Hartmandrejer5011

This study examines polypharmacy and prescription drug use patterns in cancer survivors, a growing population at risk for cancer sequelae and side effects from treatment, which can arise months or even years following diagnosis. Survivors may experience greater medication burden than the general population, increasing concerns for polypharmacy and subsequent risks of drug interactions and non-adherence.

Using the National Health and Nutrition Examination Survey (NHANES) data from 2003 to 2014, we examined the association between a cancer history and presence of polypharmacy (5+ medications). We estimated prevalence ratios and prevalence differences for polypharmacy comparing those with and without a cancer history using binomial regression models and propensity score (PS) weighting to account for baseline differences between groups.

We identified 32,238 adults aged 20 years or older; 1899 had cancer (excluding non-melanoma skin) at least 1 year before the survey. Overall, polypharmacy prevalence was 13% and 35% in those with and without a cancer history, respectively. After PS weighting, the polypharmacy prevalence was 1.26 times higher among those with versus without a cancer history (weighted prevalence ratio, 1.26; 95% CI, 1.18, 1.35). In sub-group analyses, the weighted prevalence ratio was largest for those 20-39 years old at survey (2.78; 95% CI, 1.71, 4.53), and the weighted prevalence difference was largest for those 40-64 years old at survey (9.35%; 95% CI, 5.70%, 13.01%).

Cancer survivors of all ages take more medications than those without cancer history and may benefit from discussions with providers about age-tailored medication use management.

Cancer survivors of all ages take more medications than those without cancer history and may benefit from discussions with providers about age-tailored medication use management.

Seroprevalence surveys from different countries have reported SARS CoV-2 antibodies below 20% even in the most adversely affected areas and herd immunity cannot be predicted till more than half of the population gets the disease. The purpose of this survey was to estimate the magnitude of community-based spread of the infection, associated immunity, and the future prospects and proximity to a 'herd community'.

The study was undertaken as a cluster randomized, cross-sectional countrywide survey. This largest community-based seroprevalence data of SARS-CoV-2 were collected between 15th and 31st July, 2020 from seven randomly selected cities belonging to the three most populous provinces of Pakistan. The FDA approved kit of ROCHE was used for detection of SARS-CoV-2 antibodies.

Serum samples of 15,390 participants were tested for SARS CoV-2 antibodies with an overall seroprevalence of 42.4%. The seroprevalence ranged from 31.1% to 48.1% in different cities with the highest in Punjab province (44.5%). In univariable analysis, the odds of seropositivity was higher in men compared to women (OR 1.10, 95% CI 1.01-1.19, P < 0.05). In multivariable analysis, the risk of being seropositive was lower (OR 0.72, 95% CI 0.60-0.87, P < 0.01) in younger group (≤20years) than in those aged above 60years.

The study concluded that despite a reasonable seroprevalence, the country is yet to reach the base minimum of estimations for herd immunity. The durability of immunity though debated at the moment, has shown an evidenced informed shift towards longer side.

The study concluded that despite a reasonable seroprevalence, the country is yet to reach the base minimum of estimations for herd immunity. The durability of immunity though debated at the moment, has shown an evidenced informed shift towards longer side.In drug development decision-making is often supported through model-based methods, such as physiologically-based pharmacokinetics (PBPK). Global sensitivity analysis (GSA) is gaining use for quality assessment of model-informed inference. However, the inclusion and interpretation of correlated factors in GSA has proven an issue. Here we developed and evaluated a latent variable approach for dealing with correlated factors in GSA. TG003 An approach was developed that describes the correlation between two model inputs through the causal relationship of three independent factors the latent variable and the unique variances of the two correlated parameters. The latent variable approach was applied to a set of algebraic models and a case from PBPK. Then, this method was compared to Sobol's GSA assuming no correlations, Sobol's GSA with groups and the Kucherenko approach. For the latent variable approach, GSA was performed with Sobol's method. By using the latent variable approach, it is possible to devise a unique and easy interpretation of the sensitivity indices while maintaining the correlation between the factors. Compared methods either consider the parameters independent, group the dependent variables into one unique factor or present difficulties in the interpretation of the sensitivity indices. In situations where GSA is called upon to support model-informed decision-making, the latent variable approach offers a practical method, in terms of ease of implementation and interpretability, for applying GSA to models with correlated inputs that does not violate the independence assumption. Prerequisites and limitations of the approach are discussed.Alveolar enlargement is a pathological feature of emphysema. Long-term exposure to cigarette smoke (CS) is a high-risk factor for the development of emphysema. Abnormal protein ubiquitination has been implicated to regulate the development of human disorders, however, the role of protein ubiquitination in emphysema has not been well-studied. In this study, we attempted to investigate if a deubiquitinase, USP13, regulates the development of emphysema. Under a mild CS exposure condition, USP13-deficient mice show significant increases in alveolar chord length, indicating that USP13-deficient mice are susceptible to CS-induced alveolar enlargement. It has been shown that USP13 knockout reduced fibronectin expression in lungs. Here, we found that collagen levels were reduced in USP13 siRNA-transfected lung fibroblast cells. This suggests that a loss of extracellular matrix in connective tissues contributes to alveolar enlargement in USP13-deficient mice in response to CS exposure. Further, we investigated the role of USP13 in the expression of oxidative stress markers TXNIP and HMOX1. An increase in HMOX1 abundance was observed in USP13 knockdown lung fibroblast and epithelial cells. Overexpression of USP13 reduced HMOX1 protein levels in lung fibroblast cells, suggesting that modulation of USP13 levels may affect oxidative stress. Knockdown of USP13 significantly reduced TXNIP levels in lungs or lung fibroblast cells. A protein stability pulse-chase assay showed that TXNIP is instable within USP13 knockdown lung fibroblast cells. Further, the reduction of TXNIP was observed in USP13 inhibitor-treated lung epithelial cells. USP13-deficient mice also show higher levels of IgG in bronchoalveolar lavage fluid. This study provides evidence showing that USP13 deficiency plays a role in alveolar space enlargement.Lysophosphatidic acid receptor 1 (LPA1) belongs to the G protein-coupled receptor family. The ligand for LPA1 is LPA, the simplest lysophospholipid. LPA is considered a growth factor and induces cell proliferation, anti-apoptosis, and cell migration. The pro-inflammatory and pro-fibrotic roles of LPA have also been well-demonstrated. Most of the biological functions of LPA are mostly executed through LPA1. The mature form of LPA1 is glycosylated and localized on the plasma membrane. LPA1 is bound to heterotrimetric G proteins and transduces intracellular signaling in response to ligation to LPA. Desensitization of LPA1 negatively regulates LPA1-mediated signaling and the resulting biological functions. Phosphorylation and ubiquitination are well-demonstrated posttranslational modifications of GPCR. In this review, we will discuss our knowledge of LPA1 glycosylation, maturation, and trafficking from the endoplasmic reticulum (ER)/Golgi to the plasma membrane. Moreover, in light of recent findings, we will also discuss molecular regulation of LPA1 internalization and stability.Two previously undescribed dibenzocyclooctadiene lignans, named sieverlignans D-E (1-2), as well as eight known ones (3-10), were isolated from the aerial parts of Artemisia sieversiana. Their structures were elucidated from extensive spectroscopic analysis, including HRMS, NMR and electronic circular dichroism (ECD) experiments. This study is the first to report dibenzocyclooctadiene lignans in the genus Artemisia and this plant. All the compounds were evaluated for their anti-neuroinflammatory activities on the lipopolysaccharides (LPS)-induced nitric oxide production in BV-2 murine microglial cells. Compounds 1 and 6 exhibited the moderate activities with their IC50 values of 47.7 and 21.9 μM, compared to a positive control quercetin with the IC50 value of 16.0 μM.Amomum Semen, the seed mass of Amomum xanthioides, has been imported from Southeast Asia and China and used for the treatment of gastric and intestinal disorders. A. xanthioides has been treated as a synonym of A. villosum var. xanthioides. Furthermore, A. villosum var. villosum, A. villosum var. xanthioides, or A. longiligulare have been described as the botanical origin of Amomi Fructus, which is a similar crude drug in Chinese Pharmacopoeia. Under these circumstances, the botanical origin of Amomum Semen was changed to A. villosum var. xanthioides, A. villosum var. villosum, or A. longiligulare in Supplement II to the 17th edition of the Japanese Pharmacopoeia. To develop an objective identification method for Amomum Semen and to confirm the phylogenetic relationship among Amomum taxa, the nucleotide sequences of the nuclear ribosomal DNA internal transcribed spacer region and chloroplast DNA partial matK-trnK and trnH-psbA intergenic spacer regions were determined in specimens collected from Southeast Asia and China, including those from the type localities of each taxon. Six taxa were divided into four groups. A. xanthioides from Myanmar belonging to group 1 was discriminated from A. villosum var. xanthioides from China of group 2. A. villosum and its varieties were divided into two groups group 2 included those from China, and group 3 consisted of A. villosum from Laos. A. longiligulare from China and Laos and A. uliginosum from Laos belonged to group 3 and group 4, respectively. These findings illustrate the phylogenetic basis for the need for taxonomical reorganization among the Amomum species.

In order to integrate the existing and inconsistent information from clinical trials and real-world practice on chronic lymphocytic leukemia (CLL) treated with ibrutinib, this analysis aimed to describe the prescription pattern of new users of ibrutinib affected by CLL, focusing on discontinuation, severe adverse events (AEs) and change of treatment, and to assess the integrated healthcare expenditure from the Italian National Health System (INHS) perspective.

Starting from the ReS database, adults with at least a supply of ibrutinib (ATC code L01XE27) were selected from 01/01/2016 to 12/31/2017. Those without any ibrutinib supply in the year before the index prescription were considered new users. Out of them, only patients with at least a primary or secondary in-hospital diagnosis of CLL (ICD-9-CM code 204.1*) from 01/01/2013 to 12/31/2018 were further broken down according to the ibrutinib's line treatment (first line-FL; second or later line-SLL) and analysed. They were characterized by sex and age in the selection period.