Changes in iPSC-Astrocyte morphology reflect Alzheimer's disease patient clinical markers.

Human induced pluripotent stem cells (iPSCs) provide powerful cellular models of Alzheimer's disease (AD) and offer many advantages over non-human models, including the potential to reflect variation in individual-specific pathophysiology and clinical symptoms. Previous studies have demonstrated that iPSC-neurons from individuals with Alzheimer's disease (AD) reflect clinical markers, including β-amyloid (Aβ) levels and synaptic vulnerability. However, despite neuronal loss being a key hallmark of AD pathology, many risk genes are predominantly expressed in glia, highlighting them as potential therapeutic targets.

Extraction Methods for Brain Biopsy NMR Metabolomics: Balancing Metabolite Stability and Protein Precipitation.

: Metabolic profiling of tissue samples via liquid-state nuclear magnetic resonance (NMR) requires the extraction of polar metabolites in a suitable deuterated solvent. Such methods often prioritise metabolite recovery over protein removal due to the relatively low sensitivity of NMR metabolomics and the routine use of methods able to supress residual protein signals. However, residual protein may impact metabolite integrity and the metabolite stability after NMR sample preparation is often overlooked.

From Young to Old: Mimicking Neuronal Aging in Directly Converted Neurons from Young Donors.

A substantial challenge in human brain aging is to find a suitable model to mimic neuronal aging in vitro as accurately as possible. Using directly converted neurons (iNs) from human fibroblasts is considered a promising tool in human aging since it retains the aging-associated mitochondrial donor signature. Still, using iNs from aged donors can pose certain restrictions due to their lower reprogramming and conversion efficacy than those from younger individuals.

Tuberculosis preventive treatment in eight SEAR countries - Current practices, implementation challenges and operations research priorities.

Objectives: Countries in the South East Asian region face similar challenges in control of infectious diseases. There is limited access to experiences and learnings of neighboring countries. The Indian Council - of Medical Research (ICMR) has established a Regional Enabler for the South-East Asia Research Collaboration for Health (RESEARCH) Platform for South East Asian Region (SEAR) countries to address the above issues.

Comprehensive characterization of the neurogenic and neuroprotective action of a novel TrkB agonist using mouse and human stem cell models of Alzheimer's disease.

Background: Neural stem cell (NSC) proliferation and differentiation in the mammalian brain decreases to minimal levels postnatally. Nevertheless, neurogenic niches persist in the adult cortex and hippocampus in rodents, primates and humans, with adult NSC differentiation sharing key regulatory mechanisms with development. Adult neurogenesis impairments have been linked to Alzheimer's disease (AD) pathology.

A disease-associated gene desert directs macrophage inflammation through ETS2.

Increasing rates of autoimmune and inflammatory disease present a burgeoning threat to human health. This is compounded by the limited efficacy of available treatments and high failure rates during drug development, highlighting an urgent need to better understand disease mechanisms. Here we show how functional genomics could address this challenge.

Exploring Social Interactions in the Context of Justice System Involvement: Perspectives of Patients and Psychiatric Nurses.

Psychiatric nurses who work with people who are involved with the justice system experience ethical and moral tension arising from their dual role (care and control). This is known to significantly affect the development of a therapeutic relationship between nurses and patients. (a) better understand how justice system involvement affects people living with mental disorders and the nurses who work with them; (b) explore the influence of judiciarization on social interactions between these actors.

A novel human iPSC model of COL4A1/A2 small vessel disease unveils a key pathogenic role of matrix metalloproteinases.

Cerebral small vessel disease (SVD) affects the small vessels in the brain and is a leading cause of stroke and dementia. Emerging evidence supports a role of the extracellular matrix (ECM), at the interface between blood and brain, in the progression of SVD pathology, but this remains poorly characterized. To address ECM role in SVD, we developed a co-culture model of mural and endothelial cells using human induced pluripotent stem cells from patients with COL4A1/A2 SVD-related mutations.

The Judiciarization of People Living with Mental Illness: A Grounded Theory on the Perceptions of Persons Involuntary Admitted in Psychiatric Institution.

The involvement of people living with mental illness in the judicial process, whether in civil or criminal justice system, is a growing phenomenon that can be defined as judiciarization. Such over-representation of people with mental illness in the justice system is related to several issues, including stigma, experienced coercion, loss of autonomy and social isolation. To explore this understudied phenomenon in nursing research, we conducted a study to better understand how judiciarization affects people living with mental illness.

Aneuploidy effects on human gene expression across three cell types.

Aneuploidy syndromes impact multiple organ systems but understanding of tissue-specific aneuploidy effects remains limited-especially for the comparison between peripheral tissues and relatively inaccessible tissues like brain. Here, we address this gap in knowledge by studying the transcriptomic effects of chromosome X, Y, and 21 aneuploidies in lymphoblastoid cell lines, fibroblasts and iPSC-derived neuronal cells (LCLs, FCL, and iNs, respectively). We root our analyses in sex chromosome aneuploidies, which offer a uniquely wide karyotype range for dosage effect analysis.

Investigation of Cav3.3 Dysfunction in Hemiplegic Migraine.

Familial hemiplegic migraine (FHM) is a severe neurogenetic disorder for which three causal genes, , , and , have been implicated. However, more than 80% of referred diagnostic cases of hemiplegic migraine (HM) are negative for exonic mutations in these known FHM genes, suggesting the involvement of other genes. Using whole-exome sequencing data from 187 mutation-negative HM cases, we identified rare variants in the gene encoding the T-type calcium channel Cav3.

A purine metabolic checkpoint that prevents autoimmunity and autoinflammation.

Still's disease, the paradigm of autoinflammation-cum-autoimmunity, predisposes for a cytokine storm with excessive T lymphocyte activation upon viral infection. Loss of function of the purine nucleoside enzyme FAMIN is the sole known cause for monogenic Still's disease. Here we discovered that a FAMIN-enabled purine metabolon in dendritic cells (DCs) restrains CD4 and CD8 T cell priming.

Platelet-Mediated NET Release Amplifies Coagulopathy and Drives Lung Pathology During Severe Influenza Infection.

The influenza A virus (IAV) causes a respiratory tract infection with approximately 10% of the population infected by the virus each year. Severe IAV infection is characterized by excessive inflammation and tissue pathology in the lungs. Platelet and neutrophil recruitment to the lung are involved in the pathogenesis of IAV, but the specific mechanisms involved have not been clarified.

Short Warwick-Edinburgh Mental Well-being Scale (SWEMWBS): performance in a clinical sample in relation to PHQ-9 and GAD-7.

Purpose: This study assesses the construct validity and sensitivity to change of the Short Warwick-Edinburgh Mental Well-being Scale (SWEMWBS) as an outcome measure in the treatment of common mental disorders (CMD) in primary care settings.

Methods: 127 participants attending up to 5 sessions of therapy for CMD in primary care self-rated the SWEMWBS, the Patient Health Questionnaire (PHQ-9) and General Anxiety Disorder (GAD-7) scales. SWEMWBS's construct validity and sensitivity to change was evaluated against the PHQ-9 and GAD-7 across multiple time points in two ways: correlation coefficients were calculated between the measures at each time point; and sensitivity to change over time was assessed using repeated measures ANOVA.

NOCICEPTRA: Gene and microRNA Signatures and Their Trajectories Characterizing Human iPSC-Derived Nociceptor Maturation.

Nociceptors are primary afferent neurons serving the reception of acute pain but also the transit into maladaptive pain disorders. Since native human nociceptors are hardly available for mechanistic functional research, and rodent models do not necessarily mirror human pathologies in all aspects, human induced pluripotent stem cell-derived nociceptors (iDN) offer superior advantages as a human model system. Unbiased mRNA::microRNA co-sequencing, immunofluorescence staining, and qPCR validations, reveal expression trajectories as well as miRNA target spaces throughout the transition of pluripotent cells into iDNs.

Genome-Wide Association Study Identifies Risk Loci for Cluster Headache.

Objective: This study was undertaken to identify susceptibility loci for cluster headache and obtain insights into relevant disease pathways.

Methods: We carried out a genome-wide association study, where 852 UK and 591 Swedish cluster headache cases were compared with 5,614 and 1,134 controls, respectively. Following quality control and imputation, single variant association testing was conducted using a logistic mixed model for each cohort.

Targeted single-cell RNA sequencing of transcription factors enhances the identification of cell types and trajectories.

Single-cell RNA sequencing (scRNA-seq) is a widely used method for identifying cell types and trajectories in biologically heterogeneous samples, but it is limited in its detection and quantification of lowly expressed genes. This results in missing important biological signals, such as the expression of key transcription factors (TFs) driving cellular differentiation. We show that targeted sequencing of ∼1000 TFs (scCapture-seq) in iPSC-derived neuronal cultures greatly improves the biological information garnered from scRNA-seq.

Active screening of patients with diabetes mellitus for pulmonary tuberculosis in a tertiary care hospital in Sri Lanka.

End TB strategy by the WHO suggest active screening of high-risk populations for tuberculosis (TB) to improve case detection. Present study generates evidence for the effectiveness of screening patients with diabetes mellitus (DM) for Pulmonary TB (PTB). A study was conducted among 4548 systematically recruited patients over 45 years attending DM clinic at the National Hospital of Sri Lanka.

Global proteomic analysis of extracellular matrix in mouse and human brain highlights relevance to cerebrovascular disease.

The extracellular matrix (ECM) is a key interface between the cerebrovasculature and adjacent brain tissues. Deregulation of the ECM contributes to a broad range of neurological disorders. However, despite this importance, our understanding of the ECM composition remains very limited mainly due to difficulties in its isolation.

The genetics of migraine and the path to precision medicine.

Migraine is a highly heritable complex brain disorder, imposing a huge burden of disability on sufferers. The genetic architecture of migraine ranges from the rare Mendelian forms whereby a single gene mutation is sufficient to cause disease to gene variants that individually impart only a small increase in migraine risk. Despite the considerable advances in the last decade, there are significant challenges to translate genetic findings into drug targets and eventually successful treatments.