Correlation of Increased Soluble Tumor Necrosis Factor Receptor 1 with Mortality and Dependence on Treatment in Non-Small-Cell Lung Cancer Patients: A Longitudinal Cohort Study.

BACKGROUND: Tumor necrosis factor (TNF) is a multipotent cytokine involved in inflammation and anti-tumor activity. TNF-α exerts its function upon binding to TNF-receptor 1 (TNF-R1) and TNF-receptor 2 (TNF-R2). This study investigates the relationship of soluble (s) TNF-R1 levels in non-small-cell lung cancer (NSCLC) patients with treatment and overall survival. METHODS: In total, 134 NSCLC patients treated at the Medical Faculty of Martin Luther University Halle-Wittenberg between 2017 and 2019 were included in this study. Serum levels of sTNF-R1 were measured via ELISA at baseline and during and after treatment. A linear mixed-effects model was used to assess sTNF-R1 changes over time. Linear regression was applied to investigate the association between clinical characteristics and changes in sTNF-R1. Cox regression models were used to estimate associations with overall mortality. RESULTS: The estimated average sTNFR-1 at baseline was 2091.71 pg/mL, with a change of 6.19 pg/mL per day. Cox models revealed that the individual change in sTNF-R1 was more strongly associated with mortality than its baseline value, especially after adjusting for covariates. CONCLUSIONS: This study provides evidence that the individual change in sTNF-R1 levels during and after treatment were associated with the risk of mortality, suggesting the use of the sTNF-R1 trajectory as a prognostic marker.

Physical activity trajectories at older age and all-cause mortality: A cohort study.

BACKGROUND: A physically active lifestyle is recognized as a precondition of healthy aging. However, the majority of studies exploring its association with mortality in cohorts of adults used single-time physical activity (PA) estimate, which do not consider its dynamic nature with changes that occur with aging. The aim of the present study is to explore the presence of different PA trajectories in a population-based cohort and their association with mortality. METHODS: We used data of the population-based cohort study CARLA and included 1041 older adults (45-83 years at baseline) with self-reported physical activity at baseline (2002-2006), first follow-up (2007-2010) and second follow-up (2013). Trajectories were identified using growth mixture modelling. Cox proportional hazard models were used to assess the association between trajectories of PA and all-cause mortality during ~6 years since the second follow-up after adjusting for age, sex, lifestyle factors and comorbidities and after correction for classification error. In a sensitivity analysis we weighted the models to account for selection bias during follow-up. As a further sensitivity analysis, we excluded the first year of follow-up to account for reverse causation. RESULTS: Three PA trajectories (categorized as consistently low, consistently moderate, and high at baseline but strongly decreasing PA across time) were identified, and 121 deaths due to all causes occurred. Compared with participants who had consistently low PA-levels throughout the follow-up period, participants who maintained moderate PA-levels were at a lower risk of all-cause mortality (hazard ratio [HR], 0.49; 95%CI, 0.30-0.70). Participants with high PA-levels at baseline but strongly decreasing PA across time, had similar mortality risk compared to the participants with consistently low PA-levels (hazard ratio [HR], 0.97; 95%CI, 0.50-1.80). The effects were strengthened in the analysis weighted for selection bias. CONCLUSIONS: Our results suggest that, compared to those who had consistently low PA levels, those who maintained a moderate level of PA showed a protective effect in terms of their mortality risk but not those who displayed a decline from high PA levels.

The efficient role of algae as green factories for nanotechnology and their vital applications.

Nanoscience has witnessed wide developments in various directions, in addition to its crossing through different vital medical and industrial applications. This prompted the development of green nanotechnology that is environmentally friendly with low toxicity, less energy use, and low eco-hazard. So, algae as green autotrophic organisms, gain increasing attention from nanotechnologists, giving a space for the arising of a new field "Algae nanotechnology", where the algae can be used either directly or via mimicry of their unique features and diversity. Algae can biosynthesis nanoparticles in intercellular or extracellular ways, depending on their cellular reactions inside the cells, their secondary metabolites, or extraction of the algal contents. The different ways of using algae for nanoparticles biosynthesis make it available to control the synthesizing of ecofriendly & biocompatible nanoparticles, with different types and morphologies. This review provides an overview of the previous efforts in this emerging field, giving a summary of the ability of algae in nanotechnology, besides future prospective of these trends in algal nanotechnology.

Cardiovascular risk factors, living and ageing in Halle: the CARLA study.

The CARLA study (Cardiovascular Disease, Living and Ageing in Halle) is a longitudinal population-based cohort study of the general population of the city of Halle (Saale), Germany. The primary aim of the cohort was to investigate risk factors for cardiovascular diseases based on comprehensive cardiological phenotyping of study participants and was extended to study factors associated with healthy ageing. In total, 1779 probands (812 women and 967 men, aged 45-83 years) were examined at baseline (2002-2005), with a first and second follow-up performed 4 and 8 years later. The response proportion at baseline was 64.1% and the reparticipation proportion for the first and second follow-up was 86% and 77% respectively. Sixty-four percent of the study participants were in retirement while 25% were full- or partially-employed and 11% were unemployed at the time of the baseline examination. The currently running third follow-up focuses on the assessment of physical and mental health, with an intensive 4 h examination program, including measurement of cardiovascular, neurocognitive, balance and gait parameters. The data collected in the CARLA Study resulted in answering various research questions in over 80 publications, of which two thirds were pooled analyses with other similar population-based studies. Due to the extensiveness of information on risk factors, subclinical conditions and evident diseases, the biobanking concept for the biosamples, the cohort representativeness of an elderly population, and the high level of quality assurance, the CARLA cohort offers a unique platform for further research on important indicators for healthy ageing.

Antiviral activity of algae biosynthesized silver and gold nanoparticles against Herps Simplex (HSV-1) virus in vitro using cell-line culture technique.

As therapeutic antiviral agents, biological nanoparticles can fight the drug-resistant types of viruses helping the antiviral drug development. In this study, two blue-green algal strains; Oscillatoria sp. and Spirulina platensis were used, mediated by green Ag2O|AgO-NPs and Au-NPs, respectively. For NPs characterization, the UV/Vis spectroscopy were used where their formation and crystallinity were proven with λmax values for silver and gold NPs of 432 and 552 nm, respectively. The transmission electron microscope (TEM) X-ray diffraction showed a spherical-shaped Ag2O|AgO-NPs (size; 14.42 to 48.97) while Au-NPs appeared with octahedral, pentagonal and triangular structures (size; 15.60-77.13 nm). The reducing, capping, and stabilization activities of algal polysaccharides and proteins were indicated via FTIR spectroscopy. Both Ag2O|AgO-NPs and Au-NPs were investigated against Herpes Simplex virus (HSV-1) that has been indicated by its reduction activity of cytopathic effect (CPE). Cytotoxicity was evaluated on Vero cells and measured by MTT assay. Results showed a 90% reduction in CPE of HSV-1 applying Ag2O|AgO-NPs, and Au-NPs at 31.25 µL., with a high reduction rate (49.23%) with Ag2O|AgO-NPs than that of Au-NPs (42.75%). Current results proved the efficiency of green nanotechnology application with both Ag2O|AgO-NPs, and Au-NPs as reducing and inhibitory agents for the HSV-1 replication.

Blood-Brain Barrier Crossing Renin-Angiotensin Drugs and Cognition in the Elderly: A Meta-Analysis.

[Figure: see text].

Socioeconomic disparities in head and neck cancer survival in Germany: a causal mediation analysis using population-based cancer registry data.

PURPOSE: Despite recent improvements in cancer treatment in Germany, a marked difference in cancer survival based on socioeconomic factors persists. We aim to quantify the effect of socioeconomic inequality on head and neck cancer (HNC) survival. METHODS: Information on 20,821 HNC patients diagnosed in 2009-2013 was routinely collected by German population-based cancer registries. Socioeconomic inequality was defined by the German Index of Socioeconomic Deprivation. The Cox proportional regression and relative survival analysis measured the survival disparity according to level of socioeconomic deprivation with respective confidence intervals (CI). A causal mediation analysis was conducted to quantify the effect of socioeconomic deprivation mediated through medical care, stage at diagnosis, and treatment on HNC survival. RESULTS: The most socioeconomically deprived patients were found to have the highest hazard of dying when compared to the most affluent (Hazard Ratio: 1.25, 95% CI 1.17-1.34). The most deprived patients also had the worst 5-year age-adjusted relative survival (50.8%, 95% CI 48.5-53.0). Our mediation analysis showed that most of the effect of deprivation on survival was mediated through differential stage at diagnosis during the first 6 months after HNC diagnosis. As follow-up time increased, medical care, stage at diagnosis, and treatment played no role in mediating the effect of deprivation on survival. CONCLUSION: This study confirms the survival disparity between affluent and deprived HNC patients in Germany. Considering data limitations, our results suggest that, within six months after HNC diagnosis, the elimination of differences in stage at diagnosis could reduce survival inequalities.

The association between change of soluble tumor necrosis factor receptor R1 (sTNF-R1) measurements and cardiovascular and all-cause mortality-Results from the population-based (Cardiovascular Disease, Living and Ageing in Halle) CARLA study 2002-2016.

AIMS: Single measurements of higher levels of soluble tumor necrosis factor receptor I (sTNF-R1) have been shown to be associated with increased risk of mortality. However, up to date, little is known about the underlying temporal dynamics of sTNF-R1 concentrations and their relation with mortality. We aimed to characterize the effect of changes in sTNFR-1 levels on all-cause and cardiovascular mortality, independent from other established risk factors for mortality, including other inflammatory markers. METHODS: We used data of the population based cohort study CARLA and included 1408 subjects with sTNF-R1 measured at baseline (2002-2006) and first follow-up (2007-2010). Cox proportional hazard models were used to assess the association of baseline and follow-up sTNF-R1 measurements with all-cause and cardiovascular mortality during ~10 years since the first follow-up after adjusting for relevant confounders. RESULTS: Based on 211 deaths among 1408 subjects, per each doubling of the baseline sTNF-R1, the risk of all-cause mortality was increased by about 30% (Hazard ratio 1.28, 95% Confidence Interval 0.6-2.7), while per each doubling of the follow-up level of sTNF-R1 mortality was 3-fold (3.11, 1.5-6.5) higher in a model including both measurements and adjusting for confounders. The results were mainly related to the cardiovascular mortality (5.9, 2.1-16.8 per each doubling of follow up sTNF-R1 value). CONCLUSION: Solely the follow-up value, rather than its change from baseline, predicted future mortality. Thus, while sTNF-R1 levels are associated with mortality, particularly cardiovascular, over a long-time period in the general population, if they change, the earlier measurements play no or little role.

[Design and quality control of the oral health status examination in the German National Cohort (GNC)]. / Design und Qualitätskontrolle der zahnmedizinischen Untersuchung in der NAKO Gesundheitsstudie.

BACKGROUND: Caries and periodontitis are highly prevalent worldwide. Because detailed data on these oral diseases were collected within the framework of the German National Cohort (GNC), associations between oral and systemic diseases and conditions can be investigated. OBJECTIVES: The study protocol for the oral examination was designed to ensure a comprehensive collection of dental findings by trained non-dental staff within a limited examination time. At the mid-term of the GNC baseline examination, a first quality evaluation was performed to check the plausibility of results and to propose measures to improve the data quality. MATERIALS AND METHODS: A dental interview, saliva sampling and oral diagnostics were conducted. As part of the level­1 examination, the number of teeth and prostheses were recorded. As part of the level­2 examination, detailed periodontal, cariological and functional aspects were examined. All examinations were conducted by trained non-dental personnel. Parameters were checked for plausibility and variable distributions were descriptively analysed. RESULTS: Analyses included data of 57,967 interview participants, 56,913 level­1 participants and 6295 level­2 participants. Percentages of missing values for individual clinical parameters assessed in level 1 and level 2 ranged between 0.02 and 3.9%. Results showed a plausible distribution of the data; rarely, implausible values were observed, e.g. for measurements of horizontal and vertical overbite (overjet and overbite). Intra-class correlation coefficients indicated differences in individual parameters between regional clusters, study centres and across different examiners. CONCLUSIONS: The results confirm the feasibility of the study protocol by non-dental personnel and its successful integration into the GNC's overall assessment program. However, rigorous dental support of the study centres is required for quality management.

Is There an Association between Asthma and Dental Caries and Molar Incisor Hypomineralisation?

This epidemiological study aimed to compare the caries and molar incisor hypomineralisation (MIH) experience in asthmatic and non-asthmatic adolescents assessed at 10 and 15 years of age. 730 adolescents from ongoing birth cohort studies (GINIplus/LISA) from Munich, Germany, were examined for carious lesions at the age of 10 and 15 years to determine caries experience under inclusion of non-cavitated carious lesions D1-2T and the tooth-related decay-missing-filled index. Furthermore, MIH was scored on all permanent teeth according to the criteria of the European Academy of Paediatric Dentistry. The association between caries and MIH prevalence at the 10-year and 15-year follow-up as well as caries incidence with ever having an asthma diagnosis was analysed using hurdle regression models adjusted for potential confounders. Of the 730 adolescents, 52 and 78 were identified as asthmatics at the 10- and 15-year follow-up, respectively. There were no significant differences in caries prevalence or experience between asthma-free participants and any of the asthma groups (taking metered-dose inhaler (MDI) medication vs. taking no MDI medication). However, a significant positive association was found for asthmatic adolescents who did not take MDI medication with higher MIH/T values (OR = 2.56, 95% CI = 1.03-6.37, p = 0.043) compared to non-asthmatics. In conclusion, asthma did not influence the caries status of adolescents in the present study. Interestingly, a significant association was found between adolescents with asthma who did not take MDI medication and the number of MIH-affected teeth. The association between asthma, medication, and MIH needs further confirmation.

Evaluation of the pattern and kinetics of degradation of adalimumab using a stability-indicating orthogonal testing protocol.

Forced degradation studies are crucial for the evaluation of the stability and biosimilarity. Here, adalimumab was subjected to oxidation, pH, temperature, agitation and repeated freeze-thaw in order to generate all possible degradation products. An orthogonal stability-indicating testing protocol comprising SE-HPLC, RP-HPLC, TapeStation gel electrophoresis, dynamic light scattering (DLS), and functional receptor binding assay was developed and validated. The assay protocol was used for the assessment of the pattern and kinetics of aggregation/degradation of adalimumab. SE-HPLC and DLS were used to show the formation of aggregates/fragments of adalimumab under nondenaturing conditions. TapeStation electrophoresis was performed under denaturing conditions to reveal the nature of aggregates. Results of the receptor binding assay agreed to those of SE-HPLC and DLS which indicated that it can be used as an activity-indicating assay for adalimumab. RP-HPLC demonstrated excellent selectivity for adalimumab in the presence of its oxidized forms. The kinetics of degradation was studied in each case and the results showed that it followed the first-order reaction kinetics. Correlation between the results supported the quality assessment of the tested product in industrial and clinical settings. This orthogonal protocol is a useful tool in stability assessment of monoclonal antibodies and a key criterion for the biosimilarity assessment.

Traumatic injuries of permanent teeth among 6- to 12-year-old Iraqi children: a 4-year retrospective study.

PURPOSE: The purpose of this retrospective study was to identify the types, causes, and other factors associated with traumatic dental injuries (TDIs) in the permanent teeth of children in Mosul, Iraq. METHODS: Data were collected from the dental records of 6- to 12-year-old children with TDIs who attended the Pediatric Dental Clinic at the Mosul University School of Dentistry between October 2006 and October 2010. The gathered data included: demographic information, when and where the injury occurred, type of dental injury, cause of injury, and the time elapsed between the TDI and dental care. Data were evaluated using the chi-square test. RESULTS: A total of 294 children with TDIs were examined and treated. The highest frequency of TDIs was among 12-year-old children (29%), with more males being affected (P<.001). The most common type of injury was enamel-dentin fracture (56%). The most frequent cause of TDIs was falls (53%). The majority of the injuries happened outdoors (55%), and 37% of the cases occurred in the Fall. Only 5% of patients sought dental care within 24 hours of the injury. CONCLUSION: This 4-year retrospective study showed that the majority of children with TDIs sought dental treatment after one month of the injury. Educating parents and teachers about the benefits of trauma prevention and immediate treatment of injuries is a must.