Interim Evaluation of Germany's Sugar Reduction Strategy for Soft Drinks: Commitments versus Actual Trends in Sugar Content and Sugar Sales from Soft Drinks.

INTRODUCTION: A high intake of sugar, in particular from sugar-sweetened soft drinks, increases the risk for obesity, type 2 diabetes mellitus, and dental caries. Germany has pursued a national strategy for sugar reduction in soft drinks based on voluntary commitments by industry since 2015, but its effects are unclear. METHODS: We use aggregated annual sales data from Euromonitor International to assess trends in mean sales-weighted sugar content of soft drinks and per capita sugar sales from soft drinks in Germany from 2015 to 2021. We compare these trends to the reduction path set by Germany's national sugar reduction strategy and to data for the United Kingdom, which adopted a soft drinks tax in 2017 and which we selected as best practice comparison country based on pre-defined criteria. RESULTS: Between 2015 and 2021, the mean sales-weighted sugar content of soft drinks sold in Germany decreased by 2% from 5.3 to 5.2 g/100 mL, falling short of an interim 9% reduction target and a 29% reduction observed in the United Kingdom over the same period. Sugar sales from soft drinks in Germany decreased from 22.4 to 21.6 g/capita/day (-4%) between 2015 and 2021 but remain high from a public health perspective. CONCLUSIONS: Reductions observed under Germany's sugar reduction strategy fall short of stated targets and trends observed internationally under best practice conditions. Additional policy measures may be needed to support sugar reduction in soft drinks in Germany.

Socioeconomic and risk-related drivers of compliance with measures to prevent SARS-CoV-2 infection: evidence from the Munich-based KoCo19 study.

OBJECTIVES: Although a growing share of the population in many countries has been vaccinated against the SARS-CoV-2 virus to different degrees, social distancing and hygienic non-pharmaceutical interventions still play a substantial role in containing the pandemic. The goal of this study was to investigate which factors are correlated with a higher compliance with these regulations in the context of a cohort study in the city of Munich, southern Germany, during the summer of 2020, i.e. after the first lockdown phase. METHODS: Using self-reported compliance with six regulations and personal hygiene rules (washing hands, avoiding touching face, wearing a mask, keeping distance, avoiding social gatherings, avoiding public spaces) we extracted two compliance factor scores, namely compliance with personal hygiene measures and compliance with social distancing regulations. Using linear and logistic regressions, we estimated the correlation of several socio-demographic and risk perception variables with both compliance scores. RESULTS: Risk aversion proved to be a consistent and significant driver of compliance across all compliance behaviors. Furthermore, being female, being retired and having a migration background were positively associated with compliance with personal hygiene regulations, whereas older age was related with a higher compliance with social distancing regulations. Generally, socioeconomic characteristics were not related with compliance, except for education, which was negatively related with compliance with personal hygiene measures. CONCLUSIONS: Our results suggest that for a targeted approach to improve compliance with measures to prevent SARS-CoV-2 infection, special attention should be given to younger, male and risk-prone individuals.

The effect of population-based blood pressure screening on long-term cardiometabolic morbidity and mortality in Germany: A regression discontinuity analysis.

BACKGROUND: Hypertension represents one of the major risk factors for cardiovascular morbidity and mortality globally. Early detection and treatment of this condition is vital to prevent complications. However, hypertension often goes undetected, and even if detected, not every patient receives adequate treatment. Identifying simple and effective interventions is therefore crucial to fight this problem and allow more patients to receive the treatment they need. Therefore, we aim at investigating the impact of a population-based blood pressure (BP) screening and the subsequent "low-threshold" information treatment on long-term cardiovascular disease (CVD) morbidity and mortality. METHODS AND FINDINGS: We examined the impact of a BP screening embedded in a population-based cohort study in Germany and subsequent personalized "light touch" information treatment, including a hypertension diagnosis and a recommendation to seek medical attention. We pooled four waves of the KORA study, carried out between 1984 and 1996 (N = 14,592). Using a sharp multivariate regression discontinuity (RD) design, we estimated the impact of the information treatment on CVD mortality and morbidity over 16.9 years. Additionally, we investigated potential intermediate outcomes, such as hypertension awareness, BP, and behavior after 7 years. No evidence of effect of BP screening was observed on CVD mortality (hazard ratio (HR) = 1.172 [95% confidence interval (CI): 0.725, 1.896]) or on any (fatal or nonfatal) long-term CVD event (HR = 1.022 [0.636, 1.641]) for individuals just above (versus below) the threshold for hypertension. Stratification for previous self-reported diagnosis of hypertension at baseline did not reveal any differential effect. The intermediate outcomes, including awareness of hypertension, were also unaffected by the information treatment. However, these results should be interpreted with caution since the analysis might not be sufficiently powered to detect a potential intervention effect. CONCLUSIONS: The study does not provide evidence of an effect of the assessed BP screening and subsequent information treatment on BP, health behavior, or long-term CVD mortality and morbidity. Future studies should consider larger datasets to detect possible effects and a shorter follow-up for the intermediate outcomes (i.e., BP and behavior) to detect short-, medium-, and long-term effects of the intervention along the causal pathway.

The association between childhood socioeconomic status and adult health behavior: The role of locus of control.

The socioeconomic environment in childhood is a powerful determinant for health behavior in adulthood, subsequently influencing health outcomes. However, the underlying mechanisms are insufficiently understood. This study assesses locus of control (LOC) as a mediator linking childhood socioeconomic status (SES) with health behavior (smoking, regular alcohol consumption, unhealthy diet and low physical activity). Drawing on a representative sample from Germany (SOEP), we investigated these relations using structural equations modelling. Results show that externally oriented LOC explains up to 6% of the relationship between childhood SES and health behavior in adulthood, independently from adult SES. Stratification indicates that these results hold in women but not in men, in younger and middle-aged individuals but not in older ones. Hence, control beliefs play a modest yet significant role in shaping the socioeconomic gradient in health behavior and might have far-reaching consequences on how morbidity and mortality arise and persist across generations.

Rheological Analysis of the Gelation Kinetics of an Enzyme Cross-linked PEG Hydrogel.

The diverse requirements of hydrogels for tissue engineering motivate the development of cross-linking reactions to fabricate hydrogel networks with specific features, particularly those amenable to the activity of biological materials (e.g., cells, proteins) that do not require exposure to UV light. We describe gelation kinetics for a library of thiolated poly(ethylene glycol) sulfhydryl hydrogels undergoing enzymatic cross-linking via horseradish peroxidase, a catalyst-driven reaction activated by hydrogen peroxide. We report the use of small-amplitude oscillatory shear (SAOS) to quantify gelation kinetics as a function of reaction conditions (hydrogen peroxide and polymer concentrations). We employ a novel approach to monitor the change of viscoelastic properties of hydrogels over the course of gelation (Δ tgel) via the time derivative of the storage modulus (d G'/d t). This approach, fundamentally distinct from traditional methods for defining a gel point, quantifies the time interval over which gelation events occur. We report that gelation depends on peroxide and polymer concentrations as well as system temperature, where the effects of hydrogen peroxide tend to saturate over a critical concentration. Further, this cross-linking reaction can be reversed using l-cysteine for rapid cell isolation, and the rate of hydrogel dissolution can be monitored using SAOS.

The impact of diabetes on labour market participation: a systematic review of results and methods.

BACKGROUND: Diabetes mellitus is a major chronic disease, which is connected to direct and indirect costs and productivity losses. However, its effects on labour market participation are not straightforward to identify, nor are they consistently included in cost-of-illness studies. First, this study aims to synthesise existing evidence regarding the impact of diabetes on labour market outcomes that imply a complete absence of work. Second, the analysis takes a particular look at relevant methodological choices and the resulting quality of the studies included. METHODS: We conducted a systematic literature research (PubMed, Embase, PsychINFO), by applying a standard screening, selection and results extraction process, which considered all types of studies including cross-sectional and longitudinal approaches. Risk-of-bias and quality within the studies were assessed and results were compared. We dedicated special attention to the modelling of potential reverse causality between diabetes and labour market outcomes and the consideration of comorbidities and complications. RESULTS: Overall, 30 studies satisfied our inclusion criteria. We identified four main labour participation outcomes: absence of employment, unemployment, early retirement, and disability pension. The studies reviewed show a negative impact of diabetes on the labour market participation outcomes considered. However, only a few studies controlled for endogeneity, differentiated between type 1 and type 2 diabetes or modelled the impact of comorbidities. We report how modelling choices affect the directions and interpretations of the effects. CONCLUSIONS: The available evidence mainly suggests a negative impact of diabetes on several outcomes indicating labour market participation. The methodological limitations identified can guide future research with respect to both outcomes and methods. This study provides therefore an empirical contribution to the discussion on how to model the economic impact of diabetes.

Patterning Three-Dimensional Hydrogel Microenvironments Using Hyperbranched Polyglycerols for Independent Control of Mesh Size and Stiffness.

The extracellular matrix is an environment rich with structural, mechanical, and molecular signals that can impact cell biology. Traditional approaches in hydrogel biomaterial design often rely on modifying the concentration of cross-linking groups to adjust mechanical properties. However, this strategy provides limited capacity to control additional important parameters in 3D cell culture such as microstructure and molecular diffusivity. Here we describe the use of multifunctional hyperbranched polyglycerols (HPGs) to manipulate the mechanical properties of polyethylene glycol (PEG) hydrogels while not altering biomolecule diffusion. This strategy also provides the ability to separately regulate spatial and temporal distribution of biomolecules tethered within the hydrogel. The functionalized HPGs used here can also react through a copper-free click chemistry, allowing for the encapsulation of cells and covalently tethered biomolecules within the hydrogel. Because of the hyperbranched architecture and unique properties of HPGs, their addition into PEG hydrogels affords opportunities to locally alter hydrogel cross-linking density with minimal effects on global network architecture. Additionally, photocoupling chemistry allows micropatterning of bioactive cues within the three-dimensional gel structure. This approach therefore enables us to tailor mechanical and diffusive properties independently while further allowing for local modulation of biomolecular cues to create increasingly complex cell culture microenvironments.

Operating Room Efficiency before and after Entrance in a Benchmarking Program for Surgical Process Data.

Operating room (OR) efficiency continues to be a high priority for hospitals. In this context the concept of benchmarking has gained increasing importance as a means to improve OR performance. The aim of this study was to investigate whether and how participation in a benchmarking and reporting program for surgical process data was associated with a change in OR efficiency, measured through raw utilization, turnover times, and first-case tardiness. The main analysis is based on panel data from 202 surgical departments in German hospitals, which were derived from the largest database for surgical process data in Germany. Panel regression modelling was applied. Results revealed no clear and univocal trend of participation in a benchmarking and reporting program for surgical process data. The largest trend was observed for first-case tardiness. In contrast to expectations, turnover times showed a generally increasing trend during participation. For raw utilization no clear and statistically significant trend could be evidenced. Subgroup analyses revealed differences in effects across different hospital types and department specialties. Participation in a benchmarking and reporting program and thus the availability of reliable, timely and detailed analysis tools to support the OR management seemed to be correlated especially with an increase in the timeliness of staff members regarding first-case starts. The increasing trend in turnover time revealed the absence of effective strategies to improve this aspect of OR efficiency in German hospitals and could have meaningful consequences for the medium- and long-run capacity planning in the OR.

An umbrella review of effectiveness and efficacy trials for app-based health interventions.

Health interventions based on mobile phone or tablet applications (apps) are promising tools to help patients manage their conditions more effectively. Evidence from randomized controlled trials (RCTs) on efficacy and effectiveness of such interventions is increasingly available. This umbrella review aimed at mapping and narratively summarizing published systematic reviews on efficacy and effectiveness of mobile app-based health interventions within patient populations. We followed a pre-specified publicly available protocol. Systematic reviews were searched in two databases from inception until August 28, 2023. Reviews that included RCTs evaluating integrated or stand-alone health app interventions in patient populations with regard to efficacy/effectiveness were considered eligible. Information on indications, outcomes, app characteristics, efficacy/effectiveness results and authors' conclusions was extracted. Methodological quality was assessed using the AMSTAR2 tool. We identified 48 systematic reviews published between 2013 and 2023 (35 with meta-analyses) that met our inclusion criteria. Eleven reviews included a broad spectrum of conditions, thirteen focused on diabetes, five on anxiety and/or depression, and others on various other indications. Reported outcomes ranged from medication adherence to laboratory, anthropometric and functional parameters, symptom scores and quality of life. Fourty-one reviews concluded that health apps may be effective in improving health outcomes. We rated one review as moderate quality. Here we report that the synthesized evidence on health app effectiveness varies largely between indications. Future RCTs should consider reporting behavioral (process) outcomes and measures of healthcare resource utilization to provide deeper insights on mechanisms that make health apps effective, and further elucidate their impact on healthcare systems.

Do Multiple Sex/Gender Dimensions Play a Role in the Association of Green Space and Self-Rated Health? Model-Based Recursive Partitioning Results from the KORA INGER Study.

Exposure to green space has a positive impact on health. Whether sex/gender modifies the green space-health association has so far only been studied through the use of a binary sex/gender category; however, sex/gender should be considered more comprehensively as a multidimensional concept based on theoretical approaches. We therefore explored whether sex/gender, operationalized through multiple sex/gender- and intersectionality-related covariates, modifies the green space-self-rated health association. We collected data from participants involved in the German KORA study (Cooperative Health Research in the Region of Augsburg) in 2019. Self-rated health was assessed as a one-question item. The availability of green spaces was measured subjectively as well as objectively. The multiple sex/gender- and intersectionality-related covariates were measured via self-assessment. To analyze the data, we used model-based recursive partitioning, a decision tree method that can handle complex data, considering both multiple covariates and their possible interactions. We showed that none of the covariates operationalizing an individual sex/gender self-concept led to subgroups with heterogeneous effects in the model-based tree analyses; however, we found effect heterogeneity based on covariates representing structural aspects from an intersectionality perspective, although they did not show the intersectional structuring of sex/gender dimensions. In one identified subgroup, those with a lower education level or a feeling of discrimination based on social position showed a positive green space-self-rated health association, while participants with a higher education level or no feeling of discrimination based on social position had a high level of self-rated health regardless of the availability of green spaces. Model-based recursive partitioning has the potential to detect subgroups exhibiting different exposure-outcome associations, with the possibility of integrating multiple sex/gender- and intersectionality-related covariates as potential effect modifiers. A comprehensive assessment of the relevance of sex/gender showed effect heterogeneity based on covariates representing structural aspects from an intersectionality perspective.

Preferences of women in difficult life situations for a physical activity programme: protocol of a discrete choice experiment in the German NU-BIG project.

INTRODUCTION: The BIG project ('Bewegung als Investition in die Gesundheit', ie, 'Movement as Investment in Health') was developed in 2005 as a community-based participatory research programme to offer accessible opportunities for physical activity to women in difficult life situations. Since then, the programme has been expanded to eight sites in Germany. A systematic evaluation of BIG is currently being conducted. As part of this effort, we strive to understand the preferences of participating women for different aspects of the programme, and to analyse their willingness to pay. METHODS AND ANALYSIS: In this protocol, we describe the development and analysis plan of a discrete choice experiment (DCE) to investigate participants' preferences for a physical activity programme for women in difficult life situations. The experiment will be embedded in a questionnaire covering several aspects of participation in the programme (eg, reach, efficacy and further effects) and the socioeconomic characteristics of all active participants. After a thorough search of the literature, BIG documents review and expert interviews, we identified five important attributes of the programme: course times, travel time to the course venue, additional social activities organised by BIG, consideration of wishes and interests for the further planning of courses and costs per course unit. Thereafter, we piloted the experiment with a sample of participants from the target group. After data collection, the experiment will be analysed using a conditional logit model and a latent class analysis to assess eventual heterogeneity in preferences. ETHICS AND DISSEMINATION: Understanding women's preferences will provide useful insights for the further development of the programme and ultimately increase participation and retention. The questionnaire, the included DCE and the pretest on participants received ethical approval (application no. 20-247_1-B). We plan to disseminate the results of the DCE in peer-reviewed journals, national conferences and among participants and programme coordinators and organisers.

The Role of Epigenetic Clocks in Explaining Educational Inequalities in Mortality: A Multicohort Study and Meta-analysis.

Educational inequalities in all-cause mortality have been observed for decades. However, the underlying biological mechanisms are not well known. We aimed to assess the role of DNA methylation changes in blood captured by epigenetic clocks in explaining these inequalities. Data were from 8 prospective population-based cohort studies, representing 13 021 participants. First, educational inequalities and their portion explained by Horvath DNAmAge, Hannum DNAmAge, DNAmPhenoAge, and DNAmGrimAge epigenetic clocks were assessed in each cohort via counterfactual-based mediation models, on both absolute (hazard difference) and relative (hazard ratio) scales, and by sex. Second, estimates from each cohort were pooled through a random effect meta-analysis model. Men with low education had excess mortality from all causes of 57 deaths per 10 000 person-years (95% confidence interval [CI]: 38, 76) compared with their more advantaged counterparts. For women, the excess mortality was 4 deaths per 10 000 person-years (95% CI: -11, 19). On the relative scale, educational inequalities corresponded to hazard ratios of 1.33 (95% CI: 1.12, 1.57) for men and 1.15 (95% CI: 0.96, 1.37) for women. DNAmGrimAge accounted for the largest proportion, approximately 50%, of the educational inequalities for men, while the proportion was negligible for women. Most of this mediation was explained by differential effects of unhealthy lifestyles and morbidities of the World Health Organization (WHO) risk factors for premature mortality. These results support DNA methylation-based epigenetic aging as a signature of educational inequalities in life expectancy emphasizing the need for policies to address the unequal social distribution of these WHO risk factors.

The Effect of BMI and Type 2 Diabetes on Socioeconomic Status: A Two-Sample Multivariable Mendelian Randomization Study.

OBJECTIVE: To assess the independent causal effect of BMI and type 2 diabetes (T2D) on socioeconomic outcomes by applying two-sample Mendelian randomization (MR) analysis. RESEARCH DESIGN AND METHODS: We performed univariable and multivariable two-sample MR to jointly assess the effect of BMI and T2D on socioeconomic outcomes. We used overlapping genome-wide significant single nucleotide polymorphisms for BMI and T2D as instrumental variables. Their causal impact on household income and regional deprivation was assessed using summary-level data from the UK Biobank. RESULTS: In the univariable analysis, higher BMI was related to lower income (marginal effect of 1-SD increase in BMI [ß = -0.092; 95% CI -0.138; -0.047]) and higher deprivation (ß = 0.051; 95% CI 0.022; 0.079). In the multivariable MR, the effect of BMI controlling for diabetes was slightly lower for income and deprivation. Diabetes was not associated with these outcomes. CONCLUSIONS: High BMI, but not diabetes, shows a causal link with socioeconomic outcomes.

Microphysiological systems to study tumor-stroma interactions in brain cancer.

Brain tumors still lack effective treatments, and the mechanisms of tumor progression and therapeutic resistance are unclear. Multiple parameters affect cancer prognosis (e.g., type and grade, age, location, size, and genetic mutations) and election of suitable treatments is based on preclinical models and clinical data. However, most candidate drugs fail in human trials due to inefficacy. Cell lines and tissue culture plates do not provide physiologically relevant environments, and animal models are not able to adequately mimic characteristics of disease in humans. Therefore, increasing technological advances are focusing on in vitro and computational modeling to increase the throughput and predicting capabilities of preclinical systems. The extensive use of these therapeutic agents requires a more profound understanding of the tumor-stroma interactions, including neural tissue, extracellular matrix, blood-brain barrier, astrocytes and microglia. Microphysiological brain tumor models offer physiologically relevant vascularized 'minitumors' that can help deciphering disease mechanisms, accelerating the drug discovery and predicting patient's response to anticancer treatments. This article reviews progress in tumor-on-a-chip platforms that are designed to comprehend the particular roles of stromal cells in the brain tumor microenvironment.

Behavioural and patient-individual determinants of quality of life, functioning and physical activity in older adults (MobilE-TRA 2): study protocol of an observational cohort study in a tertiary care setting.

INTRODUCTION: Vertigo, dizziness and balance problems (VDB) as well as osteoarthritis (OA) are among the health conditions with the greatest impact on mobility and social participation in older adults. Patients with VDB and OA were shown to benefit from specialised care such as vestibular rehabilitation therapy or joint replacement. However, these effects are not permanent and seem to disappear over time. One important reason might be a decreasing adherence to therapy recommendations. Findings from behavioural economics (BE) can help to shed light on individual effects on adherence behaviour and long-term outcomes of VDB and OA. OBJECTIVE: Based on insights from BE concepts (ie, self-efficacy, intention, and time and risk preferences), MobilE-TRA 2 investigates the determinants of functioning and health-related quality of life (HRQoL) 3 and 12 months after discharge from total hip replacement (THR)/total knee replacement (TKR) in patients with OA and after interdisciplinary evaluation for VDB. METHODS AND ANALYSIS: MobilE-TRA 2 is a longitudinal observational study with data collection in two specialised tertiary care centres at the university hospital in Munich, Germany between 2020 and 2023. Patients aged 60 and older presenting for their first THR/TKR or interdisciplinary evaluation of VDB at Ludwig Maximilians University (LMU) hospital will be recruited for study participation. Three and twelve months after baseline assessment, all patients will receive a follow-up questionnaire. Mixed-effect regression models will be used to examine BE concepts as determinants of adherence, HRQoL and functioning. ETHICS AND DISSEMINATION: The study was approved by the ethics committee at the medical faculty of the LMU Munich under the number 20-727. Results will be published in scientific, peer-reviewed journals and at national and international conferences. Findings will also be disseminated via newsletters, the project website and a regional conference for representatives of local and national authorities.

Response of neuroglia to hypoxia-induced oxidative stress using enzymatically crosslinked hydrogels.

Three-dimensional cultures have exciting potential to mimic aspects of healthy and diseased brain tissue to examine the role of physiological conditions on neural biomarkers, as well as disease onset and progression. Hypoxia is associated with oxidative stress, mitochondrial damage, and inflammation, key processes potentially involved in Alzheimer's and multiple sclerosis. We describe the use of an enzymatically-crosslinkable gelatin hydrogel system within a microfluidic device to explore the effects of hypoxia-induced oxidative stress on rat neuroglia, human astrocyte reactivity, and myelin production. This versatile platform offers new possibilities for drug discovery and modeling disease progression.

The effect of retirement on biomedical and behavioral risk factors for cardiovascular and metabolic disease.

Retirement is a major life event potentially associated with changes in relevant risk factors for cardiovascular and metabolic conditions. This study analyzes the effect of retirement on behavioral and biomedical risk factors for chronic disease, together with subjective health parameters using Southern German epidemiological data. We used panel data from the KORA cohort study, consisting of 11,168 observations for individuals 45-80 years old. Outcomes included health behavior (alcohol, smoking, physical activity), biomedical risk factors (body-mass-index (BMI), waist-to-hip ratio (WHR), glycosylated hemoglobin (HbA1c), total cholesterol/HDL quotient, systolic/diastolic blood pressure), and subjective health (SF12 mental and physical scales, self-rated health). We applied a parametric regression discontinuity design based on age thresholds for pension eligibility. Robust results after p-value corrections for multiple testing showed an increase in BMI in early retirees (at the age of 60) [ß = 1.11, corrected p-val. < 0.05] and an increase in CHO/HDL in regular retirees (age 65) [ß = 0.47, corrected p-val. < 0.05]. Stratified analyses indicate that the increase in BMI might be driven by women and low educated individuals retiring early, despite increasing physical activity. The increase in CHO/HDL might be driven by men retiring regularly, alongside an increase in subjective physical health. Blood pressure also increased, but the effect differs by retirement timing and sex and is not always robust to sensitivity analysis checks. Our study indicates that retirement has an impact on different risk factors for chronic disease, depending on timing, sex and education. Regular male, early female, and low educated retirees should be further investigated as potential high-risk groups for worsening risk factors after retirement. Future research should investigate if and how these results are linked: in fact, especially in the last two groups, the increase in leisure time physical activity might not be enough to compensate for the loss of work-related physical activity, leading thus to an increase in BMI.

Magnetic Resonance Monitoring of Opaque Temperature-Sensitive Polymeric Scaffolds.

The monitoring of location and degradation rates of injectable biomaterials is an area of particular interest in the design and implementation of therapeutic scaffolds and carriers for tissue repair and replacement. We describe here the fabrication and characterization of gadolinium (Gd)-labeled temperature-responsive hydrogels that can be detected noninvasively using T1-weight magnetic resonance. Two acrylamide-functionalized GdIIIDOTA-monoamide complexes with either a short n-butylene spacer (GdIII-C4-AA) or a long hydrophilic spacer (GdIII-PEG-AA) were synthesized and incorporated into the hydrogels. At temperatures above the lower critical solution temperature (LCST), 37 °C, these hydrogels have the capacity to enhance relaxivity (r1) due to the hydrophobic interactions of the polyamide chains around the gadolinium chelates. This effect is further accentuated by the presence of the polyethylene glycol groups of the Gd complex GdIII-PEG-AA.

Change in Physical Activity after Diagnosis of Diabetes or Hypertension: Results from an Observational Population-Based Cohort Study.

Background: Chronic diseases like diabetes mellitus or hypertension are a major public health challenge. Irregular physical activity (PA) is one of the most important modifiable risk factors for chronic conditions and their complications. However, engaging in regular PA is a challenge for many individuals. The literature suggests that a diagnosis of a disease might serve as a promising point in time to change health behavior. This study investigates whether a diagnosis of diabetes or hypertension is associated with changes in PA. Methods: Analyses are based on 4261 participants of the population-based KORA S4 study (1999-2001) and its subsequent 7-and 14-year follow-ups. Information on PA and incident diagnoses of diabetes or hypertension was assessed via standardized interviews. Change in PA was regressed upon diagnosis with diabetes or hypertension, using logistic regression models. Models were stratified into active and inactive individuals at baseline to avoid ceiling and floor effects or regression to the mean. Results: Active participants at baseline showed higher odds (OR = 2.16 [1.20;3.89]) for becoming inactive after a diabetes diagnosis than those without a diabetes diagnosis. No other significant association was observed. Discussion: As PA is important for the management of diabetes or hypertension, ways to increase or maintain PA levels in newly-diagnosed patients are important. Communication strategies might be crucial, and practitioners and health insurance companies could play a key role in raising awareness.

Hyaluronic acid-functionalized gelatin hydrogels reveal extracellular matrix signals temper the efficacy of erlotinib against patient-derived glioblastoma specimens.

Therapeutic options to treat primary glioblastoma (GBM) tumors are scarce. GBM tumors with epidermal growth factor receptor (EGFR) mutations, in particular a constitutively active EGFRvIII mutant, have extremely poor clinical outcomes. GBM tumors with concurrent EGFR amplification and active phosphatase and tensin homolog (PTEN) are sensitive to the tyrosine kinase inhibitor erlotinib, but the effect is not durable. A persistent challenge to improved treatment is the poorly understood role of cellular, metabolic, and biophysical signals from the GBM tumor microenvironment on therapeutic efficacy and acquired resistance. The intractable nature of studying GBM cell in vivo motivates tissue engineering approaches to replicate aspects of the complex GBM tumor microenvironment. Here, we profile the effect of erlotinib on two patient-derived GBM specimens: EGFR + GBM12 and EGFRvIII GBM6. We use a three-dimensional gelatin hydrogel to present brain-mimetic hyaluronic acid (HA) and evaluate the coordinated influence of extracellular matrix signals and EGFR mutation status on GBM cell migration, survival and proliferation, as well as signaling pathway activation in response to cyclic erlotinib exposure. Comparable to results observed in vivo for xenograft tumors, erlotinib exposure is not cytotoxic for GBM6 EGFRvIII specimens. We also identify a role of extracellular HA (via CD44) in altering the effect of erlotinib in GBM EGFR + cells by modifying STAT3 phosphorylation status. Taken together, we report an in vitro tissue engineered platform to monitor signaling associated with poor response to targeted inhibitors in GBM.