Morbidity among Adolescent Hypnotic Drug Users in Norway: An Observational Population-Based Study.

We have previously shown that the use of hypnotic drugs increased among young Scandinavians during 2012-2018. This study aimed to explore psychiatric and somatic morbidity among adolescent hypnotic drug users in a cohort study of 13-17-year-old individuals during 2008-2018 in Norway. Data sources were (i) prescription data from the Norwegian Prescription Database linked to specialist health care diagnoses from the Norwegian Patient Registry and (ii) sleep disorder diagnoses from the Primary Health Care Database.

Pharmaceutical pollution: Prediction of environmental concentrations from national wholesales data.

The regulation and monitoring of pharmaceutical pollution in Europe lag behind that of more prominent groups. However, the repurposing of sales data to predict surface water environmental concentrations is a promising supplement to more commonly used market-based risk assessment and measurement approaches. The Norwegian Institute of Public Health (NIPH) has since the 1980s compiled the Drug Wholesale Statistics database - covering all sales of both human and veterinary pharmaceuticals to retailers, pharmacies, and healthcare providers.

Predicting Environmental Risks of Pharmaceuticals from Wholesale Data: An Example from Norway.

Environmental risk assessment (ERA) of pharmaceuticals relies on available measured environmental concentrations, but often such data are sparse. Predicted environmental concentrations (PECs), calculated from sales weights, are an attractive alternative but often cover only prescription sales. We aimed to rank, by environmental risk in Norway, approximately 200 active pharmaceutical ingredients (APIs) over 2016-2019, based on sales PECs.

DNA quality evaluation of formalin-fixed paraffin-embedded heart tissue for DNA methylation array analysis.

Archived formalin-fixed and paraffin-embedded (FFPE) heart tissue from autopsied individuals represents an important resource for investigating the DNA methylation of heart tissue of deceased individuals. The DNA quality of FFPE tissue from autopsies may be decreased, affecting the DNA methylation measurements. Therefore, inexpensive screening methods for estimating DNA quality are valuable.

Neurological Complications in COVID-19 Patients: Can Analysis of Specific Antibodies and Viral RNA in Paired Cerebrospinal Fluid and Serum be Used for Accurate Diagnosis of SARS-CoV-2 Neuroinflammatory Disease? A Case Series.

Background: Neurological complications during and after SARS-CoV-2 infection have been frequently described. The detection of either SARS-CoV-2 RNA or specific antibodies against SARS-CoV-2 in cerebrospinal fluid in the context of concomitant neurological manifestations indicates neuroinfection.

Methods And Results: This is a retrospective descriptive analysis of cerebrospinal fluids and serum samples from 2 hospitalized patients and autopsy findings from 2 patients who died at home.

Stereological Estimation of Myocardial Fat and Its Associations with Obesity, Epicardial, and Visceral Adipose Tissue.

The normal human heart contains epicardial adipose tissue (EAT) and myocardial fat. The associations between obesity, myocardial fat, visceral adipose tissue (VAT), and cardiovascular disease are not fully understood. The objective of this study was to estimate myocardial fat using stereological methods and investigate its relations with obesity, EAT, and VAT.

Characterization of deceased drug users in Denmark based on treatment status: A nationwide retrospective autopsy study.

Background: Many drug users are not receiving treatment for their drug use. Little is known about drug users not receiving treatment, as they are difficult to identify and recruit for research.

Methods: We identified 479 autopsied decedents with illegal/unmarketed drug or opioid agonist treatment positive toxicological screenings from 2015 to 2016 in Denmark.

Translational deep phenotyping of deaths related to the COVID-19 pandemic: protocol for a prospective observational autopsy study.

Introduction: The COVID-19 pandemic is an international emergency with an extreme socioeconomic impact and a high mortality and disease burden. The COVID-19 outbreak is neither fully understood nor fully pictured. Autopsy studies can help understand the pathogenesis of COVID-19 and has already resulted in better treatment of patients.

Genetic investigations of 100 inherited cardiac disease-related genes in deceased individuals with schizophrenia.

Cardiac diseases and sudden cardiac death (SCD) are more prevalent in individuals diagnosed with schizophrenia compared to the general population, with especially coronary artery disease (CAD) as the major cardiovascular cause of death. Antipsychotic medications, genetics, and lifestyle factors may contribute to the increased SCD in individuals with schizophrenia. The role of antipsychotic medications and lifestyle factors have been widely investigated, while the genetic predisposition to inherited cardiac diseases in schizophrenia is poorly understood.

Differential Methylation in the Regulatory Region in Sudden Unexplained Death and Sudden Unexpected Death in Epilepsy.

Sudden cardiac death (SCD) is a diagnostic challenge in forensic medicine. In a relatively large proportion of the SCDs, the deaths remain unexplained after autopsy. This challenge is likely caused by unknown disease mechanisms.

Autopsies in pandemics - a perspective on barriers and benefits. Is it time for a revival?

Influenza virus and coronavirus pandemics regularly sweep the globe, at great cost of health and economy. Our aim was to conduct a PubMed search for autopsy studies on influenza and coronavirus to investigate the contribution of autopsies during pandemics, focussing on autopsy methods and procedures and the role of autopsy findings in pandemics. The retrieved autopsy studies generally relied on microscopy, polymerase chain reaction (PCR), immunostaining and electron microscopy.

Excision of uracil from DNA by hSMUG1 includes strand incision and processing.

Uracil arises in DNA by hydrolytic deamination of cytosine (C) and by erroneous incorporation of deoxyuridine monophosphate opposite adenine, where the former event is devastating by generation of C → thymine transitions. The base excision repair (BER) pathway replaces uracil by the correct base. In human cells two uracil-DNA glycosylases (UDGs) initiate BER by excising uracil from DNA; one is hSMUG1 (human single-strand-selective mono-functional UDG).

Undiagnosed chronic obstructive pulmonary disease in patients admitted to an acute assessment unit.

: Chronic obstructive pulmonary disease (COPD) is very prevalent worldwide, yet underdiagnosed. : This study investigates feasibility of performing spirometry in patients in need of acute hospital admission as well as the prevalence of undiagnosed COPD in the same cohort. : During a two-week period, all patients admitted to three large acute assessment units were evaluated.

Diet-induced pre-diabetes slows cardiac conductance and promotes arrhythmogenesis.

Background: Type 2 diabetes is associated with abnormal electrical conduction and sudden cardiac death, but the pathogenic mechanism remains unknown. This study describes electrophysiological alterations in a diet-induced pre-diabetic rat model and examines the underlying mechanism.

Methods: Sprague-Dawley rats were fed either high-fat diet and fructose water or normal chow and water for 6 weeks.

Myocardial impulse propagation is impaired in right ventricular tissue of Zucker diabetic fatty (ZDF) rats.

Background: Diabetes increases the risk of cardiovascular complications including arrhythmias, but the underlying mechanisms remain to be established. Decreased conduction velocity (CV), which is an independent risk factor for re-entry arrhythmias, is present in models with streptozotocin (STZ) induced type 1 diabetes. Whether CV is also disturbed in models of type 2 diabetes is currently unknown.

Valproic Acid significantly lowers serum concentrations of olanzapine-an interaction effect comparable with smoking.

Background: Preliminary reports have indicated that valproic acid (VPA) reduces serum concentrations of olanzapine (OLZ). The aim of this study was to investigate the impact of VPA and other antiepileptic drugs (AEDs) on serum concentrations of OLZ and 3 of its major metabolites in a large-scale material of therapeutic drug monitoring samples.

Methods: OLZ-treated patients were stratified into subgroups according to coadministration of various AEDs, that is, lamotrigine (LTG; 110 patients/153 samples), VPA (92/166), LTG + VPA (7/12), carbamazepine (CBZ) (8/8), oxcarbazepine (2/3), gabapentin (3/4), levetiracetam (2/3), and topiramate (2/2).

Influence of repeated short-term nitrogen limitations on leaf phenolics metabolism in tomato.

High concentrations of phenolics have been shown to play a role in plant resistance to pathogens. One way to obtain increased phenolic concentrations in plant tissues is to limit mineral nitrogen (N) availability; however, over long periods, this treatment will have a negative effect on plant growth. The aim of our study was to determine the effect of repeated short-term N limitations on plant growth and phenolic metabolism in leaves.

Angiotensin II does not acutely regulate conduction velocity in rat atrial tissue.

Aim: Atrial angiotensin II (Ang II) levels are increased in atrial fibrillation and are believed to be important in the pathogenesis of atrial arrhythmias. Ang II reduces intercellular coupling by inhibiting gap junctions (connexins) and may thereby increase the risk of reentry arrhythmia. The aim of the current study was to investigate the acute effect of Ang II on conduction velocity (CV) in atrial tissue from normal and chronically infarcted rats.

The angiotensin II type 1 receptor antagonist Losartan binds and activates bradykinin B2 receptor signaling.

The angiotensin II type 1 receptor (AT1R) blocker (ARB) Losartan has cardioprotective effects during ischemia-reperfusion injury and inhibits reperfusion arrhythmias -effects that go beyond the benefits of lowering blood pressure. The renin-angiotensin and kallikrein-kinin systems are intricately connected and some of the cardioprotective effects of Losartan are abolished by blocking the bradykinin B2 receptor (B2R) signaling. In this study, we investigated the ability of six clinically available ARBs to specifically bind and activate the B2R.

Identification and characterisation of CYP75A31, a new flavonoid 3'5'-hydroxylase, isolated from Solanum lycopersicum.

Background: Understanding the regulation of the flavonoid pathway is important for maximising the nutritional value of crop plants and possibly enhancing their resistance towards pathogens. The flavonoid 3'5'-hydroxylase (F3'5'H) enzyme functions at an important branch point between flavonol and anthocyanin synthesis, as is evident from studies in petunia (Petunia hybrida), and potato (Solanum tuberosum). The present work involves the identification and characterisation of a F3'5'H gene from tomato (Solanum lycopersicum), and the examination of its putative role in flavonoid metabolism.

Synergetic effects of nitrogen depletion, temperature, and light on the content of phenolic compounds and gene expression in leaves of tomato.

Tomato plants (Solanum lycopersicum, cv. Suzanne) were subjected to complete nutrient solution or a solution without nitrogen (N), and placed at different temperatures and light conditions to test the effects of environment on flavonoids and caffeoyl derivatives and related gene expression. N depletion during 4-8days resulted in enhanced levels of flavonoids and caffeoyl derivatives.

The endogenous GL3, but not EGL3, gene is necessary for anthocyanin accumulation as induced by nitrogen depletion in Arabidopsis rosette stage leaves.

The bHLH transcription factors EGL3 (ENHANCER OF GLABRA3) and its close homologue GL3 (GLABRA3) are important regulators of the anthocyanin pathway in Arabidopsis thaliana, and together with TTG1 (a WD40 repeat protein) and MYB transcription factors regulate specific genes in the pathway. In response to nitrogen depletion, the MYB genes PAP1/PAP2 (production of anthocyanin pigment 1/2) and GL3 are strongly induced, and anthocyanin synthesis is activated in seedlings and rosette stage plants. In this study we show that anthocyanins accumulate in both wild type and egl3, but not in gl3 loss-of-function mutants when depleted of nitrogen.