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Efficacy of CagriSema for Reaching Anthropometric Treatment Targets and Cardiometabolic Outcomes: A Secondary, Post hoc Analysis of REDEFINE 1.

AIMS: To assess the added value of absolute anthropometric targets alongside percentage weight loss in the clinical management of obesity. MATERIALS AND METHODS: The phase 3a, 68-week REDEFINE 1 trial randomised adults without diabetes with BMI &#x2265;&#x2009;30&#x2009;kg/m2, or&#x2009;&#x2265;&#x2009;27&#x2009;kg/m2 with &#x2265;&#x2009;1 obesity-related complication, to once-weekly CagriSema 2.4&#x2009;mg/2.4&#x2009;mg, semaglutide 2.4&#x2009;mg, cagrilintide 2.4&#x2009;mg, or placebo, plus lifestyle intervention. This secondary, post hoc analysis assessed the proportions of participants achieving BMI <&#x2009;27&#x2009;kg/m2 and/or WHtR <&#x2009;0.53 targets, and percentage weight loss by anthropometric target. The association between the proportion of participants maintaining or achieving normalisation of four cardiometabolic outcomes: normoglycemia (glycated haemoglobin <&#x2009;5.7% and fasting plasma glucose <&#x2009;5.6&#x2009;mmol/L); blood pressure (<&#x2009;130/80&#x2009;mmHg); triglycerides (<&#x2009;1.7&#x2009;mmol/L); lipids (high-density lipoprotein cholesterol &#x2265;&#x2009;1.3&#x2009;mmol/L [female] or &#x2265;&#x2009;1.0&#x2009;mmol/L [male]) and reaching anthropometric targets or change in body weight (%) was also assessed. RESULTS: The proportion of participants achieving both BMI <&#x2009;27&#x2009;kg/m2 and WHtR <&#x2009;0.53 targets at week 68 was 30.3%, 19.1%, 9.0%, and 3.3% in participants who received CagriSema, semaglutide, cagrilintide, or placebo respectively. Both BMI and WHtR performed similarly as indicators for all four cardiometabolic outcomes. At more stringent cut-off values, anthropometric targets were better measures than percentage weight loss. CONCLUSIONS: The proportion of participants achieving anthropometric targets was greater with CagriSema Versus other treatments. These findings support further validation of BMI and WHtR anthropometric treatment targets and indicate a potential for indicating amelioration of clinical outcomes in obesity and a greater emphasis on target-based treatment strategies.

Humans

The global potential of freshwater microbes for plastic degradation.

Plastic pollution is becoming increasingly severe on a global scale, and the potential for biodegradation as a treatment method that is environmentally friendly merits greater attention. A significant number of genes that associated the degradation of plastic (PDAGs) have been identified, however, the distribution of these genes among microorganisms in global inland waters remains to be elucidated. A global-scale meta-analysis was conducted, incorporating approximately 1000 metagenome datasets of inland waters across seven continents. A total of 13,109 metagenome-assembled genomes (MAGs) were obtained by means of metagenomics binning, and 22,621 PDAGs were identified from these. Among these recognized PDAGs, phenylacetaldehyde dehydrogenase (PAD) was the most dominant (n = 16,664), followed by catalase (n = 5931). The predominant hosts for PAD and catalase were identified as Gamma-proteobacteria and Bacteroidia, respectively. The largest number of both PAD and catalase was found in MAGs from North America, while the average gene number in single MAG was highest in MAGs from Oceania. In accordance with the prediction of traits, PDAG-carrying MAGs from Europe demonstrated the fastest growth rate and the lowest optimal growth rate. Furthermore, 25 styrene monooxygenase (StyA) enzymes were identified, which were found to cluster into two distinct groups hosted by Alpha-proteobacteria and Gamma-proteobacteria, respectively. Moreover, 11 MAGs were observed to possess the complete pathway of polystyrene degradation. These results explored the potential of inland water microorganisms as a biological resource for plastic degradation and provided valuable microbial reference information that can be used to develop biological treatment technologies for mitigating plastics.

Plastics

Robotic Needle Insertion for CT-guided Percutaneous Biopsy of Thoracoabdominal Lesions: A Prospective Multicenter Randomized Trial.

Purpose To compare safety and feasibility between a novel CT-guided robotic system and the conventional freehand technique for puncture biopsy of thoracoabdominal lesions. Materials and Methods In this prospective multicenter randomized trial, individuals with suspected lesions were enrolled between July 2023 and April 2024 across three university teaching hospitals and randomized to the robot-assisted group (n = 82) or the freehand group (n = 83). Procedure outcomes included the technical success rate, targeting error, number of CT scans and needle adjustments, puncture time, and complications. Descriptive and inferential statistics were calculated. Results A total of 165 participants (mean age, 60 years &#xb1; 10 [SD]; 83 male) were included. Compared with the freehand group, the robot-assisted group demonstrated a higher technical success rate (97.56% [80 of 82] vs 62.65% [52 of 83], P < .001), lower targeting error (mean Euclidean deviation: 1.7 mm &#xb1; 1.1 vs 4.5 mm &#xb1; 3.9, P < .001), and fewer CT scans (mean, 4.3 &#xb1; 1.9 vs 5.2 &#xb1; 2.3; P = .002) and needle adjustments (mean, 0.7 &#xb1; 0.7 vs 1.6 &#xb1; 1.6; P = .003). Despite differences in geometric precision, both groups achieved 100% (82 of 82 and 83 of 83) diagnostic yield. The median puncture time was comparable between groups (5.5 minutes &#xb1; 4.3 vs 4.8 minutes &#xb1; 7.0, P = .50). During lung biopsies, the robot-assisted approach yielded fewer complications compared with the freehand approach (4.88% [four of 82] vs 16.87% [14 of 83], P = .014). Conclusion Compared with the freehand approach, robot-assisted biopsy yielded greater precision and reduced adjustments and complications while demonstrating noninferior diagnostic efficacy and comparable duration. Keywords: Robotic Needle Insertion, Biopsy, Thoracoabdominal Lesions, Robot-assisted Biopsy, CT-guided Intervention, Percutaneous Needle Biopsy, Randomized Controlled Trial, Algorithm Development, CT, Clinical Testing, Interventional-Body, Biopsy/Needle Aspiration, Percutaneous, Thorax, Abdomen/GI, Liver, Lung, Kidney &#xa9;RSNA, 2026.

Humans

Effects of rumen fluid transplantation on longissimus dorsi muscle development in Xizang sheep: An association analysis based on transcriptomic and serum metabolomic profiles.

This study aimed to investigate the effects of rumen fluid transplantation (RFT) on the growth and development of the longissimus dorsi muscle in female Xizang sheep. After RFT, muscle lightness differed significantly between the two groups, with the LDC group showing significantly higher lightness than the LDT group. In contrast, no significant differences were observed between groups in other muscle phenotypic traits, including drip loss, pH, cooking loss, shear force, redness, and yellowness. Antioxidant-related indices (SOD, GSH-PX, MDA, CAT, and T-AOC) also showed no significant differences between groups. Histological analysis revealed that muscle fiber length, width, and density were significantly greater in the experimental group than in the control group. Transcriptomic analysis identified 515 differentially expressed genes (DEGs), of which 419 were downregulated. KEGG analysis indicated that genes involved in muscle development-related pathways, such as cell adhesion and the PI3K-Akt signaling pathway, were predominantly downregulated. Key serum metabolites (L-kynurenine, IPA, allantoin, and propionylcarnitine) showed highly significant positive correlations with muscle fiber growth indices. In contrast, metabolites such as l-carnitine, acetylcarnitine, and citrulline were negatively correlated with muscle fiber growth, but positively correlated with the expression of muscle structure-related genes (COL11A1 and EFNA5) and with meat lightness. Overall, this study provides new insights into the potential molecular basis by which RFT influences muscle growth and development. However, the mechanisms by which RFT affects muscle development and meat quality-related traits remain unclear and warrant further investigation.

Animals

Ciliochoroidal Effusion and Regional Scleral Thickening in Peripapillary Pachychoroid Syndrome.

PURPOSE: To assess anterior scleral thickness and the presence of ciliochoroidal effusion (CE) in eyes with peripapillary pachychoroid syndrome (PPS), and to compare the results with a cohort of healthy age-matched controls. DESIGN: Retrospective cross-sectional study METHODS: A total of 20 eyes from 12 patients diagnosed with PPS and 30 eyes from 15 healthy control subjects. All participants underwent a comprehensive ophthalmic examination, including spectral-domain optical coherence tomography with enhanced depth imaging (EDI-OCT) and anterior segment OCT (AS-OCT). Choroidal thickness was measured at predefined macular and peripapillary locations, while anterior scleral thickness was assessed 6 mm posterior to the scleral spur in 4 quadrants. Ciliochoroidal effusion was evaluated qualitatively using AS-OCT. Comparisons between groups were performed using linear mixed models with Bonferroni correction (scleral thickness corrected P < .010) RESULTS: The mean age of PPS patients was 75.6 &#xb1; 9.8 years, and 16% were females. Anterior scleral thickness was significantly greater in the temporal quadrant in PPS eyes compared to controls (396.85 &#xb1; 74.97 &#xb5;m vs 331.13 &#xb1; 62.65 &#xb5;m: P = .007). Ciliochoroidal effusion was detected in 60% of PPS eyes, predominantly in the superior and temporal sectors, whereas no effusion was observed in healthy controls (P < .001). Eyes with CE exhibited a thicker mean scleral thickness and a thicker subfoveal choroidal thickness compared to eyes without effusion (P < .05). CONCLUSION: Eyes with PPS demonstrated increased temporal scleral thickness and a high prevalence of CE. These findings suggest that scleral characteristics may represent a predisposing anatomical factor in PPS, although the precise pathophysiological mechanisms remain to be elucidated.

Humans

Infant Dietary Patterns and Early Childhood Weight Outcomes: A Secondary Analysis from the Starting Early Program Trial.

BACKGROUND: The Starting Early Program (StEP) promotes healthy nutrition during early life and leads to healthier child weight, but whether dietary patterns contribute to weight or mediate StEP weight outcomes has not been studied. OBJECTIVES: This secondary analysis identified infant dietary patterns in StEP, determined associations between dietary patterns and child weight outcomes, and examined whether dietary patterns mediated the relationship between StEP and child weight. METHODS: Data were from 377 mother-infant dyads in a randomized trial testing the efficacy of StEP. Dietary patterns at 10 months were identified using latent class analysis. Child weights were abstracted from medical records at 12, 24, and 36 months. Associations between infant dietary patterns and weight-for-age z-score (WFAz) and likelihood of being classified as overweight (WFA &#x2265;85th percentile) were assessed using linear and logistic multivariable regression models. Mediation was used to assess intervention effects on WFAz via impacts on infant dietary patterns. RESULTS: Four classes of infant dietary patterns were identified: Breastfed-High variety, Formula fed-High variety, Formula fed-Low variety, and Mixed fed-Low variety. Compared to the Breastfed-High variety class, infants in the Formula fed-Low variety class had higher WFAz and were more likely to be classified as overweight at 24 and 36 months. Participation in StEP increased membership in Breastfed-High variety, which mediated the association between StEP and lower WFAz at 24 months. CONCLUSIONS: Infant dietary patterns were identified, and some were associated with child overweight. StEP was associated with a dietary pattern most consistent with guidelines, which mediated intervention effects on child weight.

Humans

Effects of testosterone-augmented multimodal exercise intervention in spinal cord injury: a randomized controlled trial.

CONTEXT: Spinal cord injury (SCI) leads to profound muscle atrophy, aerobic deconditioning, and metabolic dysfunction. Exercise-based interventions alone produce modest benefits. Whether testosterone can augment physiologic responses to exercise in this population remains untested. OBJECTIVE: To evaluate efficacy and safety of home-based intervention combining functional electrical stimulation-assisted leg cycling (FES-LC), arm ergometry (AE), and testosterone compared with FES-LC, AE plus placebo in adults with SCI. METHODS: This randomized, placebo-controlled, double-blind trial enrolled 84 adults (76 males and 8 females) aged 19-70 years with SCI (neurologic levels C4-T12; AIS grades A-D). Participants were randomized to multimodality intervention (home-based FES-LC, AE and intramuscular testosterone undecanoate) (n = 38) or control intervention (FES-LC, AE plus placebo) (n = 46) for 16 weeks. The primary outcome was change in aerobic capacity (peak VO2) during AE cardiopulmonary exercise testing. Secondary outcomes included lean mass, hemoglobin, cardiometabolic markers, and safety. RESULTS: Mean (SD) age was 44 (13) years and time since injury was 13.9 (13) years). Between-group changes in peak VO2 were not statistically significant. Within-group improvements were larger in multimodality (&#x223c;19% increase; 0.10 L/min; 95% CI, 0.02-0.18 L/min) compared to controls (&#x223c;6% increase; 0.06 L/min; 95% CI, -0.01-0.13). The multimodality group gained significantly more lean mass (whole-body:1.84 kg, 95% CI: 0.52-3.16, P = .007; lower extremity 0.92 kg, 95% CI: 0.38-1.45, P = .001), and anemia was corrected in a greater proportion of participants. Adverse event rates were similar between groups. CONCLUSION: A home-based multimodality intervention combining FES-LC, AE, and testosterone was safe and associated with greater improvements in lean mass and hemoglobin. Although between-group differences in aerobic capacity were not statistically significant, greater within-group increases were observed in the multimodality group. These findings may inform future studies of testosterone-augmented exercise interventions for individuals living with SCI.

Humans

Artificial intelligence enabled social robotic interventions (PARO) in Australian dementia care: A systematic review and meta-analysis.

BACKGROUND: Although there is a growing body of research indicating that Personal Robot/Social Robot could be used in various aspects of care for individuals with dementia, little is known about how well these types of interventions work in an actual hospital setting in Australia. AIMS & OBJECTIVES: The objective of the present systematic review and meta-analysis is to assess the effectiveness of PARO-based socially assistive robotic intervention in terms of its effectiveness outcomes towards the reduction of dementia-related behavioural and psychological symptoms in Australian based healthcare settings. METHODS: A systematic search was conducted across five electronic databases, including MEDLINE (PubMed), EMBASE, CINAHL, PsycINFO, and the Cochrane Library, to identify randomised controlled trials (RCTs) investigating PARO-based socially assistive robotic interventions for dementia in Australian healthcare settings. This review was registered with PROSPERO (CRD420251251916) and followed the PRISMA 2020 guidelines. In addition, the Cochrane Risk of Bias tool (RoB 2) was used to evaluate the risk of bias across all studies. Pooled standardised mean differences (SMD) with 95&#xa0;% confidence intervals (CI) were calculated for agitation, anxiety, and depression. Heterogeneity across studies was evaluated using the I2 statistic. RESULTS: Six RCTs involving 1444 participants were identified for inclusion in this review. AI-enabled socially assistive robotic interventions, specifically the PARO therapeutic robot, significantly reduced agitation and anxiety when compared to standard treatment or control conditions. The pooled analysis showed that agitation [SMD&#xa0;=&#xa0;-0.44 (95&#xa0;% CI: -0.70, -0.18) p&#xa0;=&#xa0;0.0008] and anxiety [SMD&#xa0;=&#xa0;-0.59 (95&#xa0;% CI: -0.91, -0.27) p&#xa0;=&#xa0;0.0003] were reduced significantly, while the decrease in depression [SMD&#xa0;=&#xa0;-0.44 (95&#xa0;% CI: -0.95, -0.07) p&#xa0;=&#xa0;0.09] scores was non-significant among dementia patients receiving PARO-based socially assistive robotic interventions as compared to the control. The overall risk of bias across all six studies was considered low to moderate. CONCLUSION: PARO-based socially assistive robotic interventions may provide preliminary evidence of effectiveness in reducing agitation and anxiety in individuals with dementia in Australian healthcare, but the evidence regarding the reduction of depression remains unclear. Therefore, additional high-quality trials with consistent methodology and extended follow-up will be necessary to determine both the short-term and long-term clinical efficacy and practicality of implementing these interventions into practice.

Humans

Complementary feeding patterns in preterm and term infants.

Complementary feeding is essential for infants' nutritional status and development, marking the transition to solid foods when breast milk or formula alone is insufficient. Despite its importance, clear recommendations on which foods to introduce when initiating complementary feeding in preterm infants are lacking. By using data from our previously published randomized controlled trial on the timing of complementary feeding in preterm infants, the current study explores the complementary feeding patterns of preterm infants and compares them with those of term-born infants, providing insights into parental decision-making and potential long-term health impacts. Complementary feeding practices differed significantly between preterm (n&#x202f;=&#x202f;255) and term (n&#x202f;=&#x202f;159) infants, with preterm infants more often receiving vegetables as their first solid food (85.4% versus 68.8%, difference 17.6% with 95% CI 12-35%). The group with early introduction of vegetables had a lower BMI-for-age z-scores (&#x3b2; -0.28 [95% CI -0.55 - 0.02]) and weight-for-height z-scores (&#x3b2; -0.27 [95% CI -0.53 to -0.01]) at two years of age. Additionally, preterm infants showed a greater variety in the numbers of different fruits and vegetables consumed by six months (corrected) age than term-born counterparts (8.29 (SD 3.65) versus 6.26 (SD 3.47), p&#x202f;<&#x202f;0.001). These results indicate that complementary feeding patterns in preterm infants differ from term-born infants, with potential positive implications on growth. These data contribute to the development of accurate feeding protocols for preterm infants. Given that feeding practices are culturally influenced, further multinational research is essential to refine complementary feeding guidelines for preterm infants and support caregivers in informed decision-making.

Humans

Could creatine supplementation combined with physical rehabilitation accelerate return to play in athletes with patellar tendinopathy?

BACKGROUND: Several dietary supplements have been proposed to positively influence the rehabilitation process following injury. However, to date, no studies have specifically examined the effects of scientifically supported ergogenic aids on recovery outcomes when combined with physical performance interventions. Therefore, the aim of this study was to analyze the ergogenic effects of creatine supplementation on neuromuscular performance, tendon thickness, pain, and body composition in athletes diagnosed with patellar tendinopathy (PT). METHODS: Using a triple-blind experimental design, 20 federated athletes (age: 33.7&#x2009;&#xb1;&#x2009;9.84 years) with PT were randomly assigned to either a creatine supplementation group (CR; n&#x2009;=&#x2009;9) or a placebo group (PLA; n&#x2009;=&#x2009;11). All participants followed a physical rehabilitation intervention that included daily eccentric training combined with stretching exercises, along with one session every 10 days of extracorporeal shock wave therapy (ESWT) and manual therapy targeting the tendon and surrounding muscle tissue. At the end of each eccentric training session, the participants ingested 3 capsules of creatine monohydrate - Creapure&#xae; (CR) or sucrose (PLA). At the beginning (PRE), after 4 weeks (MID), and after 8 weeks (POST), the pain level (Victorian Institute for Sports Assessment-Patella, VISA-P), tendon thickness (echography), body composition (bioelectrical impedance system), and neuromuscular performance using a countermovement jump test (CMJ) and a strength test (5-RM) of knee extension in the injured leg. RESULTS: A significant main effect of time was observed for VISA-P scores (p&#x2009;<&#x2009;0.001; &#x3b7;2 p&#x2009;=&#x2009;0.626), indicating a reduction in pain over time in both the creatine (CR) and placebo (PLA) groups. At POST, both groups showed significant improvements compared to PRE (CR: 78.0 points [69.2-86.8] vs. 60.6 points [53.4-67.7]; p&#x2009;=&#x2009;0.002; PLA: 75.2 points [66.3-84.0] vs. 60.0 points [52.5-67.5]; p&#x2009;=&#x2009;0.003). However, only the CR group showed a statistically significant improvement in the MID compared to PRE (MID: 70.2 points [60.0-80.5]; p&#x2009;=&#x2009;0.027). A significant main effect of time was observed for both tendon thickness (p&#x2009;<&#x2009;0.001; &#x3b7;2 p&#x2009;=&#x2009;0.629) and the 5-RM leg extension test (p&#x2009;<&#x2009;0.001; &#x3b7;2 p&#x2009;=&#x2009;0.739), with both groups showing progressive improvements over time. Nevertheless, as trend toward a statistically significant time&#xb7;supplementation interaction was observed (p&#x2009;=&#x2009;0.099; &#x3b7;2p&#x2009;=&#x2009;0.126), with an increase in performance only in CMJ in MID vs PRE (36.8&#x2009; cm (33.8-39.7) vs 34.3&#x2009; cm (30.8-37.7); p&#x2009;=&#x2009;0.019) and POST vs MID (POST: 37.6&#x2009; cm (33.5-41.8); p&#x2009;=&#x2009;0.015). CONCLUSIONS: A physical rehabilitation program involving eccentric training, stretching, and ESWT is effective in reducing tendon thickness and increasing muscle strength. However. It seems that the addition of CR induces an earlier reduction of pain and a positive effect on CMJ performance. Therefore, CR could be considered as an ergogenic recovery aid in athletes with PT.

Humans

Effectiveness of a digi-physical tool and working method for paediatric obesity treatment in Abu Dhabi: a non-inferiority intervention study using an external historical comparator.

BACKGROUND: Effective paediatric obesity treatment requires high intensity, scalable interventions. A digi-physical tool for paediatric obesity treatment has shown positive results in Stockholm, Sweden. This study evaluates whether the same treatment method is effective in a different cultural setting. METHODS: This non-inferiority intervention study, using an external historical comparator, included 60 consecutively recruited children aged 6-15.9 years with obesity who initiated treatment at Sheikh Shakhbout Medical City in Abu Dhabi between June and December 2023. Patients were treated with Evira, a digi-physical tool and working method enabling high intensity individualized care, real-time monitoring, and interactive patient-clinician communication. The primary outcome was BMI z-score change at 26 weeks. Non-inferiority was assessed using a predefined margin of 0.10 BMI z-score, with outcomes compared to a prior published trial in Stockholm (n&#x2009;=&#x2009;107). RESULTS: A total of 112 children were included in the analysis (Abu Dhabi cohort, n&#x2009;=&#x2009;35; Stockholm cohort, n&#x2009;=&#x2009;77). The adjusted mean change in BMI z-score was -&#x2009;0.20 (95% CI: -&#x2009;0.28, -&#x2009;0.12) in the Abu Dhabi cohort and -&#x2009;0.20 (- 0.26, -&#x2009;0.14) in the Stockholm cohort (p&#x2009;=&#x2009;0.88). Non-inferiority was confirmed, (predefined margin 0.10 was not exceeded). A clinically significant BMI z-score reduction (&#x2265;&#x2009;0.20 units) was achieved by 45.7% of participants in Abu Dhabi and 36.4% in Stockholm (p&#x2009;=&#x2009;0.35). Non-retention rates at 26 weeks were 41.7% vs. 28.0%, respectively (p&#x2009;=&#x2009;0.07). CONCLUSIONS: The findings provide promising evidence that treatment outcomes achieved with the digi-physical treatment tool were comparable in the Abu Dhabi and Stockholm cohorts, supporting its feasibility in a second cultural and healthcare setting.

Humans

Ablative radiotherapy in castration-resistant prostate cancer.

OBJECTIVE: To prove the oncological benefit of ablative radiotherapy in patients with up to five metastases from castration-resistant prostate cancer (CRPC) a single-centre randomised trial was initiated. PATIENTS AND METHODS: This monocentric, randomised, phase II clinical trial enrolled patients with up to five prostate-specific membrane antigen-positive bone or lymph node metastases developing prostate-specific antigen (PSA) progression during androgen deprivation (ADT) or ADT and androgen-receptor targeted therapy. Participants were randomised (2:1) to receive metastasis-directed therapy (MDT) or observation (OBS) without changing systemic therapy. The primary endpoint was the proportion of patients having PSA progression within 1&#x2009;year, with statistical analyses conducted using intention-to-treat principles. Here, results of a planned interim analysis of the primary endpoint are reported. RESULTS: A total of 30 patients (12 in the observation arm and 18 in the MDT arm) were enrolled, PSA progression within 1&#x2009;year occurred in 44% of the MDT group vs 75% in the OBS group (P&#x2009;=&#x2009;0.14, not significant). The median time to PSA progression was significantly longer in the MDT arm (12.4&#x2009;months) compared to the OBS arm (2.9&#x2009;months, P&#x2009;=&#x2009;0.03). The pre-defined criteria to discontinue the study were not met. Limitations include the single-centre design and small sample size at interim analysis. CONCLUSION: This pre-planned interim analysis of the primary endpoint did not meet the discontinuation criteria of the study protocol, suggesting that MDT in oligometastatic CRPC may extend the time to PSA progression without immediate change of systemic therapy. The continuation of the study in a multicentre setting is planned (Institutional funding by the TU Dresden, ClinicalTrials.gov identifier: NCT04141709).

Humans

A New Highly Concentrated Insulin Aspart AT278 (500&#x2009;U/mL) Demonstrates Ultra-Rapid Pharmacokinetic and Pharmacodynamic Properties in Type 2 Diabetes Regardless of BMI.

AIMS: To evaluate the pharmacokinetics, pharmacodynamics, and safety of a novel U500 insulin aspart formulation (AT278 [500&#x2009;U/mL]; AT278-U500) compared with standard concentration insulin aspart (InsAsp [100&#x2009;U/mL]; InsAsp-U100) and U500 human regular insulin (HumIns [500&#x2009;IU/mL]; HumIns-U500). MATERIALS AND METHODS: This single-centre, randomised, double-blind crossover 12-h euglycaemic clamp study was conducted in 41 overweight and obese people with type 2 diabetes (BMI 25.0-38.7&#x2009;kg/m2) receiving a single subcutaneous dose (0.5&#x2009;U/kg) of AT278-U500 and InsAsp-U100. HumIns-U500 was consecutively studied open label in a 24-h clamp. RESULTS: AT278-U500 exhibited a significantly faster insulin absorption than InsAsp-U100 and HumIns-U500 (t Early50%Cmax: 9&#x2009;min vs. 35&#x2009;min vs. 55&#x2009;min), leading to a significantly higher glucose-lowering effect within the first hour (AUCGIR,0-60min) compared with both InsAsp-U100 (treatment ratio 2.02 [95% CI 1.64; 2.50]) and HumIns-U500 (3.91 [2.89; 5.27]). When divided by median BMI (29.7&#x2009;kg/m2), AUCGIR,0-60min was significantly higher with AT278-U500 in both the low-BMI and high-BMI subgroup compared to InsAsp-U100. Linear regression showed a significant inverse relationship between BMI and AUCGIR,0-60min for InsAsp-U100 (slope -0.142, p&#x2009;<&#x2009;0.0001), whereas AT278-U500 showed no such relationship. Overall insulin exposure was similar for AT278-U500 and InsAsp-U100, while overall glucose-lowering effect was comparable across all three treatments. CONCLUSIONS: AT278-U500 maintains its ultra-rapid onset characteristics independent of BMI, representing the first ultra-rapid U500 option for prandial dosing in insulin-resistant people with type 2 diabetes requiring high-dose therapy. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05754424.

Humans

Effects of faba bean-based crisping culture on phenotypic characteristics, muscle quality, and serum metabolome in Nile tilapia: Screening biomarkers to assess the degree of crisping.

Feeding Nile tilapia (Oreochromis niloticus) a faba bean-based crisping diet enhances muscle hardness (crispness) and overall flesh quality. However, the underlying mechanisms and reliable biomarkers remain insufficiently defined. This study integrated phenotypic traits, muscle texture, collagen content, serum antioxidant enzyme activities (SOD, CAT, and GSH-Px), MDA levels, and serum metabolomics to understand the determinants of muscle crisping. Fish were assigned to a crisping diet or a control group for 90&#xa0;days. Individuals in the crisping group were implanted with passive integrated transponder (PIT) tags to enable correlation analyses among phenotypic traits (body weight/length/frame changes), serum indicators (NAM, FAD, and GSH-Px) and muscle hardness. Compared with controls, the crisping diet significantly increased muscle hardness, gumminess, and chewiness, accompanied by elevated collagen content. Antioxidant profiles were altered, with higher activities of serum SOD and CAT, together with elevated MDA levels and reduced GSH-Px activity (P&#xa0;<&#xa0;0.05). Metabolomic analysis identified 830 differential metabolites (682 upregulated and 148 downregulated), predominantly comprising carboxylic acids and derivatives, glycerophospholipids, and benzene derivatives. Enrichment analysis indicated significant involvement in general metabolic pathways, ATP-binding cassette (ABC) transporters, amino acid biosynthesis, and glycine, serine, and threonine metabolism (P&#xa0;<&#xa0;0.05). Notably, acetylpyruvate was upregulated in glutathione metabolism, nicotinate and nicotinamide metabolism, and galactose metabolism; pantothenic acid was upregulated in glycine, serine, and threonine metabolism; whereas &#x3b4;-tocotrienol was downregulated. Correlation analysis revealed weak negative associations between muscle hardness and phenotypic traits (body weight/length/frame changes D5-7, D5-10, D7-8) (P&#xa0;<&#xa0;0.05). In contrast, serum NAM and FAD were weakly positively correlated with muscle hardness, whereas GSH-Px showed a weak negative correlation (P&#xa0;<&#xa0;0.05). Collectively, these findings suggest that body weight, body length, frame measurements (D5-7, D5-10, and D7-8), and serum NAM, FAD, and GSH-Px are associated with the degree of muscle crispness in Nile tilapia fed a faba bean-based crisping diet and may serve as candidate biomarkers under these culture conditions.

Animals

Effectiveness of Internet-Delivered Cognitive Behavioural Therapy (ICBT) in Improving Weight-Loss and Psychosocial Well-Being Among Adults With High BMI: A Systematic Review.

AIM: To examine the effectiveness of Internet-delivered Cognitive Behaviour Therapy (ICBT) in improving psychosocial well-being and promoting weight-loss in adults &#x2265;&#x2009;18&#x2009;years with BMI &#x2265;&#x2009;25&#x2009;kg/m2. BACKGROUND: Global obesity engenders significant physical and psychosocial health consequences. Second-wave ICBT focused on restructuring negative thoughts and behaviours has been explored as a potential intervention for elevated BMI and mental health concerns, but its effectiveness remains to be fully established, making further evaluation essential. METHODS AND DATA SOURCES: Eight databases were searched from inception to January 2025 for randomised controlled trials (RCTs), including participants &#x2265;&#x2009;18&#x2009;years with BMI &#x2265;&#x2009;25&#x2009;kg/m2 and second-wave ICBT evaluating BMI, weight, depression, eating behaviours, and self-esteem. This review followed PRISMA 2020. Study quality was assessed using the Cochrane Risk of Bias (ROB 2) and GRADE. Data were extracted using a modified Cochrane form. Random-effects meta-analysis calculated Standardised Mean Differences (SMD) with 95% confidence intervals, with subgroup analyses exploring heterogeneity. RESULTS: Nine trials with 2278 participants were included. Significant improvements were seen in BMI, weight, and depressive symptoms while self-esteem effects were small and non-significant. Compared with passive controls, ICBT showed greater improvements in BMI and weight, whereas differences versus active control were smaller and inconsistent. Face-to-face CBT demonstrated superior outcomes for depression and self-esteem. Male-tailored interventions showed greater improvements. Shorter programmes yielded larger short-term weight loss, while longer programmes supported more sustained effects. Narrative synthesis indicated improvements in emotional and external eating, with increased mindful and restrictive eating behaviours. CONCLUSION: ICBT improved weight, BMI, and depressive symptoms, with limited evidence for self-esteem. Male-tailored interventions and longer programmes may enhance sustainable outcomes. IMPACT: Future ICBT programs should integrate strategies targeting sustainable weight loss and psychosocial well-being to support long-term outcomes. NO PATIENT OR PUBLIC CONTRIBUTION: Patients or members of the public were not involved, as this study synthesised previously published data. TRIAL REGISTRATION: PROSPERO registration number: CRD42024497961.

Humans

Effects of cold-water immersion after rugby-specific training on endurance performance.

BACKGROUND: This study investigated whether whole-body cold-water immersion (CWI) following rugby-specific training influences endurance exercise performance 24 h later. METHODS: Eleven healthy male collegiate rugby players completed an incremental cycling test to determine peak oxygen uptake (V&#x307;O 2peak ) and time to exhaustion at baseline (Pre). One week later, participants performed a standardized rugby-specific training session consisting of warm-up, skill-based passing, contact drills, individual training (i.e., conversion kicking and scrummaging), and a bronco endurance test (total duration: 180 min), followed by one of two recovery interventions in a randomized order: 1) whole-body CWI for 8 min at 15 &#xb0;C (CWI) or 2) seated rest for 8 min (Control). Participants then performed the incremental cycling test 24 h after each intervention. RESULTS: Training load during the rugby-specific training, assessed using heart rate-based training load and blood lactate concentrations, did not differ between the trials. Time to exhaustion (485&#xb1;72 vs. 518&#xb1;77 s, P=0.107, d=0.45) and V&#x307;O 2peak did not differ between the Control and CWI trials, whereas the relative changes in these variables from Pre were greater in the CWI than in the Control trials (both P<0.05). Oxygen uptake, minute ventilation, and rating of perceived exertion during submaximal exercise were similar across the Pre, Control, and CWI trials. CONCLUSIONS: These results suggest that whole-body CWI following rugby-specific training may be associated with favorable changes in endurance exercise performance 24 h post-intervention compared with the control condition. However, the expectancy/placebo effect of water immersion on exercise performance could not be excluded.

Humans

Efficacy and safety of once-weekly semaglutide 2&#xb7;4 mg in Chinese adults with overweight or obesity (STEP 12): a randomised, double-blind, placebo-controlled, multicentre, phase 3b trial.

BACKGROUND: Semaglutide 2&#xb7;4 mg is a GLP-1 receptor agonist that reduces bodyweight, and provides other cardiometabolic benefits, among people with a BMI at least 30 kg/m2 or at least 27 kg/m2 and with weight-related comorbidities. This trial aimed to evaluate the efficacy, tolerability, and safety of semaglutide 2&#xb7;4 mg in adults from mainland China and Taiwan with overweight or obesity according to locally defined, BMI thresholds. METHODS: This completed randomised, double-blind, placebo-controlled, multicentre, two-armed, parallel-group, phase 3b trial (STEP 12) was conducted at 19 sites across mainland China and Taiwan. Adults with a BMI of 24-<28 kg/m2 and at least one weight-related comorbidity, or a BMI of 28-<30 kg/m2, with or without type 2 diabetes, were randomly assigned (2:1) to once-weekly subcutaneous semaglutide 2&#xb7;4 mg or placebo, plus lifestyle intervention, for 44 weeks. Randomisation was performed by the study sponsor using the Randomisation Trial Supplies Management System. Coprimary endpoints were percentage change in bodyweight and the proportion of participants achieving at least 5% bodyweight reduction. Safety was analysed descriptively in all participants who received the trial intervention. Missing data at week 44 were imputed with washout multiple imputation. This study is registered with ClinicalTrials.gov, NCT06041217, and is completed. FINDINGS: Between Sept 15, 2023, and May 7, 2025, of 254 screened participants, 161 (66&#xb7;5%) of 242 participants were randomly assigned to semaglutide 2&#xb7;4 mg and 81 (33&#xb7;5%) to placebo; 121 (50&#xb7;0%) participants were female, and 47 (19&#xb7;4%) participants had type 2 diabetes. Bodyweight reduction was greater with semaglutide versus placebo (-12&#xb7;1% [SE 0&#xb7;6] vs -2&#xb7;2% [0&#xb7;8]; estimated treatment difference -9&#xb7;9 percentage points [95% CI -11&#xb7;8 to -8&#xb7;0]; p<0&#xb7;0001), with a greater proportion of participants achieving at least 5% bodyweight reduction (80&#xb7;5% vs 24&#xb7;4%; odds ratio [OR] 14&#xb7;8 [95% CI 7&#xb7;4 to 29&#xb7;6]; p<0&#xb7;0001). Adverse events were reported in 141 (87&#xb7;6%) of 161 participants in the semaglutide 2&#xb7;4 mg group and 61 (75&#xb7;3%) of 81 participants in the placebo group, with gastrointestinal disorders being the most common. INTERPRETATION: Semaglutide 2&#xb7;4 mg provided a superior reduction in bodyweight versus placebo in Chinese adults with overweight or obesity. The safety profile was consistent with the known profile of semaglutide. FUNDING: Novo Nordisk A/S. TRANSLATION: For the Mandarin translation of the abstract see Supplementary Materials section.

Adult

Mediators of Change in Cognitive Behavioral and Mindfulness-Based Online-Interventions for Hypoactive Sexual Desire Dysfunction in Women.

Low sexual desire is a common sexual problem among women. When it is accompanied by significant personal distress, it may be diagnosed as hypoactive sexual desire dysfunction (HSDD). Both cognitive behavioral therapy (CBT) and mindfulness-based therapy (MBT) are effective treatments for HSDD when delivered in person or online. In this randomized controlled treatment study, CBT and MBT consisted of eight guided self-help modules delivered online, and participants completed measures at pretreatment and after 3, 6, and 12&#x2009;months. Nine variables were examined as potential mediators of treatment outcomes (i.e., sexual desire and sexual distress), namely mindfulness, self-compassion, rumination, body connection, self-consciousness, relationship satisfaction, sexual communication, depression, and anxiety. In total, 212 women diagnosed with HSDD were randomized to either CBT or MBT (Mage&#x2009;=&#x2009;36.3, SD&#x2009;=&#x2009;10.2). Improvements in self-compassion, rumination, body connection, and self-consciousness partially mediated treatment outcomes in at least one of the treatment groups. Mediation effects were mostly small, explaining up to 15% of the total effects. No systematic differences in mediation pathways between CBT and MBT were found. These findings emphasize the importance of emotion regulation, metacognitive processes, and embodiment for the effective treatment of HSDD. Future research should refine treatment components to enhance efficacy and ensure that psychological interventions adequately address common concerns among women with HSDD.

Humans