-
Frontiers in Pharmacology 2024Urothelial carcinoma (UC) is a refractory disease for which achieving satisfactory outcomes remains challenging with current surgical interventions. Antibody-drug...
Urothelial carcinoma (UC) is a refractory disease for which achieving satisfactory outcomes remains challenging with current surgical interventions. Antibody-drug conjugates (ADCs) are a novel class of targeted therapeutics that have demonstrated encouraging results for UC. Although there is a limited number of high-quality randomized control trials (RCTs) examining the use of ADCs in patients with UC, some prospective non-randomized studies of interventions (NRSIs) provide valuable insights and pertinent information. We aim to assess the efficacy and safety of ADCs in patients with UC, particularly those with locally advanced and metastatic diseases. A systematic search was conducted across PubMed, Embase, the Cochrane Library, and Web of Science databases to identify pertinent studies. Outcomes, such as the overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), adverse events (AEs), and treatment-related adverse events (TRAEs), were extracted for further analyses. Twelve studies involving 1,311 patients were included in this meta-analysis. In terms of tumor responses, the pooled ORR and DCR were 40% and 74%, respectively. Regarding survival analysis, the pooled median PFS and OS were 5.66 months and 12.63 months, respectively. The pooled 6-month PFS and OS were 47% and 80%, while the pooled 1-year PFS and OS were 22% and 55%, respectively. The most common TRAEs of the ADCs were alopecia (all grades: 45%, grades ≥ III: 0%), decreased appetite (all grades: 34%, grades ≥ III: 3%), dysgeusia (all grades: 40%, grades ≥ III: 0%), fatigue (all grades: 39%, grades ≥ III: 5%), nausea (all grades: 45%, grades ≥ III: 2%), peripheral sensory neuropathy (all grades: 37%, grades ≥ III: 2%), and pruritus (all grades: 32%, grades ≥ III: 1%). The meta-analysis in this study demonstrates that ADCs have promising efficacies and safety for patients with advanced or metastatic UC. https://www.crd.york.ac.uk/prospero/, identifier: CRD42023460232.
PubMed: 38933670
DOI: 10.3389/fphar.2024.1377924 -
Frontiers in Physiology 2024Oleuropein, a phenolic compound derived from olives, has known glucoregulatory effects in mammalian models but effects in birds are unknown. We investigated effects of...
Oleuropein, a phenolic compound derived from olives, has known glucoregulatory effects in mammalian models but effects in birds are unknown. We investigated effects of dietary supplementation and exogenous administration of oleuropein on broiler chick feed intake and glucose homeostasis during the first 7 days post-hatch. One hundred and forty-eight day-of-hatch broiler chicks were randomly allocated to one of four dietary treatments with varying oleuropein concentrations (0, 250, 500, or 1,000 mg/kg). Body weight and breast muscle and liver weights were recorded on day 7. In the next experiment, chicks received intraperitoneal (IP) injections of oleuropein at doses of 0 (vehicle), 50, 100, or 200 mg/kg on day 4 post-hatch, with feed intake and blood glucose levels measured thereafter. Lastly, chicks fed a control diet were fasted and administered intracerebroventricular (ICV) injections of oleuropein at doses of 0, 50, 100, or 200 μg, after which feed intake was recorded. Results indicated that IP and ICV injections led to decreased feed intake, primarily at 60 min post-injection, with effects diminishing by 90 min in the IP study. Blood glucose levels decreased 1-h post-IP injection at higher oleuropein doses. These findings suggest that oleuropein acts as a mild appetite suppressant and influences energy metabolism in broiler chickens.
PubMed: 38933363
DOI: 10.3389/fphys.2024.1409211 -
Nutrients Jun 2024This study investigated trends within a custom Sports Nutrition Assessment for Consultation (SNAC) survey designed to identify nutrition-related risk factors among...
This study investigated trends within a custom Sports Nutrition Assessment for Consultation (SNAC) survey designed to identify nutrition-related risk factors among post-operative lower-extremity youth athletes. Athletes aged 8-18 years who completed the SNAC at a sports medicine institution after lower-extremity surgery were reviewed for associations between SNAC questions and age/sex differences. Of 477 patients (15.0 ± 2.0 years; 47.8% female), 319 (66.9%) answered 'yes' to at least one question and were identified for a consult, though 216 (64.3%) declined. The most frequent questions to prompt a consult were a desire to better understand nutrition for recovery (41.5%) and regularly skipping at least one meal a day (29.8%). Inter-question responses were often significantly related, especially regarding appetite changes, weight changes, and/or meal-skipping. While consult acceptance was not significantly different between sex/age, males were more likely to report a desire to better understand nutrition ( = 0.004) and a weight change ( = 0.019), and females were more likely to report struggling with dizziness/fatigue ( < 0.001). Additionally, older athletes reported an appetite change ( = 0.022), meal-skipping ( = 0.002), a desire to better understand nutrition ( < 0.001), a weight change ( < 0.001), and an effort/recommendation to change their body composition/weight ( = 0.005). These findings demonstrate a link between risky nutrition behaviors and physical detriments.
Topics: Humans; Female; Male; Adolescent; Child; Risk Factors; Nutritional Status; Lower Extremity; Nutrition Assessment; Athletes; Postoperative Period; Athletic Injuries; Appetite; Sex Factors; Postoperative Complications
PubMed: 38931202
DOI: 10.3390/nu16121847 -
Nutrients Jun 2024The global rise in type 2 diabetes (T2D) and obesity necessitates innovative dietary interventions. This study investigates the effects of allulose, a rare sugar shown...
The global rise in type 2 diabetes (T2D) and obesity necessitates innovative dietary interventions. This study investigates the effects of allulose, a rare sugar shown to reduce blood glucose, in a rat model of diet-induced obesity and T2D. Over 12 weeks, we hypothesized that allulose supplementation would improve body weight, insulin sensitivity, and glycemic control. Our results showed that allulose mitigated the adverse effects of high-fat, high-sugar diets, including reduced body weight gain and improved insulin resistance. The allulose group exhibited lower food consumption and increased levels of glucagon-like peptide-1 (GLP-1), enhancing glucose regulation and appetite control. Additionally, allulose prevented liver triglyceride accumulation and promoted mitochondrial uncoupling in adipose tissue. These findings suggest that allulose supplementation can improve metabolic health markers, making it a promising dietary component for managing obesity and T2D. Further research is needed to explore the long-term benefits and mechanisms of allulose in metabolic disease prevention and management. This study supports the potential of allulose as a safe and effective intervention for improving metabolic health in the context of dietary excess.
Topics: Animals; Fructose; Male; Obesity; Diabetes Mellitus, Type 2; Insulin Resistance; Blood Glucose; Rats; Diet, High-Fat; Liver; Glucagon-Like Peptide 1; Triglycerides; Rats, Sprague-Dawley; Adipose Tissue; Weight Gain; Disease Models, Animal
PubMed: 38931176
DOI: 10.3390/nu16121821 -
International Journal of Environmental... Jun 2024Deoxynivalenol (DON) is a foodborne mycotoxin produced by molds that commonly infect cereal grains. It is a potent protein synthesis inhibitor that can significantly... (Review)
Review
Deoxynivalenol (DON) is a foodborne mycotoxin produced by molds that commonly infect cereal grains. It is a potent protein synthesis inhibitor that can significantly impact humans' gastrointestinal, immune, and nervous systems and can alter the microbiome landscape. Low-dose, chronic exposure to DON has been found to stimulate the immune system, inhibit protein synthesis, and cause appetite suppression, potentially leading to growth failure in children. At higher doses, DON has been shown to cause immune suppression, nausea, vomiting, abdominal pain, headache, diarrhea, gastroenteritis, the malabsorption of nutrients, intestinal hemorrhaging, dizziness, and fever. A provisional maximum tolerable daily intake (PMTDI) limit of 1 µg/kg/body weight has been established to protect humans, underscoring the potential health risks associated with DON intake. While the adverse effects of dietary DON exposure have been established, healthcare communities have not adequately investigated or addressed this threat to child health, possibly due to the assumption that current regulatory exposure limits protect the public appropriately. This integrative review investigated whether current dietary DON exposure rates in infants and children regularly exceed PMTDI limits, placing them at risk of negative health effects. On a global scale, the routine contamination of cereal grains, bakery products, pasta, and human milk with DON could lead to intake levels above PMTDI limits. Furthermore, evidence suggests that other food commodities, such as soy, coffee, tea, dried spices, nuts, certain seed oils, animal milk, and various water reservoirs, can be intermittently contaminated, further amplifying the scope of the issue. Better mitigation strategies and global measures are needed to safeguard vulnerable youth from this harmful toxicant.
Topics: Humans; Trichothecenes; Child; Dietary Exposure; Infant; Food Contamination; Child, Preschool
PubMed: 38929054
DOI: 10.3390/ijerph21060808 -
International Journal of Environmental... Jun 2024Obesity reflects excessive fat deposits. At-risk individuals are guided by healthcare professionals to eat fewer calories and exercise more, often using body mass index... (Review)
Review
Obesity reflects excessive fat deposits. At-risk individuals are guided by healthcare professionals to eat fewer calories and exercise more, often using body mass index (BMI; weight/height) thresholds for screening and to guide progress and prognosis. By conducting a mini-narrative review of original articles, websites, editorials, commentaries, and guidelines, we sought to place BMI in the context of its appropriate use in population health, clinical screening, and monitoring in clinical care. The review covers studies and publications through 2023, encompassing consensus reviews and relevant literature. Recent consensus reviews suggest that BMI is a valuable tool for population surveys and primary healthcare screening but has limitations in predicting the risk of chronic diseases and assessing excess fat. BMI can guide nutritional and exercise counseling, even if it is inadequate for reliable individual risk prediction. BMI cut-offs must be reconsidered in populations of varying body build, age, and/or ethnicity. Since BMI-diagnosed overweight persons are sometimes physically and physiologically fit by other indicators, persons who are overweight on BMI should be more fully evaluated, diagnosed, and monitored with combined anthropometric and performance metrics to better clarify risks. The use of combined anthropometric and performance metrics involves integrating measurements of body composition with assessments of physical function and fitness to provide a more comprehensive evaluation of an individual's health and fitness status. Eligibility for bariatric surgery or semaglutide satiety/appetite-reduction medications should not be determined by BMI alone. Awareness of the advantages and limitations of using BMI as a tool to assess adult obesity can maximize its appropriate use in the context of population health and in rapid clinical screening and evaluation.
Topics: Humans; Body Mass Index; Obesity; Adult
PubMed: 38929003
DOI: 10.3390/ijerph21060757 -
Brain Sciences Jun 2024Glucagon-like peptide-1 (GLP-1) is involved in a range of central and peripheral pathways related to appetitive behavior. Hence, this study explored the effects of...
Glucagon-like peptide-1 (GLP-1) is involved in a range of central and peripheral pathways related to appetitive behavior. Hence, this study explored the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on substance and behavioral addictions, including alcohol, caffeine, nicotine, cannabis, psychostimulants, compulsive shopping, and sex drive/libido. Data were collected from various social platforms. Keywords related to GLP-1 RAs and substance/behavioral addiction were used to extract relevant comments. The study employed a mixed-methods approach to analyze online discussions posted from December 2019 to June 2023 and collected using a specialized web application. Reddit entries were the focus here due to limited data from other platforms, such as TikTok and YouTube. A total of 5859 threads and related comments were extracted from six subreddits, which included threads about GLP-1 RAs drugs and associated brand names. To obtain relevant posts, keywords related to potential substance use and compulsive behavior were selected. Further analysis involved two main steps: (1) manually coding posts based on users' references to the potential impact of GLP-1 RAs on substance use and non-substance habits, excluding irrelevant or unclear comments; (2) performing a thematic analysis on the dataset of keywords, using AI-assisted techniques followed by the manual revision of the generated themes. Second, a thematic analysis was performed on the keyword-related dataset, using AI-assisted techniques followed by the manual revision of the generated themes. In total, 29.75% of alcohol-related; 22.22% of caffeine-related; and 23.08% of nicotine-related comments clearly stated a cessation of the intake of these substances following the start of GLP-1 RAs prescription. Conversely, mixed results were found for cannabis intake, and only limited, anecdotal data were made available for cocaine, entactogens, and dissociative drugs' misuse. Regarding behavioral addictions, 21.35% of comments reported a compulsive shopping interruption, whilst the sexual drive/libido elements reportedly increased in several users. The current mixed-methods approach appeared to be a useful tool in gaining insight into complex topics such as the effects of GLP-1 RAs on substance and non-substance addiction-related disorders; some GLP-1 RA-related mental health benefits could also be inferred from here. Overall, it appeared that GLP-1 RAs may show the potential to target both substance craving and maladaptive/addictive behaviors, although further empirical research is needed.
PubMed: 38928616
DOI: 10.3390/brainsci14060617 -
Brain Sciences Jun 2024Correct classification of irritability is extremely important to assess prognosis and treatment indications of juvenile mood disorders. We assessed factors associated...
Correct classification of irritability is extremely important to assess prognosis and treatment indications of juvenile mood disorders. We assessed factors associated with low versus high parent- and self-rated irritability using the affective reactivity index (ARI) in a sample of 289 adolescents diagnosed with a bipolar or a major depressive disorder. Bivariate analyses were followed by multilinear logistic regression model. Factors significantly and independently associated with high versus low parent-rated ARI score were: more severe emotional dysregulation and bipolar disorders diagnosis. Factors significantly and independently associated with high versus low self-rated ARI score were: lower children depression rating scale (CDRS-R) difficulty of having fun item score, greater children depression inventory (CDI-2) self-report score, more severe emotional dysregulation, and greater CDRS-R appetite disturbance item score. High parent-rated irritability was strictly related with a bipolar disorder diagnosis, whereas high youth-rated irritability was related to depressive phenotype characterized by appetite/food-intake dysregulation, mood lability, and less anhedonia and apathy.
PubMed: 38928611
DOI: 10.3390/brainsci14060611 -
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 -
Biomolecules Jun 2024Exogenous supplementation with ketone beverages has been shown to reduce plasma glucose levels during acute nutritional ketosis. It remains to be investigated whether... (Randomized Controlled Trial)
Randomized Controlled Trial
Exogenous supplementation with ketone beverages has been shown to reduce plasma glucose levels during acute nutritional ketosis. It remains to be investigated whether growth differentiation factor 15 (GDF-15)-an anorexigenic hormone-is involved in this process. The aim was to investigate the effect of a ketone ester beverage delivering β-hydroxybutyrate (KEβHB) on plasma levels of GDF-15, as well as assess the influence of eating behaviour on it. The study was a randomised controlled trial (registered at clinicaltrials.gov as NCT03889210). Individuals were given a KEβHB beverage or placebo in a cross-over fashion. Blood samples were collected at baseline, 30, 60, 90, 120, and 150 min after ingestion. Eating behaviour was assessed using the three-factor eating questionnaire. GDF-15 levels were not significantly different ( = 0.503) after the KEβHB beverage compared with the placebo. This finding remained consistent across the cognitive restraint, emotional eating, and uncontrolled eating domains. Changes in the anorexigenic hormone GDF-15, irrespective of eating behaviour, do not appear to play a major role in the glucose-lowering effect of exogenous ketones.
Topics: Humans; Growth Differentiation Factor 15; Male; Ketosis; Adult; 3-Hydroxybutyric Acid; Female; Cross-Over Studies; Young Adult; Beverages; Blood Glucose; Feeding Behavior
PubMed: 38927068
DOI: 10.3390/biom14060665