Publications by authors named "H. Ising"

Article Synopsis
  • Research highlights the significant role of immune processes in the development of Alzheimer's disease, which is the leading cause of dementia.
  • Various studies indicate that both innate and adaptive immune responses contribute to the disease's pathology and are influenced by genetics and lifestyle factors.
  • New therapeutic approaches targeting neuroinflammation are being explored in clinical settings, offering potential treatment options for Alzheimer's patients.
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Background: The timeliness, accuracy, and completeness of data for firearm injury surveillance is crucial for public health surveillance efforts and informing injury prevention measures. While emergency department (ED) visit data can provide near real-time information on firearms injuries, there are concerns surrounding the accuracy of intent coding in these data. We examined whether emergency medical service (EMS) data provide more accurate firearm injury intent coding in comparison to ED data.

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The highest risk factor for the development of neurodegenerative diseases like tauopathies is aging. Many physiological decrements underlying aging are linked to cellular senescence. Senescent cells are characterized by an irreversible growth arrest and formation of a senescence-associated secretory phenotype (SASP), a proinflammatory secretome that modifies the cellular microenvironment and contributes to tissue deterioration.

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Article Synopsis
  • Reduced glomerular filtration rate (GFR) is a precursor to kidney failure, influenced by factors like genetics and diabetes (DM), but the interaction between these factors is not well understood.
  • A large-scale genome-wide association study (GWAS) analyzed eGFR across almost 1.5 million individuals, revealing distinct genetic loci that differ between those with and without diabetes.
  • The findings identified potential new targets for drug development aimed at protecting kidney function, highlighting that many drug interventions could be effective for both diabetic and non-diabetic populations.
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There is an urgent need to improve the understanding of neuroinflammation in Alzheimer's disease (AD). We analyzed cerebrospinal fluid inflammatory biomarker correlations to brain structural volume and longitudinal cognitive outcomes in the DELCODE study and in a validation cohort of the F.ACE Alzheimer Center Barcelona.

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Objectives: We assessed the differences between the first version of the Centers for Disease Control and Prevention (CDC) opioid surveillance definition for suspected nonfatal opioid overdoses (hereinafter, CDC definition) and the North Carolina Disease Event Tracking and Epidemiologic Collection Tool (NC DETECT) surveillance definition to determine whether the North Carolina definition should include additional (ICD-10-CM) codes and/or chief complaint keywords.

Methods: Two independent reviewers retrospectively reviewed data on North Carolina emergency department (ED) visits generated by components of the CDC definition not included in the NC DETECT definition from January 1 through July 31, 2018. Clinical reviewers identified false positives as any ED visit in which available evidence supported an alternative explanation for patient presentation deemed more likely than an opioid overdose.

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Article Synopsis
  • Linking EMS data to ED data improves the assessment of patient outcomes for opioid overdoses in North Carolina, using new methodologies for better analysis.
  • The study analyzed EMS encounters with naloxone administration from 2017, resulting in enhanced data linkage accuracy from 47.1% to 91.1% while minimizing false linkages.
  • Enhanced linkage quality can improve surveillance and emergency medical responses, ultimately leading to better care for patients experiencing opioid overdoses.
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APOE is the strongest genetic risk factor for late-onset Alzheimer's disease. ApoE exacerbates tau-associated neurodegeneration by driving microglial activation. However, how apoE regulates microglial activation and whether targeting apoE is therapeutically beneficial in tauopathy is unclear.

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It is imperative to understand the specific and shared etiologies of major depression and cardio-metabolic disease, as both traits are frequently comorbid and each represents a major burden to society. This study examined whether there is a genetic association between major depression and cardio-metabolic traits and if this association is stratified by age at onset for major depression. Polygenic risk scores analysis and linkage disequilibrium score regression was performed to examine whether differences in shared genetic etiology exist between depression case control status (N cases = 40,940, N controls = 67,532), earlier (N = 15,844), and later onset depression (N = 15,800) with body mass index, coronary artery disease, stroke, and type 2 diabetes in 11 data sets from the Psychiatric Genomics Consortium, Generation Scotland, and UK Biobank.

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Antidepressant therapy is still associated with delays in symptomatic improvement and low response rates. Incomplete understanding of molecular mechanisms underlying antidepressant effects hampered the identification of objective biomarkers for antidepressant response. In this work, we studied transcriptome-wide expression followed by pathway analysis in lymphoblastoid cell lines (LCLs) derived from 17 patients documented for response to SSRI antidepressants from the Munich Antidepressant Response Signatures (MARS) study upon short-term incubation (24 and 48 h) with citalopram.

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Article Synopsis
  • Researchers analyzed data from genome-wide association studies (GWAS) to explore genetic correlations across four eating disorder types and eight substance-use-related traits, involving large sample sizes ranging from ~2400 to ~537,000 participants.
  • Findings indicated positive genetic associations between anorexia nervosa and alcohol use disorder, as well as cannabis initiation, while some negative correlations were found between anorexia without binge eating and smoking behaviors, suggesting a complex relationship between these disorders influenced by genetic and possibly depressive factors.
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Alzheimer's disease is characterized by the accumulation of amyloid-beta in plaques, aggregation of hyperphosphorylated tau in neurofibrillary tangles and neuroinflammation, together resulting in neurodegeneration and cognitive decline. The NLRP3 inflammasome assembles inside of microglia on activation, leading to increased cleavage and activity of caspase-1 and downstream interleukin-1β release. Although the NLRP3 inflammasome has been shown to be essential for the development and progression of amyloid-beta pathology in mice, the precise effect on tau pathology remains unknown.

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Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178).

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Adverse experiences and chronic stress are well-known risk factors for the development of major depression, and an impaired stress response regulation is frequently observed in acute depression. Impaired glucocorticoid receptor (GR) signalling plays an important role in these alterations, and a restoration of GR signalling appears to be a prerequisite of successful antidepressant treatment. Variants in genes of the stress response regulation contribute to the vulnerability to depression in traumatized subjects.

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Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest genome-wide association study to date of DSM-IV-diagnosed AD. Genome-wide data on 14,904 individuals with AD and 37,944 controls from 28 case-control and family-based studies were meta-analyzed, stratified by genetic ancestry (European, n = 46,568; African, n = 6,280).

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Recent reports have shown an increase in the number of organ donors from drug intoxication. The impact of donor drug use on survival after cardiac transplant remains unclear. The aim of our study was to illustrate changes in donor death mechanisms and assess the impact on posttransplant survival.

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Patients with an 'At risk mental state' (ARMS) for developing psychosis can be treated successfully with CBT to postpone and prevent the transition to a first psychotic episode. A characteristic of individuals that meet ARMS criteria is that they are still open for multiple explanations for extraordinary experiences. CBT aims to normalize extraordinary experiences with education and to prevent delusional explanations.

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The present study investigated the genetic contribution to alcohol dependence (AD) using genome-wide association data from three German samples. These comprised patients with: (i) AD; (ii) chronic alcoholic pancreatitis (ACP); and (iii) alcohol-related liver cirrhosis (ALC). Single marker, gene-based, and pathway analyses were conducted.

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Tauopathies are characterized by the progressive accumulation of hyperphosphorylated, aggregated forms of tau. Our laboratory has previously demonstrated that passive immunization with an anti-tau antibody, HJ8.5, decreased accumulation of pathological tau in a human P301S tau-expressing transgenic (P301S-tg) mouse model of frontotemporal dementia/tauopathy.

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Article Synopsis
  • This study investigates the genetic factors linked to alcohol dependence by conducting a genomewide association study with a sample of related cases and population controls.
  • Researchers found potential associations with genes COL6A3, KLF12, RYR3, and LOC339975; however, these were not consistently replicated in larger populations.
  • The experiment using model organisms shows that these genes may affect behaviors related to alcohol response, pointing to their possible role in human alcohol dependence, despite some findings not being statistically significant.
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Objective: Although TF treatments are effective in patients with psychosis, it is unknown whether specific psychosis-related obstacles limit the effects, and what determines good outcome.

Methods: Baseline posttraumatic stress disorder (PTSD) symptom severity and seven psychosis-specific variables were tested as predictors in patients with a psychotic disorder and PTSD (n=108), who received eight sessions of TF treatment (Prolonged Exposure, or Eye Movement Desensitization and Reprocessing therapy) in a single-blind randomized controlled trial. Multiple regression analyses were performed.

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Background: Epidemiological and retrospective studies suggest a cannabis x catechol-O-methyltransferase (COMT) Val(158)Met interaction effect on development of psychosis. The aim of this study was to examine this interaction and its association with severity of subclinical symptoms in people with an At Risk Mental State (ARMS) for psychosis.

Methods: Severity of symptoms, cannabis use and genotype were assessed at baseline in 147 help-seeking young adults who met the ARMS criteria and agreed to participate in the Dutch Early Detection and Intervention (EDIE-NL) trial.

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