Symptomatology Of Disease Research Articles

Cerebrovascular reactivity and response times describe recent ischemic symptomatology in patients with moyamoya

Abstract Moyamoya is a non-atherosclerotic intracranial steno-occlusive condition that places patients at high risk for ischemic stroke. Randomized trials of surgical revascularization demonstrating efficacy in ischemic moyamoya have not been performed, and as such, biomarkers of parenchymal hemodynamic impairment are needed to assist with triage and evaluate post-surgical response. In this prospective study, we test the hypothesis that parenchymal cerebrovascular reactivity (CVR) metrics in response to a fixed-inspired 5% carbon dioxide challenge correlate with recent focal ischemic symptoms. Hypercapnic reactivity blood oxygenation level-dependent (BOLD) MRI (echo time=35ms; spatial resolution=3.5x3.5x3.5mm) and catheter angiography assessments of cortical reserve capacity and vascular patency, respectively, in moyamoya disease and syndromic participants (n=73) were performed in sequence. Cerebrovascular reactivity uncorrected for response time (CVRRAW) was quantified, and time regression analyses were applied to quantify maximum cerebrovascular reactivity (CVRMAX) and cerebrovascular reactivity response time (CVRDELAY). Symptomatology was categorized by a stroke neurologist by hemisphere: symptomatic (lateralizing ischemic symptoms < 6 months) or asymptomatic (no ischemic symptom history). Values are presented as median [interquartile range]; logistic regression assessed the association of cerebrovascular reactivity metrics with symptoms, controlling for age and sex. A total of 109 hemispheres, including 39 symptomatic and 70 asymptomatic hemispheres, met inclusion criteria. Symptomatic hemispheres displayed reduced CVRRAW (p<0.01) (symptomatic=0.45 [0.28-0.70] z-statistic/ΔEtCO2 vs. asymptomatic=0.67 [0.44-0.98] z-statistic/ΔEtCO2), lengthened CVRDELAY (p<0.001) (symptomatic=47.6 [37.7-57.0] seconds vs. asymptomatic=37.7 [30.4-46.4] seconds), and reduced CVRMAX (p=0.037) (symptomatic=1.31 [0.99-1.94] z-statistic/ΔEtCO2 vs. asymptomatic=1.64 [1.29-2.12] z-statistic/ΔEtCO2). CVRDELAY (p<0.001) was found to be significantly related to age in asymptomatic hemispheres (0.33-unit increase/year). Of assessed measures, the receiver operating characteristic curves suggest that CVRDELAY is associated most closely with recent ischemic symptoms (p<0.001). Findings support that cerebrovascular reactivity metrics are uniquely altered in hemispheres with recent ischemic symptoms, further motivating their utilization as biomarkers of ischemic symptomatology and potential treatment efficacy in moyamoya disease and syndrome.

Covid-19 Related Seizures

Background: The Coronavirus (Sars-CoV-2, COVID-19) has been evolving its viral strains, prevalence, symptomatology, and sequelae of disease for the past three years. Although the most recognized COVID-19 symptoms involve the respiratory tract; neurological symptoms have been documented. Specifically, seizures have specifically been discussed in the literature but remain both under-recognized and under-reported in clinical practice. Aim: To review of the literature of adult patients with COVID-19 and seizures and integrate into clinical practice in the acute care environment; from presentation to the emergency Department to discharge. Methods: A narrative literature review was conducted to identify all reported clinical studies involving adult patients with COVID-19 and de novo seizures from MEDLINE, yielding 108 relevant publication titles and abstracts. Additional three relevant studies were discovered through manual search of reference lists of included studies. After excluding non-related publications, 58 publications underwent full-text review. Reporting of results was guided by the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Results: Data was organized into the following themes in the literature: prevalence of seizure occurrence in patients with COVID-19; pathophysiology discussing possible cause; CSF and EEG findings in these patients, and outcomes both in and out of hospital. Conclusion: Seizures were reported as both the presenting symptom of COVID-19 infection and a sequelae of the disease. Heterogeneity identified in both severity and pathogenesis of disease may partly account for the variability in reporting. Seizures may occur as single incidences, with no further implication to the patient or they may occur in the context of New Onset Refractory Status Epilepticus. Patients may require critical care for management of Status Epilepticus or encephalopathy with accompanying seizures. Clinician vigilance is essential in identifying COVID-19 infection in patients presenting to Emergency Services with seizures. Early recognition impacts patient care both in-hospital and at post-discharge follow-up.

Intranasal Carrier-Free Nanomodulator Addresses Both Symptomatology and Etiology of Alzheimer's Disease by Restoring Neuron Plasticity and Reprogramming Lesion Microenvironment.

The unsatisfactory treatment outcome of Alzheimer's disease (AD) can be attributed to two primary factors, the intricate pathogenic mechanisms leading to restricted treatment effectiveness against single targets and the hindered drug accumulation in brain due to blood-brain barrier obstruction. Therefore, we developed a carrier-free nanomodulator (NanoDS) through the self-assembly of donepezil and simvastatin for direct nose-to-brain delivery. This approach facilitated a rapid and efficient traversal through the nasal epithelial barrier, enabling subsequent drug release and achieving multiple therapeutic effects. Among them, donepezil effectively ameliorated the symptoms of AD and restored synaptic plasticity. Simvastatin exerted a neurotrophic effect and facilitated the clearance of amyloid-β aggregation. At the same time, NanoDS demonstrated effective anti-inflammatory and antioxidative stress effects. This therapy for AD is approached from both symptomatic and etiological perspectives. In the treatment of FAD4T transgenic mice, it highly improved spatial memory impairment and cognitive deficits while restoring the homeostasis of brain microenvironment. Collectively, our study presented a paradigm for both achieving efficient brain delivery and offering pleiotropic therapies for AD.

Evaluation of coinfection between SARS-CoV-2 and dengue virus in São Luís/MA

The COVID-19 pandemic has become a global public health emergency, especially in subtropical regions endemic for arboviruses. During the acute phase of the disease, Dengue and COVID-19 present similar laboratory profiles and symptomatology, complicating clinical diagnosis. This study analyzed the occurrence of coinfections between dengue virus and SARS-CoV-2 in patients treated at a laboratory in São Luís, Maranhão. A total of 150 random serum samples from patients, collected between April and May 2020, tested positive for IgM/IgA antibodies against SARS-CoV-2. For the detection of dengue virus (DENV), reactions were standardized using specific primers for each serotype (1-4). Subsequently, cDNA amplification was performed by conventional PCR, and the amplicons were analyzed by agarose gel electrophoresis. Through this study, it was possible to identify one sample (0.6%) positive for the DENV-4 serotype. This study validates the possibility of coinfections in dengue-endemic areas.

Characterization and Fungicide Sensitivity of Colletotrichum spp. from Capsicum peppers in South Korea.

Capsicum peppers, peppers from plants of the genus Capsicum (family Solanaceae), are widely cultivated in South Korea, where annual production was 92,756 tons in 2021, 54.4% higher than that of the previous year. Occurring throughout the production cycle, anthracnose is a major disease limiting commercial Capsicum pepper production worldwide, including in South Korea. This study investigates the diversity and pathogenicity of Colletotrichum species responsible for Capsicum pepper anthracnose in Gyeongbuk, South Korea, focusing on disease incidence and symptomatology in the field and the identification, morphological characteristics, pathogenicity, and fungicide sensitivity of the causative species. Disease incidence ranged from 30 to 50%, with samples categorized into three distinct symptom types, aiding accurate field diagnosis. Phylogenetic analysis classified 41 isolates into six species in the acutatum, gloeosporioides, and truncatum species complexes, revealing significant genetic diversity. Morphological characterization supported these identifications, providing a comprehensive profiling. Pathogenicity tests confirmed that all identified species induced typical anthracnose lesions, with lesion size variations suggesting differential aggressiveness. Temperature significantly influenced mycelial growth, with optimal growth between 20 and 26°C, and C. truncatum demonstrating high-temperature tolerance.In vitro fungicide sensitivity tests showed variable responses, with tebuconazole being generally effective. These findings underscore the need for species-specific fungicide recommendations and highlight the importance of continuous monitoring of Colletotrichum species. Future research should explore the molecular mechanisms of pathogenicity, host specificity, and fungicide resistance, integrating these findings with breeding programs to develop resistant pepper varieties. This study provides critical insights for effective anthracnose management in pepper cultivation and future research directions.

Modafinil Versus Amphetamine-Dextroamphetamine For Idiopathic Hypersomnia and Narcolepsy Type 2: A Randomized, Blinded, Non-inferiority Trial.

Although there are several treatments for narcolepsy type 2 and idiopathic hypersomnia, studies that assess amphetamines, symptoms beyond sleepiness, and comparative effectiveness are needed. We performed a randomized, fully blinded, noninferiority trial of modafinil versus amphetamine-dextroamphetamine in these disorders. Forty-four adults were randomized to modafinil or amphetamine-dextroamphetamine, individually titrated to a maximum of modafinil 200 mg twice daily or amphetamine-dextroamphetamine 20 mg twice daily, for 12 weeks. Primary outcome was change in Epworth from baseline to week 12, with a noninferiority threshold of 2 points. Secondary outcomes were (1) patient global impression of change measures of disease severity, sleepiness, sleep inertia, and cognition; (2) change from baseline in Hypersomnia Severity Index; and (3) change from baseline in Sleep Inertia Questionnaire. Adverse events were compared between groups. Epworth improved 5.0 [± standard deviation (SD) 2.7] points with modafinil and 4.4 (± SD 4.7) with amphetamine-dextroamphetamine; noninferiority of amphetamine-dextroamphetamine was not demonstrated (P = 0.11). Noninferiority of amphetamine-dextroamphetamine was demonstrated for change scores of severity, sleepiness, sleep inertia, Hypersomnia Severity Index, and Sleep Inertia Questionnaire. Dropouts due to adverse events were 31.8% for modafinil (including two severe events) and 9.1% for amphetamine-dextroamphetamine, P = 0.13. Anxiety was more common with modafinil and appetite suppression with amphetamine-dextroamphetamine. Noninferiority of amphetamine-dextroamphetamine to modafinil was not demonstrated for the primary outcome. However, amphetamine-dextroamphetamine was noninferior on multiple secondary measures of disease severity and symptomatology. These data may inform shared decision-making regarding treatment for idiopathic hypersomnia and narcolepsy type 2. Clinicaltrials.gov Registration (NCT03772314) 12/10/18. .

A gender perspective on diet, microbiome, and sex hormone interplay in cardiovascular disease.

A unique interplay between body and environment embeds and reflects host-microbiome interactions that contribute to sex-differential disease susceptibility, symptomatology, and treatment outcomes. These differences derive from individual biological factors, such as sex hormone action, sex-divergent immune processes, X-linked gene dosage effects, and epigenetics, as well as from their interaction across the lifespan. The gut microbiome is increasingly recognized as a moderator of several body systems that are thus impacted by its function and composition. In humans, biological sex components further interact with gender-specific exposures such as dietary preferences, stressors, and life experiences to form a complex whole, requiring innovative methodologies to disentangle. Here, we summarize current knowledge of the interactions among sex hormones, gut microbiota, immune system, and vascular health and their relevance for sex-differential epidemiology of cardiovascular diseases. We outline clinical implications, identify knowledge gaps, and place emphasis on required future studies to address these gaps. In addition, we provide an overview of the caveats associated with conducting cardiovascular research that require consideration of sex/gender differences. While previous work has inspected several of these components separately, here we call attention to further translational utility of a combined perspective from cardiovascular translational research, gender medicine, and microbiome systems biology.

Structure-function coupling in macroscale human brain networks.

Precisely how the anatomical structure of the brain gives rise to a repertoire of complex functions remains incompletely understood. A promising manifestation of this mapping from structure to function is the dependency of the functional activity of a brain region on the underlying white matter architecture. Here, we review the literature examining the macroscale coupling between structural and functional connectivity, and we establish how this structure-function coupling (SFC) can provide more information about the underlying workings of the brain than either feature alone. We begin by defining SFC and describing the computational methods used to quantify it. We then review empirical studies that examine the heterogeneous expression of SFC across different brain regions, among individuals, in the context of the cognitive task being performed, and over time, as well as its role in fostering flexible cognition. Last, we investigate how the coupling between structure and function is affected in neurological and psychiatric conditions, and we report how aberrant SFC is associated with disease duration and disease-specific cognitive impairment. By elucidating how the dynamic relationship between the structure and function of the brain is altered in the presence of neurological and psychiatric conditions, we aim to not only further our understanding of their aetiology but also establish SFC as a new and sensitive marker of disease symptomatology and cognitive performance. Overall, this Review collates the current knowledge regarding the regional interdependency between the macroscale structure and function of the human brain in both neurotypical and neuroatypical individuals.

Computer-aided prognosis of tuberculous meningitis combining imaging and non-imaging data

Tuberculous meningitis (TBM) is the most lethal form of tuberculosis. Clinical features, such as coma, can predict death, but they are insufficient for the accurate prognosis of other outcomes, especially when impacted by co-morbidities such as HIV infection. Brain magnetic resonance imaging (MRI) characterises the extent and severity of disease and may enable more accurate prediction of complications and poor outcomes. We analysed clinical and brain MRI data from a prospective longitudinal study of 216 adults with TBM; 73 (34%) were HIV-positive, a factor highly correlated with mortality. We implemented an end-to-end framework to model clinical and imaging features to predict disease progression. Our model used state-of-the-art machine learning models for automatic imaging feature encoding, and time-series models for forecasting, to predict TBM progression. The proposed approach is designed to be robust to missing data via a novel tailored model optimisation framework. Our model achieved a 60% balanced accuracy in predicting the prognosis of TBM patients over the six different classes. HIV status did not alter the performance of the models. Furthermore, our approach identified brain morphological lesions caused by TBM in both HIV and non-HIV-infected, associating lesions to the disease staging with an overall accuracy of 96%. These results suggest that the lesions caused by TBM are analogous in both populations, regardless of the severity of the disease. Lastly, our models correctly identified changes in disease symptomatology and severity in 80% of the cases. Our approach is the first attempt at predicting the prognosis of TBM by combining imaging and clinical data, via a machine learning model. The approach has the potential to accurately predict disease progression and enable timely clinical intervention.

A Systematic Review and Narrative Synthesis of Cognitive Training in the Treatment of Mental Illness and Substance Use Disorder.

Introduction: The one unifying and distinguishing feature of all neuropsychiatric illnesses is the co-occurrence of cognitive dysfunction. Cognitive training (CT) was developed to enhance neural connectivity and cognition and improve day-to-day functioning. However, the benefits of CT are still debated. This current systematic review aimed to examine the efficacy of CT and to identify diagnostic and CT characteristics associated with superior outcomes across a range of psychiatric disorders. Method: Studies investigating CT in psychiatric illnesses were extracted from Embase, PubMed, CINAHL, PsycINFO, and PsycARTICLES up to 17 August 2023. Inclusion criteria were randomised control trials (RCT) and English language. The primary search strategy included terms relating to cognitive training, cognitive remediation, cognitive enhancement, or cognitive rehabilitation and randomised control trials, clinical trials, or experiments. Risk of bias was assessed using RevMan Web version 8.1.1. Narrative synthesis was used to analyse findings. Due to the heterogeneity of participant demographics, diagnoses, and interventions, meta-analyses were considered inappropriate. Results: Fifteen studies, including a total of 1075 participants, were identified. Approximately 67% of studies reported significant improvements in at least one trained domain of cognitive function after CT, and 47% observed improvements in psychiatric symptoms or function. Cognitive transfer effects were not observed. Sample sizes for studies were generally small, and most CT durations were 6 weeks or less. Conclusions: Findings suggest that CT can improve cognitive function in trained domains, though little evidence of cognitive transfer effects was observed. Due to the lack of standardisation in CT format and delivery, and inadequate measures of psychiatric symptoms or daily function, there is insufficient evidence to conclude whether or not this technique may benefit cognitive impairment in psychiatric disorders, or lead to subsequent improvement in disease symptomatology. Further studies of longer duration and using consistent methodologies must be conducted to identify the benefits of CT in psychiatric disorders.

Echocardiographic Strain Abnormalities Precede Left Ventricular Hypertrophy Development in Hypertrophic Cardiomyopathy Mutation Carriers.

Hypertrophic cardiomyopathy (HCM) is a genetic disease characterized by unexplained left ventricular hypertrophy (LVH), diastolic dysfunction, and increased sudden-death risk. Early detection of the phenotypic expression of the disease in genetic carriers without LVH (Gen+/Phen-) is crucial for emerging therapies. This clinical study aims to identify echocardiographic predictors of phenotypic development in Gen+/Phen-. Sixteen Gen+/Phen- (one subject with troponin T, six with myosin heavy chain-7, and nine with myosin-binding protein C3 mutations), represented the study population. At first and last visit we performed comprehensive 2D speckle-tracking strain echocardiography. During a follow-up of 8 ± 5 years, five carriers developed LVH (LVH+). At baseline, these patients were older than those who did not develop LVH (LVH-) (30 ± 8 vs. 15 ± 8 years, p = 0.005). LVH+ had reduced peak global strain rate during the isovolumic relaxation period (SRIVR) (0.28 ± 0.05 vs. 0.40 ± 0.11 1/s, p = 0.048) and lower global longitudinal strain (GLS) (-19.8 ± 0.4 vs. -22.3 ± 1.1%; p < 0.0001) than LVH- at baseline. SRIVR and GLS were not correlated with age (overall, p > 0.08). This is the first HCM study investigating subjects before they manifest clinically significant or relevant disease burden or symptomatology, comparing at baseline HCM Gen+/Phen- subjects who will develop LVH with those who will not. Furthermore, we identified highly sensitive, easily obtainable, age- and load-independent echocardiographic predictors of phenotype development in HCM gene carriers who may undergo early preventive treatment.

Relapsing Polychondritis Masquerading as Auricular Pseudolymphoma: Case Report and Literature Review

Relapsing Polychondritis (RP) is a rare autoimmune disease associated with recurring inflammatory episodes predominantly affecting cartilage and other tissues throughout the body, including proteoglycan-rich structures. It is characterized by gradual deformation of tissue that leads to impairment of normal function. Areas involved include, but are not limited to, the respiratory tract, eyes, nose, joints, and vascular system. The inflammation targets cartilage, most commonly causing auricular and nasal chondritis but can involve cartilage throughout the body. Diagnosis of RP is often hindered by the vast variety of symptoms associated with this systemic disease and subtle symptomatology. In this paper, we demonstrate a case of relapsing polychondritis masquerading as pseudolymphoma and review recent literature relating to pathogenesis, diagnosis and treatment.

Brain-targeting autoantibodies in patients with dementia.

Autoantibodies against proteins in the brain are increasingly considered as a potential cause of cognitive decline, not only in subacute autoimmune encephalopathies but also in slowly progressing impairment of memory in patients with classical neurodegenerative dementias. In this retrospective cohort study of 161 well-characterized patients with different forms of dementia and 34 controls, we determined the prevalence of immunoglobulin (Ig) G and IgA autoantibodies to brain proteins using unbiased immunofluorescence staining of unfixed murine brain sections. Autoantibodies were detected in 21.1% of dementia patients and in 2.9% of gender-matched controls, with higher frequencies in vascular dementia (42%), Alzheimer's disease (30%), dementia of unknown cause (25%), and subjective cognitive impairment (16.7%). Underlying antigens involved glial fibrillary acidic protein (GFAP), glycine receptor, and Rho GTPase activating protein 26 (ARHGAP26), but also a range of yet undetermined epitopes on neurons, myelinated fiber tracts, choroid plexus, glial cells, and blood vessels. Antibody-positive patients were younger than antibody-negative patients but did not differ in the extent of cognitive impairment, epidemiological and clinical factors, or comorbidities. Further research is needed to understand the potential contribution to disease progression and symptomatology, and to determine the antigenic targets of dementia-associated autoantibodies.

Factors affecting anticipatory grief of family carers supporting people living with Motor Neurone disease: the impact of disease symptomatology

Objective To investigate the effect of carer- and disease-related factors on anticipatory grief (AG) in family carers supporting people living with Motor Neurone Disease. Methods Seventy-five carers from the UK and USA participated in this cross-sectional study, between July 2021 and February 2023. Participants completed assessments on: anticipatory grief (MMCGI-SF, comprising three sub-scales: Personal Sacrifice Burden, Heartfelt Sadness and Longing, Worry and Felt Isolation); person with MND (pwMND) behavioral changes (MiND-B) and disease severity (ALSFRS-R); carer-pwMND emotional bond (Relationship Closeness Scale), familism levels (Familism Scale), and reported hours of care provided. Multiple linear regression analyses were conducted to explore factors impacting carer AG. Results AG total scores showed that 50.7% of carers were experiencing common grieving reactions, 22.6% presented intense grieving emotions, and 26.7% presented low grieving responses. Disease severity (regression coefficient, β = −0.31, p = 0.01, 95%CI −0.91 to −0.13) and behavioral changes (β = −0.34, p = 0.002, 95%CI −1.45 to −0.33) predicted AG total scores (proportion of explained variation, R 2=0.38, p < 0.001). Regarding AG subscales, Personal Sacrifice Burden (R 2=0.43, p < 0.001) was predicted by disease severity (β = −0.39, p < 0.001, 95%CI −0.42 to −0.11). Behavioral changes predicted Heartfelt Sadness and Longing (β = −0.27, p = 0.03, 95%CI −0.49 to −0.03; R 2 = 0.21, p = 0.01) and Worry and Felt Isolation (β = −0.42, p < 0.001, 95%CI −0.63 to −0.20; R 2=0.33, p < 0.001). Conclusion This study suggests that disease-related factors may be the strongest predictors of carer AG. Interventions addressing carers’ understanding and management of MND symptoms seem crucial to support their experiences of loss and their acceptance of MND. Evidence-based support for carers in MND services is required.

Sex-specific plasma-proteome of incident coronary artery disease

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): This work was supported by a Leiden University Medical Center MD/PhD research grant to V.Q. Sier and Dr. R. Noordam is supported by an innovation grant from the Dutch Heart Foundation. Purpose The onset and symptomatology of coronary artery disease (CAD) are different for men and women, yet insights into sex-specific biological mechanisms causing CAD are limited. To increase insight in the onset of CAD in men and women, we performed a sex-specific proteome-wide association analysis using data from a large cohort of middle-aged participants from the UK Biobank. Methods Associations between 2,923 plasma proteins and CAD incidence (angina pectoris, acute myocardial ischemia, chronic myocardial ischemia) were examined in European-ancestry participants from the UK Biobank who were free of CAD at baseline. Plasma samples were collected at baseline (2006-2010), and CAD incidence was monitored continuously for a median (interquartile range) follow-up of 5,013 (4775-5251) days. Using Cox proportional hazard modelling, the associations between CAD incidence and plasma protein levels were examined, adjusted for age, sex, body mass index, socioeconomic status, type 2 diabetes mellitus, and cholesterol-lowering and insulin drug use at baseline. The Metascape portal was employed for pathway analyses to identify (sex-specific) biological pathways. Results In a total sample comprising 40,829 individuals (55% women, mean age (sd) 56.9 (8.10)), featuring 3,155 incident CAD cases, our sex-combined model demonstrated significant associations between 93 proteins and hazard for CAD. Pathway analyses identified early plasma proteomic changes related to cytokine-cytokine receptor interactions (p=3.42e-17), matrix remodelling (p=9.24e-14, p=1.08 e-9), regulation of innate and adaptive immune cells (p=1.92e-12, p=3.88e-9), and angiogenesis (p=5.34e-9). Stratification by sex revealed distinct sex-specific proteomic patterns linked to CAD incidence, with 10 female-specific and 49 male-specific significant proteins. Through interaction analyses, we demonstrated that 8 proteins were distinctly associated with a significant increased hazard in women, while 20 proteins were significantly associated with increased hazard for CAD in men. Pathway analyses identified a significant female-specific relation between CAD incidence and matrix remodelling (p=9.72e-15, p=3.19e-13), angiogenesis/hypoxia (p=1.41e-12), and inflammatory signalling (p=7.18e-10, p=8.01e-10) pathways, whereas male-specific top pathways related to inflammatory signalling (p=9.58e-25), matrix remodelling (p=1.22e-17), and immune cell response/recruitment (p=3.08e-16, p=8.34e-12). Conclusion Using large-scale association analyses of proteomics data with CAD, we identified sex-specific proteomic profiles. Distinct patterns in more angiogenic (women) and more immune cell response (men) profiles were found. These findings contribute novel insights to the development of CAD, potentially guiding future sex-specific research and clinical strategies for disease prevention.Proteome-wide analysis for CAD incidence

Evaluation of dry eye disease symptomatology and mental health status among patients with different COVID-19 statuses.

To evaluate dry eye disease (DED) symptomatology and mental health status in different COVID-19 patients. A cross-sectional observational design was used. Totally 123 eligible adults (46.34% of men, age range, 18-59y) with COVID-19 included in the study from August to November, 2022. Ocular Surface Disease Index (OSDI), Five-item Dry Eye Questionnaire (DEQ-5), Hospital Anxiety and Depression Scale (HADS), and Pittsburgh Sleep Quality Index (PSQI) were used in this study. OSDI scores were 6.82 (1.25, 15.91) in asymptomatic carriers, 7.35 (2.50, 18.38) in mild cases, and 16.67 (4.43, 28.04) in recurrent cases, with 30.00%, 35.56%, and 57.89%, respectively evaluated as having DED symptoms (χ2=7.049, P=0.029). DEQ-5 score varied from 2.00 (0, 6.00) in asymptomatic carriers, 3.00 (0, 8.00) in mild cases, and 8.00 (5.00, 10.00) in recurrent cases, with 27.50%, 33.33%, and 55.26%, respectively assessed as having DED symptoms (χ2=8.532, P=0.014). The prevalence of clinical anxiety (50.00%) and depression (47.37%) symptoms were also significantly higher in patients with recurrent infection (χ2=24.541, P<0.001; χ2=30.871, P<0.001). Recurrent infection was a risk factor for high OSDI scores [odds ratio, 2.562; 95% confidence interval (CI), 1.631-7.979; P=0.033] and DEQ-5 scores (odds ratio, 3.353; 95%CI, 1.038-8.834; P=0.043), whereas having a fixed occupation was a protective factor for OSDI scores (odds ratio, 0.088; 95%CI, 0.022-0.360; P=0.001) and DEQ-5 scores (odds ratio, 0.126; 95%CI, 0.039-0.405; P=0.001). Patients with recurrent COVID-19 have more severe symptoms of DED, anxiety, and depression.

High-intensity interval training in patients with glaucoma (HIT-GLAUCOMA): protocol for a multicenter randomized controlled exercise trial.

Glaucoma stands as a prominent global cause of irreversible blindness and the primary treatment approach involves reducing intraocular pressure (IOP). However, around one-third of patients exhibit disease progression despite effective IOP reduction. Microvascular endothelial function, chronic inflammation, and oxidative stress are known to affect retinal neuronal networks and have been associated with disease severity and progression. Exercise training has the potential to counteract these mechanisms as add-on treatment to usual care. The HIT-GLAUCOMA study will investigate the effects of a 6-month high-intensity interval training (HIIT) on intermediate endpoints such as local retinal microvascular and systemic large artery function, inflammation, and oxidative stress as well as clinical endpoints such as visual field indices, optic nerve rim assessment, retinal nerve fiber layer thickness, IOP, number of eye drops, vision-related quality of life and ocular surface disease symptomatology. The study is a multi-center randomized controlled clinical trial in patients with both normal tension and high-tension primary open angle glaucoma. Across two study centers, 128 patients will be enrolled and randomized on a 1:1 basis into an exercise intervention group and a usual care control group. The primary microvascular endpoints are retinal arteriolar and venular flicker light-induced dilation at 6months. The primary endpoint in the systemic circulation is brachial artery flow-mediated dilation at 6months. We hypothesize that exercise therapy will improve retinal microvascular function and thus ocular blood flow in patients with glaucoma. As clinical outcomes, we will investigate the effect of exercise on visual field indices, optic nerve rim assessment, retinal nerve fiber layer thickness, IOP, number of eye drops, vision-related quality of life and ocular surface disease symptomatology. HIT-GLAUCOMA is a blueprint trial design to study the effect of exercise training on neurodegenerative and cardiovascular diseases. Importantly, patients are also expected to benefit from improvements in general health and cardiovascular co-morbidities. If proven effective, exercise may offer a new add-on treatment strategy to slow glaucoma progression. The trial is registered at Clinicaltrials.gov under the identifier NCT06058598 and is currently in the recruitment stage.

Grapevine pruning strategy affects trunk disease symptoms, wood pathobiome and mycobiome

Vine training and pruning are cultural strategies that can be deployed to manage grapevine trunk diseases (GTDs). Forty-year-old commercial vineyards in the Cognac region, France, trained to either Guyot-Arcure (severe pruning) or Guyot-Poussard (minimal pruning), were studied to determine how the two systems affected trunk disease symptomatology. Effects of pruning practices on the pathobiome and mycobiome of asymptomatic grapevines were also assessed, using culture- and amplicon-based Illumina sequencing approaches. The hypothesis examined was that severe pruning of Guyot-Arcure increases trunk diseases incidence and severity, and causes higher pathogen load and microbial diversity, compared to Guyot-Poussard. Numbers of symptomatic and asymptomatic vines for the two training systems were recorded over 3 years, including numbers of vines with esca foliar symptoms, and partially unproductive and dead vines. Six asymptomatic vines from each pruning method were selected, and culturing and sequencing data were obtained from 27 samples per vine. Fungi in the Phaeomoniellaceae, Togniniaceae, and Botryosphaeriaceae were the most frequently identified. The data indicated that severe pruning increased risk of pathogen infections, with Phaeomoniella chlamydospora, Phaeoacremonium minimum and Diplodia sp. being the most commonly identified fungi. Greater numbers of dead or dying vines were recorded in the severely pruned vineyard, indicating that this strategy shortens vine longevity. Results also showed that severe pruning increased endophytic microbial diversity, and that the pruning methods influenced mycobiome community composition. This knowledge will improve recommendations to growers for practical and cost-effective ways to manage GTDs.

Parkinson’s Detection Using Voice Features and Spiral Drawings

Parkinson's is a dynamic neurodegenerative disease that presents multiple symptoms that advance over time. Our project proposes an innovative Parkinson's discovery machine learning model that combines both voice examination and spiral drawings assessments to capture numerous angles of the disease's symptomatology. Our approach looks for developing a comprehensive Parkinson’s detection model over different stages and symptoms of the disease. By integrating voice analysis techniques to discern subtle changes in speech patterns and spiral drawing assessments to evaluate motor function, our method aims to provide a more holistic assessment of PD symptoms. By leveraging the complementary strengths of voice analysis and spiral drawing assessments, our proposed PD detection project aims to overcome the limitations of existing approaches and provide clinicians with a more comprehensive model for early detection, diagnosis and monitoring of Parkinson's Disease. Ultimately, this initiative strives to enhance patient outcomes, improve treatment efficacy, and advance our understanding of PD progression.

Neuroligin-2 shapes individual slow waves during slow-wave sleep and the response to sleep deprivation in mice

BackgroundSleep disturbances are a common comorbidity to most neurodevelopmental disorders and tend to worsen disease symptomatology. It is thus crucial to understand mechanisms underlying sleep disturbances to improve patients’ quality of life. Neuroligin-2 (NLGN2) is a synaptic adhesion protein regulating GABAergic transmission. It has been linked to autism spectrum disorders and schizophrenia in humans, and deregulations of its expression were shown to cause epileptic-like hypersynchronized cerebral activity in rodents. Importantly, the absence of Nlgn2 (knockout: KO) was previously shown to alter sleep-wake duration and quality in mice, notably increasing slow-wave sleep (SWS) delta activity (1–4 Hz) and altering its 24-h dynamics. This type of brain oscillation is involved in memory consolidation, and is also a marker of homeostatic sleep pressure. Sleep deprivation (SD) is notably known to impair cognition and the physiological response to sleep loss involves GABAergic transmission.MethodsUsing electrocorticographic (ECoG) recordings, we here first aimed to verify how individual slow wave (SW; 0.5-4 Hz) density and properties (e.g., amplitude, slope, frequency) contribute to the higher SWS delta activity and altered 24-h dynamics observed in Nlgn2 KO mice. We further investigated the response of these animals to SD. Finally, we tested whether sleep loss affects the gene expression of Nlgn2 and related GABAergic transcripts in the cerebral cortex of wild-type mice using RNA sequencing.ResultsOur results show that Nlgn2 KO mice have both greater SW amplitude and density, and that SW density is the main property contributing to the altered 24-h dynamics. We also found the absence of Nlgn2 to accelerate paradoxical sleep recovery following SD, together with profound alterations in ECoG activity across vigilance states. Sleep loss, however, did not modify the 24-h distribution of the hypersynchronized ECoG events observed in these mice. Finally, RNA sequencing confirmed an overall decrease in cortical expression of Nlgn2 and related GABAergic transcripts following SD in wild-type mice.ConclusionsThis work brings further insight into potential mechanisms of sleep duration and quality deregulation in neurodevelopmental disorders, notably involving NLGN2 and GABAergic neurotransmission.