-
Biomedicines Jun 2024Guidelines for the management of obesity and type 2 diabetes (T2DM) emphasize the importance of lifestyle changes, including a reduced-calorie diet and increased... (Review)
Review
Guidelines for the management of obesity and type 2 diabetes (T2DM) emphasize the importance of lifestyle changes, including a reduced-calorie diet and increased physical activity. However, for many people, these changes can be difficult to maintain over the long term. Medication options are already available to treat obesity, which can help reduce appetite and/or reduce caloric intake. Incretin-based peptides exert their effect through G-protein-coupled receptors, the receptors for glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), and glucagon peptide hormones are important regulators of insulin secretion and energy metabolism. Understanding the role of intercellular signaling pathways and inflammatory processes is essential for the development of effective pharmacological agents in obesity. GLP-1 receptor agonists have been successfully used, but it is assumed that their effectiveness may be limited by desensitization and downregulation of the target receptor. A growing number of new agents acting on incretin hormones are becoming available for everyday clinical practice, including oral GLP-1 receptor agonists, the dual GLP-1/GIP receptor agonist tirzepatide, and other dual and triple GLP-1/GIP/glucagon receptor agonists, which may show further significant therapeutic potential. This narrative review summarizes the therapeutic effects of different incretin hormones and presents future prospects in the treatment of T2DM and obesity.
PubMed: 38927527
DOI: 10.3390/biomedicines12061320 -
Biomedicines May 2024Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory condition with global implications. Accurate and timely diagnosis is critical; however,...
Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory condition with global implications. Accurate and timely diagnosis is critical; however, traditional diagnostic methods (based on spirometry) show limitations, prompting the search for predictive biomarkers and modern diagnostic techniques. This study explored the validation of COPD-related biomarkers (C-reactive protein, procalcitonin, neutrophil elastase, and alpha-1 antitrypsin) in saliva. A diverse cohort, including healthy non-smokers, healthy smokers, and COPD patients of Polish origin, underwent spirometry and marker analysis. The data correlated with clinical factors, revealing noteworthy relations. Firstly, salivary biomarker levels were compared with serum concentrations, demonstrating notable positive or negative correlations, depending on the factor. Further analysis within healthy individuals revealed associations between biomarker levels, spirometry, and clinical characteristics such as age, sex, and BMI. Next, COPD patients exhibited an enhanced concentration of biomarkers compared to healthy groups. Finally, the study introduced a breathing assessment survey, unveiling significant associations between self-perceived breathing and spirometric and tested parameters. Outcomes emphasized the relevance of subjective experiences in COPD research. In conclusion, this research underscored the potential of salivary biomarkers as diagnostic tools for COPD, offering a non-invasive and accessible alternative to traditional methods. The findings paved the way for improved modern diagnostic approaches.
PubMed: 38927413
DOI: 10.3390/biomedicines12061206 -
Alzheimer's Research & Therapy Jun 2024Although several cardiovascular, demographic, genetic and lifestyle factors have been associated with cognitive function, little is known about what type of cognitive...
BACKGROUND
Although several cardiovascular, demographic, genetic and lifestyle factors have been associated with cognitive function, little is known about what type of cognitive impairment they are associated with. The aim was to examine the associations between different risk factors and future memory and attention/executive functions, and their interaction with APOE genotype.
METHODS
Participants from a large, prospective, population-based, Swedish study were included (n = 3,229). Linear regression models were used to examine baseline hypertension, body mass index (BMI), long-term glucose levels (HbA), different lipid levels, physical activity, alcohol consumption, smoking, education, APOE genotype, age and sex. All models were adjusted for follow-up time and basic demographics, and, in a second step, all significant predictors were included to examine independent effects. Follow-up outcomes were memory and attention/executive functions.
RESULTS
The mean age at baseline was 56.1 (SD 5.7) years and 59.7% were women. The mean follow-up time was 17.4 (range 14.3-20.8) years. When examining independent effects, APOE ε4 genotype(p < 0.01), and higher HbA(p < 0.001), were associated with future low memory function. Higher BMI (p < 0.05), and HbA(p < 0.05), lower high-density lipoprotein cholesterol (HDL-C)(p < 0.05)and stroke(p < 0.001) were associated with future low attention/executive function. The strongest factors associated with both better memory and attention/executive functions were higher education and alcohol consumption. Further, significant interaction effects between predictors and APOE genotype were found. For memory function, the protective effects of education were greater among ɛ4-carriers(p < 0.05). For attention/executive function, the protective effects of alcohol were greater among ɛ2 or ɛ4-carriers(p < 0.05). Also, attention/executive function was lower among ɛ4-carriers with higher BMI(p < 0.05) and ɛ2-carriers with higher HbA1c-levels(p < 0.05).
CONCLUSIONS
Targeting cardiovascular risk factors in mid-life could have greater effect on future attention/executive functions rather than memory, whereas targeting diabetes could be beneficial for multiple cognitive domains. In addition, effects of different risk factors may vary depending on the APOE genotype. The varied cognitive profiles suggest that different mechanisms and brain regions are affected by the individual risk factors. Having detailed knowledge about the specific cognitive effects of different risk factors might be beneficial in preventive health counseling.
Topics: Humans; Female; Male; Middle Aged; Risk Factors; Follow-Up Studies; Prospective Studies; Sweden; Executive Function; Cognition; Attention; Body Mass Index; Memory; Glycated Hemoglobin; Aged; Alcohol Drinking; Genotype; Apolipoprotein E4; Neuropsychological Tests; Cognitive Dysfunction
PubMed: 38926747
DOI: 10.1186/s13195-024-01497-6 -
Scientific Reports Jun 2024Heterozygous de novo mutations in the Activity-Dependent Neuroprotective Homeobox (ADNP) gene underlie Helsmoortel-Van der Aa syndrome (HVDAS). Most of these mutations...
Heterozygous de novo mutations in the Activity-Dependent Neuroprotective Homeobox (ADNP) gene underlie Helsmoortel-Van der Aa syndrome (HVDAS). Most of these mutations are situated in the last exon and we previously demonstrated escape from nonsense-mediated decay by detecting mutant ADNP mRNA in patient blood. In this study, wild-type and ADNP mutants are investigated at the protein level and therefore optimal detection of the protein is required. Detection of ADNP by means of western blotting has been ambiguous with reported antibodies resulting in non-specific bands without unique ADNP signal. Validation of an N-terminal ADNP antibody (Aviva Systems) using a blocking peptide competition assay allowed to differentiate between specific and non-specific signals in different sample materials, resulting in a unique band signal around 150 kDa for ADNP, above its theoretical molecular weight of 124 kDa. Detection with different C-terminal antibodies confirmed the signals at an observed molecular weight of 150 kDa. Our antibody panel was subsequently tested by immunoblotting, comparing parental and homozygous CRISPR/Cas9 endonuclease-mediated Adnp knockout cell lines and showed disappearance of the 150 kDa signal, indicative for intact ADNP. By means of both a GFPSpark and Flag-tag N-terminally fused to a human ADNP expression vector, we detected wild-type ADNP together with mutant forms after introduction of patient mutations in E. coli expression systems by site-directed mutagenesis. Furthermore, we were also able to visualize endogenous ADNP with our C-terminal antibody panel in heterozygous cell lines carrying ADNP patient mutations, while the truncated ADNP mutants could only be detected with epitope-tag-specific antibodies, suggesting that addition of an epitope-tag possibly helps stabilizing the protein. However, western blotting of patient-derived hiPSCs, immortalized lymphoblastoid cell lines and post-mortem patient brain material failed to detect a native mutant ADNP protein. In addition, an N-terminal immunoprecipitation-competent ADNP antibody enriched truncating mutants in overexpression lysates, whereas implementation of the same method failed to enrich a possible native mutant protein in immortalized patient-derived lymphoblastoid cell lines. This study aims to shape awareness for critical assessment of mutant ADNP protein analysis in Helsmoortel-Van der Aa syndrome.
Topics: Humans; Homeodomain Proteins; Nerve Tissue Proteins; Mutation; HEK293 Cells; Autism Spectrum Disorder; Heart Diseases; Facies; Neurodevelopmental Disorders
PubMed: 38926592
DOI: 10.1038/s41598-024-65608-x -
Scientific Reports Jun 2024Effective surveillance on the long-term public health impact due to war and terrorist attacks remains limited. Such health issues are commonly under-reported,...
Effective surveillance on the long-term public health impact due to war and terrorist attacks remains limited. Such health issues are commonly under-reported, specifically for a large group of individuals. For this purpose, efficient estimation of the size or undercount of the population under the risk of physical and mental health hazards is of utmost necessity. A novel trivariate Bernoulli model is developed allowing heterogeneity among the individuals and dependence between the sources of information, and an estimation methodology using a Monte Carlo-based EM algorithm is proposed. Simulation results show the superiority of the performance of the proposed method over existing competitors and robustness under model mis-specifications. The method is applied to analyse two real case studies on monitoring amyotrophic lateral sclerosis (ALS) cases for the Gulf War veterans and the 9/11 terrorist attack survivors at the World Trade Center, USA. The average annual cumulative incidence rate for ALS disease increases by and for deployed and no-deployed military personnel, respectively, after adjusting the undercount. The number of individuals exposed to the risk of physical and mental health effects due to WTC terrorist attacks increased by . These results provide interesting insights that can assist in effective decision-making and policy formulation for monitoring the health status of post-war survivors.
Topics: Humans; Prevalence; Amyotrophic Lateral Sclerosis; Veterans; Algorithms; Monte Carlo Method; Gulf War
PubMed: 38926444
DOI: 10.1038/s41598-024-65478-3 -
Scientific Data Jun 2024The morphology and architecture of structures formed by sediment-dwelling invertebrates, such as excavations or burrows, are often assumed to be characteristic of a...
The morphology and architecture of structures formed by sediment-dwelling invertebrates, such as excavations or burrows, are often assumed to be characteristic of a given species, consistent across a range of environmental conditions, and used to categorise species contributions to ecosystem functioning. However, very few investigations use non-invasive high-resolution techniques capable of determining fine scale variations in burrow form and complexity, or consider whether or not the form of the burrow is context dependent. Here, we provide replicate high-resolution micro-focus computed tomography data for the complete burrow systems of the Opheliid polychaete, Armandia cirrhosa, across a range of salinity and habitat conditions. These data provide reference models which can be used by ecologists investigating intraspecific variation in species traits and organism-sediment interactions and, more generally, by those tasked with pattern and shape recognition of objects that are morphologically highly variable and which adjust their architecture with changing circumstance or context.
Topics: Polychaeta; Animals; Ecosystem; Geologic Sediments; Tomography, X-Ray Computed; X-Ray Microtomography; Salinity
PubMed: 38926417
DOI: 10.1038/s41597-024-03557-w -
Scientific Reports Jun 2024Ternary oxides are currently emerging as promising materials for optoelectronic devices and spintronics, surpassing binary oxides in terms of their superior properties....
Ternary oxides are currently emerging as promising materials for optoelectronic devices and spintronics, surpassing binary oxides in terms of their superior properties. Among these, zinc stannate (ZnSnO) stands out due to its stability and attractive physical characteristics. However, despite its outstanding attributes, there is a need to further develop its magnetic properties for spintronic applications. In this study, Ni-doped ZnSnO thin films were synthesized using the sol-gel method, and their magnetic characteristics were investigated for the first time. X-ray diffraction analysis confirmed the high crystallinity of the synthesized samples, even after the incorporation of Ni dopants, without any secondary phases. SEM imaging revealed the cubic structure morphology of the thin films. An increase in the bandgap, dependent on the Ni dopant concentration, was observed for doped zinc stannate, suggesting potential for tailored electronic properties. FTIR spectroscopy confirmed the presence of functional groups within the material. Notably, the magnetic properties of the thin films were analyzed using a vibrating sample magnetometer (VSM), revealing diamagnetic behavior for pure zinc stannate and ferromagnetic properties for Ni-doped ZnSnO, which increased with dopant concentration. Overall, the results highlight the excellent structural, optical, and ferromagnetic properties of Ni-doped ZnSnO thin films, positioning them for diverse applications, particularly in optoelectronic and spintronic technology.
PubMed: 38926404
DOI: 10.1038/s41598-024-63209-2 -
Fukushima Journal of Medical Science Jun 2024Sarcopenia is prevalent among 11-25% of adult cancer survivors, depending on the cancer type, although the available data on post-treatment survivors in Japan are...
Sarcopenia is prevalent among 11-25% of adult cancer survivors, depending on the cancer type, although the available data on post-treatment survivors in Japan are limited. If cancer patients develop cachexia, they may experience sustained weight loss as a result, ultimately leading to sarcopenia. Conversely, some patients experience post-treatment weight gain, resulting in sarcopenic obesity. Both sarcopenia and obesity elevate the risk of cardiovascular diseases and mortality; therefore, the importance of sarcopenia prevention and management is undeniable. The Guidelines for Exercise for Cancer Survivors recommend continued physical activity. Recent studies have reported the effectiveness of multimodal interventions, combining pharmacological, nutritional, and exercise approaches, necessitating multidisciplinary care for post-treatment sarcopenia. Innovative health interventions using mobile devices have also gained attention. However, studies on sarcopenia in post-treatment cancer survivors, especially those regarding exercise interventions, remain scarce in Japan, primarily due to limited insurance coverage for such post-treatment interventions and workforce challenges. It is clear that some cancer survivors have sarcopenia, which can lead to worse survival and secondary illness. While the benefits of exercise are clear, a comprehensive approach to sarcopenia is a further challenge for the future.
PubMed: 38925958
DOI: 10.5387/fms.23-00019 -
BMJ Open Jun 2024Anorexia nervosa (AN) is a severe psychiatric disorder associated with frequent relapses and variability in treatment responses. Previous literature suggested that such...
Assessing biomarkers of remission in female patients with anorexia nervosa (REMANO): a protocol for a prospective cohort study with a nested case-control study using clinical, neurocognitive, biological, genetic, epigenetic and neuroimaging markers in a French specialised inpatient unit.
BACKGROUND
Anorexia nervosa (AN) is a severe psychiatric disorder associated with frequent relapses and variability in treatment responses. Previous literature suggested that such variability is influenced by premorbid vulnerabilities such as abnormalities of the reward system. Several factors may indicate these vulnerabilities, such as neurocognitive markers (tendency to favour delayed reward, poor cognitive flexibility, abnormal decision process), genetic and epigenetic markers, biological and hormonal markers, and physiological markers.The present study will aim to identify markers that can predict body mass index (BMI) stability 6 months after discharge. The secondary aim of this study will be focused on characterising the biological, genetic, epigenetic and neurocognitive markers of remission in AN.
METHODS AND ANALYSIS
One hundred and twenty-five (n=125) female adult inpatients diagnosed with AN will be recruited and evaluated at three different times: at the beginning of hospitalisation, when discharged and 6 months later. Depending on the BMI at the third visit, patients will be split into two groups: stable remission (BMI≥18.5 kg/m²) or unstable remission (BMI<18.5 kg/m²). One hundred (n=100) volunteers will be included as healthy controls.Each visit will consist in self-reported inventories (measuring depression, anxiety, suicidal thoughts and feelings, eating disorders symptoms, exercise addiction and the presence of comorbidities), neurocognitive tasks (Delay Discounting Task, Trail-Making Test, Brixton Test and Slip-of-action Task), the collection of blood samples, the repeated collection of blood samples around a standard meal and MRI scans at rest and while resolving a delay discounting task.Analyses will mainly consist in comparing patients stabilised 6 months later and patients who relapsed during these 6 months.
ETHICS AND DISSEMINATION
Investigators will ask all participants to give written informed consent prior to participation, and all data will be recorded anonymously. The study will be conducted according to ethics recommendations from the Helsinki declaration (World Medical Association, 2013). It was registered on clinicaltrials.gov on 25 August 2020 as 'Remission Factors in Anorexia Nervosa (REMANO)', with the identifier NCT04560517 (for more details, see https://clinicaltrials.gov/ct2/show/record/NCT04560517). The present article is based on the latest protocol version from 29 November 2019. The sponsor, Institut National de la Santé Et de la Recherche Médicale (INSERM, https://www.inserm.fr/), is an academic institution responsible for the monitoring of the study, with an audit planned on a yearly basis.The results will be published after final analysis in the form of scientific articles in peer-reviewed journals and may be presented at national and international conferences.
TRIAL REGISTRATION NUMBER
clinicaltrials.govNCT04560517.
Topics: Humans; Anorexia Nervosa; Female; Prospective Studies; Biomarkers; Adult; Case-Control Studies; France; Body Mass Index; Neuroimaging; Young Adult; Adolescent; Remission Induction
PubMed: 38925688
DOI: 10.1136/bmjopen-2023-077260 -
PloS One 2024Facial mimicry, the tendency to imitate facial expressions of other individuals, has been shown to play a critical role in the processing of emotion expressions. At the...
Facial mimicry, the tendency to imitate facial expressions of other individuals, has been shown to play a critical role in the processing of emotion expressions. At the same time, there is evidence suggesting that its role might change when the cognitive demands of the situation increase. In such situations, understanding another person is dependent on working memory. However, whether facial mimicry influences working memory representations for facial emotion expressions is not fully understood. In the present study, we experimentally interfered with facial mimicry by using established behavioral procedures, and investigated how this interference influenced working memory recall for facial emotion expressions. Healthy, young adults (N = 36) performed an emotion expression n-back paradigm with two levels of working memory load, low (1-back) and high (2-back), and three levels of mimicry interference: high, low, and no interference. Results showed that, after controlling for block order and individual differences in the perceived valence and arousal of the stimuli, the high level of mimicry interference impaired accuracy when working memory load was low (1-back) but, unexpectedly, not when load was high (2-back). Working memory load had a detrimental effect on performance in all three mimicry conditions. We conclude that facial mimicry might support working memory for emotion expressions when task load is low, but that the supporting effect possibly is reduced when the task becomes more cognitively challenging.
Topics: Humans; Memory, Short-Term; Facial Expression; Male; Female; Emotions; Young Adult; Adult
PubMed: 38924006
DOI: 10.1371/journal.pone.0306113