Obesity is a risk factor for high-mortality health conditions, including cardiovascular diseases and type 2 diabetes, which makes the advancement of efficacious and safe weight loss therapies a high priority in pharmacology. The causal link between obesity and its comorbid conditions is believed to be a chronic state of inflammation originating within adipose tissue, with macrophages playing central roles, an axis that is not targeted directly by current therapies. Here, we use nanocarriers to deliver an anti-inflammatory glucocorticoid receptor agonist to adipose tissue macrophages and report the impact of size on therapeutic effect. Three dextran nanocarriers between 4-30 nm in hydrodynamic diameter released molecular drug cargo at equivalent rates and exhibited similar biological potency in vitro. In vivo in a mouse model of obesity, body weight and body fat were reduced in a size-dependent manner after 2-4 weeks of treatment. Unlike current clinical pharmacotherapies for weight loss, these body composition changes were not associated with changes in food intake. Greater retention of larger dextran nanocarriers in visceral adipose tissue appears to elicit a local change to promote browning by increasing mitochondrial abundance and lipid droplet fragmentation. Further development of this platform may result in a safe and potent modulator of adipose tissue in the state of obesity without direct action on nutrient intake to address malnutrition and lean body mass deficiencies observed with current weight loss pharmacotherapies.

Pulsed-field ablation (PFA) has become an important non-thermal modality for pulmonary vein isolation in atrial fibrillation (AF), characterized by myocardial selectivity and reduced collateral tissue injury. However, the physiological biomarker response to PFA remains incompletely defined. This study assessed serial changes in myocardial (troponin T, creatine kinase - CK and its isoenzyme - CK-MB) and renal (urea, creatinine) biomarkers in patients undergoing PFA at a single center and compared these findings with current clinical evidence. The study cohort consisted of 52 patients undergoing PFA (73 % men, 27 % women), with 52 % presenting paroxysmal AF and 48 % persistent AF. The mean left atrial diameter was 45 ± 7 mm and the average left ventricular ejection fraction was 55 ± 7 % The mean ablation burden was 67 ± 23 applications per procedure. Biomarkers were measured before and after ablation. Repeated-measures ANOVA demonstrated significant time effects for all myocardial biomarkers (p < 0.001) and significant interactions with ablation burden. Troponin-T increased from near-zero baseline values to markedly elevated levels immediately and 24-hours after the procedure, while CK and CK-MB rose several-fold with only partial decline after the procedure. In contrast, urea and creatinine remained stable, indicating preserved renal function without acute kidney injury. The number of PFA applications correlated positively with late CK and CK-MB values, suggesting that myocardial biomarker load scales with procedural intensity. These findings align with current literature showing extensive myocardial biorelease after PFA but favorable extracardiac safety. By concurrently analyzing myocardial and renal markers, this study demonstrates that substantial biochemical myocardial injury induced by PFA does not translate into measurable renal dysfunction. Overall, PFA appears physiologically consistent with a profile of robust but targeted myocardial injury and preserved renal safety.

Cardiac arrest (CA) is associated with high mortality and severe neurological sequelae. Artemisinin (ARS), a natural product from Artemisia annua, has potential neuroprotective effects, but its role in brain injury after CA resuscitation remains unclear.

This study investigated the effects of ARS on hippocampal neuronal apoptosis and cognitive dysfunction in rats after CA resuscitation and explored whether these effects are associated with the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway.

Sixty male rats were randomly assigned to six groups: sham, model, artemisinin (40 mg/kg), dimethyl sulfoxide ((DMSO, 100 mg/kg), LY294002 (a phosphatidylinositol 3-kinase inhibitor, 25 mg/kg) and artemisinin plus LY294002. Cardiac arrest was induced by transcutaneous electrical stimulation. Outcome assessors were blinded. Neurological function was evaluated using the Neurological Deficit Scale. Hippocampal damage and apoptosis were assessed by hematoxylin and eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Learning and memory were tested using novel object recognition and the Morris water maze. Protein expression was measured by Western blot.

Artemisinin significantly improved Neurological Deficit Scale scores, reduced terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells and alleviated hippocampal damage. Artemisinin also prolonged novel object exploration time, shortened escape latency, increased target quadrant time and upregulated phosphatidylinositol 3-kinase expression and the ratio of phosphorylated protein kinase B to protein kinase B. Co-administration of LY294002 partially reversed these effects.

Artemisinin alleviates hippocampal neuronal apoptosis and improves neurological deficits and cognitive dysfunction in rats after cardiac arrest resuscitation, suggesting a possible association with activation of the phosphatidylinositol 3-kinase/protein kinase B pathway. Limitations include use of a single pharmacological inhibitor and lack of genetic validation.

DNA nanoswitches are programmable molecular devices that convert target recognition events into highly specific and controllable conformational changes. Nevertheless, their application in multiplexed analysis of low abundance miRNAs remains limited, and methodological breakthroughs are urgently needed for analysis in complex clinical samples. Here, we have seamlessly integrated rolling circle amplification (RCA), cloverleaf structured DNA nanoswitch arrays, and glass nanopore detection technology to construct a high throughput analysis platform, which is expected to be applied in the diagnostic research of acute myocardial infarction (AMI). The design leverages RCA to convert target miRNAs into stable DNA reporters followed by enzymatic cleavage, which enables sensitive molecular detection and effectively alleviates nanopore clogging. The cloverleaf design enhances signal amplitude by 70.77% over conventional dumbbell structures. In clinical plasma samples, the platform accurately differentiated AMI patients from healthy controls by profiling a panel of five potential AMI characteristic miRNAs. A reference free ternary encoding (RFTC) strategy further enables a 12 carrier DNA nanoswitch array capable of simultaneously detecting up to 60 targets. By combining label free DNA nanoswitch arrays with glass nanopore sensing, this work establishes a robust methodological framework for multiplex nucleic acid analysis. The platform also exhibits promising potential for analyzing circulating miRNAs and screening acute myocardial infarction related biomarkers, offering a facile modular strategy for flexible detection of diverse molecular targets in future clinical translational research.

Contemporary data on pulmonary arterial hypertension (PAH) from Central and Eastern Europe are scarce.

The aim of this study was to assess clinical characteristics, treatment, survival, and predictors of early improvement and long-term outcomes in newly diagnosed PAH in the BNP-PL database.

Consecutive patients with newly diagnosed, non-vasoreactive PAH between 2018 and 2023 were included. Changes in 4-strata risk category from diagnosis to the first available follow-up assessment within the first 12 months after diagnosis were analyzed.

Among 806 patients, 445 had idiopathic PAH, 176 connective tissue disease-associated PAH, 147 congenital heart disease-associated PAH, and 38 other PAH subtypes. Kaplan-Meier estimated 12-month mortality was 13.5%. During a median follow-up of 16 (8-33) months, mortality was highest in connective tissue disease-associated PAH and lowest in congenital heart disease-associated PAH. First-year clinical improvement occurred in 45.8%. Improvement rates were 34.8% with upfront monotherapy, 49.2% with dual therapy, and 70.5% with triple therapy (P <0.001). After adjustment for baseline 4-strata risk, more initial PAH-specific drugs and fewer cardiovascular comorbidities were associated with clinical improvement. The baseline 4-strata model better discriminated 12-month mortality than the 3-strata model (area under the curve 0.73 vs. 0.63; P = 0.004). Among first-year survivors, worsening risk category, higher baseline risk, and PAH-related unplanned hospitalization within the first year independently predicted long-term mortality.

Early combination therapy and fewer cardiovascular comorbidities were associated with greater early clinical improvement after adjustment for baseline 4-strata risk category. Baseline mortality risk, first-year change in risk category, and unplanned hospitalization were associated with subsequent mortality.

A previous genome-wide association study identified regions on canine chromosome (cfa) 13 and 14 associated with early onset myxomatous mitral valve disease (MMVD) in Cavalier King Charles Spaniels (CKCS). In the present study, whole genome sequencing (WGS) of 9 CKCS cases (mitral regurgitation (MR) before 4.5 years or congestive heart failure (CHF) at any age due to MMVD) and 10 CKCS controls (no or mild MR after 8 years of age) identified > 2000 genetic variants in the MMVD associated cfa13 and cfa14 regions. Ensembl Variant Effect Predictor (VEP) identified a possible functional impact of 18 variants. These were genotyped in 250 CKCS; 117 cases and 133 controls. The most significantly associated variants were a splice-site variant in a long noncoding RNA (lncRNA) on cfa13, a nonsynonymous variant in HYAL4, a 39 base-pair insertion in LMOD2 and a synonymous variant in ENSCAFG00000024436 (p-values from 2.03E-08 to 4.20E-06). Concomitant homozygosity for risk alleles in LMOD2 and the lncRNA gave an odds-ratio for MMVD of 52.5 compared to homozygosity for the nonrisk alleles (p = 0.00034, 95% CI: 8.8-1023.8). Upon validation of our results in an independent cohort, this gene variant combination in CKCS is expected to enable targeted breeding programs to reduce MMVD prevalence in CKCS.

Eye surgery, along with the short-term visual difficulties, often translates to anxiety in both children and their families. The emotional well-being of child's guardian can influence the child's anxiety. Virtual reality (VR) technology, which offers a 360° immersive experience, has emerged as an effective nonpharmacological method for reducing anxiety among children through virtual exposure and distraction.

To assess the effectiveness of VR in alleviating anxiety in children and their guardians during eye surgery under general anesthesia.

In total, 31 children aged 3-10 years, who were scheduled for elective eye surgery, were randomly assigned to either the VR or the control group. In the VR group, both the children and their guardians were introduced to the surgical process and the operating room environment by using a helmet-mounted VR a day before the surgery. On the day of surgery, the children in the VR group watched an animation video through VR while receiving the intravenous injection. In contrast, children in the control group were verbally informed about the surgery a day before and accepted the intravenous injection as usual on the day of surgery. The guardians' anxiety were assessed on day 1 preoperatively by using the Preoperative Anxiety Scale-7 and the Amsterdam Preoperative Anxiety and Information Needs Scale. Children's anxiety on the day of surgery was measured by using the modified Yale Preoperative Anxiety Scale (m-YPAS). Guardian satisfaction was evaluated on day 1 postoperatively.

Children in the VR group showed significantly lower m-YPAS anxiety scores than those in the control group [23.4 (23.4-28.4) vs. 38.4 (31.6-46.6), rank-biserial correlation = 0.91, p < 0.001]. Similarly, the Preoperative Anxiety Scale-7 scores of guardians in the VR group were notably lower than those in the control group [2 (0-5) vs. 11 (4-12), rank-biserial correlation = - , p < 0.001]. The Amsterdam Preoperative Anxiety and Information Needs Scale results also indicated lower anxiety scores in the VR group [4 (4-6)] than in the control group [8 (7-11), rank-biserial correlation = -0.64, p < 0.001]. Furthermore, the VR group demonstrated a reduced need for additional information [2 (2-3)] when compared with the control group [4 (2-5), rank-biserial correlation = 0.17, p = 0.008]. Guardian satisfaction scores were higher in the VR group [90 (87-100)] than in the control group [85 (80-87), rank-biserial correlation = 0.44, p < 0.001].

The use of VR technology could be a promising nonpharmacological intervention for alleviating preoperative anxiety in pediatric patients undergoing ophthalmic procedures.

Sleep disruption is common among patients with malignancy and may worsen quality of life, treatment tolerance, and symptom burden. Melatonin is a circadianregulating hormone with a favorable safety profile and potential sleep-promoting effects. This metaanalysis and systematic review evaluated the safety and efficacy of melatonin for sleep-related outcomes in patients with cancer.

Scopus, PubMed, Web of Science, ScienceDirect, Cochrane Library, ClinicalTrials.gov, and EMBASE were systematically searched from inception to 1 June 2026 without language or country restrictions. Randomized clinical trials comparing melatonin with placebo or an active control in patients with cancer and reporting sleep-related outcomes were eligible. Data extraction, study selection, and riskof- bias assessment using the Joanna Briggs Institute checklist were performed by two reviewers independently. Random-effects meta-analyses with Hartung-Knapp adjustment were conducted in Stata 17.0.

Data from seven studies were pooled in the meta-analysis, and thirteen articles were included in the systematic review. The overall effect of melatonin was insignificant (SMD = -0.85 with a 95% CI of -2.46 to 0.76) with high heterogeneity among studies (I2 = 94.5%). Subgroup analysis revealed a significant decrease in the Pittsburgh Sleep Quality Index (PSQI) in US studies (SMD = -0.57, 95% CI: [-0.99, -0.14], I2 = 31.5%). Meta-analysis of the seven PSQI components showed no significant item-level improvement with melatonin treatment. Studies using non-PSQI sleep outcomes showed mixed findings, with short-term improvement in insomnia severity in one trial but modest or non-significant effects in others.

While the overall impact of melatonin on sleep quality was not statistically significant, subgroup analyses and qualitative evidence indicate clinically relevant benefits.

Melatonin shows promising but uncertain benefits for sleep disruptions in patients with malignancies. However, the evidence should be interpreted cautiously because of substantial clinical and statistical heterogeneity, limited sample sizes, short intervention durations, and predominantly subjective sleep measures. Larger, well-standardized randomized trials using both subjective and objective sleep assessments are needed.

Lymphatic vessel thrombosis is a rare finding, and its role in the development of lymphedema remains unclear. Secondary lymphedema is usually related to oncologic lymph node dissection, radiotherapy, infection, or major tissue trauma. In contrast, focal lymphatic obstruction after minor limb trauma has rarely been described. We report the case of a 71-year-old woman who developed progressive Stage II lymphedema of the left lower limb after a minor trauma without fracture. Preoperative examination showed persistent lower-limb swelling with a focal medial proximal lower-leg nodule, and conservative treatment with manual lymphatic drainage and compression produced only partial improvement. Venous duplex ultrasound and magnetic resonance imaging excluded venous obstruction, tumor, or muscular injury. Ultrasound suggested a lymphatic rather than venous origin of the focal lesion, while lymphoscintigraphy with SPECT/CT demonstrated an interruption of lymphatic drainage at the medial proximal lower leg, associated with a 17-mm subcutaneous fluid collection consistent with a lymphocele. Intraoperatively, the lymphocele was excised and an intact but dilated collecting lymphatic vessel distal to the obstruction was identified. After opening the vessel, intraluminal thrombotic material was removed, resulting in restoration of spontaneous lymphatic flow. Lymphaticovenous anastomosis was then performed using the recovered lymphatic vessel, with intraoperative confirmation of patency and lymphatic washout. The postoperative course was uneventful, with significant clinical improvement confirmed at 6 months follow-up. This case supports the hypothesis that lymphatic thrombosis may occur after minor trauma and may directly contribute to secondary lymphedema, although longer follow-up and objective outcome assessment are required.