Combined clinical, structural, and cellular studies discriminate pathogenic and benign TRPV4 variants.

Dominant mutations in the calcium-permeable ion channel TRPV4 (transient receptor potential vanilloid 4) cause diverse and largely distinct channelopathies, including inherited forms of neuromuscular disease, skeletal dysplasias, and arthropathy. Pathogenic TRPV4 mutations cause gain of ion channel function and toxicity that can be rescued by small molecule TRPV4 antagonists in cellular and animal models, suggesting that TRPV4 antagonism could be therapeutic for patients. Numerous variants in TRPV4 have been detected with targeted and whole exome/genome sequencing, but for the vast majority, their pathogenicity remains unclear. Here, we used a combination of clinical information and experimental structure-function analyses to evaluate 30 TRPV4 variants across various functional protein domains. We report clinical features of seven patients with TRPV4 variants of unknown significance and provide extensive functional characterization of these and an additional 17 variants, including structural position, ion channel function, subcellular localization, expression level, cytotoxicity, and protein-protein interactions. We find that gain-of-function mutations within the TRPV4 intracellular ankyrin repeat domain target charged amino acid residues important for RhoA interaction, whereas ankyrin repeat domain residues outside of the RhoA interface have normal or reduced ion channel activity. We further identify a cluster of gain-of-function variants within the intracellular intrinsically disordered region that may cause toxicity via altered interactions with membrane lipids. In contrast, assessed variants in the transmembrane domain and other regions of the intrinsically disordered region do not cause gain of function and are likely benign. Clinical features associated with gain of function and cytotoxicity include congenital onset of disease, vocal cord weakness, and motor predominant disease, whereas patients with likely benign variants often demonstrated late-onset and sensory-predominant disease. These results provide a framework for assessing additional TRPV4 variants with respect to likely pathogenicity, which will yield critical information to inform patient selection for future clinical trials for TRPV4 channelopathies.

Virtual Multidisciplinary Stroke Care Clinic for Community-Dwelling Stroke Survivors: A Randomized Controlled Trial.

BACKGROUND: Stroke survivors constantly feel helpless and unprepared after discharge from hospitals. More flexible and pragmatic support are needed for their optimized recovery. We examined the effects of a virtual multidisciplinary stroke care clinic on survivors' health and self-management outcomes. METHODS: A randomized controlled trial was conducted. Survivors were recruited from 10 hospitals and randomized at 1:1 ratio into the intervention or the control groups. Intervention group participants received the Virtual Multidisciplinary Stroke Care Clinic service (monthly online consultations with a nurse, follow-up phone calls, and access to an online platform). Control group participants received the usual care. Outcomes of self-efficacy (stroke self-efficacy questionnaire; primary), self-management behaviors (Stroke Self-Management Behaviors Performance Scale), social participation (reintegration to normal living index), and depression (Geriatric Depression Scale; secondary) were measured at baseline, and 3 and 6 months after commencing the intervention (post-randomization). A generalized estimating equations model was used to compare the differential changes in outcomes at 3 and 6 months with respect to baseline between 2 groups. RESULTS: Between July 2019 and June 2022, 335 eligible participants were enrolled in the study. Participants (intervention group; n=166) showed significantly greater improvements in outcomes of self-efficacy (group-by-time interaction regression coefficient, B=4.60 [95% CI, 0.16 to 9.05]), social participation (B=5.07 [95% CI, 0.61 to 9.53]), and depression (B=-2.33 [95% CI, -4.06 to -0.61]), and no significant improvement in performance of self-management behaviors (B=3.45, [95% CI, -0.87 to 7.77]), compared with the control group (n=169) right after the intervention (6 months after its commencement). Hedges' g effect sizes of the intervention on outcomes: 0.19 to 0.36. CONCLUSIONS: The results provide some positive evidence on the usefulness of the Virtual Multidisciplinary Stroke Care Clinic service. The effect sizes are regarded as small to medium, which may not be of clinical relevance. The baseline levels in outcomes were in favor of the control group, the intervention effects might be overestimated. The service must be tested further to determine its effectiveness. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1800016101.

Messenger RNA Coronavirus Disease 2019 (COVID-19) Vaccination With BNT162b2 Increased Risk of Bell's Palsy: A Nested Case-Control and Self-Controlled Case Series Study.

BACKGROUND: Observable symptoms of Bell's palsy following vaccinations arouse concern over the safety profiles of novel coronavirus disease 2019 (COVID-19) vaccines. However, there are only inconclusive findings on Bell's palsy following messenger (mRNA) COVID-19 vaccination. This study aims to update the previous analyses on the risk of Bell's palsy following mRNA (BNT162b2) COVID-19 vaccination. METHODS: This study included cases aged ≥16 years with a new diagnosis of Bell's palsy within 28 days after BNT162b2 vaccinations from the population-based electronic health records in Hong Kong. Nested case-control and self-controlled case series (SCCS) analyses were used, where the association between Bell's palsy and BNT162b2 was evaluated using conditional logistic and Poisson regression, respectively. RESULTS: Totally 54 individuals were newly diagnosed with Bell's palsy after BNT162b2 vaccinations. The incidence of Bell's palsy was 1.58 (95% confidence interval [CI], 1.19-2.07) per 100 000 doses administered. The nested case-control analysis showed significant association between BNT162b2 vaccinations and Bell's palsy (adjusted odds ratio [aOR], 1.543; 95% CI, 1.123-2.121), with up to 1.112 excess events per 100 000 people who received 2 doses of BNT162b2. An increased risk of Bell's palsy was observed during the first 14 days after the second dose of BNT162b2 in both nested case-control (aOR, 2.325; 95% CI, 1.414-3.821) and SCCS analysis (adjusted incidence rate ratio, 2.44; 95% CI, 1.32-4.50). CONCLUSIONS: There was an overall increased risk of Bell's palsy following BNT162b2 vaccination, particularly within the first 14 days after the second dose, but the absolute risk was very low.

Bruton's tyrosine kinase-bearing B cells and microglia in neuromyelitis optica spectrum disorder.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory autoimmune disease of the central nervous system that involves B-cell receptor signaling as well as astrocyte-microglia interaction, which both contribute to evolution of NMOSD lesions. MAIN BODY: Through transcriptomic and flow cytometry analyses, we found that Bruton's tyrosine kinase (BTK), a crucial protein of B-cell receptor was upregulated both in the blood and cerebrospinal fluid of NMOSD patients. Blockade of BTK with zanubrutinib, a highly specific BTK inhibitor, mitigated the activation and maturation of B cells and reduced production of causal aquaporin-4 (AQP4) autoantibodies. In a mouse model of NMO, we found that both BTK and pBTK expression were significantly increased in microglia. Transmission electron microscope scan demonstrated that BTK inhibitor ameliorated demyelination, edema, and axonal injury in NMO mice. In the same mice colocalization of GFAP and Iba-1 immunofluorescence indicated a noticeable increase of astrocytes-microglia interaction, which was alleviated by zanubrutinib. The smart-seq analysis demonstrated that treatment with BTK inhibitor instigated microglial transcriptome changes including downregulation of chemokine-related genes and genes involved in the top 5 biological processes related to cell adhesion and migration, which are likely responsible for the reduced crosstalk of microglia and astrocytes. CONCLUSIONS: Our results show that BTK activity is enhanced both in B cells and microglia and BTK inhibition contributes to the amelioration of NMOSD pathology. These data collectively reveal the mechanism of action of BTK inhibition and corroborate BTK as a viable therapeutic target.

Acupuncture for post-stroke depression: a systematic review and network meta-analysis.

BACKGROUND: Patients with post-stroke depression (PSD) usually experience anxiety, hopelessness, and insomnia, which have a negative impact on their daily activities and post-stroke rehabilitation. Acupuncture (AC), as a minimally invasive technique, has become a popular choice for improving depression symptoms. However, it is still unclear which therapy is associated with the best outcomes for PSD. In this review, we aimed to explore the impact of AC in alleviating symptoms of PSD and to evaluate the difference in effectiveness between AC combined with pharmacotherapies and various non-pharmacotherapies. METHODS: Six databases and three clinical trials registration platforms were searched from inception to March 2023. Randomized clinical trial comparing needle-based AC with pharmacotherapy, and other non-pharmacotherapy or invalid group were included. Two independent reviewers identified eligible studies, and collected data using a pre-made form. A Bayesian network meta-analysis was conducted to assess and compare different techniques using RStudio 3.6.0 with the package 'GEMTC' V.0.8.1. The primary outcome was the efficacy for PSD assessed by scales measuring depressive symptoms. The secondary outcomes were effectiveness for neurological function and the quality of life. The ranking probabilities for all treatment interventions was performed using the Surface Under the Cumulative Ranking curve (SUCRA). The risk of bias was assessed by using the Revised Cochrane Risk of Bias tool 2. RESULTS: Sixty-two studies, involving 5308 participants published from 2003 to 2022, were included. The results showed that compared with western medicine (WM) (defined as pharmacotherapy for PSD), AC alone or with repetitive transcranial magnetic stimulation (RTMS), Traditional Chinese medicine (TCM) alone or with WM, were superior for alleviating depression symptoms. Compared to Usual Care, AC alone or plus other therapies could significantly decrease scores on the Hamilton Depression Rating scale. According to result of SUCRA, AC plus RTMS had the highest probability of improving depressive symptoms with a probability of 49.43%. CONCLUSIONS: The results of this study indicate that AC alone or combined with other therapies appears to be effective in improving depression symptoms of stroke survivors. Moreover, in comparison to WM, AC alone or plus RTMS, TCM, TCM with WM, or WM, were more effective in improving depression symptoms of PSD. Also, AC with RTMS seems to be the most effective with the highest probability. REGISTRATION: This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database in November 2020 and updated in July 2021. The registration number is CRD42020218752.

Comparing machine learning-derived MRI-based and blood-based neurodegeneration biomarkers in predicting syndromal conversion in early AD.

INTRODUCTION: We compared the machine learning-derived, MRI-based Alzheimer's disease (AD) resemblance atrophy index (AD-RAI) with plasma neurofilament light chain (NfL) level in predicting conversion of early AD among cognitively unimpaired (CU) and mild cognitive impairment (MCI) subjects. METHODS: We recruited participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) who had the following data: clinical features (age, gender, education, Montreal Cognitive Assessment [MoCA]), structural MRI, plasma biomarkers (p-tau181 , NfL), cerebrospinal fluid biomarkers (CSF) (Aß42, p-tau181 ), and apolipoprotein E (APOE) ε4 genotype. We defined AD using CSF Aß42 (A+) and p-tau181 (T+). We defined conversion (C+) if a subject progressed to the next syndromal stage within 4 years. RESULTS: Of 589 participants, 96 (16.3%) were A+T+C+. AD-RAI performed better than plasma NfL when added on top of clinical features, plasma p-tau181 , and APOE ε4 genotype (area under the curve [AUC] = 0.832 vs. AUC = 0.650 among CU, AUC = 0.853 vs. AUC = 0.805 among MCI) in predicting A+T+C+. DISCUSSION: AD-RAI outperformed plasma NfL in predicting syndromal conversion of early AD. HIGHLIGHTS: AD-RAI outperformed plasma NfL in predicting syndromal conversion among early AD. AD-RAI showed better metrics than volumetric hippocampal measures in predicting syndromal conversion. Combining clinical features, plasma p-tau181 and apolipoprotein E (APOE) with AD-RAI is the best model for predicting syndromal conversion.

User Engagement on a Novel Educational Health Intervention Aimed at Increasing HPV Vaccine Uptake in Hong Kong: a Qualitative Study.

HPV vaccine uptake rates are suboptimal in Hong Kong. A multi-disciplinary school-based HPV health-promotion programme (MDL-SHPVP) aimed at raising HPV knowledge levels and increasing vaccine uptake has therefore been developed to address vaccine hesitancy. This qualitative study was conducted to collect user feedback and identify the strengths and limitations of the educational resources developed for the programme among key vaccination stakeholders including adolescent girls and their mothers. Twenty-six participants including eight mother-daughter dyads, four teachers, three social workers, two school principals and one school nurse were recruited. To cater to the diverse audience, ten educational videos, three animations, a digital game and one booklet were developed for the programme and distributed to the participants for viewing. Semi-structured interviews were then conducted to collect feedback on the acceptability and effectiveness of the resources. Interviews were audio-recorded, transcribed verbatim, and resulting data were thematically analysed. Three themes and six sub-themes emerged. The educational materials were well-received and effective in raising HPV-knowledge levels, generating confidence in vaccine safety and effectiveness, and boosting vaccination intention. Some doubts regarding vaccine necessity remained, and recommendations for improving resource presentation and accessibility were provided. Our findings suggest that the MDL-SHPVP has the potential to boost HPV vaccine uptake. Future studies may explore educational interventions which target to increase not only HPV vaccination intention but also the sense of urgency so as to encourage timely vaccination for adolescents at the ideal age. Study findings may also provide directions for the development of future health education interventions.

Multistakeholder knowledge levels and perspectives of human papillomavirus and its vaccination: An exploratory qualitative study.

OBJECTIVE: This qualitative study was an integral part in the development of a multidisciplinary team-led school-based human papillomavirus vaccination health-promotion programme (MDL-SHPVP) aiming to increase HPV vaccine uptake in Hong Kong. Study findings will inform the design of the MDL-SHPVP by drawing on interview data regarding the expectations and needs of key stakeholders and potential programme users. METHODS: Eight mother-daughter dyads, four secondary school teachers, two school principals, three social workers and one school nurse were interviewed. All interviews were audio-recorded and transcribed verbatim for thematic analysis. RESULTS: Most participants had misconceptions about HPV and the vaccine. Alhough there was no immediate perceived need for the vaccination, most participants had favourable attitudes towards HPV inoculation and vaccines in general. Factors affecting vaccine uptake included perceptions about risk of infection, vaccine availability, and cost. Participants were largely open to suggested MDL-SHPVP components (videos, digital game, and group discussions). CONCLUSION: Findings have highlighted knowledge gaps among potential users and key stakeholders and will be used to inform the design of the MDL-SHPVP to ensure that their needs and expectations are addressed. Study findings may also aid future HPV vaccine promotion efforts and boost HPV vaccine uptake among youth in the city.

Plaque morphology in acute symptomatic intracranial atherosclerotic disease.

BACKGROUND: Intracranial atherosclerotic disease (ICAD) is globally a major ischaemic stroke subtype with high recurrence. Understanding the morphology of symptomatic ICAD plaques, largely unknown by far, may help identify vulnerable lesions prone to relapse. METHODS: We prospectively recruited patients with acute ischaemic stroke or transient ischaemic attack attributed to high-grade ICAD (60%-99% stenosis). Plaque morphological parameters were assessed in three-dimensional rotational angiography, including surface contour, luminal stenosis, plaque length/thickness, upstream shoulder angulation, axial/longitudinal plaque distribution and presence of adjoining branch atheromatous disease (BAD). We compared morphological features of smooth, irregular and ulcerative plaques and correlated them with cerebral ischaemic lesion load downstream in MRI. RESULTS: Among 180 recruited patients (median age=60 years; 63.3% male; median stenosis=75%), plaque contour was smooth (51 (28.3%)), irregular (101 (56.1%)) or ulcerative (28 (15.6%)). Surface ulcers were mostly at proximal (46.4%) and middle one-third (35.7%) of the lesions. Most (84.4%) plaques were eccentric, and half had their maximum thickness over the distal end. Ulcerative lesions were thicker (medians 1.6 vs 1.3 mm; p=0.003), had steeper upstream shoulder angulation (56.2° vs 31.0°; p<0.001) and more adjoining BAD (83.3% vs 57.0%; p=0.033) than non-ulcerative plaques. Ulcerative plaques were significantly associated with coexisting acute and chronic infarcts downstream (35.7% vs 12.5%; adjusted OR 4.29, 95% CI 1.65 to 11.14, p=0.003). Sensitivity analyses in patients with anterior-circulation ICAD lesions showed similar results in the associations between the plaque types and infarct load. CONCLUSIONS: Ulcerative intracranial atherosclerotic plaques were associated with vulnerable morphological features and had a higher cumulative infarct load downstream.

Fostering gerontology students' competence in Interprofessional collaborative practice.

BACKGROUND: Interprofessional collaborative practice (IPCP) is increasingly recognised as being crucial for the provision of holistic care and optimising health outcomes among older adults, many with multiple complex health problems. However, little is known about the challenges of facilitating this in practice. Therefore, this study explores these issues from the perspective of different healthcare professionals and how this might inform interprofessional education curricula. METHODS: Sixteen different healthcare professionals working in a variety of aged care (acute, rehabilitative and community) settings were invited to participate in individual semi-structured in-depth interviews designed to: (i) explore the meaning of IPCP; (ii) explore the facilitators of and barriers to IPCP; and (iii) examine the opportunities and challenges in interprofessional gerontological education. All interviews were tape-recorded and transcribed verbatim with thematic analysis conducted by two independent researchers. RESULTS: Three major themes emerged from the interviews: the need for IPCP; role preparedness, scope and liability; and strategies for interprofessional education. Respondents shared a common belief that IPCP improves the quality of life of older adults in both hospital and community settings by improving person-centred coordinated care and decision making in care planning. However, respondents perceived major barriers to IPCP to be lack of knowledge about healthcare professionals' scope of practice, lack of training in interprofessional collaboration, professional culture and stereotypes, and liability issues. Suggested approaches to overcome these barriers included innovative teaching and learning approaches, engaging students early on in the curriculum of health professional degree programmes, and enhancing collaborative effective communication in health and social care settings. CONCLUSIONS: It is anticipated that these findings will be used to inform the development of a new interprofessional gerontological education curriculum that aims to enhance students' competence in IPCP.

Topological Semimetals in the SnTe Material Class: Nodal Lines and Weyl Points.

We theoretically show that IV-VI semiconducting compounds with low-temperature rhombohedral crystal structure represent a new potential platform for topological semimetals. By means of minimal k·p models, we find that the two-step structural symmetry reduction of the high-temperature rocksalt crystal structure, comprising a rhombohedral distortion along the [111] direction followed by a relative shift of the cation and anion sublattices, gives rise to topologically protected Weyl semimetal and nodal line semimetal phases. We derive general expressions for the nodal features and apply our results to SnTe, showing explicitly how Weyl points and nodal lines emerge in this system. Experimentally, the topological semimetals could potentially be realized in the low-temperature ferroelectric phase of SnTe, GeTe, and related alloys.

Topological Phases without Crystalline Counterparts.

We construct a two-dimensional higher-order topological phase protected by a quasicrystalline eightfold rotation symmetry. Our tight-binding model describes a superconductor on the Ammann-Beenker tiling hosting localized Majorana zero modes at the corners of an octagonal sample. In order to analyze this model, we introduce Hamiltonians generated by a local rule, and use this concept to identify the bulk topological properties. We find a Z_{2} bulk topological invariant protecting the corner modes. Our work establishes that there exist topological phases protected by symmetries impossible in a crystal.

Relapsing optic neuritis and meningoencephalitis in a child: case report of delayed diagnosis of MOG-IgG syndrome.

BACKGROUND: Recurrent optic neuritis (ON) was previously thought to be associated with multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). Meningoencephalitis has recently been suggested to be a clinical finding typical of myelin oligodendrocyte glycoprotein (MOG) encephalomyelitis. We report a Chinese patient with recurrent ON at disease initiation, who had a delayed diagnosis of MOG-IgG syndrome, until recurrent meningoencephalitis appeared and serum MOG-IgG was detected. CASE PRESENTATION: From the age of 7 years, an AQP4-IgG negative female patient had 10 disease recurrences, including 4 episodes of recurrent ON, 4 episodes of fever and meningoencephalitis, and 2 episodes of ON as well as meningoencephalitis. She was initially diagnosed as recurrent ON and treated with glucocorticoids followed by gradual tapering when ON reoccurred. Later, she was diagnosed as central nervous system infection when fever and meningoencephalitis appeared, and antiviral drugs and glucocorticoids were used. However, when she returned to our department for follow-up on July 2017, the results of serum demyelinating autoimmune antibody revealed positive MOG-IgG (titer 1:320 by an in-house, cell-based assay using live cells transfected with full-length human MOG). A diagnosis of MOG-IgG syndrome was established. CONCLUSIONS: Testing for MOG-IgG in atypical MS and NMOSD patients, and patients with meningoencephalitis with a history of relapsing demyelinating symptoms is warranted.

Physical activities attenuate the negative cognitive impact from white matter hyperintensities in stroke and TIA patients with low education.

BACKGROUND: The objective of this study is to examine the effects of recent regular participation leisure activities upon cognitive functions between 3 and 6 months after stroke or transient ischemic attack (TIA). We also explored whether the cognitive effects interacted with the severity of white matter hyperintensities (WMH), a marker of cerebral white matter disease, in patients with low or high education. METHODS: Two-hundred and ninety-two subjects with mean age of 66.1 (11.0) years were recruited at median 161(131-180) days post index event. WMH volume was evaluated using a semi-automated method on MRI brain. Cognitive functions were measured using the Montreal Cognitive Assessment (MoCA). Multivariable linear regression analysis was conducted to explore the associations between leisure activity participation with WMH and the moderating effects of leisure activities upon relationship between WMH and MoCA. Analyses were further stratified by low (<6 years) or high education (≥6 years). All models were adjusted with age, sex, and years of education. RESULTS: Physical activity (PA), but not intellectual activity (IA), was negatively related to WMH volume (P < .05). IA exerted a main effect on MoCA performance (b = 3.21, P < .001). PA, but not IA, significantly interacted with WMH volume (b = -0.18, P < .01) on MoCA performance, but the interaction was only significant in the lower education group (b = 0.28, P < .01) but not in the higher education group. CONCLUSIONS: In patients with stroke/TIA, IA confers general cognitive benefits. Regular participation in PA negatively correlated with WMH volume. In patients with low education, PA increases resilience against vascular cognitive impairment.

Mapping the contribution and strategic distribution patterns of neuroimaging features of small vessel disease in poststroke cognitive impairment.

OBJECTIVES: Individual neuroimaging features of small vessel disease (SVD) have been reported to influence poststroke cognition. This study aimed to investigate the joint contribution and strategic distribution patterns of multiple types of SVD imaging features in poststroke cognitive impairment. METHODS: We studied 145 first-ever ischaemic stroke patients with MRI and Montreal Cognitive Assessment (MoCA) examined at baseline. The local burdens of acute ischaemic lesion (AIL), white matter hyperintensity, lacune, enlarged perivascular space and cross-sectional atrophy were quantified and entered into support vector regression (SVR) models to associate with the global and domain scores of MoCA. The SVR models were optimised with feature selection through 10-fold cross-validations. The contribution of SVD features to MoCA scores was measured by the prediction accuracy in the corresponding SVR model after optimisation. RESULTS: The combination of the neuroimaging features of SVD contributed much more to the MoCA deficits on top of AILs compared with individual SVD features, and the cognitive impact of different individual SVD features was generally similar. As identified by the optimal SVR models, the important SVD-affected regions were mainly located in the basal ganglia and white matter around it, although the specific regions varied for MoCA and its domains. CONCLUSIONS: Multiple types of SVD neuroimaging features jointly had a significant impact on global and domain cognitive functionings after stroke on top of AILs. The map of strategic cognitive-relevant regions of SVD features may help clinicians to understand their complementary impact on poststroke cognition.

Risk factors associated with 31-day unplanned readmission in 50,912 discharged patients after stroke in China.

BACKGROUND: Unplanned readmission within 31 days of discharge after stroke is a useful indicator for monitoring quality of hospital care. We evaluated the risk factors associated with 31-day unplanned readmission of stroke patients in China. METHODS: We identified 50,912 patients from 375 hospitals in 29 provinces, municipalities or autonomous districts across China who experienced an unplanned readmission after stroke between 2015 and 2016, and extracted data from the inpatients' cover sheet data from the Medical Record Monitoring Database. Patients were grouped into readmission within 31 days or beyond for analysis. Chi-squared test was used to analyze demographic information, health system and clinical process-related factors according to the data type. Multilevel logistic modeling was used to examine the effects of patient (level 1) and hospital (level 2) characteristics on an unplanned readmission ≤31 days. RESULTS: Among 50,912 patients, 14,664 (28.8%) were readmitted within 31 days after discharge. The commonest cause of readmissions were recurrent stroke (34.8%), hypertension (22.94%), cardio/cerebrovascular disease (13.26%) and diabetes/diabetic complications (7.34%). Higher risks of unplanned readmissions were associated with diabetes (OR = 1.089, P = 0.001), use of clinical pathways (OR = 1.174, P < 0.001), and being discharged without doctor's advice (OR = 1.485, P < 0.001). Lower risks were associated with basic medical insurances (OR ranging from 0.225 to 0.716, P < 0.001) and commercial medical insurance (OR = 0.636, P = 0.021), compared to self-paying for medical services. And patients aged 50 years old and above (OR ranging from 0.650 to 0.985, P < 0.05), with haemorrhagic stroke (OR = 0.467, P < 0.001), with length of stay more than 7 days in hospital (OR ranging from 0.082 to 0.566, P < 0.001), also had lower risks. CONCLUSIONS: Age, type of stroke, medical insurance status, type of discharge, use of clinical pathways, length of hospital stay and comorbidities were the most influential factors for readmission within 31 days.

Converting MMSE to MoCA and MoCA 5-minute protocol in an educationally heterogeneous sample with stroke or transient ischemic attack.

BACKGROUND: The Montreal Cognitive Assessment (MoCA) is psychometrically superior over the Mini-mental State Examination (MMSE) for cognitive screening in stroke or transient ischemic attack (TIA). It is free for clinical and research use. The objective of this study is to convert scores from the MMSE to MoCA and MoCA-5-minute protocol (MoCA-5 min) and to examine the ability of the converted scores in detecting cognitive impairment after stroke or TIA. METHODS: A total of 904 patients were randomly divided into training (n = 623) and validation (n = 281) samples matched for demography and cognition. MMSE scores were converted to MoCA and MoCA-5 min using (1) equipercentile method with log-linear smoothing and (2) Poisson regression adjusting for age and education. Receiver operating characteristics curve analysis was used to examine the ability of the converted scores in differentiating patients with cognitive impairment. RESULTS: The mean education was 5.8 (SD = 4.6; ranged 0-20) years. The entire spectrum of MMSE scores was converted to MoCA and MoCA-5 min using equipercentile method. Relationship between MMSE and MoCA scores was confounded by age and education, and a conversion equation with adjustment for age and education was derived. In the validation sample, the converted scores differentiated cognitively impaired patients with area under receiver operating characteristics curve 0.826 to 0.859. CONCLUSION: We provided 2 methods to convert scores from the MMSE to MoCA and MoCA-5 min based on a large sample of patients with stroke or TIA having a wide range of education and cognitive levels. The converted scores differentiated patients with cognitive impairment after stroke or TIA with high accuracy.

Generic Coexistence of Fermi Arcs and Dirac Cones on the Surface of Time-Reversal Invariant Weyl Semimetals.

The hallmark of Weyl semimetals is the existence of open constant-energy contours on their surface-the so-called Fermi arcs-connecting Weyl points. Here, we show that, for time-reversal symmetric realizations of Weyl semimetals, these Fermi arcs, in many cases, coexist with closed Fermi pockets originating from surface Dirac cones pinned to time-reversal invariant momenta. The existence of Fermi pockets is required for certain Fermi-arc connectivities due to additional restrictions imposed by the six Z_{2} topological invariants characterizing a generic time-reversal invariant Weyl semimetal. We show that a change of the Fermi-arc connectivity generally leads to a different topology of the surface Fermi surface and identify the half-Heusler compound LaPtBi under in-plane compressive strain as a material that realizes this surface Lifshitz transition. We also discuss universal features of this coexistence in quasiparticle interference spectra.

Platelets Play Differential Role During the Initiation and Progression of Autoimmune Neuroinflammation.

RATIONALE: Platelets are known to participate in vascular pathologies; however, their role in neuroinflammatory diseases, such as multiple sclerosis (MS), is unknown. Autoimmune CD4 T cells have been the main focus of studies of MS, although the factors that regulate T-cell differentiation toward pathogenic T helper-1/T helper-17 phenotypes are not completely understood. OBJECTIVE: We investigated the role of platelets in the modulation of CD4 T-cell functions in patients with MS and in mice with experimental autoimmune encephalitis, an animal model for MS. METHODS AND RESULTS: We found that early in MS and experimental autoimmune encephalitis, platelets degranulated and produced soluble factors serotonin (5-hydroxytryptamine), platelet factor 4, and platelet-activating factor, which specifically stimulated differentiation of T cells toward pathogenic T helper-1, T helper-17, and interferon-γ/interleukin-17-producing CD4 T cells. At the later stages of MS and experimental autoimmune encephalitis, platelets became exhausted in their ability to produce proinflammatory factors and stimulate CD4 T cells but substantially increased their ability to form aggregates with CD4 T cells. Formation of platelet-CD4 T-cell aggregates involved the interaction of CD62P on activated platelets with adhesion molecule CD166 on activated CD4 T cells, contributing to downmodulation of CD4 T-cell activation, proliferation, and production of interferon-γ. Blocking of formation of platelet-CD4 T-cell aggregates during progression of experimental autoimmune encephalitis substantially enhanced proliferation of CD4 T cells in the central nervous system and the periphery leading to exacerbation of the disease. CONCLUSION: Our study indicates differential roles for platelets in the regulation of functions of pathogenic CD4 T cells during initiation and progression of central nervous system autoimmune inflammation.