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Background A technologically integrated, multidisciplinary approach to stroke rehabilitation service was delivered and embedded into conventional health care practice. This article reports an evaluation of cost‐effectiveness analysis of a new Virtual Multidisciplinary Stroke Care Clinic (VMSCC) service for community‐dwelling survivors of stroke. Methods and Results A randomized controlled trial was conducted. Adults with a first/recurrent ischemic/hemorrhagic stroke were recruited from 10 hospitals. Eligible participants were randomly assigned to receive the VMSCC service (individual virtual consultations with a registered nurse, home blood pressure telemonitoring, and unlimited access to an online resource platform) plus usual care or usual care alone. Cost‐effectiveness analyses were performed based on incremental cost‐effectiveness ratios expressed as incremental cost per emergency admission reduced, and day of hospitalization reduced over the study period. A total of 256 participants (intervention group n=141 versus control group n=115) with complete cost and health care use data were included in the cost‐effectiveness analyses. The VMSCC service, on average, resulted in a greater reduction in the number of emergency admission (−0.06 [95% bootstrapped CI, −0.14 to 0.01]) and fewer days of hospitalization (−0.08, [95% bootstrapped CI −0.40 to 0.24]) but incurred a higher total cost of HK$375 (95% bootstrapped CI, −2103 to 2743) compared with the usual care. The incremental cost‐effectiveness ratios of the VMSCC service compared with the usual care were HK$6070 and HK$4826 per an emergency admission and a day of hospital stay reduced respectively. Conclusions The study provides preliminary but not confirmative evidence that the VMSCC service could be more effective but more costly than usual care in reducing health service use. Registration URL: https://www.chictr.org.cn. Unique identifier: ChiCTR1800016101.

Despite the advancements in the treatment of localized pancreatic cancer, several unresolved issues persist in clinical practice, especially in the neoadjuvant setting. These include determining the criteria for selecting patients for treatment, identifying the most effective chemotherapy regimens, understanding the role of radiotherapy, and accurately assessing how patients respond to treatment. Current strategies for assessing patients before surgery involve thoroughly evaluating their overall health status, analyzing tumor markers, and using advanced imaging techniques. However, existing methods for staging the disease still have limitations when it comes to accurately detecting metastatic cancer. The ongoing debate between performing surgery upfront or administering neoadjuvant therapy highlights the need for robust clinical evidence to guide treatment decisions effectively. This review analyzes the evidence regarding controversial topics in neoadjuvant pancreatic cancer treatment and discusses further research efforts to enhance patient outcomes. To improve the outcomes found with surgery alone, multimodal treatment with chemotherapy.

Abstract Background This trial explores SM‐88 used with methoxsalen, phenytoin, and sirolimus (MPS) in pretreated metastatic pancreatic ductal adenocarcinoma (mPDAC) Methods Forty‐nine patients were randomized to daily 460 or 920 mg oral SM‐88 with MPS (SM‐88 Regimen). The primary endpoint was objective response rate (RECIST 1.1). Results Thirty‐seven patients completed ≥ one cycle of SM‐88 Regimen (response evaluable population). Disease control rate (DCR), overall survival (OS), and progression‐free survival (PFS) did not differ significantly between dose levels. Stable disease was achieved in 9/37 patients (DCR, 24.3%); there were no complete or partial responses. Quality‐of‐life (QOL) was maintained and trended in favor of 920 mg. SM‐88 Regimen was well tolerated; a single patient (1/49) had related grade 3 and 4 adverse events, which later resolved. In the intention‐to‐treat population of 49 patients, the median overall survival (mOS) was 3.4 months (95% CI: 2.7–4.9 months). Those treated in the second line had an mOS of 8.1 months and a median PFS of 3.8 months. Survival was higher for patients with stable versus progressive disease (any line; mOS: 10.6 months vs. 3.9 months; p = 0.01). Conclusions SM‐88 Regimen has a favorable safety profile with encouraging QOL effects, disease control, and survival trends. This regimen should be explored in the second‐line treatment of patients with mPDAC. ClinicalTrials.gov Identifier: NCT03512756.

Abstract Patients with Parkinson’s disease (PD) were described less extraverted and more neurotic. It remained unclear whether similar personality traits could be found in idiopathic rapid eye movement sleep behavior disorder (iRBD), a prodromal stage of PD, and could predict phenoconversion to neurodegenerative disorders. We aimed to investigate the personality profile and its association with future neurodegenerative phenoconversion in iRBD patients. One hundred and eighty-five video-polysomnography confirmed iRBD patients and 91 age- and sex-matched controls underwent personality assessment using the NEO five-factor inventory, and 171 iRBD patients were followed up. Our results showed that iRBD was marginally negatively associated with extraverted personality trait (B = −0.28, 95% confidence interval (CI) = −0.55, −0.001). During a median follow-up of 5.9 years, 47 iRBD patients (27.5%) had phenoconversion. More neurotic (adjusted hazard ratio (HR) = 2.0, 95% CI = 1.3, 3.1) and less extraverted personality traits (adjusted HR = 0.53, 95% CI = 0.36, 0.77) were associated with an increased risk of phenoconversion in iRBD patients. Our findings suggest that personality profile may be a potential prodromal marker of iRBD.

Abstract Age-related white matter lesion (WML) is considered a manifestation of sporadic cerebral small vessel disease and an important pathological substrate for dementia. Asia is notable for its large population with a looming dementia epidemic. Yet, the burden of WML and its associated risk factors across different Asian societies are unknown. Subjects from 9 Asian cities (Bangkok, Bandung, Beijing, Bengaluru, Hong Kong, Kaohsiung, Manila, Seoul, and Singapore) were recruited (n = 5701) and classified into (i) stroke/transient ischemic attack (TIA), (ii) Alzheimer’s disease (AD)/mild cognitive impairment (MCI), or (iii) control groups. Data on vascular risk factors and cognitive performance were collected. The severity of WML was visually rated on MRI or CT. The prevalence of moderate-to-severe WML was the highest in subjects with stroke/TIA (43.3%). Bandung Indonesia showed the highest prevalence of WML, adjusted for age, sex, education, disease groups, and imaging modality. Hypertension and hyperlipidemia were significant risk factors for WML, and WML was negatively associated with MMSE in all groups. WML is highly prevalent in Asia and is associated with increasing age, hypertension, hyperlipidemia, and worse cognitive performance. Concerted efforts to prevent WML will alleviate the huge dementia burden in the rapidly aging Asian societies.

Summary: Background: This study aims to evaluate the association between thromboembolic events and hemorrhagic stroke following BNT162b2 and CoronaVac vaccination. Methods: Patients with incident thromboembolic events or hemorrhagic stroke within 28 days of covid-19 vaccination or SARS-CoV-2 positive test during 23 February to 30 September 2021 were included. The incidence per 100,000 covid-19 vaccine doses administered and SARS-CoV-2 test positive cases were estimated. A modified self-controlled case series (SCCS) analysis using the data from the Hong Kong territory-wide electronic health and vaccination records. Seasonal effect was adjusted by month. Findings: A total of 5,526,547 doses of BNT162b2 and 3,146,741 doses of CoronaVac were administered. A total of 334 and 402 thromboembolic events, and 57 and 49 hemorrhagic stroke cases occurred within 28 days after BNT162b2 and CoronaVac vaccination, respectively. The crude incidence of thromboembolic events and hemorrhagic stroke per 100,000 doses administered for both covid-19 vaccines were smaller than that per 100,000 SARS-CoV-2 test positive cases. The modified SCCS detected an increased risk of hemorrhagic stroke in BNT162b2 14-27 days after first dose with adjusted IRR of 2.53 (95% CI 1.48-4.34), and 0-13 days after second dose with adjusted IRR 2.69 (95% CI 1.54-4.69). No statistically significant risk was observed for thromboembolic events for both vaccines. Interpretation: We detected a possible safety signal for hemorrhagic stroke following BNT162b2 vaccination. The incidence of thromboembolic event or hemorrhagic stroke following vaccination is lower than that among SARS-CoV-2 test positive cases; therefore, vaccination against covid-19 remains an important public health intervention. Funding: This study was funded by a research grant from the Food and Health Bureau, The Government of the Hong Kong Special Administrative Region (reference COVID19F01).

Abstract. Age-related sporadic cerebral small vessel disease (CSVD) has gained increasing attention over the past decades because of its increasing prevalence associated with an aging population. The widespread application of and advances in brain magnetic resonance imaging in recent decades have significantly increased researchers’ understanding in the in vivo evolution of CSVD, its impact upon the brain, its risk factors, and the mechanisms that explain the various clinical manifestation associated with sporadic CSVD. In this review, we aimed to provide an update on the pathophysiology, risk factors, biomarkers, and the determinants and spectrum of the clinical manifestation of sporadic CSVD.

Pancreatic cancer (PC), the third leading cause of cancer-related death in the U.S., is frequently found too late to be cured by traditional chemotherapy. Expression of B7 homolog 6 (B7H6), a member of the B7 family of immunoreceptors, has been found in PC and several other cancers. B7H6 is a ligand for cytotoxicity triggering receptor 3 (NKp30), which is expressed on NK cells. Here, we demonstrate that B7H6 can be detected in PC tissues but not normal organs. Its expression in patients associated significantly with tumor differentiation grade and lymphatic metastasis. The soluble form of B7H6 was detected in the PC patients’ sera, and its concentration associated with tumor differentiation grade and tumor, node, metastasis (TNM) stages. Also, higher levels of B7H6 in PC patients’ malignant tissues or serum correlated with shorter overall survival. In vitro, downregulation of B7H6 by CRISPR/Cas9 or siRNA technology had no significant impact on the viability or mobility of PC cells. Instead, knocking out B7H6 sensitized PC cells to NK-mediated cytotoxicity and cytokine production. These results indicate that B7H6 not only serves as a negative prognostic marker but also acts as an immune modulator in PC.

PurposeThere is a major shortage of reliable early detection methods for pancreatic cancer in high-risk groups. The focus of this preliminary study was to use Time Intensity-Density Curve (TIDC) and Marley Equation analyses, in conjunction with 3D volumetric and perfusion imaging to demonstrate their potential as imaging biomarkers to assist in the early detection of Pancreatic Ductal Adenocarcinoma (PDAC).Experimental DesignsA quantitative retrospective and prospective study was done by analyzing multi-phase Computed Tomography (CT) images of 28 patients undergoing treatment at different stages of pancreatic adenocarcinoma using advanced 3D imaging software to identify the perfusion and radio density of tumors.ResultsTIDC and the Marley Equation proved useful in quantifying tumor aggressiveness. Perfusion delays in the venous phase can be linked to Vascular Endothelial Growth Factor (VEGF)-related activity which represents the active part of the tumor. 3D volume analysis of the multiphase CT scan of the patient showed clear changes in arterial and venous perfusion indicating the aggressive state of the tumor.ConclusionTIDC and 3D volumetric analysis can play a significant role in defining the response of the tumor to treatment and identifying early-stage aggressiveness.

Abstract Introduction Only two studies investigated the associations between peak width of skeletonized mean diffusivity (PSMD) and age‐related cognitive alterations, whereas none of the studies investigated the association with vascular risk factors. Methods We evaluated 801 stroke‐ and dementia‐free elderlies with baseline and 3‐year follow‐up assessments. Regression analyses were used to assess the association between age‐related cognitive functions and PSMD. Simple mediation models were used to study the mediation effect of PSMD between vascular risk factors and age‐related cognitive outcomes. Results PSMD was negatively associated with processing speed at baseline and negatively associated with processing and memory scores at 3‐year follow‐up. The association between vascular risk factors and age‐related cognition was mediated by PSMD, as well as other diffusion tensor imaging markers. Discussion PSMD is preferred over other diffusion tensor imaging markers as it is sensitive to age‐related cognitive alterations and calculation is fully automated. PSMD is proposed as a research tool to monitor age‐related cognitive alterations.

Abstract Purpose The American Society of Clinical Oncology guidelines recommend adjuvant chemoradiation (ACR) for margin‐positive (R1) and/or node‐positive (N+) pancreatic cancers. Our goal was to investigate if there is evidence of superiority of adjuvant chemoradiation (ACR) over adjuvant chemotherapy (AC). Methods We utilized data from the National Cancer Database (NCDB) for N+ and/or R1 pancreatic adenocarcinoma patients diagnosed from 2004 to 2012 who underwent ACR or AC. Patients who received neoadjuvant radiation, no adjuvant treatment, or adjuvant radiation alone were excluded. Propensity score nearest‐neighbor 1:1 matching (PSM) was performed between ACR and AC groups based on age, sex, race, insurance, year of diagnosis, comorbidities, tumor site and size, T‐stage, nodal status, margin status, grade, and treatment facility. Primary outcome was overall survival (OS). Results A total of 8297 patients were eligible. After PSM, two well‐balanced groups of 3244 patients each were analyzed. ACR resulted in superior OS compared with AC alone (Hazard ratio [HR] 0.83, 95% CI 0.79‐0.87; median OS 22 vs 19 months, P

This study aimed to characterize chemotherapy-induced transient increase and surge of CA 19–9 level to treatment response in patients with advanced pancreatic ductal adenocarcinoma (PDAC). A retrospective case series was performed of advanced PDAC patients treated with first-line chemotherapy at City of Hope Comprehensive Cancer Center from Jan 2017 to May 2020. CA 19–9 surge was defined as an increase of >20% from baseline followed by a >20% drop in one or more subsequent CA 19–9 levels compared to baseline. Out of 106 advanced PDAC patients, 38 were evaluable for CA 19–9 surge. Fourteen (51.9%) patients treated with FOLFIRINOX and 3 (27.3%) patients treated with nab-P + Gem chemotherapy demonstrated an early transient rise in CA 19–9 level. A CA 19–9 surge was documented in 9 (23.7%) patients, all with duration of surge lasting < 16 weeks. Five out of 9 (55.6%) patients (4: FOLFIRINOX, 1: nab-P + Gem) with CA 19–9 surge demonstrated partial objective response rate on surveillance cross-sectional imaging. One patient (FOLFIRINOX) had stable disease, and 2 patients (1: FOLFIRINOX, 1: nab-P + Gem) were found to have disease progression after treatment interruption. The initial early rise of CA 19–9 levels during chemotherapy in patients with advanced PDAC may not indicate tumor progression. Rather, it may represent a chemotherapy-induced transient increase or surge phenomenon of the tumor marker in patients responding to treatment.

Abstract Introduction The benefit and risk of aerobic exercise among older people harboring advanced cerebral small vessel disease (CSVD) upon cognition, mood, and motor functions are unknown. Methods This rater‐blind randomized trial examined effects of a 24‐week aerobic exercise training (60 min/session, twice/week) upon clinical (cognition, mood, motor functions) and hemodynamic (pulse pressure [PP], blood pressure [BP], pulsatility index) measures in older people harboring moderate to severe CSVD, as evidenced by confluent white matter hyperintensity and/or ≥2 lacunes on magnetic resonance imaging. We further investigated interactions between treatment conditions and hemodynamics measures. Results Fifty‐three and 54 subjects were randomized into the active and control group, respectively. There was no between‐group difference in any of the clinical outcomes. The active group had a greater between‐group reduction in systolic BP and PP than the control group. Within‐group comparison showed that global cognition of the active group remained similar at end of the study compared to baseline, whereas it declined significantly in the control group. We observed “diverging” interaction effects in that greater reduction in systolic BP/PP was associated with greater improvement in memory functions and global cognition but worsening in processing speed in the active group. Side effects were comparable between the two groups. Discussion Future study should investigate the mechanisms of the diverging impacts of aerobic exercise upon different cognitive domains so that the benefit–risk ratio of aerobic exercise in older people harboring more advanced CSVD can be better defined.

Alzheimer’s disease (AD) was recently defined as a biological construct to reflect neuropathologic status, and both abnormal amyloid and tau are required for a diagnosis of AD. We aimed to determine the proton MR spectroscopic (1H-MRS) patterns of the posterior cingulate in biologically defined AD. A total of 68 participants were included in this study, comprising 37 controls, 16 early AD, and 15 late AD, who were classified according to their amyloid and tau status and presence of hippocampal atrophy. Compared with controls, early AD showed lower N-acetylaspartate (NAA)/creatine (Cr) (p = 0.003), whereas late AD showed lower NAA/Cr and higher myoInositol (mI)/Cr (all with p < 0.05). Lower NAA/Cr correlated with a greater global amyloid load (r = −0.47, p < 0.001) and tau load (r = −0.51, p < 0.001) and allowed a discrimination of early AD from controls (p < 0.001). Subgroup analysis showed that NAA/Cr also allowed a differentiation of early AD from controls in the cognitively unimpaired subjects, with an area under the receiver operating characteristics curve, sensitivity, and specificity of 0.96, 100%, and 83.8%, respectively. Lower posterior cingulate NAA levels may help to inform underlying neuropathologic changes in the early stage of AD.

Abstract Immune checkpoint inhibitors have demonstrated broad single-agent antitumor activity and a favorable safety profile that render them attractive agents to combine with other systemic anticancer therapies. Pancreatic cancer has been fairly resistant to monotherapy blockade of programmed cell death protein 1 receptor, programmed death ligand 1, and cytotoxic T-lymphocyte associated protein 4. However, there is a growing body of preclinical evidence to support the rational combination of checkpoint inhibitors and various systemic therapies in pancreatic cancer. Furthermore, early clinical evidence has begun to support the feasibility and efficacy of checkpoint inhibitor-based combination therapy in advanced pancreatic cancer. Despite accumulating preclinical and clinical data, there remains several questions as to the optimal dosing and timing of administration of respective agents, toxicity of combination strategies, and mechanisms by which immune resistance to single-agent checkpoint blockade are overcome. Further development of biomarkers is also important in the advancement of combination systemic therapies incorporating checkpoint blockade in pancreatic cancer. Results from an impressive number of ongoing prospective clinical trials are eagerly anticipated and will seek to validate the viability of combination immuno-oncology strategies in pancreatic cancer.

Abstract Background Psychological distress is prevalent among people with Parkinson’s disease (PD) and aggravates their motor symptoms, thereby leading to increased disability, high healthcare costs, and poor health-related quality of life (HRQoL). The under-recognition and adverse effects of the pharmacological management of anxiety and depression among the PD population are considerable. Thus, adopting a Complementary and Alternative Management (CAM) approach to address this problem is important. Yoga, one of the most common “mind-body” CAM therapies, can improve the psychological wellbeing of people with chronic illnesses. However, limited research on the effects of yoga in people with PD has been conducted. This study will determine the effects of yoga on the psychological wellbeing of people with mild-to-moderate PD and will compare these effects with those of stretching and resistance training exercises. Methods A community-based, single-blind, randomized trial will be conducted. A total of 126 subjects will be recruited and randomly divided into yoga (n = 63) or stretching and resistance exercise (n = 63) groups. For 8 weeks, the yoga group will receive a weekly 90-min session of yoga, and the control group will receive a weekly 60-min session of stretching and resistance exercises. The primary outcome will be the level of psychological distress measured using the Hospital Anxiety and Depression Scale. The secondary outcomes will include the severity of motor symptoms measured by the Movement Disorders Society – Unified Parkinson’s Disease Scale − Part III Motor Examination; mobility, balance, and fall risk measured by the Timed Up and Go test; spiritual wellbeing measured by the Holistic Wellbeing Scale; and HRQoL measured by the Parkinson’s Disease Questionnaire-8. Assessment will be conducted at baseline, 8th, and 20th weeks of follow-ups. Discussion This study will be the first randomized trial to compare the effect of yoga versus stretching and resistance training exercises in a PD population. Results will contribute to the value of yoga as a therapeutic option for managing psychological distress in PD patients. Multiple outcomes including psychological, physiological, and spiritual and HRQoL will also be measured to elucidate the potential mechanisms of yoga. The effect of yoga on people with chronic illnesses will further be elucidated. This information should contribute to future research, practice, and policy related to PD management. Trial registration WHO Primary Registry – Chinese Clinical Trials Registry (ChiCTR): CUHK_CCRB00522 Registered on 8 October 2016; date of approval 19 August 2016.

Objective: All types of cerebral small vessel disease (SVD) markers including lacune, white matter hyperintensities (WMH), cerebral microbleeds, and perivascular spaces were found to be associated with poststroke depressive symptoms (PDS). This study explored whether the combination of the four markers constituting an overall SVD burden was associated with PDS.Methods: A cohort of 563 patients with acute ischemic stroke were followed over a 15-month period after the index stroke. A score of ≥7 on the 15-item Geriatric Depression Scale was defined as clinically significant PDS. Scores of the four SVD markers ascertained on magnetic resonance imaging were summed up to represent total SVD burden. The association between SVD burden and PDS was assessed with generalized estimating equation models.Results: The study sample had a mean age of 67.0 ± 10.2 years and mild-moderate stroke [National Institutes of Health Stroke Scale score: 3, interquartile, 1–5]. PDS were found in 18.3%, 11.6%, and 12.3% of the sample at 3, 9, and 15 months after stroke, respectively. After adjusting for demographic characteristics, vascular risk factors, social support, stroke severity, physical and cognitive functions, and size and locations of stroke, the SVD burden was associated with an increased risk of PDS [odds ratio = 1.30; 95% confidence interval = 1.07–1.58; p = 0.010]. Other significant predictors of PDS were time of assessment, female sex, smoking, number of acute infarcts, functional independence, and social support.Conclusion: SVD burden was associated with PDS examined over a 15-month follow-up in patients with mild to moderate acute ischemic stroke.

Aim. We assessed the impact of cerebral white matter lesions (WMLs) on lower urinary tract symptoms in subjects with normal neurological and cognitive function. Methods. A cohort of community-dwelling subjects aged ≥65 years were recruited to undergo MRI brain assessment. WMLs were graded using the Fazekas scale from 0 to 3. A separate telephone interview was carried out to assess the urinary symptoms in these subjects using the questionnaire Overactive Bladder-Validated 8-Question Awareness Tool (OAB-V8). Results. 800 community-dwelling elderly subjects were recruited to undergo MRI brain. In this cohort, 431 subjects responded to the telephone interview concerning their urinary symptoms. Among the respondents, 21.1% did not exhibit any WML on their MRI brain. Most of the subjects (52.6%) exhibited grade 1 WML. On logistic regression, age was found to be positively correlated with the Fazekas score (correlation coefficient 0.203, p≤0.01). Using a cutoff of 8 on OAB-V8, 22% of the respondents experienced OAB. Presence of WML, hypertension, or diabetes mellitus was not found to be correlated with storage urinary symptoms or OAB-V8 total score. Multiple logistic regression analysis did not show the presence of WML to be associated with the diagnosis of OAB (adjusted OR 1.13, 95% CI 0.65–1.96, p=0.659). Conclusions. WML is associated with age and is common in the elderly population. Mild WML is subclinical, with no obvious neurological and urinary symptoms. Our cohort did not demonstrate a relationship between WML and lower urinary tract symptoms.

A heavily pretreated patient with triple negative breast cancer distinguished by cutaneous metastases received p53MVA vaccine in combination with pembrolizumab. Her cutaneous metastases regressed and after 2 cycles of therapy, a skin biopsy showed a complete pathological response. Systemic response was confirmed with restaging CT and bone scans. Activation of p53-specific T cell responses and elevation of multiple immune response genes in peripheral blood correlated with the rapid clinical response which lasted for 6 months after the initiation of combined therapy.

As genomic datasets continue to grow, the feasibility of downloading data to a local organization and running analysis on a traditional compute environment is becoming increasingly problematic. Current large-scale projects, such as the ICGC PanCancer Analysis of Whole Genomes (PCAWG), the Data Platform for the U.S. Precision Medicine Initiative, and the NIH Big Data to Knowledge Center for Translational Genomics, are using cloud-based infrastructure to both host and perform analysis across large data sets. In PCAWG, over 5,800 whole human genomes were aligned and variant called across 14 cloud and HPC environments; the processed data was then made available on the cloud for further analysis and sharing. If run locally, an operation at this scale would have monopolized a typical academic data centre for many months, and would have presented major challenges for data storage and distribution. However, this scale is increasingly typical for genomics projects and necessitates a rethink of how analytical tools are packaged and moved to the data. For PCAWG, we embraced the use of highly portable Docker images for encapsulating and sharing complex alignment and variant calling workflows across highly variable environments. While successful, this endeavor revealed a limitation in Docker containers, namely the lack of a standardized way to describe and execute the tools encapsulated inside the container. As a result, we created the Dockstore (https://dockstore.org), a project that brings together Docker images with standardized, machine-readable ways of describing and running the tools contained within. This service greatly improves the sharing and reuse of genomics tools and promotes interoperability with similar projects through emerging web service standards developed by the Global Alliance for Genomics and Health (GA4GH).

Schizotypal personality disorder (SPD) is considered one of the classic disconnection syndromes. However, the specific cortical disconnectivity pattern has not been fully investigated. In this study, we aimed to explore significant alterations in whole-cortex structural connectivity in SPD individuals (SPDs) by combining the techniques of brain surface morphometry and white matter (WM) tractography. Diffusion and structural MR data were collected from twenty subjects with SPD (all males; age, 19.7 ± 0.9 yrs) and eighteen healthy controls (all males; age, 20.3 ± 1.0 yrs). To measure the structural connectivity for a given unit area of the cortex, the fiber connectivity density (FiCD) value was proposed and calculated as the sum of the fractional anisotropy of all the fibers connecting to that unit area in tractography. Then, the resultant whole-cortex FiCD maps were compared in a vertex-wise manner between SPDs and controls. Compared with normal controls, SPDs showed significantly decreased FiCD in the rostral middle frontal gyrus (crossing BA9 and BA10) and significantly increased FiCD in the anterior part of the fusiform/inferior temporal cortex (P < 0.05, Monte Carlo simulation corrected). Moreover, the gray matter volume extracted from the left rostral middle frontal cluster was observed to be significantly greater in the SPD group (P = 0.02). Overall, this study identifies a decrease in connectivity in the left middle frontal cortex as a key neural deficit at the whole-cortex level in SPD, thus providing insight into its neuropathological basis.

Puffer fish, Takifugu niphobles, collected from the Hong Kong coastal waters were screened for tetrodotoxin-producing bacteria. A Gram-negative, non-acid-fast, non-sporing and rod shaped bacterial strain (designated as gutB01) was isolated from the intestine of the puffer fish and was shown to produce tetrodotoxin (TTX). Based on the Microbial Identification (MIDI) and 16S-23S rDNA internal transcribed spacer (ITS) phylogenetic analysis, the strain was identified as Raoultella terrigena. The TTX production ability of the strain was confirmed by mouse bioassay, ELISA and mass spectrometry (MALDI-TOF). Our results reiterate that the TTX found in puffer fish was likely produced by the associated bacteria and TTX are widely produced amongst a diversity of bacterial species.

Worldwide, around 50 million people live with dementia, and this number is projected to triple by 2050. It has been estimated that 20% of all dementia cases have a predominant cerebrovascular pathology, while perhaps another 20% of vascular diseases contribute to a mixed dementia picture. Therefore, the vascular contribution to dementia affects 20 million people currently and will increase markedly in the next few decades, particularly in lower- and middle-income countries. In this review, we discuss the mechanisms of vascular cognitive impairment (VCI) and review management. VCI refers to the spectrum of cerebrovascular pathologies that contribute to any degree of cognitive impairment, ranging from subjective cognitive decline, to mild cognitive impairment, to dementia. While acute cognitive decline occurring soon after a stroke is the most recognized form of VCI, chronic cerebrovascular disease, in particular cerebral small-vessel disease, can cause insidious cognitive decline in the absence of stroke. Moreover, cerebrovascular disease not only commonly co-occurs with Alzheimer's disease (AD) and increases the probability that AD pathology will result in clinical dementia, but may also contribute etiologically to the development of AD pathologies. Despite its enormous health and economic impact, VCI has been a neglected research area, with few adequately powered trials of therapies, resulting in few proven treatments. Current management of VCI emphasizes prevention and treatment of stroke and vascular risk factors, with most evidence for intensive hypertension control. Reperfusion therapies in acute stroke may attenuate the risk of VCI. Associated behavioral symptoms such as apathy and poststroke emotionalism are common. We also highlight novel treatment strategies that will hopefully lead to new disease course-modifying therapies. Finally, we highlight the importance of including cognitive endpoints in large cardiovascular prevention trials and the need for an increased research focus and funding for this important area. [ABSTRACT FROM AUTHOR]

Background The diagnostic accuracy of frameless stereotactic brain biopsy has been reported, but there is limited literature focusing on the reasons for nondiagnostic cases. In this study, we evaluate the diagnostic accuracy of frameless stereotactic brain biopsy, compare it with the current international standard, and review the field for improvement. Methods This is a retrospective analysis of consecutive, prospectively collected frameless stereotactic brain biopsies from 2007 to 2020. We evaluated the diagnostic accuracy of the frameless stereotactic brain biopsies using defined criteria. The biopsy result was classified as conclusive, inconclusive, or negative, based on the pathologic, radiologic, and clinical diagnosis concordance. For inconclusive or negative results, we further evaluated the preoperative planning and postoperative imaging to review the errors. A literature review for the diagnostic accuracy of frameless stereotactic biopsy was performed for the validity of our results. Results There were 106 patients with 109 biopsies performed from 2007 to 2020. The conclusive diagnosis was reached in 103 (94.5%) procedures. An inconclusive diagnosis was noted in four (3.7%) procedures and the biopsy was negative in two (1.9%) procedures. Symptomatic hemorrhage occurred in one patient (0.9%). There was no mortality in our series. Registration error (RE) and inaccurate targeting occurred in three trigonal lesions (2.8%), sampling of the nonrepresentative part of the lesion occurred in two cases (1.8%), and one biopsy (0.9%) for lymphoma was negative due to steroid treatment. The literature review suggested that our diagnostic accuracy was comparable with the published literature. Conclusion The frameless stereotactic biopsy is a safe procedure with high diagnostic accuracy only if meticulous preoperative planning and careful intraoperative registration is performed. The common pitfalls precluding a conclusive diagnosis are RE and biopsies at nonrepresentative sites. [ABSTRACT FROM AUTHOR]