The Temporal Pattern of Repeat Intimate Partner Violence Incidents Among High-Risk Survivors in Taiwan: A Survival Analysis.

Intimate partner violence (IPV) is rarely an isolated incident, with survivors often experiencing repeat violence. Few studies, however, have been conducted to investigate the temporal pattern of IPV revictimization using a validated risk assessment instrument. In Taiwan, service professionals are mandated to report any known IPV incidents using the Taiwan Intimate Partner Violence Danger Assessment (TIPVDA), a validated risk assessment designed to assess the level of lethality faced by IPV survivors. The mandatory reporting policy and the universal use of the TIPVDA provide a unique opportunity to investigate the time course of repeat IPV victimization. This study analyzes high-risk IPV incidents (n = 18,740) reported in Taiwan from 2017 to 2019 using Cox regression analysis. Analysis results suggested three main findings: (a) The time interval between IPV victimizations shortened and the severity of violence increased; (b) the TIPVDA score was consistently associated with repeat victimization, unlike self-assessed dangerousness; (c) specific TIPVDA items, such as IPV history and financial stress, predicted the rate of repeat victimization. Those who reported ever being hurt by their partner during pregnancy, an escalation in physical violence during the past year, their partner threatening to kill them, and their partner being stressed about their financial situation were likely to have a faster rate of reporting the second and third high-risk victimization reports. These findings highlight the importance of using validated risk assessments in practice, not only for predicting reassault, severe reassault, or homicide but also for estimating the timing of revictimization. This can significantly inform intervention strategies and policy decisions.

Cerebral white matter burden is linked to cognitive function in patients undergoing hemodialysis.

INTRODUCTION: Chronic kidney disease is related to neurodegeneration and structural changes in the brain which might lead to cognitive decline. The Fazekas scale used for assessing white matter hyperintensities (WMHs) was associated with poor cognitive performance. Therefore, this study investigated the associations between the mini-mental status examination (MMSE), Montreal cognitive assessment (MoCA), cognitive abilities screening instrument (CASI), and Fazekas scale in patients under hemodialysis (HD). METHODS: The periventricular (PV) WMHs and deep WMHs (DWMHs) in brain magnetic resonance images of 59 patients under dialysis were graded using the Fazekas scale. Three cognition function tests were also performed, then multivariable ordinal regression and logistic regression were used to identify the associations between cognitive performance and the Fazekas scale. RESULTS: There were inverse associations between the three cognitive function tests across the Fazekas scale of PVWMHs (p = .037, .006, and .008 for MMSE, MoCA, and CASI, respectively), but the associations were attenuated in the DWMHs group. In CASI, significant differences were identified in short-term memory, mental manipulation, abstract thinking, language, spatial construction, and name fluency in the PVWMHs group. However, DWMHs were only significantly correlated with abstract thinking and short-term memory. CONCLUSION: An inverse correlation existed between the Fazekas scale, predominantly in PVWMHs, and cognition in patients undergoing HD. The PVWMHs were associated with cognitive performance assessed by MMSE, MoCA, and CASI, as well as with subdomains of CASI such as memory, language and name fluency in patients undergoing HD.

An inverse correlation existed between the Fazekas scale and cognition in patients undergoing hemodialysis, predominantly in periventricular white matter hyperintensities.The periventricular white matter hyperintensities were associated with cognitive performance assessed by mini-mental status examination (MMSE), Montreal cognitive assessment (MoCA), cognitive abilities screening instrument (CASI), as well as with subdomains of CASI such as memory, language and name fluency in patients undergoing HD.

Thrombospondin-1 associated with carotid intima-media thickness among individuals with hypertension.

In vivo and in vitro studies have demonstrated that thrombospondin-1 (TSP-1) is involved in atherosclerotic pathogenesis. However, the role of TSP-1 in clinical atherosclerosis remains unknown. This cross-sectional study investigated the relationship between TSP-1 and carotid intima-media thickness (IMT) and examined whether it interacts with conventional cardiovascular risk factors. A total of 587 participants were enrolled from February 2018 to December 2021. TSP-1 was dichotomized based on median value. Carotid IMT was measured bilaterally in each segment, and the average value was taken as the overall IMT variable. Analysis of covariance models were used to ascertain the main and interaction effects of cardiovascular risk factors and circulating TSP-1 levels on carotid IMT. Those with high TSP-1 (n = 294) had significantly higher carotid IMT than did those with low TSP-1 (n = 293; 0.74 ± 0.12 vs 0.72 ± 0.11 mm; p = 0.011). After the combined effects of TSP-1 and vascular risk factors on carotid IMT were evaluated, an interaction effect on IMT was observed between TSP-1 and hypertension (adjusted F = 8.760; p = 0.003). Stratification analysis revealed that individuals with hypertension and high TSP-1 had significantly higher IMT than did those with low TSP-1 (adjusted p = 0.007). However, this difference was not observed in normotensive individuals (adjusted p = 0.636). In conclusion, this is the first study to provide clinical data supporting the correlation between TSP-1 and atherosclerosis. TSP-1 may be a crucial marker of increased susceptibility to atherosclerosis in individuals with hypertension.

The impact of blood pressure variability on the development of parenchymal hematoma in acute cerebral infarction with atrial fibrillation.

Although blood pressure variability (BPV) and reperfusion are associated with parenchymal hematoma (PH) after stroke, the relationship between BPV and PH in atrial fibrillation (AF) patients who are at risk of reperfusion injury with frequent spontaneous recanalization is unknown. This study aimed to investigate whether BPV within the first 48 h is associated with PH within 72 h in patients with AF and stroke in terms of major vessel occlusion status. A total of 131 patients with AF that were admitted within 24 h after stroke onset were enrolled. PH was defined as a confluent hemorrhage with mass effect. The maximum (max), minimum (min), and average blood pressure (BP) during the first 48 h after admission were calculated. BPV was analyzed by using range between maximum and minimum (max-min), successive variation (SV), standard deviation (SD), and coefficient of variation (CV). All parameters were applied for systemic (SBP), diastolic (DBP), and pulse pressure (PP). After adjusting for confounding variables, various BPV parameters were associated with PH, including SBPmax (p = 0.0426), SBPSV (p = 0.0006), DBPmax-min (p = 0.0437), DBPSV (p = 0.0358), DBPSD (p = 0.0393), PPmax-min (p = 0.0478), PPSV (p < 0.0001), PPSD (p = 0.0034), and PPCV (p = 0.0120). The relationship remained significant in patients with a patent major vessel responsible for infarction but not in patients with an occluded major vessel. In conclusion, this study revealed that high BPV was associated with PH in patients with AF and acute stroke, particularly for those with a patent major vessel. The control of BP and BPV after stroke may be considered in patients with AF.

Minimal Clinically Important Difference (MCID) in the Functional Status Measures in Patients with Stroke: Inverse Probability Treatment Weighting.

This study proposed to evaluate the temporal trend, define the minimal clinically important difference (MCID) for five functional status measures, and identify risk factors for reaching deterioration in the MCID. This prospective cohort study analyzed 680 patients with ischemic stroke and 151 patients with hemorrhagic stroke at six hospitals between April 2015 and October 2021. All patients completed the functional status measures before rehabilitation (baseline), and at the 12th week and 2nd year after rehabilitation. Patients in the post-acute care (PAC) group exhibited significantly larger improvements for the functional status measures compared to those in the non-PAC group (p < 0.05). Patients with hemorrhagic stroke also displayed larger improvements in the functional status measures when compared to patients with ischemic stroke. Furthermore, the improvement in MCID ranged from 0.01 to 16.18 points when comparing baseline and the 12th week after rehabilitation, but the deterioration in MCID ranged from 0.38 to 16.12 points. Simultaneously, assessing the baseline and the second year after rehabilitation, the improvement in MCID ranged from 0.01 to 18.43 points, but the deterioration in MCID ranged from 0.68 to 17.26 points. Additionally, the PAC program, age, education level, body mass index, smoking, readmission within 30 days, baseline functional status score, use of Foley catheter and nasogastric tube, as well as a history of previous stroke are significantly associated with achieving deterioration in MCID (p < 0.05). These findings suggest that if the mean change scores of the functional status measures have reached the thresholds, the change scores can be perceived by patients as clinically important.

IPV Experiences and Financial Strain Over Time: Insights from the Blinder-Oaxaca Decomposition Analysis.

Financial strain is one hardship faced by female survivors of intimate partner violence (IPV) that is often overlooked. This paper examined the relationships between multiple forms of abuse-with a focus on economic abuse-and financial strain. Guided by stress process model, this study tested two hypotheses: (1) economic abuse is associated with financial strain more than other types of IPV; and (2) decreased economic abuse relates to financial strain over time. The study sample consists of 229 female IPV survivors who participated in a longitudinal, randomized controlled study evaluating an economic empowerment curriculum. Results from regression models suggest that physical abuse and economic abuse were significantly and positively associated with the magnitude of financial strain. Oaxaca-Blinder decomposition was used to partition the mean differences of financial strain over time that was mainly attributed to the decrease in economic and physical abuse (78%). Particularly, the decrease of economic abuse contributed to over half (58%) of the decrease in financial strain over time. Advocates should assess survivors' risk of economic abuse, evaluate financial strain, and utilize financial safety planning skills to help survivors build economic security and independence. In addition, policy makers should address issues concerning economic security among female IPV survivors.

Stabilizing Li-Rich Layered Cathode Materials Using a LiCoMnO4 Spinel Nanolayer for Li-Ion Batteries.

Lithium-rich cathodes have excess lithium in the transition metal layer and exhibit an extremely high specific capacity and good energy density. However, they still have some disadvantages. Here, we propose LiCoMnO4, a new nanolayer coating material with a spinel structure, to modify the surface of lithium cathode oxide (Li7/6Mn1/2Ni1/6Co1/6O2) with a layered structure. The designed cathode with nanolayer spinel coating delivers an excellent reversible capacity, outstanding rate capability, and superior cycling ability whilst exhibiting discharge capacities of 300, 275, 220, and 166 mAh g-1 at rates of 0.1 C at 2.0-4.8 V formation and 0.1, 1, and 5 C, respectively, between 2.0 and 4.6 V. The cycling ability and voltage fading at a high operational voltage of 4.9 V were also investigated, with results showing that the nanolayer spinel coating can depress the surface of the lithium cathode oxide layer, leading to phase transformation that enhances the electrochemical performance.

Predicting 30-Day Readmission for Stroke Using Machine Learning Algorithms: A Prospective Cohort Study.

Background: Machine learning algorithms for predicting 30-day stroke readmission are rarely discussed. The aims of this study were to identify significant predictors of 30-day readmission after stroke and to compare prediction accuracy and area under the receiver operating characteristic (AUROC) curve in five models: artificial neural network (ANN), K nearest neighbor (KNN), random forest (RF), support vector machine (SVM), naive Bayes classifier (NBC), and Cox regression (COX) models. Methods: The subjects of this prospective cohort study were 1,476 patients with a history of admission for stroke to one of six hospitals between March, 2014, and September, 2019. A training dataset (n = 1,033) was used for model development, and a testing dataset (n = 443) was used for internal validation. Another 167 patients with stroke recruited from October, to December, 2019, were enrolled in the dataset for external validation. A feature importance analysis was also performed to identify the significance of the selected input variables. Results: For predicting 30-day readmission after stroke, the ANN model had significantly (P < 0.001) higher performance indices compared to the other models. According to the ANN model results, the best predictor of 30-day readmission was PAC followed by nasogastric tube insertion and stroke type (P < 0.05). Using a machine learning ANN model to obtain an accurate estimate of 30-day readmission for stroke and to identify risk factors may improve the precision and efficacy of management for these patients. Conclusion: Using a machine-learning ANN model to obtain an accurate estimate of 30-day readmission for stroke and to identify risk factors may improve the precision and efficacy of management for these patients. For stroke patients who are candidates for PAC rehabilitation, these predictors have practical applications in educating patients in the expected course of recovery and health outcomes.

Case Report: Late-Onset Mitochondrial Disease Uncovered by Metformin Use in a Patient With Acute Verbal Auditory Agnosia.

Introduction: Verbal auditory agnosia is rarely caused by mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. Lactate acidosis, which is the adverse effect of metformin, has proposed links to mitochondrial dysfunction and may trigger clinical features of mitochondrial diseases. Case Presentation: A 43-year-old right-handed man presented to our emergency department with acute onset fever and headache accompanied by impaired hearing comprehension. He could communicate well through handwritten notes but could not understand what others were saying. He had been diagnosed as having diabetes mellitus 2 months prior to this event. Vildagliptin 100 mg/day and metformin 1,700 mg/day were prescribed for glucose control. Laboratory tests revealed elevated lactate levels in serum and cerebrospinal fluid of the patient. Brain MRI disclosed bilateral temporal lesions. Acute encephalitis with temporal involved was initially diagnosed and acyclovir was given empirically. However, follow-up MRI after acyclovir treatment revealed a progression of prior lesions. Further mitochondrial genome analysis revealed a mitochondrial DNA point mutation at position 3,243 (m.3243A > G) with 25% heteroplasmy, which is compatible with MELAS. His clinical symptoms and serum lactate levels were improved after discontinuing the metformin use. Conclusions: To our knowledge, this is the first report of a patient having late-onset MELAS syndrome that manifested as acute verbal auditory agnosia, which was identified after the patient began using metformin. Metformin is known to inhibit mitochondrial function and could trigger clinical features of MELAS syndrome. We encourage clinicians to maintain a high level of awareness that diabetes mellitus can be caused by mitochondrial disease and to exercise caution in the prescription of metformin.

Cost Utility Analysis of Multidisciplinary Postacute Care for Stroke: A Prospective Six-Hospital Cohort Study.

Background: Few studies have compared the optimal duration and intensity of organized multidisciplinary neurological/rehabilitative care delivered in a regional/district hospital with the standard rehabilitative care delivered in the general neurology/rehabilitation ward of a medical center. This study measured functional outcomes and conducted cost-utility analysis of an organized multidisciplinary postacute care (PAC) project in secondary care compared with standard rehabilitative care delivered in tertiary care. Methods: This prospective cohort study enrolled 1,476 patients who had a stroke between March 2014 and March 2018 and had a modified Rankin scale score of 2-4. After exact matching for age ± 1 year, sex, year of stroke diagnosis, nasogastric tube, and Foley catheter and propensity score matching for the other covariates, we obtained 120 patients receiving PAC (the PAC group) from four regional/district hospitals and 120 patients not receiving PAC (the non-PAC group) from two medical centers. Results: At baseline, the non-PAC group showed significantly better functional outcomes than the PAC group, including EuroQol-5 dimensions (EQ-5D), Mini-Mental State Examination (MMSE) and Barthel index (BI). During weeks 7-12 of rehabilitation, improvements in all functional outcomes were significantly larger in the PAC group (P < 0.001) except for Functional Oral Intake Scale (FOIS). Cost-utility analysis revealed that the PAC group had a significantly lower mean (± standard deviation) of direct medical costs (US$3,480 ± $1,758 vs. US$3,785 ± $3,840, P < 0.001) and a significantly higher average gain of quality-adjusted life years (0.1993 vs. 0.1233, P < 0.001). The PAC project was an economically "dominant" strategy. Conclusions: The PAC project saved costs and significantly improved the functional outcomes of patients with stroke with slight to moderately severe disabilities. Randomized control trials are required to corroborate these results.

Neuropsychiatric symptoms and mortality among patients with mild cognitive impairment and dementia due to Alzheimer's disease.

BACKGROUND: Neuropsychiatric symptoms (NPS) could increase mortality risk in people with dementia due to Alzheimer's disease (AD). However, whether NPS affects mortality risk in people with mild cognitive impairment (MCI) and whether any specific syndrome of NPS influences this risk are still unclear. METHODS: In total, 984 participants with dementia due to AD, 338 with MCI, and 365 controls were enrolled. Over a mean of 5-year follow-up, cause of death data were obtained from the Ministry of Health and Welfare in Taiwan. NPS were assessed using Neuropsychiatric Inventory Questionnaire (NPI-Q), and psychosis, mood, and frontal domain scores were determined. Survival analyses were conducted to determine the hazard ratio (HR) of death. RESULTS: In controlled analyses, HR of death for AD was 2.19 (95% confidence interval [CI] = 1.29-3.71) compared with the control group, whereas no statistical significance was noted for the MCI group. A high NPI-Q score (above the median score) increased mortality risk for both the MCI and AD groups, with HRs of 2.32 (95% CI = 1.07-5.03) and 2.60 (95% CI = 1.51-4.47), respectively. Among NPI-Q domain scores, only high mood domain, but not psychosis or frontal domain, scores increased death risk for both the MCI (HR = 2.89, 95% CI = 1.00-8.51) and AD (HR = 2.59, 95% CI = 1.47-4.55) groups. CONCLUSION: Mortality risk is high for patients with AD. Not only for AD, patients with MCI presenting with NPS, particularly mood symptoms, have high death risk.

Women's Economic Abuse Experiences: Results from the UN Multi-Country Study on Men and Violence in Asia and the Pacific.

Economic abuse is a poorly understood form of intimate partner violence but may have far-reaching implications for the financial health of the survivor. Additionally, very little is known about whether depressive symptoms, education, employment, or attitudes about relations between men and women mediate or moderate the relationship between economic abuse and their financial circumstances. The purpose of this study was to answer these two research questions: (a) Is there a relationship between the experience of economic abuse and food insecurity (as a measure of poverty)? (b) Is the relationship between economic abuse and food insecurity impacted by women's education, women's and men's employment, women's attitudes towards gender relations, or women's depressive symptoms? We used quantitative data from the "UN Multi-Country Study on Men and Violence," analyzing data on 3,105 women aged 18-49 years who were interviewed. Initial logistic regressions were conducted followed by introducing moderators and mediators to the model using path analyses to test the relationship between economic abuse and food insecurity in the household. Significant predictors of food insecurity included several types of abuse and partners' employment, women's own employment, and education. The only type of IPV not associated with food insecurity was physical abuse. Experiences of economic abuse were associated with a 1.69 times greater likelihood of reporting food insecurity which was higher than experiences of psychological or sexual abuse. Additionally, women's experiences of economic abuse over their lifetime were significantly associated with an increase in depressive symptoms which in turn was associated with greater likelihood of experiencing food insecurity. Such relationships warrant attention to economic abuse and depressive symptoms as part of the interventions used when working with survivors. Additional research could also help further our understanding of how these variables interact together and how best to address its impact on survivors.

Multidisciplinary Care after Acute Care for Stroke: A Prospective Comparison between a Multidisciplinary Post-Acute Care Group and a Standard Group Matched by Propensity Score.

In this large-scale prospective cohort study, a propensity score matching method was applied in a natural experimental design to investigate how post-acute care (PAC) after stroke affects functional status and to identify predictors of functional status. The main objective of this study was to examine longitudinal changes in various measures of functional status in stroke patients and predictors of scores for these measures before and after PAC. A group of patients who had received PAC for stroke at one of two medical centers (PAC group, n = 273) was compared with a group who had received standard care for stroke at one of four hospitals (three regional hospital and one district hospital; non-PAC group, n = 273) in Taiwan from March, 2014, to October, 2018. The patients completed the functional status measures before rehabilitation, the 12th week and the 1st year after rehabilitation. Generalized estimating equations were used to estimate differences-in-differences models for examining the effects of PAC. The average age was 68.0 (SD = 8.1) years, and males accounted for 57.9%. During the follow-up period, significant risk factors for poor functional outcomes were advanced age, hemorrhagic stroke, and poor function scores before rehabilitation (p < 0.05). Between-group comparisons at subsequent time points revealed significantly higher functional status scores in the PAC group versus the non-PAC group (p < 0.001). Notably, for all functional status measures, between-group differences in total scores significantly increased over time from baseline to 1 year post-rehabilitation (p < 0.001). The contribution of this study is its further elucidation of the clinical implications and health policy implications of rehabilitative care after stroke. Specifically, it improves understanding of the effects of PAC in stroke patients at different follow-up times. Therefore, a policy implication of this study is that standard care for stroke should include intensive rehabilitative PAC to maximize recovery of overall function.

Impact of Multidisciplinary Stroke Post-Acute Care on Cost and Functional Status: A Prospective Study Based on Propensity Score Matching.

Few papers discuss how the economic burden of patients with stroke receiving rehabilitation courses is related to post-acute care (PAC) programs. This is the first study to explore the economic burden of stroke patients receiving PAC rehabilitation and to evaluate the impact of multidisciplinary PAC programs on cost and functional status simultaneously. A total of 910 patients with stroke between March 2014 and October 2018 were separated into a PAC group (at two medical centers) and a non-PAC group (at three regional hospitals and one district hospital) by using propensity score matching (1:1). A cost-illness approach was employed to identify the cost categories for analysis in this study according to various perspectives. Total direct medical cost in the per-diem-based PAC cohort was statistically lower than that in the fee-for-service-based non-PAC cohort (p < 0.001) and annual per-patient economic burden of stroke patients receiving PAC rehabilitation is approximately US $354.3 million (in 2019, NT $30.5 = US $1). Additionally, the PAC cohort had statistical improvement in functional status vis-à-vis the non-PAC cohort and total score of each functional status before rehabilitation and was also statistically significant with its total score after one-year rehabilitation training (p < 0.001). Early stroke rehabilitation is important for restoring health, confidence, and safe-care abilities in these patients. Compared to the current stroke rehabilitation system, PAC rehabilitation shortened the waiting time for transfer to the rehabilitation ward and it was indicated as an efficient policy for treatment of stroke in saving medical cost and improving functional status.

Carotid atherosclerosis among middle-aged individuals predicts cognition: A 10-year follow-up study.

BACKGROUND AND AIMS: There is a lack of studies simultaneously evaluating the impact of structural and functional atherosclerosis on cognition. We investigated the long-term predictive and interaction effects of structural and functional carotid atherosclerosis markers on future cognitive decline. METHODS: Five hundred and twenty-eight middle-aged participants enrolled in the carotid atherosclerosis examination in Kaohsiung Atherosclerosis Longitudinal Study (KALS) between 2006 and 2009 were tested for cognition between 2016 and 2019. The Montreal Cognitive Assessment (MoCA) was used for the cognitive test. Baseline structural atherosclerosis was assessed by carotid intima-media thickness (cIMT) and plaque, whereas functional atherosclerosis was evaluated by carotid stiffness (ß, Ep, and pulse wave velocity). Participants in the top quartile of cIMT and those with plaques were considered to have advanced structural atherosclerosis, whereas participants with all three stiffness parameters in the top quartile were defined to have advanced functional atherosclerosis. RESULTS: The mean participant age at baseline was 53.88 ± 8.37 years. Each case of advanced structural atherosclerosis and advanced functional atherosclerosis was associated with low 10-year MoCA scores with p < 0.001 and p = 0.03, respectively. An interaction effect was observed between structural and functional atherosclerosis on the MoCA score 10 years later (p = 0.02). Participants with both advanced structural and functional markers showed a marked impact on future cognitive function, especially executive and language domains. CONCLUSION: Carotid atherosclerosis in middle-aged individuals can predict their cognitive function in 10 years. Integrated information regarding both arterial wall and stiffness could help improve the predictive power for cognitive decline.

miR-195 reduces age-related blood-brain barrier leakage caused by thrombospondin-1-mediated selective autophagy.

Blood-brain barrier (BBB) disruption contributes to neurodegenerative diseases. Loss of tight junction (TJ) proteins in cerebral endothelial cells (ECs) is a leading cause of BBB breakdown. We recently reported that miR-195 provides vasoprotection, which urges us to explore the role of miR-195 in BBB integrity. Here, we found cerebral miR-195 levels decreased with age, and BBB leakage was significantly increased in miR-195 knockout mice. Furthermore, exosomes from miR-195-enriched astrocytes increased endothelial TJ proteins and improved BBB integrity. To decipher how miR-195 promoted BBB integrity, we first demonstrated that TJ proteins were metabolized via autophagic-lysosomal pathway and the autophagic adaptor p62 was necessary to promote TJ protein degradation in cerebral ECs. Next, proteomic analysis of exosomes revealed miR-195-suppressed thrombospondin-1 (TSP1) as a major contributor to BBB disruption. Moreover, TSP1 was demonstrated to activate selective autophagy of TJ proteins by increasing the formation of claudin-5-p62 and ZO1-p62 complexes in cerebral ECs while TSP1 impaired general autophagy. Delivering TSP1 antibody into the circulation showed dose-dependent reduction of BBB leakage by 20%-40% in 25-month-old mice. Intravenous or intracerebroventricular injection of miR-195 rescued TSP1-induced BBB leakage. Dementia patients with BBB damage had higher levels of serum TSP1 compared to those without BBB damage (p = 0.0015), while the normal subjects had the lowest TSP1 (p < 0.0001). Taken together, the study implies that TSP1-regulated selective autophagy facilitates the degradation of TJ proteins and weakens BBB integrity. An adequate level of miR-195 can suppress the autophagy-lysosome pathway via a reduction of TSP1, which may be important for maintaining BBB function.

Activation of acid-sensing ion channel 3 by lysophosphatidylcholine 16:0 mediates psychological stress-induced fibromyalgia-like pain.

OBJECTIVES: Fibromyalgia is commonly considered a stress-related chronic pain disorder, and daily stressors are known triggers. However, the relation between stress and pain development remains poorly defined by clinical approaches. Also, the aetiology remains largely unknown. METHODS: We used a newly developed mouse model and lipidomic approaches to probe the causation and explore the biological plausibility for how perceived stress translates into chronic non-inflammatory pain. Clinical and lipidomic investigations of fibromyalgia were conducted for human validation. RESULTS: Using non-painful sound stimuli as psychological stressors, we demonstrated that mice developed long-lasting non-inflammatory hyperalgesia after repeated and intermittent sound stress exposure. Elevated serum malondialdehyde level in stressed mice indicated excessive oxidative stress and lipid oxidative damage. Lipidomics revealed upregulation of lysophosphatidylcholine 16:0 (LPC16:0), a product of lipid oxidisation, in stressed mice. Intramuscular LPC16:0 injection triggered nociceptive responses and a hyperalgesic priming-like effect that caused long-lasting hypersensitivity. Pharmacological or genetic inhibition of acid-sensing ion channel 3 impeded the development of LPC16:0-induced chronic hyperalgesia. Darapladib and antioxidants could effectively alleviate the stress-induced hyperalgesia by inhibiting LPC16:0 synthesis. Clinical investigations showed that excessive oxidative stress and LPC16:0 expression also exist in patients with fibromyalgia. Moreover, LPC16:0 expression was correlated with pain symptoms in patients with high oxidative stress and disease severity. CONCLUSIONS: Our study provides experimental evidence for the causal effect of psychological stressors on chronic pain development. The findings identify a possible pathophysiological mechanism of stress-induced chronic non-inflammatory pain at molecular, behavioural and clinical levels that might indicate a new therapeutic approach for fibromyalgia.

Treatment experience of Taiwanese patients with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase myopathy.

Immune-mediated necrotizing myopathy (IMNM) has emerged as a new subgroup of idiopathic inflammatory myopathy in the past decade, associated with the presence of two autoantibodies against signal recognition particle and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). We aim to analyze the clinical, pathological, and imaging phenotypes of the patients with anti-HMGCR myopathy in our cohort. Five patients with anti-HMGCR myopathy have been enrolled who were all female; three were pediatric and two were adult patients. The muscle pathology of patients met the diagnostic criteria of IMNM. On muscle magnetic resonance imaging, adductors were earliest affected while lower legs were relatively preserved with highest degree of involvement in medial head of gastrocnemius. In upper extremities, biceps brachii was the most severely involved, followed by triceps. All patients were refractory to steroid mono-therapy. For pediatric patients, all three patients eventually became responsive to steroid with either intravenous immunoglobulin or rituximab despite variable motor function recovered at present due to different intervention timing. For adult patients, one with statin exposure responded well to steroid and azathioprine use and the motor function returned to the baseline. The other adult patient finally got stabilized and slowly improved with steroid and methotrexate 13 years after the start of therapy. The creatine kinase (CK) levels of all patients were decreased along with clinical severity. In conclusion, muscle imaging might be of help for the diagnosis. Treatment with immuno-suppressants could be considered together with steroid from the beginning.

Multidiscipline Stroke Post-Acute Care Transfer System: Propensity-Score-Based Comparison of Functional Status.

Few studies have investigated the characteristics of stroke inpatients after post-acute care (PAC) rehabilitation, and few studies have applied propensity score matching (PSM) in a natural experimental design to examine the longitudinal impacts of a medical referral system on functional status. This study coupled a natural experimental design with PSM to assess the impact of a medical referral system in stroke patients and to examine the longitudinal effects of the system on functional status. The intervention was a hospital-based, function oriented, 12-week to 1-year rehabilitative PAC intervention for patients with cerebrovascular diseases. The average duration of PAC in the intra-hospital transfer group (31.52 days) was significantly shorter than that in the inter-hospital transfer group (37.1 days) (p < 0.001). The intra-hospital transfer group also had better functional outcomes. The training effect was larger in patients with moderate disability (Modified Rankin Scale, MRS = 3) and moderately severe disability (MRS = 4) compared to patients with slight disability (MRS = 2). Intensive post-stroke rehabilitative care delivered by per-diem payment is effective in terms of improving functional status. To construct a vertically integrated medical system, strengthening the qualified local hospitals with PAC wards, accelerating the inter-hospital transfer, and offering sufficient intensive rehabilitative PAC days are the most essential requirements.