and the hippocampus, preferentially migrate to tumor masses. Thus, they have two main advantages: They can minimize the side effects associated with systemic radio/chemotherapy while simultaneously maximizing drug delivery to the tumor site. Another feature of stem cell therapy is the variety of treatment approaches it allows. Stem cells can be genetically engineered into expressing a wide variety of immunomodulatory substances that can inhibit tumor growth. They can also be used as delivery vehicles for oncolytic viral vectors, which can then be used to combat the tumorous mass. An alternative approach would be to combine stem cells with prodrugs, which can subsequently convert them into the active form upon migration to the tumor mass. As with any therapeutic modality still in its infancy, much of the research regarding their use is primarily based upon knowledge gained from animal studies, and a number of ongoing clinical trials are currently investigating their effectiveness in humans. The aim of this review is to highlight the current state of stem cell therapy in the treatment of gliomas, exploring the different mechanistic approaches, clinical applicability, and the existing limitations.

The interaction between insulin resistance and Alzheimer's disease: a review article.

Insulin serves multiple functions as a growth-promoting hormone in peripheral tissues. It manages glucose metabolism by promoting glucose uptake into cells and curbing the production of glucose in the liver. Beyond this, insulin fosters cell growth, drives differentiation, aids protein synthesis, and deters degradative processes like glycolysis, lipolysis, and proteolysis. Receptors for insulin and insulin-like growth factor-1 are widely expressed in the central nervous system. Their widespread presence in the brain underscores the varied and critical functions of insulin signaling there. Insulin aids in bolstering cognition, promoting neuron extension, adjusting the release and absorption of catecholamines, and controlling the expression and positioning of gamma-aminobutyric acid (GABA). Importantly, insulin can effortlessly traverse the blood-brain barrier. Furthermore, insulin resistance (IR)-induced alterations in insulin signaling might hasten brain aging, impacting its plasticity and potentially leading to neurodegeneration. Two primary pathways are responsible for insulin signal transmission: the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway, which oversees metabolic responses, and the mitogen-activated protein kinase (MAPK) pathway, which guides cell growth, survival, and gene transcription. This review aimed to explore the potential shared metabolic traits between Alzheimer's disease (AD) and IR disorders. It delves into the relationship between AD and IR disorders, their overlapping genetic markers, and shared metabolic indicators. Additionally, it addresses existing therapeutic interventions targeting these intersecting pathways.

Endothelial Function Responses to Nigella sativa (Black Seed) Supplementation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Nigella sativa (NS), commonly known as black cumin or black seed, is a medicinal plant with a rich history of traditional use in various cultures. Recent research has shed light on its potential therapeutic properties, particularly its effects on endothelial markers involved in inflammatory processes. This systematic review and meta-analysis evaluated the endothelial function responses, including intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM), to NS supplementation. We systematically searched Medline via PubMed, Scopus, Web of Science, and Embase databases from inception until August 5, 2023. Comparative randomized controlled trials (RCTs) were included. Pairwise meta-analysis was conducted using RevMan version 5.4 for Windows. Pooled data were reported as mean difference (MD), with their 95% confidence interval (CI). The present meta-analysis included three RCTs, which included 146 patients. The pooled random-effect size showed no difference between the NS group and the control group in terms of ICAM (MD = -59.32, 95% CI: -137.18 to 18.54; p = 0.14) and VCAM (MD = -200.1, 95% CI: -429.9 to 29.69; p = 0.09). The pooled data were severely heterogeneous. In conclusion, NS supplementation does not have a significant impact on the endothelial function of patients with CVD or the risks of CVD. Further comparative RCTs with larger sample sizes and more diverse populations are needed to establish the efficacy and safety of NS in different clinical settings.

Do cerebral microbleeds increase the risk of dementia? A systematic review and meta-analysis.

Background: Dementia is a neurological disorder that commonly affects the elderly. Cerebral microbleeds (CMBs) are small, tiny lesions of the cerebral blood vessels and have been suggested as a possible risk factor for dementia. However, data about the association between CMBs and dementia risk are inconsistent and inconclusive. Therefore, we conducted this systematic review and meta-analysis to investigate the association between CMBs and dementia and highlight the possible explanations. Methods: We followed the standard PRISMA statement and the Cochrane Handbook guidelines to conduct this study. First, we searched medical electronic databases for relevant articles. Then, we screened the retrieved articles for eligibility, extracted the relevant data, and appraised the methodological quality using the Newcastle-Ottawa Scale. Finally, the extracted data were pooled as risk ratios (RR) and hazard ratios (HR) in the random-effects meta-analysis model using the Review Manager software. Results: We included nine studies with 14,221 participants and follow-up periods > 18 months. Overall, CMBs significantly increased the risk of developing dementia (RR 1.84, 95% CI [1.27-2.65]). This association was significant in the subgroups of studies on high-risk populations (RR 2.00, 95% CI [1.41-2.83], n = 1657 participants) and those in the general population (RR 2.30, 95% CI [1.25-4.26], n = 12,087 participants) but not in the memory clinic patients. Further, CMBs increased the risk of progressing to incident dementia over time (HR 2, 95% CI [1.54-2.61]). Conclusion: Individuals with CMBs have twice the risk of developing dementia or progressing to MCI than those without CMBs. The detection of CMBs will help identify the population at higher risk of developing dementia. Physicians should educate individuals with CMBs and their families on the possibility of progressing to dementia or MCI. Regular cognitive assessments, cognitive training, lifestyle modifications, and controlling other dementia risk factors are recommended for individuals with CMBs to decrease the risk of cognitive decline and dementia development.

Oxidative stress and early mortality in acute ischemic stroke: A prospective cohort study.

BACKGROUND: Malondialdehyde (MDA) is an oxidative stress biomarker, which represents a unifying mechanism of brain injury that occurs throughout the ischemic stroke cascade. The current study aimed to examine whether or not acute ischemic stroke (AIS) patients who had elevated serum MDA levels at admission had an increased risk of mortality and a worse functional outcome three months later. METHODS: An observational, prospective cohort study that enrolled 90 patients with AIS. The patients were examined in the first 24 hours and then followed up for three months to assess mortality, short-term neurological functional outcome, and neurological disability by the Modified Rankin Scale (MRS). RESULTS: The mean of serum MDA level among AIS patients was 6.3 ± 3.7 nmol/ml. Non-survivor cases were associated with statistically significantly higher serum MDA levels compared to survivors (9.7 ± 4.3 vs. 5.3 ± 2.8, p < 0.001), respectively. Patients with severe stroke, according to NIHSS score, were associated with significantly (p < 0.05) higher MDA levels compared to moderate and mild cases (7.4 ± 4.3 vs. 5.4 ± 2.6 vs. 3.3 ± .6). At a cutoff point of ≥ 6.7 nmol/ml, the area under the curve (AUC) for serum MDA levels as a predictor of mortality was 0.8 (0.69-0.91; p < 0.05). The sensitivity, specificity, positive predictive value, and negative predictive value were 77%, 80%, 89.5%, and 48.5%, respectively. Multivariate regression demonstrated that MDA level was a significant independent predictor of mortality among patients with AIS (OR = 1.29, 95% CI: 1.01 to 1.65; p = 0.041). CONCLUSION: MDA serum level was significantly higher in non-survivors than in survivors patients, so MDA could be used as a predictor for early mortality and short-term outcome of cases with AIS.

The Role of RIN3 Gene in Alzheimer's Disease Pathogenesis: a Comprehensive Review.

Alzheimer's disease (AD) is a globally prevalent form of dementia that impacts diverse populations and is characterized by progressive neurodegeneration and impairments in executive memory. Although the exact mechanisms underlying AD pathogenesis remain unclear, it is commonly accepted that the aggregation of misfolded proteins, such as amyloid plaques and neurofibrillary tau tangles, plays a critical role. Additionally, AD is a multifactorial condition influenced by various genetic factors and can manifest as either early-onset AD (EOAD) or late-onset AD (LOAD), each associated with specific gene variants. One gene of particular interest in both EOAD and LOAD is RIN3, a guanine nucleotide exchange factor. This gene plays a multifaceted role in AD pathogenesis. Firstly, upregulation of RIN3 can result in endosomal enlargement and dysfunction, thereby facilitating the accumulation of beta-amyloid (Aß) peptides in the brain. Secondly, RIN3 has been shown to impact the PICLAM pathway, affecting transcytosis across the blood-brain barrier. Lastly, RIN3 has implications for immune-mediated responses, notably through its influence on the PTK2B gene. This review aims to provide a concise overview of AD and delve into the role of the RIN3 gene in its pathogenesis.

Vibration Controlled Transient Elastography in Screening for Silent Liver Diseases.

OBJECTIVES: The objective of this study was to screen for significant hepatic fibrosis or steatosis in asymptomatic, apparently healthy subjects by using Vibration-controlled transient elastography and controlled attenuation parameter (CAP). METHODS: Prospectively, 433 asymptomatic apparently healthy adults were included. Fibroscan/CAP examination was performed for all of them. Subjects with liver stiffness measurement > 6 kPa or CAP >248 dB/m were further evaluated to assess underlying chronic liver disease. RESULTS: According to fibroscan/CAP examination, subjects were classified into four subgroups: normal (119) with CAP score of 215.85 ± 24.81 dB/m and fibrosis score of 4.47 ± 0.81 kPa, subjects with steatosis only 133 with CAP score of 309.41 ± 42.6 dB/m and fibrosis score of 4.74 ± 0.82 kPa, subjects with both steatosis and fibrosis 95 with CAP score of 318.20 ± 39.89 dB/m and fibrosis score of 7.92 ± 2.58 kPaand subjects with fibrosis only 86 with CAP score of 213.48 ± 22.62 dB/m and fibrosis score of 6.96 ± 1.11 kPa. S0 was present in 205 (47.3%), S1 in 48 (10.2%), S2 in 16 (3.7%) and S3 in 168 (38.8%) of studied subjects, whereas F0-1 was present in 371 (85.7%), F2 in 44 (10.16%), F3 in 16 (3.7%) subjects and F4 in only one (0.23%) subject. Subjects with both steatosis and fibrosis showed significantly higher transaminases, triglycerides and total cholesterol levels than other subgroups. CONCLUSIONS: Most asymptomatic, apparently healthy subjects (72%) have significant steatosis and fibrosis. Liver stiffness measurement and CAP might represent promising first-line noninvasive procedures to screen for silent liver diseases in the general population.

Continuous vs. intermittent terlipressin infusion for portal hypertension: a systematic review and meta-analysis.

Background: Portal hypertension, a major complication of chronic liver disease, often leads to life-threatening variceal bleeding, managed effectively with vasoactive drugs like terlipressin. However, the most optimal method of terlipressin administration, continuous versus intermittent infusion, remains a subject of debate, necessitating this systematic review and meta-analysis for evidence-based decision-making in managing this critical condition. Methods: This systematic review and meta-analysis adhered to the PRISMA standards and explored multiple databases until 6 April 2023, such as MEDLINE through PubMed, Scopus, Web of Science, and CENTRAL. Independent reviewers selected randomized controlled trials (RCTs) that met specific inclusion criteria. After assessing study quality and extracting necessary data, statistical analysis was performed using Review Manager (RevMan), with results presented as risk ratios (RR) or mean differences. Results: Five RCTs (n=395 patients) were included. The continuous terlipressin group had a significantly lower risk of rebleeding (RR=0.43, P=0.0004) and treatment failure (RR=0.22, P=0.02) and fewer total adverse effects (RR=0.52, P<0.00001) compared to the intermittent group. However, there were no significant differences between the two groups in mean arterial pressure (P=0.26), length of hospital stays (P=0.78), and mortality rates (P=0.65). Conclusion: This study provides robust evidence suggesting that continuous terlipressin infusion may be superior to intermittent infusions in reducing the risk of rebleeding, treatment failure, and adverse effects in patients with portal hypertension. However, further large-scale, high-quality RCTs are required to confirm these findings and to investigate the potential benefits of continuous terlipressin infusion on mortality and hospital stays.

Effect of COVID-19 vaccine on menstrual experience among females in six Arab countries: A cross sectional study.

BACKGROUND: There have been varying reports on the potential occurrence and severity of changes to menstruation including the median cycle length, days of bleeding, bleeding heaviness, and menstrual pain, following receipt of COVID-19 vaccinations. We aimed to assess potential postvaccination menstrual changes in women residing in the Middle East. METHODS: We implemented a cross-sectional online survey-based study. Data about the participants' demographic characteristics, menstruation experience, and vaccination status were collected and analyzed among six Arab countries. RESULTS: Among 4942 menstruating females included in this study, females who had received one or more doses of COVID-19 vaccination reported a higher frequency of back pain, nausea, tiredness, pelvic pain with periods, unprescribed analgesics use, and passage of loose stools. They also reported higher scores describing average and worst menstrual pain. Fully vaccinated females reported heavier flow and more days of bleeding. CONCLUSION: Our findings indicate that COVID-19 vaccine may have an effect on menstruation in terms of menstrual pain and bleeding heaviness. The evidence needs to be further investigated in longitudinal studies.

A Literature Review of Traumatic Brain Injury Biomarkers.

Research into TBI biomarkers has accelerated rapidly in the past decade owing to the heterogeneous nature of TBI pathologies and management, which pose challenges to TBI evaluation, management, and prognosis. TBI biomarker proteins resulting from axonal, neuronal, or glial cell injuries are widely used and have been extensively studied. However, they might not pass the blood-brain barrier with sufficient amounts to be detected in peripheral blood specimens, and further might not be detectable in the cerebrospinal fluid owing to flow limitations triggered by the injury itself. Despite the advances in TBI research, there is an unmet clinical need to develop and identify novel TBI biomarkers that entirely correlate with TBI pathologies on the molecular level, including mild TBI, and further enable physicians to predict patient outcomes and allow researchers to test neuroprotective agents to limit the extents of injury. Although the extracellular vesicles have been identified and studied long ago, they have recently been revisited and repurposed as potential TBI biomarkers that overcome the many limitations of the traditional blood and CSF assays. Animal and human experiments demonstrated the accuracy of several types of exosomes and miRNAs in detecting mild, moderate, and severe TBI. In this paper, we provide a comprehensive review of the traditional TBI biomarkers that are helpful in clinical practice. Also, we highlight the emerging roles of exosomes and miRNA being the promising candidates under investigation of current research.

The Effect of Gut Microbe Dysbiosis on the Pathogenesis of Alzheimer's Disease (AD) and Related Conditions.

It has been hypothesized that the shift in gut microbiota composition, known as gut microbe dysbiosis, may be correlated with the onset of Alzheimer's disease (AD), which is the most common cause of dementia characterized by a gradual deterioration in cognitive function associated with the development of amyloid-beta (Aß) plaques. The gut microbiota dysbiosis induces the release of significant amounts of amyloids, lipopolysaccharides, and neurotoxins, which might play a role in modulating signaling pathways and immune activation, leading to the production of proinflammatory cytokines related to the pathogenesis of AD. The dysbiosis of gut microbe is associated with various diseases such as type 2 diabetes, obesity, hypertension, and some neuropsychiatric disorders like depression, anxiety, and stress. It is conceivable that these diseases trigger the onset of AD. Thus, modifying the gut microbiota composition with probiotic and prebiotic supplementation can reduce depression and anxiety symptoms, lower stress reactivity, and improve memory. This narrative review aimed to examine the possible role of gut microbe dysbiosis in AD's pathogenesis.

Should intravenous acetaminophen be considered for post craniotomy pain management? A meta-analysis of randomized controlled trials.

INTRODUCTION: Post-craniotomy pain management with opioids is challenging due to their side effects, which might mask neurological deterioration symptoms. Recently, intravenous (IV) acetaminophen has been tested in this population. This meta-analysis aimed to synthesize evidence from published randomized controlled trials (RCTs) about the efficacy of IV acetaminophen in reducing pain scores in postoperative craniotomy patients. EVIDENCE ACQUISITION: A computer literature search of PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) was conducted. We selected RCTs comparing IV acetaminophen versus placebo for postoperative pain management in craniotomy patients. Data on the Visual Analog Scale (VAS), opioid requirements, hospital stay, and patients' satisfaction were extracted and pooled as standardized mean difference (SMD) with the corresponding 95% confidence intervals (CI) in the meta-analysis model. EVIDENCE SYNTHESIS: Five RCTs, with a total of 493 patients, were pooled in the final analysis. Patients in the IV acetaminophen group had significantly lower VAS pain scores compared to the placebo group (SMD=-0.28, 95% CI: -0.46 to -0.10). However, in terms of opioid requirement, hospital stay, and patients' satisfaction, there were no statistically significant differences between both groups (P>0.05). CONCLUSIONS: This meta-analysis provides class one evidence that IV Acetaminophen can significantly reduce postoperative pain in craniotomy patients with an excellent safety profile; however, there are not benefits in terms of hospital stay, opioid requirement, or patients' satisfaction.