No relationship between male pubertal timing and depression - new insights from epidemiology and Mendelian randomization.

Background: In males, the relationship between pubertal timing and depression is understudied and less consistent than in females, likely for reasons of unmeasured confounding. To clarify this relationship, a combined epidemiological and genetic approach was chosen to exploit the methodological advantages of both approaches.

Methods: Data from 2026 males from a nationwide, representative study were used to investigate the non-/linear relationship between pubertal timing defined by the age at voice break and depression, considering a multitude of potential confounders and their interactions with pubertal timing.

Bridging the gap - estimation of 2022/2023 SARS-CoV-2 healthcare burden in Germany based on multidimensional data from a rapid epidemic panel.

Objectives: Throughout the SARS-CoV-2 pandemic, Germany like other countries lacked adaptive population-based panels to monitor the spread of epidemic diseases.

Methods: To fill a gap in population-based estimates needed for winter 2022/23 we resampled in the German SARS-CoV-2 cohort study MuSPAD in mid-2022, including characterization of systemic cellular and humoral immune responses by interferon-γ-release assay (IGRA) and CLIA/IVN assay. We were able to confirm categorization of our study population into four groups with differing protection levels against severe COVID-19 courses based on literature synthesis.

Treatment-Resistant Depression in Real-World Clinical Practice: A Systematic Literature Review of Data from 2012 to 2022.

Objective: Real-world evidence in treatment-resistant depression (TRD; commonly defined as non-response to ≥ 2 consecutive treatments at adequate dosage and duration) is lacking. A systematic literature review was conducted to understand disease burden and treatment outcomes for patients with TRD, studied in a real-world setting over the last decade.

Data Sources: A literature search was conducted in May 2022 in MEDLINE, Embase, The Cochrane Libraries and PsycINFO, comprising studies published from 2012 to 2022.

Esketamine Nasal Spray versus Quetiapine for Treatment-Resistant Depression.

Background: In treatment-resistant depression, commonly defined as a lack of response to two or more consecutive treatments during the current depressive episode, the percentage of patients with remission is low and the percentage with relapse is high. The efficacy and safety of esketamine nasal spray as compared with extended-release quetiapine augmentation therapy, both in combination with ongoing treatment with a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI), in patients with treatment-resistant depression are unknown.

Methods: In an open-label, single-blind (with raters unaware of group assignments), multicenter, phase 3b, randomized, active-controlled trial, we assigned patients, in a 1:1 ratio, to receive flexible doses (according to the summary of product characteristics) of esketamine nasal spray (esketamine group) or extended-release quetiapine (quetiapine group), both in combination with an SSRI or SNRI.

Attributes Characterizing Colorectal Cancer Screening Tests That Influence Preferences of Individuals Eligible for Screening in Germany: A Qualitative Study.

Purpose: This qualitative study is part of the SIGMO study, which evaluates general populations' preferences for colorectal cancer (CRC) screening in Germany using a discrete choice experiment. Attribute identification and selection are essential in the construction of choice tasks and should be evidence-based ensuring that attributes are relevant to potential beneficiaries and contribute to overall utility. Therefore, this qualitative study aims to identify relevant attributes characterizing CRC screening tests from the perspective of those eligible for screening in Germany.

Regular Benzodiazepine and Z-Substance Use and Risk of Dementia: An Analysis of German Claims Data.

Background: While acute detrimental effects of benzodiazepine (BDZ), and BDZ and related z-substance (BDZR) use on cognition and memory are known, the association of BDZR use and risk of dementia in the elderly is controversially discussed. Previous studies on cohort or claims data mostly show an increased risk for dementia with the use of BDZs or BDZRs. For Germany, analyses on large population-based data sets are missing.

Association of Proton Pump Inhibitors With Risk of Dementia: A Pharmacoepidemiological Claims Data Analysis.

Importance: Medications that influence the risk of dementia in the elderly can be relevant for dementia prevention. Proton pump inhibitors (PPIs) are widely used for the treatment of gastrointestinal diseases but have also been shown to be potentially involved in cognitive decline.

Objective: To examine the association between the use of PPIs and the risk of incident dementia in the elderly.

Risk of dementia in elderly patients with the use of proton pump inhibitors.

Drugs that modify the risk of dementia in the elderly are of potential interest for dementia prevention. Proton pump inhibitors (PPIs) are widely used to reduce gastric acid production, but information on the risk of dementia is lacking. We assessed association between the use of PPIs and the risk of dementia in elderly people.

Loss of PDCD4 contributes to enhanced chemoresistance in Glioblastoma multiforme through de-repression of Bcl-xL translation.

Glioblastoma multiforme (GBM) is the most common and aggressive form of tumor of the central nervous system. Despite significant efforts to improve treatments, patient survival rarely exceeds 18 months largely due to the highly chemoresistant nature of these tumors. Importantly, misregulation of the apoptotic machinery plays a key role in the development of drug resistance.

Smoking and atherosclerotic cardiovascular disease: part III: functional biomarkers influenced by smoking.

Smoking cigarettes induces rapidly occurring and reversible functional changes in the cardiovascular system, which precede morphologic changes. These functional changes are also related to atherosclerotic disease development and thus may qualify as prognostic parameters in chronic smokers. As opposed to smoking-induced morphologic changes functional alterations occur and revert within minutes, thus, allowing for the detection of smoking-induced effects on the cardiovascular system within minutes following exposure to mainstream smoke.

Smoking and atherosclerotic cardiovascular disease: part II: role of cigarette smoking in cardiovascular disease development.

Potential mechanisms and biomarkers of atherosclerosis related to cigarette smoking - a modifiable risk factor for that disease - are discussed in this article. These include smoking-associated inflammatory markers, such as leukocytes, high-sensitivity C-reactive protein, serum amyloid A, ICAM-1 and IL-6. Other reviewed markers are indicative for smoking-related impairment of arterial endothelial function (transcapillary leakage of albumin, inhibition of endogenous nitric oxide synthase activity and reduced endothelium-dependent vasodilation) or point to oxidative stress caused by various chemicals (cholesterol oxidation, autoantibodies to oxidized low-density lipoprotein, plasma levels of malondialdehyde and F(2)-isoprostanes and reduced antioxidant capacity).

Smoking and atherosclerotic cardiovascular disease: Part I: atherosclerotic disease process.

The normal endothelium inhibits platelet and leukocyte adhesion to the vascular surface maintaining a balance of profibrinolytic and prothrombotic activity. Endothelial function is assessed largely as endothelium-dependent vasomotion, partly based on the assumption that impaired endothelium-dependent vasodilation reflects the alteration of important endothelial functions. Atherosclerotic risk factors, such as hypercholesterolemia, hypertension, diabetes and smoking, are associated with endothelial dysfunction.

Smoking and atherosclerotic cardiovascular disease: part IV: genetic markers associated with smoking.

Genes influence smoking behavior, affect the metabolism of nicotine and specific chemicals produced during combustion, and enhance (or diminish) pathomechanistic pathways associated with the atherogenic potential of smoking, including oxidative stress, its inflammatory burden or procoagulant potential. Genome-wide association studies have revolutionized the search for new functional genetic markers with ever increasing marker density and the precision in identifying new genetic loci without the need for prior knowledge of functional pathways. Nevertheless, the statistical challenge remains to identify the few true positives, the need for replication of findings and the tedious work of identifying functional genetic variants and their mode of action.

Progression of atherosclerosis in the Apo E-/- model: 12-month exposure to cigarette mainstream smoke combined with high-cholesterol/fat diet.

This study was performed to gain information about the influence of two cardiovascular risk factors, cigarette mainstream smoke (MS) and high-cholesterol/fat diet, on the progression of atherosclerosis in apolipoprotein E-deficient (Apo E-/-) mice. Eight to 12-week-old mice were whole-body exposed for up to 12 months (6h/day, 5 days/week) to diluted cigarette mainstream smoke at total particulate matter (TPM) concentrations of 100 or 200mg/m(3), or to filtered fresh air (sham) in combination with a normal chow diet or a high-cholesterol/fat diet. Cholesterol in the aortic arch was elevated in the high-cholesterol/fat diet groups exposed to 200 mg TPM/m(3) compared to sham at all time points.

Smoking accelerates the progression of hypertension-induced myocardial hypertrophy to heart failure in spontaneously hypertensive rats.

Objective: Myocardial hypertrophy often develops in response to hypertension, and it is causal to and an independent predictor of heart failure. Several risk factors modify the progression of hypertrophy, the associated progressive impairment of myocardial function, and eventually the transition to overt congestive heart failure. The aim of the present study was to investigate the effects of smoking on the progression of pressure-dependent myocardial hypertrophy.

Biomarkers of exposure and potential harm in adult smokers of 3-7 mg tar yield (Federal Trade Commission) cigarettes and in adult non-smokers.

The paper reports levels of 24-h urine nicotine and five of its major metabolites (expressed as nicotine-equivalents) and blood carboxyhaemoglobin as biomarkers of exposure to particulate- and gas-phase cigarette smoke, respectively, from an exploratory pilot study of adult smokers of 3.0-6.9 mg tar delivery (Federal Trade Commission (FTC) method) cigarettes.

CYP1A2 and NAT2 phenotyping and 3-aminobiphenyl and 4-aminobiphenyl hemoglobin adduct levels in smokers and non-smokers.

Some aromatic amines are considered to be putative bladder carcinogens. Hemoglobin (Hb) adducts of 3-aminobiphenyl (3-ABP) and 4-aminobiphenyl (4-ABP) have been used as biomarkers of exposure to aromatic amines from cigarette smoke. One of the goals of this study was to determine intra- and inter-individual variability in 3-ABP and 4-ABP Hb adducts and to explore the predictability of ABP Hb adduct levels based on caffeine phenotyping.

A 46 kDa NTPase common to rat liver nuclear envelope, mitochondria, plasma membrane, and endoplasmic reticulum.

A 46 kDa ATP binding polypeptide of the nuclear envelope, virtually identical to the nuclear envelope NTPase putatively involved in mRNA efflux [6], is present in all rat liver cell membranes. Its presence in nuclear envelope is not the result of cross contamination during isolation.

Negative supercoiling and nucleosome cores. II. The effect of negative supercoiling on the positioning of nucleosome cores in vitro.

The influence of unrestrained negative superhelical stress on nucleosome core positioning was investigated in vitro for a core located on a section of the early H1-H4 histone gene spacer of Psammechinus miliaris. We show that the position of this core on a reconstituted molecule occupied by 11 nucleosome cores is identical on a linear DNA molecule and a circular DNA molecule in the absence of unrestrained negative superhelical stress. This position is also identical to that previously found on a 337 base-pair fragment of corresponding sequence.

Negative supercoiling and nucleosome cores. I. The effect of negative supercoiling on the efficiency of nucleosome core formation in vitro.

The efficiency of nucleosome core formation in vitro as a function of DNA topology was investigated. We show that the reconstitution of nucleosome cores by urea/salt dialysis on both negatively supercoiled and linearized plasmid proceed co-operatively, and that negatively supercoiled molecules are reconstituted significantly more efficiently compared with linearized molecules. The free energy of supercoiling, related to the square of the linking deficit, is further shown to be sufficient to account for this difference, which is particularly pronounced at low molar reconstitution ratios of octamer: DNA.

Bitis arietans nerve growth factor is a disulphide-linked homodimer.

1. Nerve growth factor from Bitis arietans venom was isolated in high yield and purified to homogeneity using a rapid two-step procedure involving gel exclusion chromatography and reversed-phase HPLC. 2.

Stage- and adult tissue-specific expression of a homeobox gene in embryo and adult Parechinus angulosus sea urchins.

We report the isolation of a gene (PaHbox6), encoding a homeobox-containing protein of the South African sea urchin, Parechinus angulosus. Sequencing identified an Antennapedia-class gene encoding a homeobox that is the homologue of the Hawaiian sea urchin Tripneustes gratilla homeobox gene. Extensive restriction-fragment length polymorphism surrounds the gene.