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Due to demographic changes in people living with HIV (PLHIV), physicians are challenged with age-related comorbidities and their management. In the absence of comprehensive data collection, the burden of comorbidities and co-medication in addition to antiretroviral therapy (ART) remains unclear for the German real-world setting. BESIDE was an observational, cross-sectional study evaluating the prevalence of comorbidities and use of co-medication in treated PLHIV. Regional distribution of study centers (n = 20), consecutive patient recruitment, and age-stratified sampling in alignment with national epidemiologic data aimed to ensure a representative sample (n = 453). The overall prevalence of comorbidities was 91.2%; 31.6% of patients had ≥4 comorbidities. The most common diagnoses were vitamin D deficiency (29.1%), depressive episode (27.8%), arterial hypertension (16.3%), and hypercholesterolemia (10.8%). 83.7% of patients were on co-medication; 21.2% taking ≥4 medications. The most common medications or supplements were vitamins (31.6%), anti-inflammatory agents (16.1%), renin-angiotensin system agents (12.1%), acid suppressants (11.7%), lipid modifying agents (10.8%); 1.3% of patients were on co-medication that should not be co-administered with ART, 41.5% on co-medication with potential for drug-drug interactions. The prevalence of comorbidities and use of co-medication among treated PLHIV in Germany is consistently high and increases across age groups, illustrating the complexity of HIV care involving appropriate ART selection. [ABSTRACT FROM AUTHOR]

Recreational drug use is higher in people living with HIV (PLHIV) than in the general population in Europe. This use increases the risk for drug-drug interactions (DDIs) and adverse events. We assessed the prevalence and clinical consequences of substance abuse among PLHIV. BESIDE was a cross-sectional, multi-center study in 2016/18, evaluating comorbidities, polypharmacy and recreational/illicit drug use in PLHIV on antiretroviral therapy (ART) in Germany. Legal and illicit drug use was recorded using two anonymous patient questionnaires one year apart (Q1 and Q2). The BESIDE study population consisted of 453 PLHIV (22% female, median age 46 years). Recreational drug use was reported by the majority (Q1: ever used 73%, within previous 6 months 56%): nitrite inhalants ("poppers"), cannabis and PDE-5 inhibitors were common across all age groups; ecstasy, (meth-)amphetamine and gamma-hydroxybutyrate/gamma-butyrolactone were predominantly reported by younger PLHIV. Based on Q2, two-thirds of PLHIV (67%) had been informed about potential risks of drug abuse by their doctors, whereas one-third (33%) had talked to their doctors on their own initiative with only 7% considering drug use in combination with ART a problem. Strikingly, 44% and 42% had undergone medical treatment or had been hospitalized due to drug use. These data emphasize the high clinical relevance of recreational drug use in PLHIV and the need for treating physicians to pro-actively communicate the potential risks. [ABSTRACT FROM AUTHOR]

Only limited efficacy and tolerability data on raltegravir (RAL) use are currently available. Study objectives were to describe the efficacy and tolerability profile of RAL-based antiretroviral therapy (ART) in routine clinical practice in Germany. The WIP study (WIP = "Wirksamkeit von Isentress unter Praxisbedingungen", Efficacy of Isentress under routine clinical conditions) was a prospective, multi-centre cohort study in Germany. Human immunodeficiency virus (HIV)-infected patients aged ≥ 18 years in whom combinational ART with RAL 400 mg BID was indicated were enrolled. The primary endpoint was virologic response (HIV-RNA <50 copies/mL; non-completion equals failure) after 48 weeks. Of 451 patients, 85.1% (n = 384) were still receiving RAL at week 48. At baseline (BL), the prevalence of concomitant diseases was higher in patients of the age group ≥50 years (94.2% vs. 75.7%) as well as concomitant medications (74.8 % vs. 55.4%). Virologic response at week 48 was 74.7% (overall), 75.0% (naïve at BL), 81.5% (suppressed at BL), 47.1% (interrupted previous treatment at BL) and 64.9% (failing at BL), without significant differences by age group. A significant correlation of achievement of HIV-RNA <50 copies/mL was seen with treatment status at BL (p = 0.004). In addition, 77.3 % of the patients with a CD4 cell count >200 cells/µL at BL achieved HIV-RNA <50 copies/mL (p = 0.029). RAL was well tolerated with 80 adverse events (AEs) in 49 patients (10.9%) and 8 serious AEs (SAEs) in 6 patients (1.3%) reported to be drug related. A total of 22 patients (4.9%) discontinued treatment due to AEs. The WIP study shows that the previously reported efficacy and safety profile of RAL can be achieved in a population with multiple comorbidities and comedications, with no major difference observed in ageing patients (≥50 years) vs. younger patients. RAL is therefore an attractive treatment option in routine medical care in Germany. [ABSTRACT FROM AUTHOR]

The rs17070145 polymorphism (C → T substitution, intron 9) of the KIBRA gene has recently been associated with episodic memory and cognitive flexibility. These findings were inconsistent across reports though, and largely lacked gene-gene or gene-environment interactions. The aim of the present study was to determine the impact of the rs17070145 polymorphism on clinically relevant cognitive domains and its interaction with the modifiers 'lifestyle' and 'cardiovascular risk factors'. Five-hundred forty-five elderly volunteers (mean age 64 years, ±7 years, 56% women) accomplished a comprehensive cognitive testing. Principal component analysis was used to reveal the internal structure of the data, rendering four composite scores: verbal memory, word fluency, executive function/psychomotor speed, and working memory. Lifestyle was assessed with a detailed questionnaire, age-associated risk factors by clinical interview and examination. There was no main effect of the rs17070145 genotype on any cognitive composite scores. However, we found worse performance in executive functions for T-allele carriers in the presence of arterial hypertension (β=−0.365, p=0.0077 and 0.031 after Bonferroni correction). This association was further modified by gender, showing the strongest association in hypertensive females (β=−0.500, p=0.0072 and 0.029 after Bonferroni correction). The effect of KIBRA on cognitive function seems to be complex and modified by gender and arterial hypertension. [ABSTRACT FROM AUTHOR]

Abstract: The equation adjoint to the linearization of the periodic orbit equations in a dynamical system is fundamental in the study of sensitivity issues for periodic orbits, e.g. in the synchronization of networks of weakly coupled oscillators. It is also fundamental in the computation of normal form coefficients for bifurcations of limit cycles. Numerically, the adjoint equations can be solved in a variety of ways. In the case where the periodic orbit equations are solved as a boundary value problem by collocation at Gauss points, a recent method allows one to compute the solution to the adjoint equations as a byproduct of Newton''s method applied to solve the boundary value problem. This method is practically cost-free since it requires only the solution to an already factorized linear system. Moreover, it provides the solution to the adjoint equations in exactly the form needed in the applications. So far, the method has not been analyzed carefully and no rigorous convergence results have been proved. We prove that the method is equivalent to a collocation method for the adjoint equations so that convergence of order holds at all points and of order at the points of the coarse mesh; here h is the maximum length of the mesh intervals and m is the degree of the approximating piecewise polynomials. We support this by extensive numerical tests. [Copyright &y& Elsevier]

Pseudacteon brevicauda Schmitz parasitizes Myrmica rubra in the Middle Rhine region in Germany. Female flies are attracted to disturbed ant colonies, where they attack Myrmica workers for oviposition. We experimented with different body parts of the ants, with dissected mandibular glands, and with synthetic gland constituents to locate the source of the fly attractant and the chemical basis of the signal. The attracting kairomone originates from the mandibular glands, which are used by Myrmica ants in alarm communication. Among the gland constituents, the ketones 3-octanone and 3-nonanone attracted and alerted the parasitic flies. The alcohol 3-octanol did not attract flies over long distance but it released an alerting response over short distance. A comparison of the chemical compositions of mandibular glands between ant species, focusing on the bioactive compounds, can explain both host specificity of P. brevicauda and the extension of the host spectrum to the (chemically similar) Myrmica scabrinodis. [ABSTRACT FROM AUTHOR]

Vision in general and images in particular have always played an important and essential role in human life. Today, image processing is a very active research area with many applications. In order to cope with the wide variety of image processing problems, several techniques have been introduced and developed, quite often with great success. Among the different techniques that are currently in use, we also encounter fuzzy techniques. The use of fuzzy techniques in image processing is one of the main topics of the Fuzziness and Uncertainty Modelling Research Group of Prof. Kerre. In this paper, we briefly summarize some achievements of the past years. [ABSTRACT FROM AUTHOR]

White matter hyperintensities index structural abnormalities in the cerebral white matter, including axonal damage. The latter may promote atrophy of the cerebral cortex, a key feature of dementia. Here, we report a study of 51,065 individuals from 10 cohorts demonstrating that higher white matter hyperintensity volume associates with lower cortical thickness. The meta-GWAS of white matter hyperintensities-associated cortical 'atrophy' identifies 20 genome-wide significant loci, and enrichment in genes specific to vascular cell types, astrocytes, and oligodendrocytes. White matter hyperintensities-associated cortical 'atrophy' showed positive genetic correlations with vascular-risk traits and plasma biomarkers of neurodegeneration, and negative genetic correlations with cognitive functioning. 15 of the 20 loci regulated the expression of 54 genes in the cerebral cortex that, together with their co-expressed genes, were enriched in biological processes of axonal cytoskeleton and intracellular transport. The white matter hyperintensities-cortical thickness associations were most pronounced in cortical regions with higher expression of genes specific to excitatory neurons with long-range axons traversing through the white matter. The meta-GWAS-based polygenic risk score predicts vascular and all-cause dementia in an independent sample of 500,348 individuals. Thus, the genetics of white matter hyperintensities-related cortical atrophy involves vascular and neuronal processes and increases dementia risk., (© 2024. The Author(s).)

Background: We recently reported that Mediterranean (MED) and green-MED diets significantly attenuated age-related brain atrophy by ∼50% within 18 mo., Objective: The objective of this study was to explore the contribution of specific diet-induced parameters to brain-volume deviation from chronologic age., Methods: A post hoc analysis of the 18-mo DIRECT PLUS trial, where participants were randomly assigned to the following groups: 1) healthy dietary guidelines, 2) MED diet, or 3) green-MED diet, high in polyphenols, and low in red meat. Both MED groups consumed 28 g walnuts/d (+440 mg/d polyphenols). The green-MED group further consumed green tea (3-4 cups/d) and Mankai green shake (Wolffia globosa aquatic plant) (+800 mg/d polyphenols). We collected blood samples through the intervention and followed brain structure volumes by magnetic resonance imaging (MRI). We used hippocampal occupancy (HOC) score (hippocampal and inferior lateral-ventricle volumes ratio) as a neurodegeneration marker and brain-age proxy. We applied multivariate linear regression models., Results: Of 284 participants [88% male; age = 51.1 y; body mass index = 31.2 kg/m 2 ; hemoglobin A1c (HbA1c) = 5.48%; APOE-ε4 genotype = 15.7%], 224 completed the trial with eligible whole-brain MRIs. Individuals with higher HOC deviations (i.e., younger brain age) presented lower body weight [r = -0.204; 95% confidence interval (CI): -0.298, -0.101], waist circumference (r = -0.207; 95% CI: -0.310, -0.103), diastolic (r = -0.186; 95% CI: -0.304, -0.072), systolic blood pressure (r = -0.189; 95% CI: -0.308, -0.061), insulin (r = -0.099; 95% CI: -0.194, -0.004), and HbA1c (r = -0.164; 95% CI: -0.337, -0.006) levels. After 18 mo, greater changes in HOC deviations (i.e., brain-age decline attenuation) were independently associated with improved HbA1c (β = -0.254; 95% CI: -0.392, -0.117), HOMA-IR (β = -0.200; 95% CI: -0.346, -0.055), fasting glucose (β = -0.155; 95% CI: -0.293, -0.016), and c-reactive protein (β = -0.153; 95% CI: -0.296, -0.010). Improvement in diabetes status was associated with greater HOC deviation changes than either no change in diabetes status (0.010; 95% CI: 0.002, 0.019) or with an unfavorable change (0.012; 95% CI: 0.002, 0.023). A decline in HbA1c was further associated with greater deviation changes in the thalamus, caudate nucleus, and cerebellum (P < 0.05). Greater consumption of Mankai and green tea (green-MED diet components) were associated with greater HOC deviation changes beyond weight loss., Conclusions: Glycemic control contributes to the neuroprotective effects of the MED and green-MED diets on brain age. Polyphenols-rich diet components as Mankai and green tea may contribute to a more youthful brain age. This trial was registered at clinicaltrials.gov at clinicaltrials.gov as NCT03020186., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Alzheimer's disease (AD) is characterized by progressive cognitive decline and specific brain atrophy patterns, primarily involving the medial temporal lobes. A number of studies have discussed hypothalamic involvement in AD with consecutive metabolic and/or autonomic disturbances yet only few studies have investigated hypothalamic atrophy in AD and its early stages in particular., Methods: We applied semi-automated volumetry of the hypothalamus (HTH) in 3 T MRI in a sample N = 175 participants [age 74.9 ± 7.22; gender 85 m/90f; cognitively normal controls (CN; N = 56); amnestic mild cognitive impairment (MCI; N = 78); AD (N = 41)] from the Alzheimer's Disease Neuroimaging Initiative (ADNI). In addition, we used voxel-based morphometry (VBM), cortical thickness (CTH) analyses and source-based morphometry (SBM) derived networks of structural covariance to investigate brain structural covariance patterns of the HTH under consideration of diagnostic groups, β-amyloid (AB) positivity and apolipoprotein E (APOE) ε4 status., Results: Hypothalamic atrophy was observed in both early and advanced disease stages (i.e. hypothalamic volume CN > MCI > AD). VBM, CTH analysis and SBM revealed positive associations between hypothalamic volume (HV) and AD-vulnerable regions, largely corresponding to the Papez circuit and brain regions implicated in autonomic regulation, however, group differences regarding HTH structural covariance were not observed. Similar observations were made in carriers and non-carriers of the ε4 allele, yet more pronounced in ε4 carriers. Although not reaching significance, comparisons of AB positive vs. negative subjects indicated stronger HTH atrophy in biomarker positive participants. HV was not associated with body mass index or longitudinal weight change., Conclusions: Our findings support early structural changes of the HTH in AD. HV covaries with regional volumes of AD-vulnerable regions. This could point to secondary atrophy of the HTH following atrophy of the hippocampus and other structures of the Papez circuit in AD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

There is an empirical association between stress and symptoms of food addiction (FA), but it is still not clear which domains of stress are the most relevant when it comes to FA, limiting the ability of researchers and practitioners to address problematic eating-related health outcomes. In order to address this gap in the literature, we analysed how different domains of chronic stress are related to FA. We used data from a subsample of the LIFE-Adult-Study (N = 1172), a German cohort study. We conducted a linear regression analysis with stress domains (Trier Inventory for Chronic Stress, TICS) as predictors of FA (Yale Food Addiction Scale, YFAS). In the second regression analysis we included sociodemographic variables, personality, and smoking as control variables. There was a significant and positive association between Social Overload, Work Discontent, Excessive Demands from Work, and Chronic Worrying and FA. After adding control variables, only Social Overload, Excessive Demands from Work, and Chronic Worrying remained significant predictors. Connections between stress domains and FA can serve as starting points for the development of meaningful interventions that support individuals self-care strategies (Social Overload), complexity management (Excessive Demands from Work), and coping with negative emotions (Chronic Worrying)., (© 2023 The Authors. Stress and Health published by John Wiley & Sons Ltd.)

Background: Obesity is a multifactorial condition. Genetic variants, such as the fat mass and obesity related gene (FTO) polymorphism, may increase the vulnerability of developing obesity by disrupting dopamine signaling within the reward network. Yet, the association of obesity, genetic risk of obesity, and structural connectivity of the reward network in adolescents and young adults remains unexplored. We investigate, in adolescents and young adults, the structural connectivity differences in the reward network and at the whole-brain level according to body mass index (BMI) and the FTO rs9939609 polymorphism., Methods: One hundred thirty-two adolescents and young adults (age range: [10, 21] years, BMI z-score range: [-1.76, 2.69]) were included. Genetic risk of obesity was determined by the presence of the FTO A allele. Whole-brain and reward network structural connectivity were analyzed using graph metrics. Hierarchical linear regression was applied to test the association between BMI-z, genetic risk of obesity, and structural connectivity., Results: Higher BMI-z was associated with higher (B = 0.76, 95% CI = [0.30, 1.21], P = 0.0015) and lower (B = -0.003, 95% CI = [-0.006, -0.00005], P = 0.048) connectivity strength for fractional anisotropy at the whole-brain level and of the reward network, respectively. The FTO polymorphism was not associated with structural connectivity nor with BMI-z., Conclusions: We provide evidence that, in healthy adolescents and young adults, higher BMI-z is associated with higher connectivity at the whole-brain level and lower connectivity of the reward network. We did not find the FTO polymorphism to correlate with structural connectivity. Future longitudinal studies with larger sample sizes are needed to assess how genetic determinants of obesity change brain structural connectivity and behavior., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Studies show a connection between anxiety and stress, but with little differentiation between different domains of stress. In this article, we utilize a multi-dimensional approach to better understand the relationship between different chronic stress domains and anxiety. This will allow researchers to identify and address those areas of stress that are most relevant with regard to anxiety. We used data from a sub sample of the LIFE-Adult-Study (n = 1085) to analyze the association between nine different areas of chronic stress (Trier Inventory for Chronic Stress, TICS) and anxiety (General Anxiety Disorder 7, GAD-7), controlling for sociodemographic variables, personality, and social support. There was a significant and positive association between Work Overload, Pressure to Perform, Social Tensions, Social Isolation, Chronic Worrying, and anxiety. After including the control variables, only Work Overload and Chronic Worrying remained significant. By focusing on Work Overload and Chronic Worrying researchers, practitioners, and policy makers can help to mitigate anxiety and related health problems in the population in an efficient way.

Purpose: Adult idiopathic condylar resorption (AICR) mainly affects young women, but generally accepted diagnostic standards are lacking. Patients often need temporomandibular joint (TMJ) surgery, and often jaw anatomy is assessed by CT as well as MRI to observe both bone and soft tissue. This study aims to establish reference values for mandible dimensions in women from MRI only and correlate them to, e.g., laboratory parameters and lifestyle, to explore new putative parameters relevant in AICR. MRI-derived reference values could reduce preoperative effort by allowing physicians to rely on only the MRI without additional CT scan., Methods: We analyzed MRI data from a previous study (LIFE-Adult-Study, Leipzig, Germany) of 158 female participants aged 15-40 years (as AICR typically affects young women). The MR images were segmented, and standardized measuring of the mandibles was established. We correlated morphological features of the mandible with a large variety of other parameters documented in the LIFE-Adult study., Results: We established new reference values for mandible morphology in MRI, which are consistent with previous CT-based studies. Our results allow assessment of both mandible and soft tissue without radiation exposure. Correlations with BMI, lifestyle, or laboratory parameters could not be observed. Of note, correlation between SNB angle, a parameter often used for AICR assessment, and condylar volume, was also not observed, opening up the question if these parameters behave differently in AICR patients., Conclusion: These efforts constitute a first step towards establishing MRI as a viable method for condylar resorption assessment., (© 2023. The Author(s).)

Background: So far, previous research suggests positive effects of mental demands at the workplace. However, it may depend on how stressfull these demands are perceived on an individual level., Objective: The aim was to build on previous research by investigating how mental demands are related to stress, overload, and work discontent and whether this relationship is mediated by individuals resources, such as resilience., Method: A sub-sample of the LIFE Adult Cohort (n = 480) was asked to answer questions on sociodemographic characteristics, objective stress (using the Trier Inventory of Chronic Stress (TICS)), and perceptions of stress with regard to verbal and executive mental demands at work., Results: According to generalized linear regression models, higher verbal as well as executive mental demands were associated with higher levels of chronic stress, work overload and discontent. Higher levels of resilience were associated with lower levels of these outcomes. Analyses regarding interaction effects revealed that the interaction between resilience and perceived stress of verbal mental demands was significant only in terms of work overload., Conclusion: Higher perceived stressfulness of mental demands was associated with higher chronic stress, work overload and work discontent. Therefore, mental demands should be targeted by occupational interventions that aim to improve job conditions and employees' overall well-being. Besides resilience, other potential influencers or personal resources should be focused on in future studies to develop interventions., (© 2023. BioMed Central Ltd., part of Springer Nature.)

While there are studies connecting everyday physical activity (PA) to mental health, they mostly use self-report measures for PA which are biased in multiple ways. Nevertheless, a realistic assessment of everyday PA is important for the development and implementation of low-threshold public health interventions. Therefore, we want to analyze the relationship between objectively measured daily steps and mental health. We included 1451 subjects from a subsample of the population-based LIFE-Adult-Study (2011-2014) with an average age of 55.0 years, 52.1% were female. We analyzed the effects of PA (step count measured via SenseWear Pro 3) on depression (CES-D), anxiety (GAD-7), and quality of sleep (PSQI). The regression analysis showed a significant negative association between low to moderate PA [Incidence rate ratio: 0.87 (0.77; 0.98)] as well as high to very high PA [0.84 (0.74; 0.95)] and depression and no significant associations between PA and anxiety [l-m: 0.98 (0.81; 1.18)/h-vh: 1.00 (0.82; 1.21)] or quality of sleep [l-m: 0.94 (0.84, 1.06)/h-vh: 0.92 (0.82, 1.03)], controlling for sociodemographic variables and personality. Low-threshold interventions that increase daily step count could be a useful approach for the prevention of depression. The use of objective PA measurement for research is highly encouraged.