Aß Amyloid Scaffolds the Accumulation of Matrisome and Additional Proteins in Alzheimer's Disease.

We report a highly significant correlation in brain proteome changes between Alzheimers disease (AD) and CRND8 APP695NL/F transgenic mice. However, integrating protein changes observed in the CRND8 mice with co-expression networks derived from human AD, reveals both conserved and divergent module changes. For the most highly conserved module (M42, matrisome) we find many proteins accumulate in plaques, cerebrovascular amyloid (CAA), dystrophic processes, or a combination thereof. Overexpression of two M42 proteins, midkine (Mdk) and pleiotrophin (PTN), in CRND8 mice brains leads to increased accumulation of A ß ; in plaques and in CAA; further, recombinant MDK and PTN enhance A ß ; aggregation into amyloid. Multiple M42 proteins, annotated as heparan sulfate binding proteins, bind to fibrillar A ß 42 and a non-human amyloid fibril in vitro. Supporting this binding data, MDK and PTN co-accumulate with transthyretin (TTR) amyloid in the heart and islet amyloid polypeptide (IAPP) amyloid in the pancreas. Our findings establish several critical insights. Proteomic changes in modules observed in human AD brains define an A ß ; amyloid responsome that is well conserved from mouse model to human. Further, distinct amyloid structures may serve as scaffolds, facilitating the co-accumulation of proteins with signaling functions. We hypothesize that this co-accumulation may contribute to downstream pathological sequalae. Overall, this contextualized understanding of proteomic changes and their interplay with amyloid deposition provides valuable insights into the complexity of AD pathogenesis and potential biomarkers and therapeutic targets.

Gut microbiome and psychiatric disorders.

Several pieces of evidence show that gut microbiota can impact psychiatric disorders. However, no mechanism behind the relationship has been identified. Host genetics and their diets have a significant impact on the gut microbiota. More advanced studies are needed to find the mechanism and develop new therapeutic strategies.

Separating Inhibitory and Excitatory Responses of Epileptic Brain to Single-Pulse Electrical Stimulation.

To enable an accurate recognition of neuronal excitability in an epileptic brain for modeling or localization of epileptic zone, here the brain response to single-pulse electrical stimulation (SPES) has been decomposed into its constituent components using adaptive singular spectrum analysis (SSA). Given the response at neuronal level, these components are expected to be the inhibitory and excitatory components. The prime objective is to thoroughly investigate the nature of delayed responses (elicited between 100[Formula: see text]ms-1 s after SPES) for localization of the epileptic zone. SSA is a powerful subspace signal analysis method for separation of single channel signals into their constituent uncorrelated components. The consistency in the results for both early and delayed brain responses verifies the usability of the approach.

Perceptions about Telemedicine among Populations with Chronic Diseases amid COVID-19: Data from a Cross-Sectional Survey.

Chronic diseases, including non-communicable diseases (NCDs), have arisen as a severe threat to health and socio-economic growth. Telemedicine can provide both the highest level of patient satisfaction and the lowest risk of infection during a pandemic. The factors associated with its usage and patient adherence are not visible in Bangladesh's resource-constrained settings. Therefore, this study aimed to identify perceptions about telemedicine among populations with chronic diseases amid the COVID-19 pandemic. A closed-ended self-reported questionnaire was created, and the questionnaire was written, reviewed, and finalized by a public health investigator, a psychiatrist, and an epidemiologist. The data for this study were collected from individuals using simple random sampling and snowball sampling techniques. Ethics approval was granted, and written/verbal consent was taken before interviews. Most of the participants showed a positive attitude towards telemedicine. People aged 35-54 years old and a higher level of education were less frequently associated with willingness to receive telemedicine services for current chronic disease (WRTCCD) than their counterparts. People living in urban areas and lower-income participants were more strongly associated with WRTCCD. Additionally, people who did not lose their earnings due to the pandemic were less strongly associated with WRTCCD. However, the main strength of this research is that it is a broad exploration of patient interest in several general forms of telehealth. In Bangladesh, there are many opportunities for telemedicine to be integrated into the existing healthcare system, if appropriate training and education are provided for healthcare professionals.

COVID-19 vaccine acceptance in South Asia: a multi-country study.

OBJECTIVES: With COVID-19 vaccination underway, this study aimed to understand belief, attitude and intention of the people in the South Asia region towards the vaccine. METHODS: We conducted a cross-sectional study using semi-structured questionnaires among 18201 individuals in four South Asian countries; Bangladesh, India, Pakistan, and Nepal between January 17 and February 2, 2021. We used the Health Belief Model (HBM) to identify the predictors related to vaccine acceptance. STATA (v16.1) was used for all analyses. RESULTS: The percentage of respondents willing to be vaccinated against COVID-19 was 65%, 66%, 72% and 74% for Bangladesh, India, Pakistan and Nepal, respectively. Perceived destructive impact of COVID-19, positive perception of vaccines and concern about possible side effects were significant in modifying respondents' intentions.. In multivariable logistic regression, age, sex, marital status, education, comorbidities, worry about getting infected, perceived COVID-19 impact, belief regarding vaccine efficacy, positive attitude towards mandatory measures, and vaccine availability were found to be associated with vaccine acceptance across countries. CONCLUSION: Nearabout two-third of the respondants were willing to take COVID-19 vaccine in the four South Asia countries.

Quality of life of COVID-19 recovered patients in Bangladesh.

Coronavirus Disease-2019 (COVID-19) quickly surged the whole world and affected people's physical, mental, and social health thereby upsetting their quality of life. Therefore, we aimed to investigate the quality of life (QoL) of COVID-19 positive patients after recovery in Bangladesh. This was a study of adult (aged ≥18 years) COVID-19 individuals from eight divisions of Bangladesh diagnosed and confirmed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) from June 2020 to November 2020. Given a response rate of 60% in a pilot study, a random list of 6400 COVID-19 patients was generated to recruit approximately 3200 patients from eight divisions of Bangladesh and finally a total of 3244 participants could be recruited for the current study. The validated Bangla version of the World Health Organization Quality of Life Brief (WHOQOL-BREF) questionnaire was used to assess the QoL. Data were analyzed by STATA (Version 16.1) and R (Version 4.0.0). All the procedures were conducted following ethical approval and in accordance with the Declaration of Helsinki. The mean scores of QoL were highest for the physical domain (68.25±14.45) followed by social (65.10±15.78), psychological (63.28±15.48), and environmental domain (62.77±13.07). Psychological and physical domain scores among females were significantly lower than the males (p<0.001). The overall quality of life was lower in persons having a chronic disease. Participants over 45 years of age were 52% less likely to enjoy good physical health than the participants aged below 26 years (AOR: 0.48, CI: 0.28-0.82). The quality of life of employed participants was found 1.8 times higher than the unemployed (AOR: 1.80, CI: 1.11-2.91). Those who were admitted to hospitals during infection had a low QoL score in physical, psychological, and socials domains. However, QoL improved in all aspect except the psychological domain for each day passed after the diagnosis. These findings call for a focus on the quality of life of the COVID-19 affected population, with special emphasis given to females, older adults, unemployed, and people with comorbidities.

Acceptance of COVID-19 vaccine and its determinants: evidence from a large sample study in Bangladesh.

AIM: Our study aimed to understand the acceptance level of the COVID-19 vaccine and its determinants among the adult Bangladeshi population. METHODOLOGY: This cross-sectional study was conducted in all eight divisions of Bangladesh. Data from 7,357 adult respondents were collected between January 17 and February 2, 2021, using a self-administered semi-structured questionnaire. Statistical software STATA (Version 16.1) was used for all analyses. RESULTS: The majority of study participants were from the Dhaka division (34.24%). The most common age group was ≤30 years (46.18%). Almost two-thirds of respondents were male (65.50%) and married (67.76%). A large portion (79.85%) of people who had positive vaccine intentions believed that vaccination should be made mandatory for everyone. The majority of the respondents thought that the vaccine would work against COVID-19 infection (67%). In the binary logistic regression analysis, participants who had the education level of graduation or above (AOR = 1.80), age ≥50 years (AOR = 1.97), students (AOR = 2.98), monthly income ≥41,000 BDT (AOR = 2.22), being resident of rural area (AOR = 2.24), respondents from Khulna division (AOR = 6.43) were more likely to receive a COVID-19 vaccine. Those who had family members diagnosed with COVID-19 (AOR = 1.24), presence of chronic disease (AOR = 0.72), and those who were vaccinated in the last few years (AOR = 1.32) were also more likely to accept the COVID-19 vaccine. CONCLUSION: Most of the respondents were willing to be vaccinated based on the belief that the vaccine will work against COVID-19. As rumors are generating daily, there is a need for policy-level initiative and evidence-based mass media promotion to keep inspired the general Bangladeshi people to accept the COVID-19 vaccine whenever it will be available at the individual level.

24-Hour video EEG in the evaluation of the first unprovoked seizure.

OBJECTIVE: To assess the gain in detection of epileptiform abnormalities in 24-hour EEG recordings following the first seizure. METHODS: We identified patients who underwent 24-hour video EEG (VEEG) with "first seizure" as an indication. We noted the presence or absence of epileptiform discharges (EDs) in the VEEG study and the latency for the appearance of such discharges. We compared the rate of EDs during the initial 60 min with those occurring only later during the recording. RESULTS: Data from 25 patients, aged 15 to 59, were included. Of the 11 patients with EDs, eight (73%) appeared only after 60 min of recording. This equates to a 32% absolute increase in the detection of EDs across all patients. The latency to first EDs varied from one to 1080 min with a median of 170 min. In four cases, actual subtle seizures were recorded. CONCLUSION: This study suggests an increase in the detection of EDs with the 24-hour studies compared to the traditional shorter recordings, in the context of a first seizure. SIGNIFICANCE: A standard EEG can be performed close to the seizure, followed by a longer up to 24-hour recording if the initial shorter study is unrevealing.

Altered gut microbiome and autism like behavior are associated with parental high salt diet in male mice.

Neurodevelopmental disorders are conditions caused by the abnormal development of the central nervous system. Autism spectrum disorder (ASD) is currently the most common form of such disorders, affecting 1% of the population worldwide. Despite its prevalence, the mechanisms underlying ASD are not fully known. Recent studies have suggested that the maternal gut microbiome can have profound effects on neurodevelopment. Considering that the gut microbial composition is modulated by diet, we tested the hypothesis that ASD-like behavior could be linked to maternal diet and its associated gut dysbiosis. Therefore, we used a mouse model of parental high salt diet (HSD), and specifically evaluated social and exploratory behaviors in their control-fed offspring. Using 16S genome sequencing of fecal samples, we first show that (1) as expected, HSD changed the maternal gut microbiome, and (2) this altered gut microbiome was shared with the offspring. More importantly, behavioral analysis of the offspring showed hyperactivity, increased repetitive behaviors, and impaired sociability in adult male mice from HSD-fed parents. Taken together, our data suggests that parental HSD consumption is strongly associated with offspring ASD-like behavioral abnormalities via changes in gut microbiome.

Subacute neocortical stimulation (SNCS) and its effects on epileptic activity in adults and children diagnosed with focal cortical dysplasia (FCD).

BACKGROUND: Chronic intracranial electrical stimulation is now widely used as treatment for drug resistant epilepsy. Subacute neocortical stimulation (SNCS) can also be performed during EEG recordings with intracranial electrodes (iEEG), but its diagnostic value remains largely unknown. METHODS: We assessed the effects of SNCS on the frequency of seizures and epileptiform discharges (EDs) during 290 h of iEEG- from 12 patients (6 adults, 6 children) with epilepsy secondary to focal cortical dysplasia (FCD). RESULTS: In 9/12 patients, SNCS periods showed decreased seizure-frequency (Median -73 %, p = 0.0093). At baseline, incidence of EDs were correlated with seizure-frequency (Spearman r = 0.59). However, this correlation disappeared during SNCS and a significant change in the incidence of EDs was observed. In addition, there was a trend towards greater reduction in seizure-frequency during SNCS in patients who underwent surgery. CONCLUSION: In summary, SNCS can reduce seizure-frequency and changes ED-frequency. The variability in ED changes may be explained by different effects of SNCS depending on electrode location. The magnitude of seizure reduction during SNCS suggests that this technique could contribute to preoperative assessment in epilepsy surgery.

Maternal elevated salt consumption and the development of autism spectrum disorder in the offspring.

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental condition with no known etiology or cure. Several possible contributing factors, both genetic and environmental, are being actively investigated. Amongst these, maternal immune dysregulation has been identified as potentially involved in promoting ASD in the offspring. Indeed, ASD-like behaviors have been observed in studies using the maternal immune activation mouse model. Furthermore, recent studies have shed light on maternal dietary habits and their impact on the gut microbiome as factors possibly facilitating ASD. However, most of these studies have been limited to the effects of high fat and/or high sugar. More recent data, however, have shown that elevated salt consumption has a significant effect on the immune system and gut microbiome, often resulting in gut dysbiosis and induction of pro-inflammatory pathways. Specifically, high salt alters the gut microbiome and induces the differentiation of T helper-17 cells that produce pro-inflammatory cytokines such as interleukin-17 and interleukin-23. Moreover, elevated salt can also reduce the differentiation of regulatory T cells that help maintaining a balanced immune system. While in the innate immune system, high salt can cause over activation of M1 pro-inflammatory macrophages and downregulation of M2 regulatory macrophages. These changes to the immune system are alarming because excessive consumption of salt is a documented worldwide problem. Thus, in this review, we discuss recent findings on high salt intake, gut microbiome, and immune system dysregulation while proposing a hypothesis to link maternal overconsumption of salt and children's ASD.

Intracranial stimulation for children with epilepsy.

OBJECTIVES: To evaluate the efficacy of intracranial stimulation to treat refractory epilepsy in children. METHODS: This is a retrospective analysis of a pilot study on all 8 children who had intracranial electrical stimulation for the investigation and treatment of refractory epilepsy at King's College Hospital between 2014 and 2015. Five children (one with temporal lobe epilepsy and four with frontal lobe epilepsy) had subacute cortical stimulation (SCS) for a period of 20-161 h during intracranial video-telemetry. Efficacy of stimulation was evaluated by counting interictal discharges and seizures. Two children had thalamic deep brain stimulation (DBS) of the centromedian nucleus (one with idiopathic generalized epilepsy, one with presumed symptomatic generalized epilepsy), and one child on the anterior nucleus (right fronto-temporal epilepsy). The incidence of interictal discharges was evaluated visually and quantified automatically. RESULTS: Among the three children with DBS, two had >60% improvement in seizure frequency and severity and one had no improvement. Among the five children with SCS, four showed improvement in seizure frequency (>50%) and one chid did not show improvement. Procedures were well tolerated by children. CONCLUSION: Cortical and thalamic stimulation appear to be effective and well tolerated in children with refractory epilepsy. SCS can be used to identify the focus and predict the effects of resective surgery or chronic cortical stimulation. Further larger studies are necessary.

Women have higher left ventricular ejection fractions than men independent of differences in left ventricular volume: the Dallas Heart Study.

BACKGROUND: Although gender-specific criteria are common for defining cardiac traits such as left ventricular hypertrophy, left ventricular ejection fraction (LVEF) thresholds widely used in clinical practice have traditionally been the same for women and men, perhaps because it remains uncertain whether there is a systematic difference in LVEF between genders. METHODS AND RESULTS: Using cardiac magnetic resonance imaging in a probability-based sample of Dallas County residents aged 30 to 65 years (1435 women and 1183 men), we compared LVEF in women and men. The association of gender with stroke volume independent of end-diastolic volume (EDV) or other potential confounders was assessed by multivariable analysis. Gender-specific thresholds for a low LVEF were defined at the 2.5th percentile in women and men from a healthy reference subpopulation. The median (25th, 75th percentile) LVEF was higher in women than in men (75% [70%, 79%] in women versus 70% [65%, 75%] in men, P<0.001). Left ventricular EDV and end-systolic volume indexed to body surface area were smaller in women than in men (P<0.001 for both). Gender remained significantly associated with stroke volume, independent of EDV and other potential confounders in multivariable analysis. A low LVEF was defined as below 61% in women and below 55% in men. CONCLUSIONS: Women have a higher LVEF than men in the general population, secondary to a higher stroke volume for a given EDV independent of known potential confounders.

Left ventricular hypertrophy is more prevalent in blacks than whites in the general population: the Dallas Heart Study.

Although recent studies have suggested that blacks compared with whites have an increased prevalence of left ventricular hypertrophy, it remains uncertain whether this is true despite adjustment for body composition (fat mass and fat-free mass) and when assessed by cardiac MRI in the general population. The Dallas Heart Study is a population-based study of Dallas County in which 1335 black and 858 white participants 30 to 67 years of age underwent detailed assessment including dual-energy x-ray absorptiometry scan to measure body composition and cardiac MRI. Left ventricular hypertrophy, whether defined by indexation to body surface area (P<0.001), fat-free mass (P=0.002), or height2.7 (P<0.001) was 2- to 3-fold more common in black versus white women. Similar results were seen when comparing black and white men (P<0.001 when left ventricular hypertrophy was indexed to body surface area or height2.7 and P=0.05 when indexed to fat-free mass). Ethnic disparities in left ventricular mass persisted in multivariable models despite adjustment for fat mass, fat-free mass, systolic blood pressure, age, gender, and measures of socioeconomic status. We conclude that blacks compared with whites have increased left ventricular mass and a 2- to 3-fold higher prevalence of left ventricular hypertrophy in the general population, as assessed by cardiac MRI. The ethnic differences in left ventricular mass are independent of differences in body composition.