Impact of gut-brain interaction in emerging neurological disorders.

The central nervous system (CNS) is a reservoir of immune privilege. Specialized immune glial cells are responsible for maintenance and defense against foreign invaders. The blood-brain barrier (BBB) prevents detrimental pathogens and potentially overreactive immune cells from entering the periphery. When the double-edged neuroinflammatory response is overloaded, it no longer has the protective function of promoting neuroregeneration. Notably, microbiota and its derivatives may emerge as pathogen-associated molecular patterns of brain pathology, causing microbiome-gut-brain axis dysregulation from the bottom-up. When dysbiosis of the gastrointestinal flora leads to subsequent alterations in BBB permeability, peripheral immune cells are recruited to the brain. This results in amplification of neuroinflammatory circuits in the brain, which eventually leads to specific neurological disorders. Aggressive treatment strategies for gastrointestinal disorders may protect against specific immune responses to gastrointestinal disorders, which can lead to potential protective effects in the CNS. Accordingly, this study investigated the mutual effects of microbiota and the gut-brain axis, which may provide targeting strategies for future disease treatment.

Subdural Lesions Linking Additional Intracranial Spaces and Chronic Subdural Hematomas: A Narrative Review with Mutual Correlation and Possible Mechanisms behind High Recurrence.

The purpose of this study was two-fold. The first was to investigate the pathologic mechanisms underlying the formation of subdural fluid collection, an umbrella term referring to a condition commonly seen in the clinical setting. Accumulation of the cerebrospinal fluid (CSF) in the subdural space can be referred to in this disease category, disregarding the underlying source of the subdural fluid. However, in these two clinical situations, especially after trauma or brain surgery, fluid collection from the subarachnoid space (subdural hygroma) or from the ventricle to the subarachnoid space and infusion into the subdural space (external hydrocephalus), surgical management of critical patients may adopt the strategies of burr-hole, subduroperitoneal shunt, or ventriculoperitoneal shunt, which present distinctly different thoughts. Crucially, the former can be further transformed into chronic subdural hematoma (CSDH). The second significant theme was the pathogenesis of CSDH. Once the potential dural border cell (DBC) layer is separated such as if a wound is formed, the physiological mechanisms that seem to promote wound healing will resume in the subdural space as follows: coagulation, inflammation, fibroblast proliferation, neovascularization, and fibrinolysis. These aptly correspond to several key characteristics of CSDH formation such as the presence of both coagulation and fibrinolysis signals within the clot, neomembrane formation, angiogenesis, and recurrent bleeding, which contribute to CSDH failing to coagulate and absorb easily. Such a complexity of genesis and the possibility of arising from multiple pathological patterns provide a reasonable explanation for the high recurrence rate, even after surgery. Among the various complex and clinically challenging subdural lesions, namely, CSDH (confined to the subdural space alone), subdural hygroma (linked in two spaces), and external hydrocephalus (linked in three spaces), the ability to fully understand the different pathological mechanisms of each, differentiate them clinically, and devote more interventional strategies (including anti-inflammatory, anti-angiogenic, and anti-fibrinolysis) will be important themes in the future.

Association between systemic rheumatic diseases and dementia risk: A meta-analysis.

Background and aims: Epidemiological studies have been conducted on the relationship between systemic rheumatic diseases (SRDs) and dementia. Therefore, we focused on determining the extent of alliances bounded by SRDs, along with the risk of dementia. Materials and methods: Two independent reviewers assessed all studies retrieved from the PubMed, EMBASE, Scopus, and Web of Science databases between January 1, 2000 and November 30, 2021. Only observational studies that estimated the possibility of dementia in participants with SRD were considered. The random-effects model was applied to forecast pooled risk ratios (RRs) and 95% confidence intervals (CI). Heterogeneity among the studies was evaluated using the Q and I2 statistics. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. Funnel plots were used to calculate the risk of bias. Results: Seventeen observational studies with 17,717,473 participants were recruited. Our findings showed that among the participants with SRDs, those with osteoarthritis, systemic lupus erythematosus, and Sjogren's syndrome were highly related to an elevated risk of dementia (pooled RR: 1.31; 95% CI: 1.15-1.49, p<0.001; pooled RR: 1.43; 95% CI: 1.19-1.73, p<0.001; and pooled RR: 1.26; 95% CI: 1.14-1.39, p<0.001, respectively). However, participants with rheumatoid arthritis (RA) were not associated with an increased risk of dementia (pooled RR: 0.98; 95% CI: 0.90-1.07, p<0.001). Conclusion: This systematic review and meta-analysis demonstrated an increased dementia risk among SRDs participants, except for RA.

Homogeneous Chronic Subdural Hematoma with Diverse Recurrent Possibilities.

Background: Evidence suggests that hyperdense (HD) chronic subdural hematomas (CSDHs) have a higher recurrence than hypodense (LD) chronic subdural hematomas. The value of mean hematoma density (MHD) has been proven to be associated with postoperative recurrence. The MHD levels in homogeneous CSDHs likely underestimate the risk of recurrence in HD homogeneous subtypes. Methods: This study investigated 42 consecutive CSDH cases between July 2010 and July 2014. The area of the hematoma was quantified to determine the MHD level using computer-based image analysis of preoperative brain CT scans. Results: In terms of the MHD distribution of the four types of CSDHs (homogeneous, laminar, separated, and trabecular), wide 95% CI (11.80-16.88) and high standard deviation (4.59) can be found in homogeneous types, reflecting a high variability in the MHD levels between cases (from low to high density). The categorization of homogeneous types into LD and HD (type five) displayed a minor standard deviation in the MHD levels for LD and HD subtypes (1.15, and 0.88, respectively). MHD values demonstrated concentrated distributions among the respective five types, compared to the four-type setting. Conclusions: In the current research, we provide a consideration that if LD and HD hematomas are separated from homogeneous CSDHs, the variability of the MHD quantification can potentially be reduced, thereby avoiding the possibility of undetected high-risk groups.

Anti-Inflammatory CDGSH Iron-Sulfur Domain 2: A Biomarker of Central Nervous System Insult in Cellular, Animal Models and Patients.

Spinal cord injury (SCI) promotes brain inflammation; conversely, brain injury promotes spinal neuron loss. There is a need to identify molecular biomarkers and therapeutic targets for central nervous system (CNS) injury. CDGSH iron-sulfur structural domain 2 (CISD2), an NF-κB antagonist, is downregulated after injury in vivo and in vitro. We aimed to examine the diagnostic value of CISD2 in patients with CNS insult. Plasma and cerebrospinal fluid (CSF) CISD2 levels were decreased in 13 patients with CNS insult and were negatively correlated with plasma IL6 levels (associated with disease severity; r = −0.7062; p < 0.01). SCI-induced inflammatory mediators delivered through CSF promoted mouse brain inflammation at 1 h post-SCI. Anti-CISD2 antibody treatment exacerbated SCI-induced inflammation in mouse spine and brain. Lipopolysaccharide-stimulated siCISD2-transfected EOC microglial cells exhibited proinflammatory phenotypes (enhanced M1 polarization, decreased M2 polarization, and increased intranuclear NF-κB p65 translocation). Plasma and CSF CISD2 levels were increased in three patients with CNS insult post-therapeutic hypothermia. CISD2 levels were negatively correlated with plasma and CSF levels of inflammatory mediators. CISD2 inhibition and potentiation experiments in cells, animals, and humans revealed CISD2 as a biomarker for CNS insult and upregulation of CISD2 anti-inflammatory properties as a potential therapeutic strategy for CNS insult.

Freshwater Clam Extract Mitigates Neuroinflammation and Amplifies Neurotrophic Activity of Glia: Insights from In Vitro Model of Neurodegenerative Pathomechanism.

BACKGROUND: An extensive body of research suggests that brain inflammation and oxidative stress are the underlying causes of Parkinson's disease (PD), for which no potent therapeutic approach exists to mitigate the degradation of dopamine neurons. Freshwater clams, an ancient health food of Chinese origin, have been documented to exhibit anti-inflammatory and antioxidant effects. We previously reported that freshwater clam extract (FCE) can attenuate astrocytic activation and subsequent proinflammatory cytokine production from substantia nigra in an MPTP-induced PD mouse model. This article provides insight into the potential mechanisms through which FCE regulates neuroinflammation in a glia model of injury. MATERIALS AND METHODS: In total, 1 µg/mL lipopolysaccharide (LPS) and 200 µM rotenone were conducted in primary glial cell cultures to mimic the respective neuroinflammation and oxidative stress during injury-induced glial cell reactivation, which is relevant to the pathological process of PD. RESULTS: FCE markedly reduced LPS-induced neuroinflammation by suppressing NO and TNF-α production and the expression of pro-inflammatory cytokines. In addition, FCE was effective at reducing rotenone-induced toxicity by diminishing ROS production, promoting antioxidant enzymes (SOD, catalase, and GPx) and minimizing the decline in glial-cell-secreted neurotrophic factors (GDNF, BDNF). These impacts ultimately led to a decrease in glial apoptosis. CONCLUSIONS: Evidence reveals that FCE is capable of stabilizing reactive glia, as demonstrated by reduced neuroinflammation, oxidative stress, the increased release of neurotrophic factors and the inhibition of apoptosis, which provides therapeutic insight into neurodegenerative diseases, including PD.

Ultrarapid Inflammation of the Olfactory Bulb After Spinal Cord Injury: Protective Effects of the Granulocyte Colony-Stimulating Factor on Early Neurodegeneration in the Brain.

The correlation among olfactory dysfunction, spinal cord injury (SCI), subjective cognitive decline, and neurodegenerative dementia has been established. Impaired olfaction is considered a marker for neurodegeneration. Hence, there is a need to examine if SCI leads to olfactory dysfunction. In this study, the brain tissue of mice with spinal cord hemisection injury was subjected to microarray analysis. The mRNA expression levels of olfactory receptors in the brain began to decline at 8 h post-SCI. SCI promoted neuroinflammation, downregulated the expression of olfactory receptors, decreased the number of neural stem cells (NSCs), and inhibited the production of neurotrophic factors in the olfactory bulbs at 8 h post-SCI. In particular, the SCI group had upregulated mRNA and protein expression levels of glial fibrillary acidic protein (GFAP; a marker of astrocyte reactivation) and pro-inflammatory mediators [IL-1ß, IL-6, and Nestin (marker of NSCs)] in the olfactory bulb compared to levels in the sham control group. The mRNA expression levels of olfactory receptors (Olfr1494, Olfr1324, Olfr1241, and Olfr979) and neurotrophic factors [brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), and nerve growth factor (NGF)] were downregulated in the olfactory bulb of the SCI group mice at 8 h post-SCI. The administration of granulocyte colony-stimulating factor (G-CSF) mitigated these SCI-induced pathological changes in the olfactory bulb at 8 h post-SCI. These results indicate that the olfactory bulb is vulnerable to environmental damage even if the lesion is located at sites distant from the brain, such as the spinal cord. Additionally, SCI initiated pathological processes, including inflammatory response, and impaired neurogenesis, at an early stage. The findings of this study will provide a basis for future studies on pathological mechanisms of early neurodegenerative diseases involving the olfactory bulb and enable early clinical drug intervention.

Anemia and the Risk of Cognitive Impairment: An Updated Systematic Review and Meta-Analysis.

BACKGROUND: Cognitive impairment is one of the most common, burdensome, and costly disorders in the elderly worldwide. The magnitude of the association between anemia and overall cognitive impairment (OCI) has not been established. OBJECTIVE: We aimed to update and expand previous evidence of the association between anemia and the risk of OCI. METHODS: We conducted an updated systematic review and meta-analysis. We searched electronic databases, including EMBASE, PubMed, and Web of Science for published observational studies and clinical trials between 1 January 1990 and 1 June 2020. We excluded articles that were in the form of a review, letter to editors, short reports, and studies with less than 50 participants. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. We estimated summary risk ratios (RRs) with random effects. RESULTS: A total of 20 studies, involving 6558 OCI patients were included. Anemia was significantly associated with an increased risk of OCI (adjusted RR (aRR) 1.39 (95% CI, 1.25-1.55; p < 0.001)). In subgroup analysis, anemia was also associated with an increased risk of all-cause dementia (adjusted RR (aRR), 1.39 (95% CI, 1.23-1.56; p < 0.001)), Alzheimer's disease [aRR, 1.59 (95% CI, 1.18-2.13; p = 0.002)], and mild cognitive impairment (aRR, 1.36 (95% CI, 1.04-1.78; p = 0.02)). CONCLUSION: This updated meta-analysis shows that patients with anemia appear to have a nearly 1.39-fold risk of developing OCI than those without anemia. The magnitude of this risk underscores the importance of improving anemia patients' health outcomes, particularly in elderly patients.

Simulating Expansion of the Intracranial Space to Accommodate Brain Swelling after Decompressive Craniectomy: Volumetric Quantification in a 3D CAD Skull Model with Contour Elevation.

Background: Decompressive craniectomy (DC) can be used to augment intracranial space and halt brainstem compromise. However, a widely adopted recommendation for optimal surgical extent of the DC procedure is lacking. In the current study, we utilized three-dimensional (3D) computer-assisted design (CAD) skull models with defect contour elevation for quantitative assessment. Methods: DC was performed for 15 consecutive patients, and 3D CAD models of defective skulls with contour elevations (0-50 mm) were reconstructed using commercial software. Quantitative assessments were conducted in these CAD subjects to analyze the effects of volumetric augmentation when elevating the length of the contour and the skull defect size. The final positive results were mathematically verified using a computerized system for numerical integration with the rectangle method. Results: Defect areas of the skull CAD models ranged from 55.7-168.8 cm2, with a mean of 132.3 ± 29.7 cm2. As the contour was elevated outward for 6 mm or above, statistical significance was detected in the volume and the volume-increasing rate, when compared to the results obtained from the regular CAD model. The volume and the volume-increasing rate increased by 3.665 cm3, 0.285% (p < 0.001) per 1 mm of contour elevation), and 0.034% (p < 0.001) per 1 cm2 of increase of defect area, respectively. Moreover, a 1 mm elevation of the contour in Groups 2 (defect area 125-150 cm2) and 3 (defect area >150 cm2, as a proxy for an extremely large skull defect) was shown to augment the volume and the volume-increasing rate by 1.553 cm3, 0.101% (p < 0.001) and 1.126 cm3, 0.072% (p < 0.001), respectively, when compared to those in Group 1 (defect area <125 cm2). The volumetric augmentation achieved by contour elevation for an extremely large skull defect was smaller than that achieved for a large skull defect. Conclusions: The 3D CAD skull model contour elevation method can be effectively used to simulate the extent of a space-occupying swollen brain and to quantitatively assess the extent of brainstem protection in terms of volume augmentation and volume-increasing rate following DC. As the tangential diameter (representing the degree of DC) exceeded the plateau value, volumetric augmentation was attenuated. However, an increasing volumetric augmentation was detected before the plateau value was reached.

Beneficial Impacts of Alpha-Eleostearic Acid from Wild Bitter Melon and Curcumin on Promotion of CDGSH Iron-Sulfur Domain 2: Therapeutic Roles in CNS Injuries and Diseases.

Neuroinflammation and abnormal mitochondrial function are related to the cause of aging, neurodegeneration, and neurotrauma. The activation of nuclear factor κB (NF-κB), exaggerating these two pathologies, underlies the pathogenesis for the aforementioned injuries and diseases in the central nervous system (CNS). CDGSH iron-sulfur domain 2 (CISD2) belongs to the human NEET protein family with the [2Fe-2S] cluster. CISD2 has been verified as an NFκB antagonist through the association with peroxisome proliferator-activated receptor-ß (PPAR-ß). This protective protein can be attenuated under circumstances of CNS injuries and diseases, thereby causing NFκB activation and exaggerating NFκB-provoked neuroinflammation and abnormal mitochondrial function. Consequently, CISD2-elevating plans of action provide pathways in the management of various disease categories. Various bioactive molecules derived from plants exert protective anti-oxidative and anti-inflammatory effects and serve as natural antioxidants, such as conjugated fatty acids and phenolic compounds. Herein, we have summarized pharmacological characters of the two phytochemicals, namely, alpha-eleostearic acid (α-ESA), an isomer of conjugated linolenic acids derived from wild bitter melon (Momordica charantia L. var. abbreviata Ser.), and curcumin, a polyphenol derived from rhizomes of Curcuma longa L. In this review, the unique function of the CISD2-elevating effect of α-ESA and curcumin are particularly emphasized, and these natural compounds are expected to serve as a potential therapeutic target for CNS injuries and diseases.

The NFκB Antagonist CDGSH Iron-Sulfur Domain 2 Is a Promising Target for the Treatment of Neurodegenerative Diseases.

Proinflammatory response and mitochondrial dysfunction are related to the pathogenesis of neurodegenerative diseases (NDs). Nuclear factor κB (NFκB) activation has been shown to exaggerate proinflammation and mitochondrial dysfunction, which underlies NDs. CDGSH iron-sulfur domain 2 (CISD2) has been shown to be associated with peroxisome proliferator-activated receptor-ß (PPAR-ß) to compete for NFκB and antagonize the two aforementioned NFκB-provoked pathogeneses. Therefore, CISD2-based strategies hold promise in the treatment of NDs. CISD2 protein belongs to the human NEET protein family and is encoded by the CISD2 gene (located at 4q24 in humans). In CISD2, the [2Fe-2S] cluster, through coordinates of 3-cysteine-1-histidine on the CDGSH domain, acts as a homeostasis regulator under environmental stress through the transfer of electrons or iron-sulfur clusters. Here, we have summarized the features of CISD2 in genetics and clinics, briefly outlined the role of CISD2 as a key physiological regulator, and presented modalities to increase CISD2 activity, including biomedical engineering or pharmacological management. Strategies to increase CISD2 activity can be beneficial for the prevention of inflammation and mitochondrial dysfunction, and thus, they can be applied in the management of NDs.

Cryogen spray cooling mitigates inflammation and injury-induced CISD2 decline in rat spinal cord hemisection model.

Therapeutic strategies for traumatic spinal cord injury generally involve rectifying concomitant destruction to the spinal cord from inflammation, mitochondrial dysfunction, and eventual neuronal apoptosis. Elevating the expression of spinal cord injury-attenuated CDGSH iron-sulfur domain-2 has been shown to mitigate the pathologies above. In the current work, hypothermia was induced via continuous cryogen spray cooling in a rat spinal cord hemisection model. Spinal cord injury was shown to elevate the mRNA expression of proinflammatory mediators, including NFκB, iNOS, TNF-α, and regulated upon activation, normal T-cell expressed and secreted as well as lower CDGSH iron-sulfur domain-2 expression. Cryogen spray cooling treatment was shown to attenuate inflammatory reactions and elevate CDGSH iron-sulfur domain-2 expression. Immunohistochemical analysis of the glial fibrillary acidic protein, caspase-3 and NeuN in spinal cord injured rats that underwent cryogen spray cooling treatment revealed notable reductions in injury-induced astrocytic activation, apoptosis, neuronal loss, and decline in CDGSH iron-sulfur domain-2 expression. These results demonstrate the CDGSH iron-sulfur domain-2 preserving effects of cryogen spray cooling, which could contribute to the prevention of astrocytic activation, astrocyte-mediated neuroinflammation, apoptosis, and neuron loss.

CISD2 Attenuates Inflammation and Regulates Microglia Polarization in EOC Microglial Cells-As a Potential Therapeutic Target for Neurodegenerative Dementia.

Background: Accumulating evidence has demonstrated a significant association between microglia-driven inflammation in the brain and neurodegenerative dementia. We previously showed a significant decline in CISD2 expression in mice models with advanced age. Moreover, we observed that the knockdown of CISD2 led to remarkable inflammation and mitochondrial dysfunction in neural cells. In the present study, we investigated whether CISD2 attenuation influences anti-inflammatory effects and M1-M2 polarization in microglia. Materials and Methods: The knockdown of CISD2 expression by siRNA (siCISD2) in EOC microglial cells was performed to mimic the age-driven decline of CISD2 expression. The extent of the inflammatory reaction, polarization in the M1/M2 spectrum, and NFκB activation were verified in EOC microglial cells exhibiting CISD2 deficiency. Results: In the cellular model of microglia, loss of CISD2 function mediated by siCISD2 exhibited a significant augmentation of proinflammatory signaling, as well as reduced expression levels of Arg-1, Ym1, IL-10, and BCL2. Attenuation of CISD2 expression led to a decrease in the proportion of the M2 phenotype of microglia (compared to M1). Enhanced DNA-binding activity of the NFκB p65 subunit was confirmed in cells transfected with siCISD2, as demonstrated by enzyme-linked immunosorbent assay (ELISA). Conclusions: To the best of our knowledge, this is the first report examining the following phenomena: (1) anti-inflammatory effects of CISD2 in microglia via NFκB regulation; and (2) microglial CISD2 assistance in the restoration of M2 microglia phenotype. The anti-inflammatory effects of CISD2 in microglia eventually augment anti-apoptotic effects, which provides a rationale for the development of potential therapeutic target for neurodegenerative diseases and neurodegenerative dementia.

Wild Bitter Melon Exerts Anti-Inflammatory Effects by Upregulating Injury-Attenuated CISD2 Expression following Spinal Cord Injury.

BACKGROUND: Spinal cord injuries (SCIs) induce secondary neuroinflammation through astrocyte reactivation, which adversely affects neuronal survival and eventually causes long-term disability. CDGSH iron sulfur domain 2 (CISD2), which has been reported to be involved in mediating the anti-inflammatory responses, can serve as a target in SCI therapy. Wild bitter melon (WBM; Momordica charantia Linn. var. abbreviata Ser.) contains an anti-inflammatory agent called alpha-eleostearic acid (α-ESA), a peroxisome proliferator-activated receptor-ß (PPAR-ß) ligand. Activated PPAR-ß inhibits the nuclear factor κB (NF-κB) signaling pathway via the inhibition of IκB (inhibitor of NF-κB) degradation. The role of astrocyte deactivation and CISD2 in anti-inflammatory mechanisms of WBM in acute SCIs is unknown. MATERIALS AND METHODS: A mouse model of SCI was generated via spinal cord hemisection. The SCI mice were administered WBM intraperitoneally (500 mg/kg bodyweight). Lipopolysaccharide- (LPS-) stimulated ALT cells (astrocytes) were used as an in vitro model for studying astrocyte-mediated inflammation post-SCI. The roles of CISD2 and PPAR-ß in inflammatory signaling were examined using LPS-stimulated SH-SY5Y cells transfected with si-CISD2 or scramble RNA. RESULTS: WBM mitigated the SCI-induced downregulation of CISD2, PPAR-ß, and IκB and upregulation of glial fibrillary acidic protein (GFAP; marker of astrocyte reactivation) in the spinal cord of SCI mice. Additionally, WBM (1 µg/mL) mitigated LPS-induced CISD2 downregulation. Furthermore, SH-SY5Y neural cells with CISD2 knockdown exhibited decreased PPAR-ß expression and augmented NF-κB signaling. CONCLUSION: To the best of our knowledge, this is the first study to report that CISD2 is an upstream modulator of the PPAR-ß/NF-κB proinflammatory signaling pathway in neural cells, and that WBM can mitigate the injury-induced downregulation of CISD2 in SCI mice and LPS-stimulated ALT astrocytes.

An investigation of the correlation between the S-glutathionylated GAPDH levels in blood and Alzheimer's disease progression.

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by two aggregates, namely, amyloid-ß (Aß) plaques and neurofibrillary tangles (NFTs) of hyperphosphorylated tau protein (tau-p), which are released into the blood in a very small amount and cannot be easily detected. An increasing number of recent studies have suggested that S-glutathionylated glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is highly correlated with Aß in patients with AD and that S-glutathionylated GAPDH plays a role as a proapoptotic factor in AD. We found that S-glutathionylated GAPDH is abundant in the blood of AD patients, which is unusual because S-glutathionylated GAPDH cannot exist in the blood under normal conditions. The aim of this study was to further explore the correlation between the S-glutathionylated GAPDH levels in blood plasma and AD progression. As controls, we recruited 191 people without AD, which included 111 healthy individuals and 37 patients with depression and insomnia, in the psychosomatic clinic. Moreover, 47 patients with AD (aged 40-89 years) were recruited at the neurology clinic. The blood S-glutathionylated GAPDH levels in the AD patients were significantly (p < 0.001) higher (752.7 ± 301.7 ng/dL) than those in the controls (59.92 ± 122.4 ng/dL), irrespective of gender and age. For AD diagnosis, the criterion blood S-glutathionylated GAPDH level > 251.62 ng/dL exhibited 95.74% sensitivity and 92.67% specificity. In fact, the individuals aged 70-89 years, namely, 37 patients from the psychosomatic clinic and 42 healthy individuals, showed significant blood S-glutathionylated GAPDH levels (230.5 ± 79.3 and 8.05 ± 20.51 ng/dL, respectively). This finding might indicate neurodegenerative AD progression in psychosomatic patients and suggests that the degree of neuronal apoptosis during AD progression might be sensitively evaluated based on the level of S-glutathionylated GAPDH in blood.

Relationship Between Exercise and Alzheimer's Disease: A Narrative Literature Review.

This narrative review aimed to summarize evidence regarding the responses to exercise among patients with preclinical Alzheimer's disease (AD) and the effectiveness of long-term exercise interventions in improving cognitive function and neuropsychiatric symptoms. We performed a narrative review of existing literature on the effectiveness of long-term exercise interventions in improving cognitive function and neuropsychiatric symptoms in patients with AD. Patients with AD who presented with long-term exercise interventions appeared to have improved blood flow, increased hippocampal volume, and improved neurogenesis. Most prospective studies have proven that physical inactivity is one of the most common preventable risk factors for developing AD and that higher physical activity levels are associated with a reduced risk of AD development. Physical exercise seems to be effective in improving several neuropsychiatric symptoms of AD, notably cognitive function. Compared with medications, exercise has been shown to have fewer side effects and better adherence.

CT-Based Quantitative Analysis for Pathological Features Associated With Postoperative Recurrence and Potential Application Upon Artificial Intelligence: A Narrative Review With a Focus on Chronic Subdural Hematomas.

Chronic subdural hematomas (CSDHs) frequently affect the elderly population. The postoperative recurrence rate of CSDHs is high, ranging from 3% to 20%. Both qualitative and quantitative analyses have been explored to investigate the mechanisms underlying postoperative recurrence. We surveyed the pathophysiology of CSDHs and analyzed the relative factors influencing postoperative recurrence. Here, we summarize various qualitative methods documented in the literature and present our unique computer-assisted quantitative method, published previously, to assess postoperative recurrence. Imaging features of CSDHs, based on qualitative analysis related to postoperative high recurrence rate, such as abundant vascularity, neomembrane formation, and patent subdural space, could be clearly observed using the proposed quantitative analysis methods in terms of mean hematoma density, brain re-expansion rate, hematoma volume, average distance of subdural space, and brain shifting. Finally, artificial intelligence (AI) device types and applications in current health care are briefly outlined. We conclude that the potential applications of AI techniques can be integrated to the proposed quantitative analysis method to accomplish speedy execution and accurate prediction for postoperative outcomes in the management of CSDHs.