Search Results (1,314)

The effects of long-term adjustments in body weight on the lipid balance in patients with severe obesity are not well understood. This study aimed to evaluate a non-invasive lipidomic approach to identifying biomarkers that could help predict which patients may require additional therapies before and after weight loss. Using mass spectrometry, 275 lipid species were analysed in non-obese controls, patients with severe obesity, and patients one year after bariatric surgery. The results showed that severe obesity disrupts lipid pathways, contributing to lipotoxicity, inflammation, mitochondrial stress, and abnormal lipid metabolism. Although weight loss improved these disturbances, surgery did not fully normalise the lipid profiles of all patients. Outcomes varied depending on their baseline liver health and genetic differences. Persistent alterations in cholesterol handling, membrane composition, and mitochondrial function were observed in partial responders. Elevated levels of sterol lipids, glycerophospholipids, and sphingolipids emerged as markers of complete metabolic recovery, identifying candidates for targeted post-surgical interventions. These findings support the use of lipidomics to personalise obesity treatment and follow-up. Full article

Background: Ulcerative colitis (UC), characterized by chronic intestinal inflammation, epithelial barrier dysfunction, and immune imbalance demands novel ameliorative strategies beyond conventional approaches. Methods: In this study, the probiotic properties of Lactobacillus paracaseiL21 (L. paracaseiL21) and its ability to ameliorate colitis were evaluated using an in vitro lipopolysaccharide (LPS)-induced intestinal crypt epithelial cell (IEC-6) model and an in vivo dextran sulfate sodium (DSS)-induced UC mouse model. Results: In vitro, L. paracaseiL21 decreased levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-8) while increasing anti-inflammatory IL-10 levels (p < 0.05) in LPS-induced IEC-6 cells, significantly enhancing the expression of tight junction proteins (ZO-1, occludin, claudin-1), thereby restoring the intestinal barrier. In vivo, both viable L. paracaseiL21 and its heat-inactivated postbiotic (H-L21) mitigated weight loss, colon shortening, and disease activity indices, concurrently reducing serum LPS and proinflammatory mediators. Interventions inhibited NF-κB signaling while activating HIF1α/AhR pathways, increasing IL-22 and mucin MUC2 to restore goblet cell populations. Gut microbiota analysis showed that both interventions increased the abundance of beneficial gut bacteria (Lactobacillus, Dubococcus, and Akkermansia) and improved faecal propanoic acid and butyric acid levels. H-L21 uniquely exerted an anti-inflammatory effect, marked by the regulation of Dubosiella, while L. paracaseiL21 marked by the Akkermansia. Conclusions: These results highlight the potential of L. paracaseiL21 as a candidate for the development of both probiotic and postbiotic formulations. It is expected to provide a theoretical basis for the management of UC and to drive the development of the next generation of UC therapies. Full article

Background and Objectives: The management of type 2 diabetes (T2D) extends beyond glycemic control, requiring a more global strategy that includes optimization of body composition, even more so in the context of sarcopenia and visceral adiposity, as they contribute to poor outcomes. Past reviews have typically been focused on weight reduction or glycemic effectiveness, with limited inclusion of new therapies’ effects on muscle and fat distribution. In addition, the emergence of incretin-based therapies and dual agonists such as tirzepatide requires an updated synthesis of their impacts on body composition. This review attempts to bridge the gap by taking a systematic approach to how current blood-glucose lowering therapies affect lean body mass, fat mass, and the risk of sarcopenia in T2D patients. Materials and Methods: Between January 2015 and March 2025, we conducted a narrative review by searching the PubMed, Scopus, and Web of Science databases for English-language articles. The keywords were combinations of the following: “type 2 diabetes,” “lean body mass,” “fat mass,” “body composition,” “sarcopenia,” “GLP-1 receptor agonists,” “SGLT2 inhibitors,” “tirzepatide,” and “antidiabetic pharmacotherapy.” Reference lists were searched manually as well. The highest precedence was assigned to studies that aimed at adult type 2 diabetic subjects and reported body composition results. Inclusion criteria for studies were: (1) type 2 diabetic mellitus adult patients and (2) reporting measures of body composition (e.g., lean body mass, fat mass, or muscle function). We prioritized randomized controlled trials and large observational studies and excluded mixed diabetic populations, non-pharmacological interventions only, and poor reporting of body composition. Results: Metformin was widely found to be weight-neutral with minimal effects on muscle mass. Insulin therapy, being an anabolic hormone, often leads to fat mass accumulation and increases the risk of sarcopenic obesity. Incretin-based therapies induced substantial weight loss, mostly from fat mass. Notable results were observed in studies with tirzepatide, demonstrating superior reduction not only in fat mass, but also in visceral fat. Sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) promote fat loss but are associated with a small yet significant decrease in lean muscle mass. Conclusions: Blood-glucose lowering therapies demonstrated clinically relevant effects on body composition. Treatment should be personalized, balancing glycemic control, cardiovascular, and renal benefits, together with optimal impact on muscle mass along with glycemic, cardiovascular, and renal benefits. Full article

Obesity is a growing global health concern with widespread impacts on physical, psychological, and social well-being. Clinically, it is a major driver of type 2 diabetes (T2D), cardiovascular disease (CVD), non-alcoholic fatty liver disease (NAFLD), and cancer, reducing life expectancy by 5–20 years and imposing a staggering economic burden of USD 2 trillion annually (2.8% of global GDP). Despite its significant health and socioeconomic impact, earlier obesity medications, such as fenfluramine, sibutramine, and orlistat, fell short of expectations due to limited effectiveness, serious side effects including valvular heart disease and gastrointestinal issues, and high rates of treatment discontinuation. The advent of glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., semaglutide, tirzepatide) has revolutionized obesity management. These agents demonstrate unprecedented efficacy, achieving 15–25% mean weight loss in clinical trials, alongside reducing major adverse cardiovascular events by 20% and T2D incidence by 72%. Emerging therapies, including oral GLP-1 agonists and triple-receptor agonists (e.g., retatrutide), promise enhanced tolerability and muscle preservation, potentially bridging the efficacy gap with bariatric surgery. However, challenges persist. High costs, supply shortages, and unequal access pose significant barriers to the widespread implementation of obesity treatment, particularly in low-resource settings. Gastrointestinal side effects and long-term safety concerns require close monitoring, while weight regain after medication discontinuation emphasizes the need for ongoing adherence and lifestyle support. This review highlights the transformative potential of incretin-based therapies while advocating for policy reforms to address cost barriers, equitable access, and preventive strategies. Future research must prioritize long-term cardiovascular outcome trials and mitigate emerging risks, such as sarcopenia and joint degeneration. A multidisciplinary approach combining pharmacotherapy, behavioral interventions, and systemic policy changes is critical to curbing the obesity epidemic and its downstream consequences. Full article

Malignant mediastinal tumors are a group representing some of the most demanding oncological challenges for early, multi-level, and successful management. The timely identification of any suspicious clinical symptomatology is urgent in achieving an accurate, staged histological diagnosis, in order to follow up with an equally detailed medical therapeutic plan (interventional or not) and determine the principal goals regarding efficient overall treatment in these patients. We report a case of a 24-year-old male patient with an incident-free prior medical history. An initial chest X-ray was performed after the patient reported short-term, consistent moderate chest pain symptomatology, early work fatigue, and shortness of breath. The following imaging procedures (chest CT, PET-CT) indicated the presence of an anterior mediastinal mass (meas. ~11 cm × 10 cm × 13 cm, SUV: 8.7), applying additional pressure upon both right heart chambers. The Alpha-Fetoprotein (aFP) blood levels had exceeded at least 50 times their normal range. Two consecutive diagnostic attempts with non-specific histological results, a negative-for-malignancy fine-needle aspiration biopsy (FNA-biopsy), and an additional tumor biopsy, performed via mini anterior (R) thoracotomy with “suspicious” cellular gatherings, were performed elsewhere. After admission to our department, an (R) Video-Assisted Thoracic Surgery (VATS) was performed, along with multiple tumor biopsies and moderate pleural effusion drainage. The tumor’s measurements had increased to DMax: 16 cm × 9 cm × 13 cm, with a severe degree of atelectasis of the Right Lower Lobe parenchyma (RLL) and a pressure-displacement effect upon the Superior Vena Cava (SVC) and the (R) heart sinus, based on data from the preoperative chest MRA. The histological report indicated elements of a combined, non-seminomatous germ-cell mediastinal tumor, posthuberal-type teratoma, and embryonal carcinoma. The imminent chemotherapeutic plan included a “BEP” (Bleomycin^®/Cisplatin^®/Etoposide^®) scheme, which needed to be modified to a “VIP” (Cisplatin^®/Etoposide^®/Ifosfamide^®) scheme, due to an acute pulmonary embolism incident. While the aFP blood levels declined, even reaching normal measurements, the tumor’s size continued to increase significantly (DMax: 28 cm × 25 cm × 13 cm), with severe localized pressure effects, rapid weight loss, and a progressively worsening clinical status. Thus, an emergency surgical intervention took place via median sternotomy, extended with a complementary “T-Shaped” mini anterior (R) thoracotomy. A large, approx. 4 Kg mediastinal tumor was extracted, with additional RML and RUL “en-bloc” segmentectomy and partial mediastinal pleura decortication. The following histological results, apart from verifying the already-known posthuberal-type teratoma, indicated additional scattered small lesions of combined high-grade rabdomyosarcoma, chondrosarcoma, and osteosarcoma, as well as numerous high-grade glioblastoma cellular gatherings. No visible findings of the previously discovered non-seminomatous germ-cell and embryonal carcinoma elements were found. The patient’s postoperative status progressively improved, allowing therapeutic management to continue with six “TIP” (Cisplatin^®/Paclitaxel^®/Ifosfamide^®) sessions, currently under his regular “follow-up” from the oncological team. This report underlines the importance of early, accurate histological identification, combined with any necessary surgical intervention, diagnostic or therapeutic, as well as the appliance of any subsequent multimodality management plan. The diversity of mediastinal tumors, especially for young patients, leaves no place for complacency. Such rare examples may manifest, with equivalent, unpredictable evolution, obliging clinical physicians to stay constantly alert and not take anything for granted. Full article

Maternal and child health during pregnancy is an important issue in global public health, and the classification accuracy of fetal cardiotocography (CTG), as a key tool for monitoring fetal health during pregnancy, is directly related to the effectiveness of early diagnosis and intervention. Due to the serious category imbalance problem of CTG data, traditional models find it challenging to take into account a small number of categories of samples, increasing the risk of leakage and misdiagnosis. To solve this problem, this paper proposes a two-step innovation: firstly, we design a method of adaptive adjustment of misclassification loss function weights (MAAL), which dynamically identifies and increases the focus on misclassified samples based on misclassification rates. Secondly, a primary and secondary correction network model (MAC-NET) is constructed to carry out secondary correction for the misclassified samples of the primary model. Experimental results show that the method proposed in this paper achieves 99.39% accuracy on the UCI publicly available fetal health dataset, and also obtains excellent performance on other domain imbalance datasets. This demonstrates that the model is not only effective in alleviating the problem of category imbalance, but also has very high clinical utility. Full article

Objective: This study aimed to identify plasma exosomal microRNAs (miRNAs) associated with weight loss and type 2 diabetes (T2D) remission following low-calorie diet (LCD) intervention. Methods: A 6-month dietary intervention targeting T2D remission was conducted among individuals with T2D. Participants underwent a 3-month intensive weight loss phase consuming LCD (815–835 kcal/day) and a 3-month weight maintenance phase (N = 32). Sixteen participants were randomly selected for characterization of plasma-derived exosomal miRNA profiles at baseline, 3 months, and 6 months using small RNA sequencing. Linear mixed-effects models were used to identify differentially expressed exosomal miRNAs between responders and non-responders. Pathway enrichment analyses were conducted using target mRNAs of differentially expressed miRNAs. Logistic regression models assessed the predictive value of differentially expressed miRNAs for T2D remission. Results: Among the 16 participants, 6 achieved weight loss ≥10% and 12 achieved T2D remission. Eighteen exosomal miRNAs, including miR-92b-3p, miR-495-3p, and miR-452b-5p, were significantly associated with T2D remission and weight loss. Pathway analyses revealed enrichment in PI3K-Akt pathway, FoxO signaling pathway, and insulin receptor binding. The addition of individual miRNAs including miR-15b-3p, miR-26a-5p, and miR-3913-5p to base model improved the area under the curve values by 0.02–0.08 at 3 months and by 0.02–0.06 at 6 months for T2D remission. Conclusions: This study identified exosomal miRNAs associated with T2D remission and weight loss following LCD intervention. Several exosomal miRNAs might serve as valuable predictors of T2D remission in response to LCD intervention. Full article

Cordyceps sinensis (C. sinensis) is widely recognized for its bioactive compounds and associated health benefits. However, due to its delicate nature, conventional chilled storage often results in the rapid degradation of valuable compounds, leading to loss of nutritional value and overall quality. This study integrated and evaluated comprehensive strategies: three gas-conditioning and two light-based preservation methods for maintaining both quality and nutritional integrity during 12-day chilled storage at 4 °C. The results revealed that vacuum packaging significantly inhibited weight loss (3.49%) compared to in the control group (10.77%) and preserved sensory quality (p < 0.05). UV-based interventions notably suppressed polyphenol oxidase and tyrosinase activities by 36.4% and 29.7%, respectively (p < 0.05). Modified atmosphere packaging (MAP) with 80% N₂ and 20% CO₂ (MAP-N₂CO₂) maintained higher levels of cordycepin (1.77 µg/g) and preserved energy charge above 0.7 throughout storage. The results suggest that MAP-based treatments are superior methods for the chilled storage of C. sinensis, with diverse advantages and their corresponding shelf lives associated with different gas compositions. Full article

Childhood obesity is a major global health problem, and its management involves a multidisciplinary approach that includes lifestyle changes, dietary interventions, and the use of dietary supplements. In this review, we summarize current findings on the role of amino acids in pediatric obesity, with a particular focus on their involvement in metabolic pathways and weight regulation. The involvement of branched-chain and aromatic amino acids in the pathophysiology and potential management of pediatric obesity is highlighted in recent studies. Both experimental and clinical studies have shown that obese children often exhibit altered plasma amino acid profiles, including increased levels of leucine, isoleucine, valine, phenylalanine, and tyrosine, as well as decreased levels of glycine and serine. These imbalances are correlated with insulin resistance, inflammation, and early metabolic dysfunction. One of the mechanisms through which branched-chain amino acids can promote insulin resistance is the activation of the mammalian target of rapamycin (mTOR) signaling pathway. Metabolomic profiling has demonstrated the potential of specific amino acid patterns to predict obesity-related complications before they become clinically evident. Early identification of these biomarkers could be of great help for individualized interventions. Although clinical studies indicate that changes in dietary amino acids could lead to modest weight loss, improved metabolic profiles, and increased satiety, further studies are needed to establish standardized recommendations. Full article

Background/Objectives: Knee osteoarthritis is one of the most significant diseases globally and in Portugal. Despite the availability of international guidelines, there is a lack of tailored, evidence-based recommendations specifically for Portuguese physiotherapists to manage their knee osteoarthritis patients with non-pharmacological and non-surgical interventions. This study aimed to develop a clinical practice guideline that integrates the latest international evidence with local clinical practice data to enhance patient outcomes. Methods: To achieve the objective, a comprehensive search was conducted in November 2024 across major health-related databases, to identify robust and recent evidence regarding the efficacy of non-pharmacological and non-surgical interventions, as well as their usage in the national context. Two key sources were identified: An umbrella and a mixed-methods study. Data from both sources were independently reviewed and integrated through a comparative analysis to identify interventions with robust scientific support and high local acceptability. Recommendations were then formulated and categorized into gold (strong), silver (moderate), and bronze (weak) levels based on evidence quality and clinical relevance. A decision-making flowchart was developed to support guideline implementation and clinical usage. Results: The integrated analysis identified three gold-level interventions, namely Nutrition/Weight Loss, Resistance Exercise, and Self-care/Education. Five silver-level recommendations were Aerobic Exercise, Balneology/Spa, Extracorporeal Shockwave Therapy, Electrical Stimulation, and Manual Therapy. Similarly, five bronze-level recommendations comprised Kinesio Taping, Stretching, Ultrasound Therapy, Thermal Agents, and Walking Aids. Conclusions: This clinical practice guideline provides a context-specific, evidence-based framework for Portuguese physiotherapists managing knee osteoarthritis. By bridging international evidence with local clinical practice, the guideline aims to facilitate optimal patient care and inform future research and guideline updates. Full article

Background/Objectives: Daily caloric restriction (DCR) is a common dietary weight loss strategy, but leads to metabolic and behavioral adaptations, including maladaptive eating behaviors and dysregulated appetite. Intermittent fasting (IMF) may mitigate these effects by offering diet flexibility during energy restriction. This secondary analysis compared changes in eating behaviors and appetite-related hormones between 4:3 intermittent fasting (4:3 IMF) and DCR and examined their association with weight loss over 12 months. Methods: Adults with overweight or obesity were randomized to 4:3 IMF or DCR for 12 months. Both randomized groups received a matched targeted weekly dietary energy deficit (34%), comprehensive group-based behavioral support, and a prescription to increase moderate-intensity aerobic activity to 300 min/week. Eating behaviors were assessed using validated questionnaires at baseline and months 3, 6, and 12. Fasting levels of leptin, ghrelin, peptide YY, brain-derived neurotrophic factor, and adiponectin were measured at baseline and months 6 and 12. Linear mixed models and Pearson correlations were used to evaluate outcomes. Results: Included in this analysis were 165 adults (mean ± SD; age 42 ± 9 years, BMI 34.2 ± 4.3 kg/m², 74% female) randomized to 4:3 IMF (n = 84) or DCR (n = 81). At 12 months, binge eating and uncontrolled eating scores decreased in 4:3 IMF but increased in DCR (p < 0.01 for between-group differences). Among 4:3 IMF, greater weight loss was associated with decreased uncontrolled eating (r = −0.27, p = 0.03), emotional eating (r = −0.37, p < 0.01), and increased cognitive restraint (r = 0.35, p < 0.01) at 12 months. There were no between-group differences in changes in fasting appetite-related hormones at any time point. Conclusions: Compared to DCR, 4:3 IMF exhibited improved binge eating and uncontrolled eating behaviors at 12 months. This may, in part, explain the greater weight loss achieved by 4:3 IMF versus DCR. Future studies should examine mechanisms underlying eating behavior changes with 4:3 IMF and their long-term sustainability. Full article

Obesity is a global epidemic with substantial health and economic impacts, making scalable weight management strategies essential. A comprehensive synthesis of eHealth interventions for weight management is needed to guide clinical practice. This umbrella review evaluated mobile and web-based interventions for weight loss in adults with overweight or obesity, compared to conventional or non-intervention controls. Systematic reviews were identified across five electronic databases from inception to February 2025. Two reviewers independently selected studies and assessed methodological quality using AMSTAR 2. Pooled estimates were calculated using random-effects models. Eleven systematic reviews (261 primary studies, 62,407 participants) were included. Mobile app interventions yielded a significant reduction in body weight (MD = −1.32 kg; I² = 82%), as did long-term eHealth interventions (MD = −1.13 kg; I² = 76%). Most meta-analyses showed high heterogeneity. Web-based interventions showed no significant effect. In conclusion, mobile apps and long-term eHealth interventions resulted in modest but statistically significant reductions in body weight, body mass index, and waist circumference. The evidence for web-based approaches remains inconclusive. Further research should focus on low-resource settings, primary care, and the integration of emerging technologies such as artificial intelligence. (PROSPERO CRD42025644218). Full article

Polycystic liver disease (PLD) is a rare genetic disorder characterized by the development of >10 fluid-filled cysts in the liver. While PLD can occur in isolation, it is most commonly associated with autosomal dominant polycystic kidney disease, adding complexity to its management. PLD is often asymptomatic but can lead to hepatomegaly, causing symptoms such as abdominal distension, pain and discomfort, early satiety, gastroesophageal reflux, and malnutrition, ultimately affecting patients’ quality of life. Current treatment strategies, including pharmacological and interventional approaches, focus on reducing liver volume and alleviating symptoms. However, management remains largely symptomatic, as no definitive therapies exist to halt cyst progression. Liver transplantation is the only curative option for patients with severe, progressive disease and refractory complications. The EASL guidelines recognize that PLD-related symptoms, primarily due to hepatomegaly, can contribute to involuntary weight loss and recommend assessing symptomatic patients for malnutrition and sarcopenia. Although evidence suggests that patients with PLD may be at risk of malnutrition, original data on the quality and extent of nutritional alterations remain scarce. The potential influence of nutrition on disease progression, symptom burden, and overall well-being is also largely unexplored. Given these knowledge gaps, addressing nutritional challenges, such as early satiety, is essential for optimizing symptom management and maintaining overall nutritional status. This review outlines a possible pathophysiology of malnutrition, specific dietary considerations and recommendations, and weight management in patients with PLD. Additionally, dietary complexities in patients with concurrent renal involvement are discussed, offering a practical framework for clinicians and dietitians in managing this challenging condition. Full article

In recent decades, the Brazilian Cerrado has faced rapid land conversion, resulting in the loss of approximately half of its original vegetation cover. Most existing conservation units within the biome are increasingly threatened by the expansion of land use around their boundaries. The establishment of buffer zones with land use regulations may protect biodiversity within these protected areas. In this study, we evaluated and ranked the 10 km buffer zones of 15 national parks (NPs) located in the Cerrado biome, identifying their priority for biodiversity conservation and sustainable land use interventions. The analysis considered the following data: land use and land cover change from 2012 to 2020, extent of natural vegetation fragments, presence or absence of state and municipal conservation units within the buffer zones, and drainage density. Two multicriteria analysis methods, the analytic hierarchy process and the weighted linear combination, were applied to classify the buffer zones into five levels of threat: very high, high, moderate, low, and very low. Among the 15 buffer zones analyzed, 11 were classified as having high to very high priority for conservation actions. The buffer zones surrounding the Serra da Bodoquena, Emas, Canastra, and Brasília NPs were ranked as having very high priority. Between 2012 and 2020, the most severe reductions in ecological connectivity were observed in the buffer zones of Grande Sertão Veredas (44.5%), Nascentes do Rio Parnaíba (40.4%), and Serra das Confusões (36.7%). Given the relatively high proportion of natural vegetation in the buffer zones located in the northern Cerrado, we recommend prioritizing conservation efforts in this region. In contrast, in the southern portion of the biome, where land occupation is more intense, strategies should focus on promoting environmentally sustainable land use practices. Full article

Background: The gut microbiota is increasingly recognized as a key modulator in obesity management, influencing host energy balance, lipid metabolism, and inflammatory pathways. With obesity prevalence continuing to rise globally, dietary interventions that promote beneficial microbial shifts are essential for enhancing weight loss outcomes and long-term health. Objective: This study investigated the effects of the multicomponent Weight Loss Maintenance 3 Phases Program (WLM3P), which integrates caloric restriction, a high-protein low-carbohydrate diet, time-restricted eating (10h TRE), dietary supplementation (prebiotics and phytochemicals), and digital app-based support on gut microbiota composition compared to a standard low-carbohydrate diet (LCD) in adults with obesity. The analysis focused exclusively on the 6-month weight loss period corresponding to Phases 1 and 2 of the WLM3P intervention. Methods: In this sub-analysis of a randomized controlled trial (ClinicalTrials.gov Identifier: NCT04192357), 58 adults with obesity (BMI 30.0–39.9 kg/m²) were randomized to the WLM3P (n = 29) or LCD (n = 29) groups. Stool samples were collected at baseline and 6 months for 16S rRNA sequencing. Alpha and beta diversity were assessed, and genus-level differential abundance was determined using EdgeR and LEfSe. Associations between microbial taxa and clinical outcomes were evaluated using regression models. Results: After 6-month, the WLM3P group showed a significant increase in alpha diversity (p = 0.03) and a significant change in beta diversity (p < 0.01), while no significant changes were observed in the LCD group. Differential abundance analysis revealed specific microbial signatures in WLM3P participants, including increased levels of Faecalibacterium. Notably, higher Faecalibacterium abundance was associated with greater reductions in fat mass (kg, %) and visceral adiposity (cm²) in the WLM3P group compared to LCD (p < 0.01). Conclusions: These findings suggest a potential microbiota-mediated mechanism in weight loss, where Faecalibacterium may enhance fat reduction effectiveness in the context of the WLM3P intervention. Full article