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  • 1
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    Online Resource
    Different Areas of Chronic Stress and Their Associations with Depression
    MDPI AG ; 2022
    In:  International Journal of Environmental Research and Public Health Vol. 19, No. 14 ( 2022-07-19), p. 8773-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 19, No. 14 ( 2022-07-19), p. 8773-
    Abstract: Background: Research shows a connection between stress and depression, but there is little differentiation between areas of stress, making it difficult to identify and address specific areas in the context of public health measures. We utilized a multi-dimensional approach to chronic stress to better understand the relationship between different areas of stress and depression. Methods: We conducted linear regression analyses and used data from a sub-sample of the LIFE-Adult-Study (N = 1008) to analyze the connection between nine different areas of chronic stress (TICS) and depression (CES-D). In the second analysis, we controlled for sociodemographic variables, personality, physical activity, and social support. Results: There was a significant positive association between the stress domains Excessive Demands from Work, Lack of Social Recognition, Social Isolation, and Chronic Worrying and depression and a significant negative association between Pressure to Perform and depression. After adding control variables, only Pressure to Perform, Social Isolation, and Chronic Worrying remained significant predictors. Conclusions: By focusing on the connections between chronic stress and depression, researchers can help identify the areas that matter most and contribute to the creation of meaningful and efficient interventions. On the basis of our results, measures for the prevention of depression that focus on the reduction of worrying and social isolation are recommended.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph19148773
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2175195-X
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  • 2
    Online Resource
    Online Resource
    Fatigue in Cancer and Neuroinflammatory and Autoimmune Disease: CNS Arousal Matters
    MDPI AG ; 2020
    In:  Brain Sciences Vol. 10, No. 9 ( 2020-08-19), p. 569-
    Details
    In: Brain Sciences, MDPI AG, Vol. 10, No. 9 ( 2020-08-19), p. 569-
    Abstract: The term fatigue is not only used to describe a sleepy state with a lack of drive, as observed in patients with chronic physical illnesses, but also a state with an inhibition of drive and central nervous system (CNS) hyperarousal, as frequently observed in patients with major depression. An electroencephalogram (EEG)-based algorithm has been developed to objectively assess CNS arousal and to disentangle these pathophysiologically heterogeneous forms of fatigue. The aim of this study was to test the hypothesis that fatigued patients with CNS hyperarousal score higher on depressive symptoms than those without this neurophysiological pattern. Methods: Subjects with fatigue (Multidimensional Fatigue Inventory sum-score 〉 40) in the context of cancer, neuroinflammatory, or autoimmune diseases were drawn from the 60+ cohort of the Leipzig Research Center for Civilization Diseases. CNS arousal was assessed by automatic EEG-vigilance stage classification using the Vigilance Algorithm Leipzig (VIGALL 2.1) based on 20 min EEG recordings at rest with eyes closed. Depression was assessed by the Inventory of Depressive Symptomatology (IDS-SR). Results: Sixty participants (33 female; median age: 67.5 years) were included in the analysis. As hypothesized, fatigued patients with CNS hyperarousal had higher IDS-SR scores than those without hyperarousal (F1,58 = 18.34; p 〈 0.0001, η2 = 0.240). Conclusion: hyperaroused fatigue in patients with chronic physical illness may be a sign of comorbid depression.
    Type of Medium: Online Resource
    ISSN: 2076-3425
    URL: Article
    DOI: 10.3390/brainsci10090569
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2651993-8
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  • 3
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    Uncovering the Contribution of Moderate-Penetrance Susceptibility Genes to Breast Cancer by Whole-Exome Sequencing and Targeted Enrichment Sequencing of Candidate Genes in Women of European Ancestry
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 14 ( 2022-07-11), p. 3363-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 14 ( 2022-07-11), p. 3363-
    Abstract: Rare variants in at least 10 genes, including BRCA1, BRCA2, PALB2, ATM, and CHEK2, are associated with increased risk of breast cancer; however, these variants, in combination with common variants identified through genome-wide association studies, explain only a fraction of the familial aggregation of the disease. To identify further susceptibility genes, we performed a two-stage whole-exome sequencing study. In the discovery stage, samples from 1528 breast cancer cases enriched for breast cancer susceptibility and 3733 geographically matched unaffected controls were sequenced. Using five different filtering and gene prioritization strategies, 198 genes were selected for further validation. These genes, and a panel of 32 known or suspected breast cancer susceptibility genes, were assessed in a validation set of 6211 cases and 6019 controls for their association with risk of breast cancer overall, and by estrogen receptor (ER) disease subtypes, using gene burden tests applied to loss-of-function and rare missense variants. Twenty genes showed nominal evidence of association (p-value 〈 0.05) with either overall or subtype-specific breast cancer. Our study had the statistical power to detect susceptibility genes with effect sizes similar to ATM, CHEK2, and PALB2, however, it was underpowered to identify genes in which susceptibility variants are rarer or confer smaller effect sizes. Larger sample sizes would be required in order to identify such genes.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14143363
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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  • 4
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    Calculating Protein Content of Expressed Breast Milk to Optimize Protein Supplementation in Very Low Birth Weight Infants with Minimal Effort—A Secondary Analysis
    MDPI AG ; 2020
    In:  Nutrients Vol. 12, No. 5 ( 2020-04-27), p. 1231-
    Details
    In: Nutrients, MDPI AG, Vol. 12, No. 5 ( 2020-04-27), p. 1231-
    Abstract: Breast milk does not meet the nutritional needs of preterm infants, necessitating fortification. Breast milk is particularly variable in protein content, hence standardized (fixed dosage) supplementation results in inadequate supply. This was a secondary analysis of 589 breast milk protein content measurements of 51 mothers determined by mid-infrared spectroscopy during a clinical trial of higher versus lower protein supplementation in very low birth weight infants. Mothers (and breast milk samples) were divided into a test (41 mothers) and a validation cohort (10 mothers). In the test cohort, the decrease in protein content by day of lactation was modeled resulting in the breast milk-equation (BME)). In the validation cohort, five supplementation strategies to optimize protein supply were compared: standardized supplementation (adding 1.0 g (S1) or 1.42 g protein/100 mL (S2)) was compared with ‘adapted’ supplementation, considering variation in protein content (protein content according to Gidrewicz and Fenton (A1), to BME (A2) and to BME with adjustments at days 12 and 26 (A3)). S1 and S2 achieved 5% and 24% of adequate protein supply, while the corresponding values for A1–A3 were 89%, 96% and 95%. Adapted protein supplementation based on calculated breast milk protein content is easy, non-invasive, inexpensive and improves protein supply compared to standardized supplementation.
    Type of Medium: Online Resource
    ISSN: 2072-6643
    URL: Article
    DOI: 10.3390/nu12051231
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2518386-2
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  • 5
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    Online Resource
    Screening and Comparative Characterization of Microorganisms from Iranian Soil Samples Showing ω-Transaminase Activity toward a Plethora of Substrates
    MDPI AG ; 2019
    In:  Catalysts Vol. 9, No. 10 ( 2019-10-22), p. 874-
    Details
    In: Catalysts, MDPI AG, Vol. 9, No. 10 ( 2019-10-22), p. 874-
    Abstract: In this study, soil microorganisms from Iran were screened for ω-transaminase (ω-TA) activity based on growth on minimal media containing (rac)-α-methylbenzylamine (rac-α-MBA) as a sole nitrogen source. Then, for the selection of strains with high enzyme activity, a colorimetric o-xylylendiamine assay was conducted. The most promising strains were identified by 16S rDNA sequencing. Five microorganisms showing high ω-TA activity were subjected to determine optimal conditions for ω-TA activity, including pH, temperature, co-solvent, and the specificity of the ω-TA toward different amine donors and acceptors. Among the five screened microorganisms, Bacillus halotolerans turned out to be the most promising strain: Its cell-free extract showed a highly versatile amino donor spectrum toward aliphatic, aromatic chiral amines and a broad range of pH activity. Transaminase activity also exhibited excellent solvent tolerance, with maximum turnover in the presence of 30% (v/v) DMSO.
    Type of Medium: Online Resource
    ISSN: 2073-4344
    URL: Article
    DOI: 10.3390/catal9100874
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2662126-5
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  • 6
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    No Difference in Penetrance between Truncating and Missense/Aberrant Splicing Pathogenic Variants in MLH1 and MSH2: A Prospective Lynch Syndrome Database Study
    MDPI AG ; 2021
    In:  Journal of Clinical Medicine Vol. 10, No. 13 ( 2021-06-28), p. 2856-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 10, No. 13 ( 2021-06-28), p. 2856-
    Abstract: Background. Lynch syndrome is the most common genetic predisposition for hereditary cancer. Carriers of pathogenic changes in mismatch repair (MMR) genes have an increased risk of developing colorectal (CRC), endometrial, ovarian, urinary tract, prostate, and other cancers, depending on which gene is malfunctioning. In Lynch syndrome, differences in cancer incidence (penetrance) according to the gene involved have led to the stratification of cancer surveillance. By contrast, any differences in penetrance determined by the type of pathogenic variant remain unknown. Objective. To determine cumulative incidences of cancer in carriers of truncating and missense or aberrant splicing pathogenic variants of the MLH1 and MSH2 genes. Methods. Carriers of pathogenic variants of MLH1 (path_MLH1) and MSH2 (path_MSH2) genes filed in the Prospective Lynch Syndrome Database (PLSD) were categorized as truncating or missense/aberrant splicing according to the InSiGHT criteria for pathogenicity. Results. Among 5199 carriers, 1045 had missense or aberrant splicing variants, and 3930 had truncating variants. Prospective observation years for the two groups were 8205 and 34,141 years, respectively, after which there were no significant differences in incidences for cancer overall or for colorectal cancer or endometrial cancers separately. Conclusion. Truncating and missense or aberrant splicing pathogenic variants were associated with similar average cumulative incidences of cancer in carriers of path MLH1 and path_MSH2.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm10132856
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662592-1
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  • 7
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    Sperm Lipid Composition in Early Diverged Fish Species: Internal vs. External Mode of Fertilization
    MDPI AG ; 2020
    In:  Biomolecules Vol. 10, No. 2 ( 2020-01-22), p. 172-
    Details
    In: Biomolecules, MDPI AG, Vol. 10, No. 2 ( 2020-01-22), p. 172-
    Abstract: The lipid composition of sperm membranes is crucial for fertilization and differs among species. As the evolution of internal fertilization modes in fishes is not understood, a comparative study of the sperm lipid composition in freshwater representatives of externally and internally fertilizing fishes is needed for a better understanding of taxa-specific relationships between the lipid composition of the sperm membrane and the sperm physiology. The lipidomes of spermatozoa from stingray, a representative of cartilaginous fishes possessing internal fertilization, and sterlet, a representative of chondrostean fishes with external fertilization, have been studied by means of nuclear magnetic resonance (NMR), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), electrospray MS, gas chromatography-(GC) MS, and thin-layer chromatography (TLC). NMR experiments revealed higher cholesterol content and the presence of phosphatidylserine in stingray compared to sterlet sperm. Unknown MS signals could be assigned to different glycosphingolipids in sterlet (neutral glycosphingolipid Gal-Cer(d18:1/16:0)) and stingray (acidic glycosphingolipid sulpho-Gal-Cer(d18:1/16:0)). Free fatty acids in sterlet sperm indicate internal energy storage. GC-MS experiments indicated a significant amount of adrenic acid, but only a low amount of docosahexaenoic acid in stingray sperm. In a nutshell, this study provides novel data on sperm lipid composition for freshwater stingray and sterlet possessing different modes of fertilization.
    Type of Medium: Online Resource
    ISSN: 2218-273X
    URL: Article
    DOI: 10.3390/biom10020172
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2701262-1
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  • 8
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    Small Dimension—Big Impact! Nanoparticle-Enhanced Non-Invasive and Intravascular Molecular Imaging of Atherosclerosis In Vivo
    MDPI AG ; 2020
    In:  Molecules Vol. 25, No. 5 ( 2020-02-25), p. 1029-
    Details
    In: Molecules, MDPI AG, Vol. 25, No. 5 ( 2020-02-25), p. 1029-
    Abstract: Extensive translational research has provided considerable progress regarding the understanding of atherosclerosis pathophysiology over the last decades. In contrast, implementation of molecular in vivo imaging remains highly limited. In that context, nanoparticles represent a useful tool. Their variable shape and composition assure biocompatibility and stability within the environment of intended use, while the possibility of conjugating different ligands as well as contrast dyes enable targeting of moieties of interest on a molecular level and visualization throughout various imaging modalities. These characteristics have been exploited by a number of preclinical research approaches aimed at advancing understanding of vascular atherosclerotic disease, in order to improve identification of high-risk lesions prior to oftentimes fatal thromboembolic events. Furthermore, the combination of these targeted nanoparticles with therapeutic agents offers the potential of site-targeted drug delivery with minimized systemic secondary effects. This review gives an overview of different groups of targeted nanoparticles, designed for in vivo molecular imaging of atherosclerosis as well as an outlook on potential combined diagnostic and therapeutic applications.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules25051029
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2008644-1
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  • 9
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    Is High-Risk Sexual Behavior a Risk Factor for Oropharyngeal Cancer?
    MDPI AG ; 2023
    In:  Cancers Vol. 15, No. 13 ( 2023-06-26), p. 3356-
    Details
    In: Cancers, MDPI AG, Vol. 15, No. 13 ( 2023-06-26), p. 3356-
    Abstract: (1) Background: Several lines of evidence established a link between high-risk (HR) sexual behavior (SB), the persistence of human papillomavirus (HPV) DNA in saliva, and the presence of oncogenic HR-HPV subtypes in oropharyngeal squamous cell carcinoma (OPSCC). A highly influential case-control study by D’Souza et al. comparing OPSCC patients and ENT patients with benign diseases (hospital controls) established HR-SB as a putative etiological risk factor for OPSCC. Aiming to replicate their findings in a nested case-control study of OPSCC patients and propensity score (PS)-matched unaffected controls from a large population-based German cohort study, we here demonstrate discrepant findings regarding HR-SB in OPSCC. (2) Methods: According to the main risk factors for HNSCC (age, sex, tobacco smoking, and alcohol consumption) PS-matched healthy controls invited from the population-based cohort study LIFE and HNSCC (including OPSCC) patients underwent interviews, using AUDIT and Fagerström, as well as questionnaires asking for SB categories as published. Afterwards, by newly calculating PSs for the same four risk factors, we matched each OPSCC patient with two healthy controls and compared responses utilizing chi-squared tests and logistic regression. (3) Results: The HNSCC patients and controls showed significant differences in sex distribution, chronologic age, tobacco-smoking history (pack years), and alcohol dependence (based on AUDIT score). However, PS-matching decreased the differences between OPSCC patients and controls substantially. Despite confirming that OPSCC patients were more likely to self-report their first sexual intercourse before age 18, we found no association between OPSCC and HR-SB, neither for practicing oral-sex, having an increased number of oral- or vaginal-sex partners, nor for having casual sex or having any sexually transmitted disease. (4) Conclusions: Our data, by showing a low prevalence of HR-SB in OPSCC patients, confirm findings from other European studies that differ substantially from North American case-control studies. HR-SB alone may not add excess risk for developing OPSCC.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers15133356
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527080-1
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  • 10
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    Risk-Reducing Gynecological Surgery in Lynch Syndrome: Results of an International Survey from the Prospective Lynch Syndrome Database
    MDPI AG ; 2020
    In:  Journal of Clinical Medicine Vol. 9, No. 7 ( 2020-07-18), p. 2290-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 9, No. 7 ( 2020-07-18), p. 2290-
    Abstract: Purpose: To survey risk-reducing hysterectomy and bilateral salpingo-oophorectomy (BSO) practice and advice regarding hormone replacement therapy (HRT) in women with Lynch syndrome. Methods: We conducted a survey in 31 contributing centers from the Prospective Lynch Syndrome Database (PLSD), which incorporates 18 countries worldwide. The survey covered local policies for risk-reducing hysterectomy and BSO in Lynch syndrome, the timing when these measures are offered, the involvement of stakeholders and advice regarding HRT. Results: Risk-reducing hysterectomy and BSO are offered to path_MLH1 and path_MSH2 carriers in 20/21 (95%) contributing centers, to path_MSH6 carriers in 19/21 (91%) and to path_PMS2 carriers in 14/21 (67%). Regarding the involvement of stakeholders, there is global agreement (~90%) that risk-reducing surgery should be offered to women, and that this discussion may involve gynecologists, genetic counselors and/or medical geneticists. Prescription of estrogen-only HRT is offered by 15/21 (71%) centers to women of variable age range (35–55 years). Conclusions: Most centers offer risk-reducing gynecological surgery to carriers of path_MLH1, path_MSH2 and path_MSH6 variants but less so for path_PMS2 carriers. There is wide variation in how, when and to whom this is offered. The Manchester International Consensus Group developed recommendations to harmonize clinical practice across centers, but there is a clear need for more research.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm9072290
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2662592-1
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