The Well-Being of the German Adult Population Measured with the WHO-5 over Different Phases of the COVID-19 Pandemic: An Analysis within the COVID-19 Snapshot Monitoring Study (COSMO)

The aim of this study is to evaluate factors associated with the subjective well-being (SWB) and suspected depression measured with WHO-5 among German adults during different phases of the COVID-19 pandemic. Survey data were analyzed from the COVID-19 Snapshot Monitoring (COSMO) study, which collected data from 972, 1013, and 973 participants in time point 1 (19–20 May 2020), time point 2 (15–16 September 2020), and time point 3 (21–22 December 2020), respectively. Descriptive analyses and logistic regression analyses to identify the factors associated with suspected depression (WHO-5 ≤ 50) were conducted. Data showed that the mean WHO-5 scores in three time points were 56.17, 57.27, and 53.93, respectively. The risk of suspected depression was increased by about 1.5 times for females, 2.5–3 times among 18–24 year-olds compared to ages above 65 years, 1.5 times for singles, 2 times for those with chronic illnesses, and 2–3 times for people living in poverty. The main study findings show that German adult SWB is lower than pre-pandemic reference values. Special focus should be placed on vulnerable groups, such as females, younger persons, and people living in poverty who are most prone to a reduction in SWB and therefore suspected depression

Alcohol Use of German Adults during Different Pandemic Phases: Repeated Cross-Sectional Analyses in the COVID-19 Snapshot Monitoring Study (COSMO)

There is little evidence on how different COVID-19 pandemic phases influence the alcohol use behaviour of adults. The objective of this study is to investigate alcohol use frequency over different COVID-19 pandemic phases and to identify vulnerable subgroups for risky use behaviour in the German adult population. Survey waves of 14/15 April 2020 (n = 1032), 23/24 June 2020 (n = 993), and 26/27 January 2021 (n = 1001) from the COVID-19 Snapshot Monitoring (COSMO) were analysed. The mean age was 46 ± 15.3 years in April, 46 ± 15.5 years in June, and 45 ± 15.5 years in January. The gender ratio was mostly equal in each survey wave. Descriptive analyses and univariate and multivariate logistic regression analyses for individuals with increased alcohol use frequency (AUF) were performed. 13.2% in April (lockdown), 11.3% in June (easement), and 8.6% in January (lockdown) of participants showed an increased AUF. Individuals with perceived burden, high frustration levels due to protective measures, and young to middle-aged adults were more likely to increase their AUF during different pandemic phases. In conclusion, unfavourable alcohol behaviour might occur as a potentially maladaptive coping strategy in pandemics. Because of potential negative long-term consequences of problematic alcohol use behaviour on health, public health strategies should consider mental health consequences and target addictive behaviour, while also guiding risk groups towards healthy coping strategies such as physical activities during pandemics/crises

Protective Effects of Statin Therapy in Cirrhosis Are Limited by a Common SLCO1B1 Transporter Variant

Complications of cirrhosis and portal hypertension (PH) can be reduced by statin therapy. The common loss-of-function variant p.V174A in the solute carrier organic anion transporter gene 1B1 (SLCO1B1) gene encoding the organic anion transporting polypeptide 1B1 results in decreased hepatic uptake of statins. Our specific aim was to assess the impact of this variant in patients with cirrhosis and statin treatment while controlling for the stage of cirrhosis and other potential confounders with propensity score matching (PSM), availing of a large cohort of genotyped study patients. In total, from 1,088 patients with cirrhosis in two German academic medical centers, PSM yielded 154 patients taking statins and 154 matched controls. The effect on PH was assessed by the liver stiffness–spleen size–to–platelet score (LSPS), and complications of cirrhosis were retrospectively recorded applying consensus criteria. As hypothesized, patients on statin treatment presented less frequently with signs of PH: Esophageal varices (41% vs. 62%; P < 0.001) were less common, and LSPS (4.8 ± 11.5 vs. 5.6 ± 6.4; P = 0.01) was reduced. Correspondingly, decompensation events were also reduced in patients on statins (odds ratio [OR] = 0.54, 95% confidence interval [CI] 0.32-0.90; P = 0.02). When the variant in SLCO1B1 was present in patients on statins, esophageal varices (OR = 2.68, 95% CI 1.24-5.81; P = 0.01) and bacterial infections (OR = 2.50, 95% CI 1.14-5.47; P = 0.02) were more common as compared with wild type carriers on statins. Conclusion: In this cohort, signs and complications of PH were reduced in patients with cirrhosis treated with statins. Notably, this effect was diminished by the common loss-of-function variant in SLCO1B1. Further prospective studies in independent cohorts are warranted to confirm these genotype-specific observations

Emotional Situation of Children and Adolescents during the COVID-19 Pandemic in Germany: Results from the COVID-19 Snapshot Monitoring Study (COSMO)

The COVID-19 pandemic led to numerous restrictions in daily life that had a significant impact on the well-being and mental health of the population. Among others, children and adolescents were particularly affected, being a vulnerable group at risk. The aim of this study was to assess the emotional situation of children and adolescents during different phases of the pandemic and to identify modifying factors. Data from the serial cross-sectional COVID-19 Snapshot Monitoring (COSMO) survey in Germany were used for this study. The survey waves 12 (19th/20th May 2020) and 21 (15th/16th September 2020) were investigated as examples of two different pandemic phases. The psychosocial and emotional situation and well-being of children were measured with the emotional subscale of the Strengths and Difficulties Questionnaire (SDQ) assessed by parents. Descriptive analyses and logistic regressions were calculated. In total, a third of the participating parents in wave 12 and in wave 21 reported having children and adolescents with emotional symptoms. Especially children with younger parents seemed to be more affected by emotional symptoms. Sociodemographic aspects, such as household language, showed a significant association with reported emotional symptoms in children (Wave 12: OR = 2.22; 95% CI: 1.20–4.09). Reported prevalences of emotional symptoms in children did not differ between the pandemic phases. In conclusion, the pandemic had negative influences on the emotional symptoms of children and adolescents in COVID-19 pandemic waves in 2020, indicating a forecasted reoccurrence and need for preventive measures for upcoming waves and other pandemics in the future

Solid-phase-assisted synthesis of targeting peptide-PEG-oligo(ethane amino)amides for receptor-mediated gene delivery.

In the forthcoming era of cancer gene therapy, efforts will be devoted to the development of new efficient and non-toxic gene delivery vectors. In this regard, the use of Fmoc/Boc-protected oligo(ethane amino)acids as building blocks for solid-phase-supported assembly represents a novel promising approach towards fully controlled syntheses of effective gene vectors. Here we report on the synthesis of defined polymers containing the following: (i) a plasmid DNA (pDNA) binding domain of eight succinoyl-tetraethylenpentamine (Stp) units and two terminal cysteine residues; (ii) a central polyethylene glycol (PEG) chain (with twenty-four oxyethylene units) for shielding; and (iii) specific peptides for targeting towards cancer cells. Peptides B6 and c(RGDfK), which bind transferrin receptor and αvβ3 integrin, respectively, were chosen because of the high expression of these receptors in many tumoral cells. This study shows the feasibility of designing these kinds of fully controlled vectors and their success for targeted pDNA-based gene transfer

The influence of bisphosphonates on human osteoblast migration and integrin aVb3/tenascin C gene expression in vitro

<p>Abstract</p> <p>Background</p> <p>Bisphosphonates are therapeutics of bone diseases, such as Paget's disease, multiple myeloma or osteoclastic metastases. As a severe side effect the bisphosphonate induced osteonecrosis of the jaw (BONJ) often requires surgical treatment and is accompanied with a disturbed wound healing.</p> <p>Therefore, the influence on adhesion and migration of human osteoblasts (hOB) after bisphosphonate therapy has been investigated by morphologic as well as gene expression methods.</p> <p>Methods</p> <p>By a scratch wound experiment, which measures the reduction of defined cell layer gap, the morphology and migration ability of hOB was evaluated. A test group of hOB, which was stimulated by zoledronate 5 × 10^-5M, and a control group of unstimulated hOB were applied. Furthermore the gene expression of integrin aVb3 and tenascin C was quantified by Real-Time rtPCR at 5data points over an experimental period of 14 days. The bisphosphonates zoledronate, ibandronate and clodronate have been compared with an unstimulated hOB control.</p> <p>Results</p> <p>After initially identical migration and adhesion characteristics, zoledronate inhibited hOB migration after 50 h of stimulation. The integrinavb3 and tenascin C gene expression was effected by bisphosphonates in a cell line dependent manner with decreased, respectively inconsistent gene expression levels over time. The non-nitrogen containing bisphosphonates clodronate led to decreased gene expression levels.</p> <p>Conclusion</p> <p>Bisphosphonates seem to inhibit hOB adhesion and migration. The integrin aVb3 and tenascin C gene expression seem to be dependent on the cell line. BONJ could be enhanced by an inhibition of osteoblast adhesion and migration. The gene expression results, however, suggest a cell line dependent effect of bisphosphonates, which could explain the interindividual differences of BONJ incidences.</p

The impact of bisphosphonates on the osteoblast proliferation and Collagen gene expression in vitro

<p>Abstract</p> <p>Background</p> <p>Bisphosphonates are widely used in the clinical treatment of bone diseases with increased bone resorption. In terms of side effects, they are known to be associated with osteonecrosis of the jaw (BONJ).</p> <p>The objective of this study was to evaluate the effect of bisphosphonates on osteoblast proliferation by cell count and gene expression analysis of cyclin D1 <it>in vitro</it>. Furthermore, the gene expression of the extracellular matrix protein collagen type I was evaluated. Nitrogen-containing and non-nitrogen-containing bisphosphonates have been compared on gene expression levels.</p> <p>Methods</p> <p>Human osteoblast obtained from hip bone were stimulated with zoledronate, ibandronate and clodronate at concentrations of 5 × 10^-5M over the experimental periods of 1, 2, 5, 10 and 14 days. At each point in time, the cells were dissolved, the mRNA extracted, and the gene expression level of cyclin D1 and collagen type I were quantified by Real-Time RT-PCR. The gene expression was compared to an unstimulated osteoblast cell culture for control.</p> <p>Results</p> <p>The proliferation appeared to have been influenced only to a small degree by bisphosphonates. Zolendronate led to a lower cyclin D1 gene expression after 10 days. The collagen gene expression was enhanced by nitrogen containing bisphosphonates, decreased however after day 10. The non-nitrogen-containing bisphosphonate clodronate, however, did not significantly influence cyclin D1 and collagen gene expression.</p> <p>Conclusions</p> <p>The above data suggest a limited influence of bisphosphonates on osteoblast proliferation, except for zoledronate. The extracellular matrix production seems to be initially advanced and inhibited after 10 days. Interestingly, clodronate has little influence on osteoblast proliferation and extracellular matrix production in terms of cyclin D1 and collagen gene expression.</p