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World Journal of Gastroenterology Jun 2024In this editorial, we commented on a recently released manuscript by Zeng in the W. We focused specifically on lifestyle changes in patients with non-alcoholic fatty...
In this editorial, we commented on a recently released manuscript by Zeng in the W. We focused specifically on lifestyle changes in patients with non-alcoholic fatty liver disease (NAFLD). NAFLD is a hepatic manifestation of the metabolic syndrome, which ultimately leads to advanced hepatic fibrosis, cirrhosis, and hepatocellular carcinoma and affects more than 25% of the population globally. Existing therapeutic strategies against NAFLD such as pharmacologic therapies focus on liver protection, anti-inflammation, and regulating disease-related metabolic disorder symptoms. Although several drugs are in late-stage development, potent drugs against the diseases are lacking. Additionally, existing surgical approaches such as bariatric surgery are not routinely used to treat NAFLD. Intervening in patients' unhealthy lifestyles, such as weight loss through dietary changes and exercises to ameliorate patient-associated metabolic disorders and metabolic syndrome, is the first-line treatment for patients with NAFLD. With sufficient intrinsic motivation and adherence, the management of unhealthy lifestyles can reduce the severity of the disease, improve the quality of life, and increase the survival expectancy of patients with NAFLD.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Metabolic Syndrome; Quality of Life; Life Style; Weight Loss; Exercise; Bariatric Surgery; Risk Reduction Behavior; Healthy Lifestyle; Risk Factors
PubMed: 38947294
DOI: 10.3748/wjg.v30.i22.2829 -
World Journal of Orthopedics Jun 2024The integration of WhatsApp, a widely-used instant messaging application (IMA), into the realm of orthopaedics and trauma surgery has emerged as a significant... (Review)
Review
The integration of WhatsApp, a widely-used instant messaging application (IMA), into the realm of orthopaedics and trauma surgery has emerged as a significant development in recent years. This paper explores the multifaceted role of WhatsApp in orthopaedics, focusing on its clinical and non-clinical applications, advantages, disadvantages, and future prospects. The study synthesizes findings from various research papers, emphasizing the growing reliance on mobile technology in healthcare. WhatsApp's role in orthopaedics is notable for its ease of use, real-time communication, and accessibility. Clinically, it facilitates triage, teleconsultation, diagnosis, treatment, patient advice, and post-operative monitoring. Non-clinically, it supports telemedicine, teleradiology, virtual fracture clinics, research, and education in orthopaedic surgery. The application has proven beneficial in enhancing communication among healthcare teams, providing quick responses, and motivating junior physicians. Its use in educational settings has been shown to improve learner's understanding and patient care. However, the use of WhatsApp in orthopaedics is not without challenges. Risks include the potential spread of misleading information, privacy concerns, and issues with image quality affecting diagnosis and treatment decisions. The paper acknowledges the importance of maintaining professional boundaries and the need for oversight measures to ensure content accuracy. Looking forward, the potential of WhatsApp and similar IMAs in orthopaedics lies in their ability to streamline data collection and retrieval, improve doctor-patient communication, and address challenges like bureaucratic red tape and limited resources. The paper suggests that future orthopaedic practice, particularly in emergency departments, will increasingly rely on such technologies for efficient patient management. This shift, however, must be approached with an understanding of the ethical, legal, and practical implications of integrating social media and mobile technology in healthcare.
PubMed: 38947267
DOI: 10.5312/wjo.v15.i6.529 -
Frontiers in Psychiatry 2024Forensic psychiatric patients receive treatment to address their violent and aggressive behavior with the aim of facilitating their safe reintegration into society. On...
INTRODUCTION
Forensic psychiatric patients receive treatment to address their violent and aggressive behavior with the aim of facilitating their safe reintegration into society. On average, these treatments are effective, but the magnitude of effect sizes tends to be small, even when considering more recent advancements in digital mental health innovations. Recent research indicates that wearable technology has positive effects on the physical and mental health of the general population, and may thus also be of use in forensic psychiatry, both for patients and staff members. Several applications and use cases of wearable technology hold promise, particularly for patients with mild intellectual disability or borderline intellectual functioning, as these devices are thought to be user-friendly and provide continuous daily feedback.
METHOD
In the current randomized crossover trial, we addressed several limitations from previous research and compared the (continuous) usability and acceptance of four selected wearable devices. Each device was worn for one week by staff members and patients, amounting to a total of four weeks. Two of the devices were general purpose fitness trackers, while the other two devices used custom made applications designed for bio-cueing and for providing insights into physiological reactivity to daily stressors and events.
RESULTS
Our findings indicated significant differences in usability, acceptance and continuous use between devices. The highest usability scores were obtained for the two fitness trackers (Fitbit and Garmin) compared to the two devices employing custom made applications (Sense-IT and E4 dashboard). The results showed similar outcomes for patients and staff members.
DISCUSSION
None of the devices obtained usability scores that would justify recommendation for future use considering international standards; a finding that raises concerns about the adaptation and uptake of wearable technology in the context of forensic psychiatry. We suggest that improvements in gamification and motivational aspects of wearable technology might be helpful to tackle several challenges related to wearable technology.
PubMed: 38947186
DOI: 10.3389/fpsyt.2024.1330993 -
MedRxiv : the Preprint Server For... Jun 2024Fine-mapping and gene-prioritisation techniques applied to the latest Genome-Wide Association Study (GWAS) results have prioritised hundreds of genes as causally...
Fine-mapping and gene-prioritisation techniques applied to the latest Genome-Wide Association Study (GWAS) results have prioritised hundreds of genes as causally associated with disease. Here we leverage these recently compiled lists of high-confidence causal genes to interrogate where in the body disease genes operate. Specifically, we combine GWAS summary statistics, gene prioritisation results and gene expression RNA-seq data from 46 tissues and 204 cell types in relation to 16 major diseases (including 8 cancers). In tissues and cell types with well-established relevance to the disease, the prioritised genes typically have higher absolute and relative (i.e. tissue/cell specific) expression compared to non-prioritised 'control' genes. Examples include brain tissues in psychiatric disorders ( -value < 1×10 ), microglia cells in Alzheimer's Disease ( -value = 9.8×10 ) and colon mucosa in colorectal cancer ( -value < 1×10 ). We also observe significantly higher expression for disease genes in multiple tissues and cell types with no established links to the corresponding disease. While some of these results may be explained by cell types that span multiple tissues, such as macrophages in brain, blood, lung and spleen in relation to Alzheimer's disease ( -values < 1×10 ), the cause for others is unclear and motivates further investigation that may provide novel insights into disease etiology. For example, mammary tissue in Type 2 Diabetes ( -value < 1×10 ); reproductive tissues such as breast, uterus, vagina, and prostate in Coronary Artery Disease ( -value < 1×10 ); and motor neurons in psychiatric disorders ( -value < 3×10 ). In the GTEx dataset, tissue type is the major predictor of gene expression but the contribution of each predictor (tissue, sample, subject, batch) varies widely among disease-associated genes. Finally, we highlight genes with the highest levels of gene expression in relevant tissues to guide functional follow-up studies. Our results could offer novel insights into the tissues and cells involved in disease initiation, inform drug target and delivery strategies, highlighting potential off-target effects, and exemplify the relative performance of different statistical tests for linking disease genes with tissue and cell type gene expression.
PubMed: 38947033
DOI: 10.1101/2024.06.20.24309121 -
MedRxiv : the Preprint Server For... Jun 2024Weekly Steroids in Muscular Dystrophy (WSiMD) was a pilot study to evaluate once weekly prednisone in patients with Limb Girdle and Becker muscular dystrophy (LGMD and...
BACKGROUND
Weekly Steroids in Muscular Dystrophy (WSiMD) was a pilot study to evaluate once weekly prednisone in patients with Limb Girdle and Becker muscular dystrophy (LGMD and BMD, respectively). At study endpoint, there were trends towards increased lean mass, reduced fat mass, reduced creatine kinase and improved motor function. The investigation was motivated by studies in mouse muscular dystrophy models in which once weekly glucocorticoid exposure enhanced muscle strength and reduced fibrosis.
METHODS
WSiMD participants provided blood samples for aptamer serum profiling at baseline and after 6 months of weekly steroids. A subset completed magnetic resonance (MR) evaluation of muscle at study onset and endpoint.
RESULTS/CONCLUSIONS
At baseline compared to age and sex-matched healthy controls, the aggregate serum protein profile in the WSiMD cohort was dominated by muscle proteins, reflecting leak of muscle proteins into serum. Disease status produced more proteins differentially present in serum compared to steroid-treatment effect. Nonetheless, a response to prednisone was discernable in the WSiMD cohort, even at this low dose. Glucocorticoids downregulated muscle proteins and upregulated certain immune process- and matrix-associated proteins. Muscle MR fat fraction showed trends with functional status. The prednisone-responsive markers could be used in larger trial of prednisone efficacy.
PubMed: 38947030
DOI: 10.1101/2024.06.14.24308858 -
Research Square Jun 2024Among individuals living with psychotic disorders, social impairment is common, debilitating, and challenging to treat. While the roots of this impairment are...
Among individuals living with psychotic disorders, social impairment is common, debilitating, and challenging to treat. While the roots of this impairment are undoubtedly complex, converging lines of evidence suggest that social motivation and pleasure (MAP) deficits play a key role. Yet most neuroimaging studies have focused on monetary rewards, precluding decisive inferences. Here we leveraged parallel social and monetary incentive delay fMRI paradigms to test whether blunted reactivity to social incentives in the ventral striatum-a key component of the distributed neural circuit mediating appetitive motivation and hedonic pleasure-is associated with more severe MAP symptoms in a transdiagnostic sample enriched for psychosis. To maximize ecological validity and translational relevance, we capitalized on naturalistic audiovisual clips of an established social partner expressing positive feedback. Although both paradigms robustly engaged the ventral striatum, only reactivity to social incentives was associated with clinician-rated MAP deficits. This association remained significant when controlling for other symptoms, binary diagnostic status, or ventral striatum reactivity to monetary incentives. Follow-up analyses suggested that this association predominantly reflects diminished striatal activation during the receipt of social reward. These observations provide a neurobiologically grounded framework for conceptualizing the social-anhedonia symptoms and social impairments that characterize many individuals living with psychotic disorders and underscore the need to establish targeted intervention strategies.
PubMed: 38947025
DOI: 10.21203/rs.3.rs-4468839/v1 -
MedRxiv : the Preprint Server For... Jun 2024Individuals with major depressive disorder (MDD) can experience reduced motivation and cognitive function, leading to challenges with goal-directed behavior. When...
Individuals with major depressive disorder (MDD) can experience reduced motivation and cognitive function, leading to challenges with goal-directed behavior. When selecting goals, people maximize 'expected value' by selecting actions that maximize potential reward while minimizing associated costs, including effort 'costs' and the opportunity cost of time. In MDD, differential weighing of costs and benefits are theorized mechanisms underlying changes in goal-directed cognition and may contribute to symptom heterogeneity. We used the Effort Foraging Task to quantify cognitive and physical effort costs, and patch leaving thresholds in low effort conditions (hypothesized to reflect perceived opportunity cost of time) and investigated their shared versus distinct relationships to clinical features in participants with MDD (N=52, 43 in-episode) and comparisons (N=27). Contrary to our predictions, none of the decision-making measures differed with MDD diagnosis. However, each of the measures were related to symptom severity, over and above effects of ability (i.e., performance). Greater anxiety symptoms were selectively associated with cognitive effort cost (i.e. greater willingness to exert effort). Anhedonia symptoms were associated with increased physical effort costs. Finally, greater physical anergia was related to decreased patch leaving thresholds. Markers of effort-based decision-making may inform understanding of MDD heterogeneity. Increased willingness to exert cognitive effort may contribute to anxiety symptoms such as rumination and worry. The association of decreased leaving thresholds with symptom severity is consistent with reward rate-based accounts of reduced vigor in MDD. Future research should address subtypes of depression with or without anxiety, which may relate differentially to cognitive effort decisions.
PubMed: 38947009
DOI: 10.1101/2024.02.18.24302985 -
Frontiers in Cell and Developmental... 2024We describe exciting recent advances in fusion-driven sarcoma etiology, from an epigenetics perspective. By exploring the current state of the field, we identify and...
We describe exciting recent advances in fusion-driven sarcoma etiology, from an epigenetics perspective. By exploring the current state of the field, we identify and describe the central mechanisms that determine sarcomagenesis. Further, we discuss seminal studies in translational genomics, which enabled epigenetic characterization of fusion-driven sarcomas. Important context for epigenetic mechanisms include, but are not limited to, cell cycle and metabolism, core regulatory circuitry, 3-dimensional chromatin architectural dysregulation, integration with ATP-dependent chromatin remodeling, and translational animal modeling. Paradoxically, while the genetic requirements for oncogenic transformation are highly specific for the fusion partners, the epigenetic mechanisms we as a community have uncovered are categorically very broad. This dichotomy prompts the question of whether the investigation of rare disease epigenomics should prioritize studying individual cell populations, thereby examining whether the mechanisms of chromatin dysregulation are specific to a particular tumor. We review recent advances focusing on rhabdomyosarcoma, synovial sarcoma, alveolar soft part sarcoma, clear cell sarcoma, undifferentiated round cell sarcoma, Ewing sarcoma, myxoid/round liposarcoma, epithelioid hemangioendothelioma and desmoplastic round cell tumor. The growing number of groundbreaking discoveries in the field, motivated us to anticipate further exciting advances in the area of mechanistic epigenomics and direct targeting of fusion transcription factors in the years ahead.
PubMed: 38946804
DOI: 10.3389/fcell.2024.1416946 -
The Journal of Toxicological Sciences 2024To examine the effects of decreased food consumption on toxicological parameters in juvenile rats, rats on postnatal day 21 were fed 40%, 50% (only four weeks), and 60%...
To examine the effects of decreased food consumption on toxicological parameters in juvenile rats, rats on postnatal day 21 were fed 40%, 50% (only four weeks), and 60% less food, compared to that of controls for four or eight weeks, and clinical observations, measurement of body and organ weights, morphological differentiation analysis, clinical pathology, and macroscopic and microscopic examinations were conducted. The body weight decreased depending on the degree of food restriction (FR). Cleavage of the balano-preputial skinfold was delayed, and cell debris in the epididymal lumen was noted as a related finding after four-week FR. Vaginal opening was also delayed, and some histopathological findings, such as absence of corpus luteum in the ovary, mucinous degeneration in the vagina, and immature uterus, were noted after eight-week FR. Erythrocyte count increased after four-week FR, but slightly decreased in males only after eight-week FR, and decreased leukocyte and/or reticulocyte counts, accompanied by related histopathological findings were noted after four- and eight-week FR. In blood chemistry, the levels of total protein including globulin, glucose, triglyceride, and calcium decreased, and sodium and chloride increased after four- and eight-week FR. Increases in activities of aspartate transaminase and lactate dehydrogenase and total bilirubin levels were noted after four-week FR, which were attenuated after eight-week FR. The effects of FR seemed to be more remarkable after four weeks. In drug safety evaluation, findings caused by malnutrition should be considered in juvenile toxicity studies when decreased food consumption is observed.
Topics: Animals; Male; Female; Body Weight; Organ Size; Rats; Caloric Restriction; Time Factors; Food Deprivation; Rats, Sprague-Dawley; Rats, Wistar
PubMed: 38945843
DOI: 10.2131/jts.49.321 -
Physiology & Behavior Jun 2024The roles of metabolic signals, including Glucagon-like peptide 1 (GLP-1), have been implicated in multiple domains outside metabolic regulation. There is a growing... (Review)
Review
INTRODUCTION
The roles of metabolic signals, including Glucagon-like peptide 1 (GLP-1), have been implicated in multiple domains outside metabolic regulation. There is a growing interest in repurposing Glucagon-like peptide 1 receptor agonists (GLP-1RAs) as therapeutics for motivation and reward-related behavioural disturbances. Herein, we aim to systematically review the extant evidence on the potential effects of GLP-1RAs on the reward system.
METHODS
The study followed PRISMA guidelines using databases such as OVID, PubMed, Scopus, and Google Scholar. The search focused on "Reward Behavior" and "Glucagon Like Peptide 1 Receptor Agonists" and was restricted to human studies. Quality assessment achieved by the NIH's Quality Assessment of Controlled Intervention Studies RESULTS: GLP-1RAs consistently reduced energy intake and influenced reward-related behaviour. These agents have been associated with decreased neurocortical activation in response to higher rewards and food cues, particularly high-calorie foods, and lowered caloric intake and hunger levels.
DISCUSSION
GLP-1RAs show promise in addressing reward dysfunction linked to food stimuli, obesity, and T2DM. They normalize insulin resistance, and might also modulate dopaminergic signalling and reduce anhedonia. Their effects on glycemic variability and cravings suggest potential applications in addiction disorders.
PubMed: 38945189
DOI: 10.1016/j.physbeh.2024.114622