Quantitative thermal testing as a screening and follow-up tool for diabetic sensorimotor polyneuropathy in patients with type 2 diabetes and prediabetes.

Introduction: The diagnosis and assessment of neuropathy severity of diabetic sensorimotor polyneuropathy (DSPN) are mainly based on clinical neuropathy scores and electrophysiologic studies. This study aimed to determine whether quantitative thermal testing (QTT) can be used as a screening and follow-up tool for DSPN of prediabetes and type 2 diabetes at baseline and at 1-year follow-up. Methods: All patients were assessed using the Toronto Clinical Neuropathy Score (TCNS) and underwent electrophysiological testing, including a nerve conduction study (NCS) and QTT, at baseline and at a 1-year follow-up. The TCNS and the composite scores of nerve conduction were used to assess the severity of DSPN. The DSPN status at the 1-year follow-up was classified as remaining no DSPN, remaining DSPN, regression to no DSPN, or progression to DSPN. Results: Diabetic sensorimotor polyneuropathy was initially diagnosed in 89 patients with prediabetes and type 2 diabetes (22%). The regressed to no DSPN in 29 patients and progressed to DSPN in 20 patients at the 1-year follow-up. TCNS was significantly correlated with composite scores of nerve conduction, hand cold detection threshold (CDT), hand warm detection threshold (WDT), foot CDT, and foot WDT. Stepwise logistic regression demonstrated that the foot CDT (p < 0.0001) was independently associated with the presence of DSPN. The TCNS, composite scores of the nerve conduction, hand WDT, hand CDT, foot WDT, and foot CDT were all statistically significant among the four different DSPN status groups at two different time periods (baseline and the 1-year follow-up). Conclusion: The foot CDT can be used as an initial screening tool for DSPN alternatively. The characteristics of nerve damage after 1 year of DSPN can be progressive or reversible, and the neurological functions of large and small fibers have a parallel trend, which can be objectively measured by NCS and QTT.

Alternative role of glucagon-like Peptide-1 receptor agonists in neurodegenerative diseases.

Aging is a crucial risk factor for common neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). Limited options are available for the treatment of age-related, multiple pathogenic mechanism-contributed diseases that usually advance to irreversible conditions with severe neurological deficits and result in a heavy socioeconomic burden on patients, families, and society. A therapy that decelerates disease progression and reduces the socioeconomic burden stemming from these diseases is required. Glucagon-like peptide-1 receptor (GLP-1R) is an important class of medication for type 2 diabetes mellitus (T2DM). Through pancreatic effects, GLP-1R agonists can stimulate insulin secretion, increase ß-cell proliferation, reduce ß-cell apoptosis, and inhibit glucagon secretion in patients with T2DM. Currently, seven clinically approved GLP-1R agonists are used for T2DM: exenatide, liraglutide, lixisenatide, extended-release exenatide, albiglutide, dulaglutide, and semaglutide. Besides the pancreas, GLP-1Rs are also expressed in organs, such as the gastrointestinal tract, heart, lung, kidney, and brain, indicating their potential use in diseases other than T2DM. Emerging evidence reveals that GLP-1R agonists possess pleiotropic effects that enrich neurogenesis, diminish apoptosis, preclude neurons from oxidative stress, and reduce neuroinflammation in various neurological conditions. These favorable effects may also be employed in neurodegenerative diseases. Herein, we reviewed the recent progress, both in preclinical studies and clinical trials, regarding these clinically used GLP-1R agonists in aging-related neurodegenerative diseases, mainly AD and PD. We stress the pleiotropic characteristics of GLP-1R agonists as repurposing drugs to target multiple pathological mechanisms and for use in the future for these devastating neurodegenerative conditions.

Iron Brain Menace: The Involvement of Ferroptosis in Parkinson Disease.

Parkinson disease (PD) is the second-most common neurodegenerative disease. The characteristic pathology of progressive dopaminergic neuronal loss in people with PD is associated with iron accumulation and is suggested to be driven in part by the novel cell death pathway, ferroptosis. A unique modality of cell death, ferroptosis is mediated by iron-dependent phospholipid peroxidation. The mechanisms of ferroptosis inhibitors enhance antioxidative capacity to counter the oxidative stress from lipid peroxidation, such as through the system xc-/glutathione (GSH)/glutathione peroxidase 4 (GPX4) axis and the coenzyme Q10 (CoQ10)/FSP1 pathway. Another means to reduce ferroptosis is with iron chelators. To date, there is no disease-modifying therapy to cure or slow PD progression, and a recent topic of research seeks to intervene with the development of PD via regulation of ferroptosis. In this review, we provide a discussion of different cell death pathways, the molecular mechanisms of ferroptosis, the role of ferroptosis in blood-brain barrier damage, updates on PD studies in ferroptosis, and the latest progress of pharmacological agents targeting ferroptosis for the intervention of PD in clinical trials.

The clinical and imaging features of FLNA positive and negative periventricular nodular heterotopia.

BACKGROUND: Periventricular nodular heterotopia (PVNH) is caused by abnormal neuronal migration, resulting in the neurons accumulate as nodules along the surface of the lateral ventricles. PVNH often cause epilepsy, psychomotor development or cognition problem. Mutations in FLNA (Filamin A) is the most common underlying genetic etiology. Our purpose is to delineate the clinical and imaging spectrum that differentiates FLNA-positive and FLNA-negative PVNH patients. METHODS: We included 21 patients with confirmed PVNH. The detailed clinical information, electroencephalography, and other clinical findings were recorded. Detailed brain MR imaging was assessed. Mutation analysis of the FLNA gene was used Sanger sequencing or a next generation sequencing based assay. RESULTS: FLNA mutations were identified in 9 patients (7 females and 2 males), including two nonsense, two splice site, three frameshift, and two missense mutations. In FLNA-positive group, 8 patients had anterior predominant bilateral symmetric presentation and only one had asymmetrical distribution and dilated ventricles. Extra-cerebral features were more often observed in FLNA-positive group than FLNA-negative group. CONCLUSION: Genetics of PVNH is heterogenous, and mutations in FLNA gene account for less than half of the patients in our cohort. Our finding between FLNA-positive and FLNA-negative patients could guide the clinicians to select relevant genetic testing.

Correction: Lin et al. Grounding the Body Improves Sleep Quality in Patients with Mild Alzheimer's Disease: A Pilot Study. Healthcare 2022, 10, 581.

The authors would like to make the following corrections to the published paper [...].

Static postural stability and neuropsychological performance after awakening from REM and NREM sleep in patients with chronic insomnia: a randomized, crossover, overnight polysomnography study.

STUDY OBJECTIVES: Chronic insomnia disorder (CID) is a common sleep disorder, with a prevalence ranging from 6%-10% worldwide. Individuals with CID experience more fragmented sleep than healthy control patients do. They awaken frequently during the night and have a higher risk of injury from falling. Awakening from different sleep stages may have different effects on postural stability and waking performance. However, limited research has been conducted on this topic. METHODS: This prospective randomized crossover study was conducted between January 2015 and January 2017. We included 20 adults aged 20-65 years who fulfilled the diagnosis criteria for CID. Participants underwent 2 overnight polysomnography studies with an interval of at least 7 days. They were awakened during either rapid eye movement (REM) sleep or stage N1/N2 sleep alternatively. We compared measurements of static postural stability, vigilance scores, and neuropsychological tests between REM sleep and stage N1/N2 sleep awakening. RESULTS: Polysomnography parameters between the 2 nights were comparable. Participants who were awakened from REM sleep had worse static postural stability than those with stage N1/N2 sleep awakening. Compared with stage N1/N2 sleep awakening, larger mean sway areas of center of pressure (P = .0413) and longer center-of-pressure mean distances (P = .0139) were found in REM sleep awakening. There were no statistically significant differences in vigilance scores or neuropsychological tests between the 2 nights. CONCLUSIONS: REM sleep awakening was associated with worse static postural stability than was stage N1/N2 sleep awakening. No statistically significant differences were found in waking performance in alertness or in neuropsychological tests between stage N1/N2 and REM sleep awakening. CITATION: Yeh W-C, Chuang Y-C, Yen C-W, et al. Static postural stability and neuropsychological performance after awakening from REM and NREM sleep in patients with chronic insomnia: a randomized, crossover, overnight polysomnography study. J Clin Sleep Med. 2022;18(8):1983-1992.

Grounding the Body Improves Sleep Quality in Patients with Mild Alzheimer's Disease: A Pilot Study.

BACKGROUND: Grounding refers to having direct contact with the Earth, such as by walking barefoot or lying on the ground. Research has found that grounding can improve inflammation, free radical damage, blood pressure, sleep quality, pain, stress, mood, and wound healing. However, there has been no research on the effect of utilizing grounding for patients with Alzheimer's disease (AD). Thus, in this study, we investigated the effectiveness of grounding as a non-pharmacological therapy for treating sleep disturbances, anxiety, and depression in patients with mild AD. METHODS: Patients with mild AD were enrolled in the study. The electrochemical analyzer CHI 1205b was employed to check the electrochemical signals at acupoints KI1 and GV16. We used the Pittsburgh Sleep Quality Index (PSQI), Beck Anxiety Inventory (BAI), and Beck Depression Inventory-II (BDI-II) to evaluate sleep quality, anxiety, and depression, respectively, at weeks 0 and 12. RESULTS: This 12-week placebo-controlled study enrolled 22 patients, but only 15 patients completed the 12-week intervention and survey. Grounding significantly improved PSQI scores compared to the sham-grounding group (mean ± SD: 0.3 ± 0.7 vs. 3.0 ± 1.9, p = 0.006). The scores on the BAI and BDI-II did not change significantly after grounding in comparison to the sham-grounding group. CONCLUSIONS: Grounding can improve sleep quality, but it does not significantly improve anxiety and depression among patients with mild AD.

Two Birds One Stone: The Neuroprotective Effect of Antidiabetic Agents on Parkinson Disease-Focus on Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors.

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease affecting more than 1% of the population over 65 years old. The etiology of the disease is unknown and there are only symptomatic managements available with no known disease-modifying treatment. Aging, genes, and environmental factors contribute to PD development and key players involved in the pathophysiology of the disease include oxidative stress, mitochondrial dysfunction, autophagic-lysosomal imbalance, and neuroinflammation. Recent epidemiology studies have shown that type-2 diabetes (T2DM) not only increased the risk for PD, but also is associated with PD clinical severity. A higher rate of insulin resistance has been reported in PD patients and is suggested to be a pathologic driver in this disease. Oral diabetic drugs including sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and dipeptidyl peptidase-4 (DPP-4) inhibitors have been shown to provide neuroprotective effects in both PD patients and experimental models; additionally, antidiabetic drugs have been demonstrated to lower incidence rates of PD in DM patients. Among these, the most recently developed drugs, SGLT2 inhibitors may provide neuroprotective effects through improving mitochondrial function and antioxidative effects. In this article, we will discuss the involvement of mitochondrial-related oxidative stress in the development of PD and potential benefits provided by antidiabetic agents especially focusing on sglt2 inhibitors.

The Mediation Effects of Aluminum in Plasma and Dipeptidyl Peptidase Like Protein 6 (DPP6) Polymorphism on Renal Function via Genome-Wide Typing Association.

Aluminum (Al) toxicity is related to renal failure and the failure of other systems. Although there were some genome-wide association studies (GWAS) in Australia and England, there were no GWAS about Han Chinese to our knowledge. Thus, this research focused on using whole genomic genotypes from the Taiwan Biobank for exploring the association between Al concentrations in plasma and renal function. Participants, who underwent questionnaire interviews, biomarkers, and genotyping, were from the Taiwan Biobank database. Then, we measured their plasma Al concentrations with ICP-MS in the laboratory at Kaohsiung Medical University. We used this data to link genome-wide association (GWA) tests while looking for candidate genes and associated plasma Al concentration to renal function. Furthermore, we examined the path relationship between Single Nucleotide Polymorphisms (SNPs), Al concentrations, and estimated glomerular filtration rates (eGFR) through the mediation analysis with 3000 replication bootstraps. Following the principles of GWAS, we focused on three SNPs within the dipeptidyl peptidase-like protein 6 (DPP6) gene in chromosome 7, rs10224371, rs2316242, and rs10268004, respectively. The results of the mediation analysis showed that all of the selected SNPs have indirectly affected eGFR through a mediation of Al concentrations. Our analysis revealed the association between DPP6 SNPs, plasma Al concentrations, and eGFR. However, further longitudinal studies and research on mechanism are in need. Our analysis was still be the first study that explored the association between the DPP6, SNPs, and Al in plasma affecting eGFR.

Disrupted Sleep Homeostasis and Altered Expressions of Clock Genes in Rats with Chronic Lead Exposure.

Sleep disturbance is one of the neurobehavioral complications of lead neurotoxicity. The present study evaluated the impacts of chronic lead exposure on alteration of the sleep-wake cycle in association with changes of clock gene expression in the hypothalamus. Sprague-Dawley rats with chronic lead exposure consumed drinking water that contained 250 ppm of lead acetate for five weeks. Electroencephalography and electromyography were recorded for scoring the architecture of the sleep-wake cycle in animals. At six Zeitgeber time (ZT) points (ZT2, ZT6, ZT10, ZT14, ZT18, and ZT22), three clock genes, including rPer1, rPer2, and rBmal1b, were analyzed. The rats with chronic lead exposure showed decreased slow wave sleep and increased wakefulness in the whole light period (ZT1 to ZT12) and the early dark period (ZT13 to ZT15) that was followed with a rebound of rapid-eye-movement sleep at the end of the dark period (ZT22 to ZT24). The disturbance of the sleep-wake cycle was associated with changes in clock gene expression that was characterized by the upregulation of rPer1 and rPer2 and the feedback repression of rBmal1b. We concluded that chronic lead exposure has a negative impact on the sleep-wake cycle in rats that predominantly disrupts sleep homeostasis. The disruption of sleep homeostasis was associated with a toxic effect of lead on the clock gene expression in the hypothalamus.

Exploring factors associated with interictal heart rate variability in patients with medically controlled focal epilepsy.

PURPOSE: Heart rate variability (HRV) reflects the balance between the functional outputs of the sympathetic and parasympathetic nervous systems. It is lower in patients with epilepsy than in the healthy controls. However, HRV has been inadequately studied in different patient subgroups with medically controlled epilepsy. Hence, this study aimed to investigate factors associated with interictal HRV in patients with medically controlled epilepsy. METHODS: This retrospective cohort study included 54 patients (24 males and 30 females) with medically controlled focal epilepsy who only received monotherapy to eliminate the confounding effect of different antiseizure medications (ASMs). Patients with major systemic or psychiatric disorder comorbidities were excluded. For HRV analysis, electroencephalography and 5-minute well-qualified electrocardiogram segment recording were conducted during stage N1 or N2 sleep. In addition, the association between age, gender, seizure onset type, ASMs, and the time domain and frequency-domain HRV measures was analyzed. RESULTS: HRV negatively correlated with advanced age. Patients with focal to bilateral tonic-clonic seizure (FBTCS) had a significantly lower HRV than focal impaired awareness seizures (FIAS). HRV was not associated with any gender and ASMs. CONCLUSIONS: HRV negatively correlated with age, and patients with FBTCS had a decreased HRV. Thus, these patients may have a declining autonomic function. Therefore, different seizure types may carry different risks of autonomic dysfunction in patients with medically controlled focal epilepsy.

Quantitative evaluation of the microstructure of rapid eye movement sleep in refractory epilepsy: a preliminary study using electroencephalography and heart rate variability analysis.

INTRODUCTION: Patients with epilepsy have a disturbed sleep architecture. Polysomnographic studies have shown that patients with refractory epilepsy have decreased rapid eye movement (REM) sleep and longer REM latency than those with medically controlled epilepsy. However, little is known about the differences in the REM sleep microstructure between these patient groups. METHODS: We conducted a retrospective case-control study of 20 patients with refractory epilepsy (refractory group) and 28 patients with medically controlled epilepsy (medically controlled group). All patients completed sleep questionnaires and underwent overnight in-lab polysomnography. Five-minute electroencephalogram recordings at the C3 and C4 electrodes from each REM sleep were selected for spectral analysis, and 5-min electrocardiogram segments recorded during REM sleep were used for heart rate variability analysis. The groups' scores on the sleep questionnaires, polysomnographic sleep parameters, indices of sleep-related breathing disorders, and REM sleep electroencephalogram spectra were compared. RESULTS: The refractory group had decreased REM sleep (p < 0.001) and longer REM latency (p = 0.0357) than those of the medically controlled group. Moreover, electroencephalogram spectral analysis revealed that the refractory group had decreased absolute beta power (p = 0.0039) and relative beta power (p = 0.0035) as well as increased relative delta power (p = 0.0015) compared with the medically controlled group. CONCLUSIONS: Differences in the polysomnographic macrostructure and REM sleep microstructure between the study groups suggest REM sleep dysregulation in patients with refractory epilepsy.

Zonisamide Therapy Reduces Metabolic Consequences and Diminishes Nonalcoholic Fatty Liver Disease in Patients with Epilepsy.

Antiepileptic drugs that can reduce aberrant metabolism are beneficial for patients. Zonisamide (ZNS) is a chemical with antiepileptic and antioxidant activities. Here, we evaluate the efficacy of ZNS therapy on reducing obesity and decreasing risks of vascular diseases and hepatic steatosis. Clinical and metabolic indicators including body weight, body mass index (BMI), serum lipid profiles, glycated hemoglobin (HbA1c), homocysteine, and an inflammatory marker, high-sensitivity C-reactive protein (hs-CRP), were assessed at baseline and at the end of 12 and 24 weeks of treatment. Nonalcoholic fatty liver disease was evaluated using the hepatic steatosis index (HSI). A body weight reduction of ≥5% was observed in 24.6% and 32.8% of patients after 12 and 24 weeks of ZNS treatment, respectively. After adjusting for age, sex, time, and the corresponding dependent variable at baseline, the generalized estimating equation analysis revealed that the body weight, BMI, serum levels of HbA1c, triglycerides, hs-CRP, and the index for HSI were significantly declined. These results suggest that ZNS provides benefits in patients with obesity and metabolic syndrome at high vascular risk.

Interaction of Smoking and Lead Exposure among Carriers of Genetic Variants Associated with a Higher Level of Oxidative Stress Indicators.

Smoking and lead (Pb) exposure increased oxidative stress in human body, and people with some gene variants may be susceptible to Pb and smoking via oxidative stress. The aim of this study is to evaluate oxidative stress by measuring thiobarbituric acid reactive substances (TBARS) and the relationship of lipid peroxidation markers in Pb workers with different gene polymorphisms (rs4673 and rs1050450) in both smokers and nonsmokers. Blood samples were collected from 267 Pb workers who received their annual health examination in the Kaohsiung Medical University Hospital. Glutathione peroxidase 1 (GPx-1) rs1050450 and cytochrome B-245 Alpha Chain (CYBA) rs4673 single-nucleotide polymorphisms (SNP) were analyzed by specific primer-probes using Real-Time PCR methods. The interaction between blood Pb and smoking increased serum levels of TBARS and the ratio of oxidative low-density lipoprotein and low-density lipoprotein (oxLDL/LDL). Analysis of workers with rs1050450 SNPs showed higher blood Pb levels in the workers with CC genotype than those with CT genotype. Smokers had significantly higher blood Pb, alanine transaminase (ALT), TBARS, and OxLDL levels than nonsmokers. TBARS increased 0.009 nmol/mL when blood Pb increased one µg/dL in smokers compared to nonsmokers. The ratio of OxLDL/LDL increased 0.223 when blood Pb increased one µg/dL in smokers compared to nonsmokers. TBARS levels and the ratio of OxLDL/LDL were positively correlated and interacted between blood Pb and smoking after the adjustment of confounders, suggesting that smoking cessation is an important issue in the Pb-exposed working environment.

Factors Affecting Rapid Cognitive Decline in Patients with Alzheimer's Disease: A Longitudinal Follow-Up Study.

We investigated the preventive and risk factors of rapid cognitive decline in patients with Alzheimer's disease (AD). Using the Chang Gung Research Database (CGRD), we enrolled patients with AD aged over 65 years between 1 January 2001 and 30 May 2019, and followed up for at least two years. Rapid cognitive decline was defined by a Mini-Mental State Examination (MMSE) score decline of ≥4 in 2 years. A longer prescription of acetylcholinesterase inhibitors (AChEIs) was defined as 22 months based on the median treatment duration of the cohorts. The Cox proportional hazards regression model adjusted for age, sex, medication, and physical comorbidities was used to examine the candidate risk and protective factors. We analyzed data from 3846 patients with AD (1503 men, 2343 women) with a mean age and percentage of females of 77.8 ± 6.2 years and 60.9%, respectively. The mean duration of patients with AD receiving AChEIs was 658.7 ± 21.9 days. In general, 310 patients with AD showed a rapid cognitive decline, accounting for 8.1%. Treatment of a consecutive AChEI prescription for >22 months in patients with AD was a protective factor against rapid cognitive decline (adjusted hazard ratio (aHR) = 0.41, 95% confidence interval (CI) = 0.33-0.52, p < 0.001). Patients with AD aged >85 years (aHR = 0.53, 95% CI = 0.36-0.79, p < 0.01) and aged 75-85 years (aHR = 0.73, 95% CI = 0.57-0.93, p < 0.05) had a significantly lower risk of rapid cognitive decline than those aged 65-75 years. Additionally, patients with mild and moderate AD (clinical dementia rating (CDR = 1, aHR = 1.61, 95% CI = 1.26-2.07, p < 0.001; CDR = 2, aHR = 2.64, 95% CI = 1.90-3.65, p < 0.001) were more likely to have rapid cognitive decline than those with early AD (CDR = 0.5). Sex, medication with different types of AChEIs, and physical comorbidities were not associated with rapid cognitive decline. These findings indicate that it is important to maintain longer consecutive AChEI prescriptions in patients with AD to prevent cognitive decline.

Quality Matters? The Involvement of Mitochondrial Quality Control in Cardiovascular Disease.

Cardiovascular diseases are one of the leading causes of death and global health problems worldwide. Multiple factors are known to affect the cardiovascular system from lifestyles, genes, underlying comorbidities, and age. Requiring high workload, metabolism of the heart is largely dependent on continuous power supply via mitochondria through effective oxidative respiration. Mitochondria not only serve as cellular power plants, but are also involved in many critical cellular processes, including the generation of intracellular reactive oxygen species (ROS) and regulating cellular survival. To cope with environmental stress, mitochondrial function has been suggested to be essential during bioenergetics adaptation resulting in cardiac pathological remodeling. Thus, mitochondrial dysfunction has been advocated in various aspects of cardiovascular pathology including the response to ischemia/reperfusion (I/R) injury, hypertension (HTN), and cardiovascular complications related to type 2 diabetes mellitus (DM). Therefore, mitochondrial homeostasis through mitochondrial dynamics and quality control is pivotal in the maintenance of cardiac health. Impairment of the segregation of damaged components and degradation of unhealthy mitochondria through autophagic mechanisms may play a crucial role in the pathogenesis of various cardiac disorders. This article provides in-depth understanding of the current literature regarding mitochondrial remodeling and dynamics in cardiovascular diseases.

Autonomic Dysfunction Contributes to Impairment of Cerebral Autoregulation in Patients with Epilepsy.

Patients with epilepsy frequently experience autonomic dysfunction and impaired cerebral autoregulation. The present study investigates autonomic function and cerebral autoregulation in patients with epilepsy to determine whether these factors contribute to impaired autoregulation. A total of 81 patients with epilepsy and 45 healthy controls were evaluated, assessing their sudomotor, cardiovagal, and adrenergic functions using a battery of autonomic nervous system (ANS) function tests, including the deep breathing, Valsalva maneuver, head-up tilting, and Q-sweat tests. Cerebral autoregulation was measured by transcranial Doppler examination during the breath-holding test, the Valsalva maneuver, and the head-up tilting test. Autonomic functions were impaired during the interictal period in patients with epilepsy compared to healthy controls. The three indices of cerebral autoregulation-the breath-holding index (BHI), an autoregulation index calculated in phase II of the Valsalva maneuver (ASI), and cerebrovascular resistance measured in the second minute during the head-up tilting test (CVR2-min)-all decreased in patients with epilepsy. ANS dysfunction correlated significantly with impairment of cerebral autoregulation (measured by BHI, ASI, and CVR2-min), suggesting that the increased autonomic dysfunction in patients with epilepsy may augment the dysregulation of cerebral blood flow. Long-term epilepsy, a high frequency of seizures, and refractory epilepsy, particularly temporal lobe epilepsy, may contribute to advanced autonomic dysfunction and impaired cerebral autoregulation. These results have implications for therapeutic interventions that aim to correct central autonomic dysfunction and impairment of cerebral autoregulation, particularly in patients at high risk for sudden, unexplained death in epilepsy.

Serum Levels of Soluble Triggering Receptor Expressed on Myeloid Cells-1 Associated with the Severity and Outcome of Acute Ischemic Stroke.

Stroke is a neurological emergency, where the mechanism of the blood supply to the brain is impaired, resulting in brain cell ischemia and death. Neuroinflammation is a key component in the ischemic cascade that results in cell damage and death after cerebral ischemia. The triggering receptor expressed on myeloid cells-1 (TREM-1) modulates neuroinflammation after acute ischemic stroke. In the present study, 60 patients with acute ischemic stroke, who had been subjected to neurological examinations and National Institutes of Health Stroke Scale (NIHSS) and brain magnetic resonance imaging studies, were enrolled in the emergency room of Kaohsiung Chang Gung Memorial Hospital. Twenty-four healthy volunteers were recruited as controls. The serum levels of soluble TREM-1 (sTREM-1), human S100 calcium-binding protein B (S100B), and proinflammatory cytokines and chemokines, including tumor necrosis α (TNF-α), interleukin 1ß, interleukin 6 (IL-6), interleukin 8, and interferon-γ were measured immediately after acute ischemic stroke. The serum levels of sTREM-1, TNFα, IL-6, and S100B were correlated with the stroke volume and NIHSS, after acute ischemic stroke. Additionally, the serum levels of sTREM-1 were significantly positively correlated with S100B. The functional outcomes were evaluated 6 months after ischemic stroke by the Barthel index, which was correlated with the age and levels of sTREM-1 and S100B. We suggest that acute ischemic stroke induces neuroinflammation by the activation of the TREM-1 signaling pathway and the downstream inflammatory machinery that modulates the inflammatory response and ischemic neuronal cell death. From a translational perspective, our results may allow for the development of a new therapeutic strategy for acute ischemic stroke by targeting the TREM-1 signaling pathway.

When Friendship Turns Sour: Effective Communication Between Mitochondria and Intracellular Organelles in Parkinson's Disease.

Parkinson's disease (PD) is a complex neurodegenerative disease with pathological hallmarks including progressive neuronal loss from the substantia nigra pars compacta and α-synuclein intraneuronal inclusions, known as Lewy bodies. Although the etiology of PD remains elusive, mitochondrial damage has been established to take center stage in the pathogenesis of PD. Mitochondria are critical to cellular energy production, metabolism, homeostasis, and stress responses; the association with PD emphasizes the importance of maintenance of mitochondrial network integrity. To accomplish the pleiotropic functions, mitochondria are dynamic not only within their own network but also in orchestrated coordination with other organelles in the cellular community. Through physical contact sites, signal transduction, and vesicle transport, mitochondria and intracellular organelles achieve the goals of calcium homeostasis, redox homeostasis, protein homeostasis, autophagy, and apoptosis. Herein, we review the finely tuned interactions between mitochondria and surrounding intracellular organelles, with focus on the nucleus, endoplasmic reticulum, Golgi apparatus, peroxisomes, and lysosomes. Participants that may contribute to the pathogenic mechanisms of PD will be highlighted in this review.

Constipation and Its Associated Factors among Patients with Dementia.

Constipation is one of the most frequent non-motor problems in older adults. As constipation is commonly ignored by dementia patients, it is not usually reported on time. Constipation has a serious impact on the activity of daily living and quality of life in dementia patients. The relationships between constipation, demographic variables, and the nutritional status of patients with dementia remain unknown. This study aimed to assess the possible factors associated with constipation. This cross-sectional study was conducted at the Kaohsiung Chang Gung Memorial Hospital from January to November 2019. This hospital is a medical center and the main referral hospital of southern Taiwan, serving 3 million inhabitants. In total, 119 patients with dementia were evaluated using the Rome III diagnostic criteria for functional constipation. There were 30 patients with dementia included in the constipation group and 89 patients with dementia included in the no constipation group. Mini-Nutritional Assessment and 3-day diet diary records were employed. The clinical dementia rating score was used to evaluate the severity of dementia in patients of the outpatient clinic. Approximately 25.2% of dementia patients had constipation. Patients in the dementia with constipation group were older, had severer dementia, and displayed a lower water intake. After multivariable adjustment, low liquid consumption was the predictor of constipation among patients with dementia. The findings support the clinical recommendations to treat constipation with an increased liquid intake, but not exercise, in dementia patients.