Surgeon fatigue is a recognized risk factor for patient safety; however, reduced working hours may limit surgical training exposure. In 2005, Switzerland introduced a maximum 50-hour workweek for resident surgeons. In view of current discussions on further reductions (42 + 4 h), concerns persist regarding training quality and workforce capacity. This study evaluates the impact of the 2005 Swiss labor law on patient outcomes, operative characteristics, and intraoperative teaching utilizing a standardized trauma procedure. A retrospective analysis of anonymized data from a national database was performed. All patients undergoing operative fixation of trochanteric femur fractures (ICD-10 S72.1) were included. Two four-year periods were compared: pre-regulation (2001-2004) and post-regulation (2016-2019). Primary endpoints were in-hospital complications, mortality, and length of stay. Secondary endpoints included patient characteristics, surgeon seniority, teaching status, operative duration, and time to surgery. Post-regulation patients were older and exhibited higher American Society of Anesthesiologists classifications despite fewer comorbidities. Complications increased from 9.1% to 17.7%, and mortality from 1.6% to 3.5%. Length of stay decreased from 14 to 9 days. Operative duration decreased by 10 min across all surgeon levels. Resident surgeons independently performed 10% fewer procedures, but teaching operations increased significantly among resident surgeons. Following the introduction of working hour limitations, supervised teaching increased substantially. Although complication and mortality rates rose-likely reflecting an older and more complex patient population-hospital stays shortened. The proposed 42 + 4-hour model will require targeted compensatory measures to maintain surgical training quality and patient safety.
Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins constitute the core molecular machinery that drives intracellular vesicular trafficking and membrane fusion in eukaryotic cells. Beyond their canonical roles in neurotransmitter release, autophagic flux, and exosome secretion, accumulating evidence indicates that dysregulated SNARE expression and function contribute to tumor progression. In central nervous system tumors (CNSTs), aberrant SNARE activity has been increasingly implicated in invasive growth, chemotherapy resistance, and tumor microenvironment remodeling. Guided by the 2021 World Health Organization classification of tumors of the central nervous system (WHO CNS5), this review summarizes current advances on the pathogenic roles of SNARE proteins in glioblastoma, medulloblastoma, meningioma, and pituitary neuroendocrine tumors, and discusses their translational potential as molecular biomarkers and therapeutic targets for precision neuro-oncology.
The development of incisional hernias (IH) is an uncommon but complex outcome following pancreatic surgery, especially through the open approaches. The etiology of this complication is multifactorial and can be related to the patient and to the surgical technique. We aimed to perform a systematic review and meta-analysis assessing the risk factors for development of IH following pancreatic surgery. Pubmed, Cochrane, and EMBASE databases were systematically searched from inception to September 2024. Observational studies and randomized controlled trials assessing patients > 18 years old undergoing pancreatic surgery and reporting data on incidence and risk factors for IH were selected. Outcomes were mean age, mean body mass index (BMI), diabetes mellitus, female and male gender, active smoking, and surgical site infections (SSI). We used RStudio for statistical analysis. 686 records were reviewed, and 7 observational retrospective studies were included, totaling 3,391 patients. The incidence of IH in the pooled analysis was 368 (10.8%), and after performing a proportional meta-analysis, we found that 12.5 per 100 (95% CI 7.1, 20.9) patients undergoing pancreatic surgery develop IH. Our pooled analysis found that older patients (MD 2.7 years; 95% CI 0.5, 4.8; p = 0.014) and patients with higher BMI (MD 1.8; 95% CI 0.9, 2.7; p < 0.001) present higher risk of developing IH. Female and male gender, active smoking, diabetes mellitus, and SSI were not significant risk factors for IH after pancreatic surgery. Our study showed that patients with older age and higher weight present a significantly higher risk of developing IH after pancreatic surgery. Considering pancreatic surgery is frequently carried out in emergent conditions, sometimes due to malignant causes, the preoperative optimization to reduce weight before surgery is not always a possible alternative. On the other hand, surgeons must consider the possibility of optimizing the patient in terms of weight loss if feasible, to reduce morbidity after the procedure.
A yellow strain, designated YCB016T, was isolated from rhizosphere soil of Camellia oleifera Abel collected from Xingning city, Guangdong Province, PR China. The strain was aerobic, rod-shaped, without flagella. Phylogenetic analysis of 16S rRNA gene revealed strain YCB016T showed the highest similarities of 98.9% and 98.2% to Trinickia terrae 7GSK02T, Trinickia mobilis DHG64T and Trinickia fusca GDMCC 1.1449T, respectively. The phylogenomic tree revealed strain YCB016T formed a clade with Trinickia violacea DHOD12T. The major cellular fatty acids of strain YCB016T included C16:0, C17:0 cyclo, C19:0 cyclo ɷ8c and summed feature 8. The major polar lipids were phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol and hydroxyphosphatidylethanolamine. The predominant respiratory quinone was ubiquinone-8. The average nucleotide identities (ANI) and the digital DNA-DNA hybridization (dDDH) values among strain YCB016T and all 11 species of the genus Trinickia were 77.7-92.8% and 22.3-50.4%, respectively, which are interspersed on the intra-species cutoff values. The draft genome size of strain YCB016T was 7.3 Mbp with a DNA G + C content of 63.5%. Based on phenotypic, chemotaxonomic, phylogenetic analysis, genomic DNA G + C content, ANI and dDDH values, strain YCB016T represents a novel species of the genus Trinickia, for which the name Trinickia camelliae sp. nov. is proposed. The type strain is YCB016T (= GDMCC 1.3849T = JCM 36232T). Additionally, strain YCB016T produced siderophore, cellulase and lipase whereas T. fusca GDMCC 1.1449T produced siderophore and indoleacetic acid (IAA). The Trinickia symbiotica JPY-345T and Trinickia caryophylli DSM 50341T contained nifH and nifD genes while other species did not. The nodD gene was present in all species. Collectively, the genus Trinickia exhibited potential plant growth-promoting activities.
Lymphatic filariasis (LF) remains a significant public health challenge in many tropical regions where the disease is endemic. In Malaysia, LF is found in small pockets across the country. Asymptomatic carriers play a critical role in transmission but are often undetected. This report details an investigation of an asymptomatic filariasis reported by local health authorities involving an 83-year-old female patient residing in the Bako area, Sarawak. Despite being immobile due to a stroke, routine screening identified an infection with Brugia malayi through microscopy and a rapid diagnostic test. Interestingly, the patient exhibited no acute or chronic symptoms typically associated with filariasis. Contact tracing among her family members revealed that her son was also infected. Both patients received treatment with diethylcarbamazine (DEC) at a dosage of 6 mg/kg, along with albendazole 400 mg and ivermectin 12 mg. Preventive measures included health education, entomological studies, and the implementation of a 'Test & Treat Filariasis' program in the village. By documenting both the index case and a secondary asymptomatic case within the same household, the study provides a strong example of how routine screening and contact tracing can identify hidden sources of infection. This adds significant value to LF elimination strategies and emphasizes the importance of community-level surveillance programs. Coordinated efforts by health authorities, including contact tracing, environmental assessments, and targeted treatment, are essential for controlling the spread of LF and safeguarding public health.
Child Sexual Abuse (CSA) remains deeply silenced in many Black communities, where cultural stigma, historical trauma, and systemic mistrust often discourage disclosure and limit access to supportive resources. These barriers contribute to delayed intervention, untreated trauma, and long-term psychological, emotional, and relational harms. This theoretical manuscript synthesizes interdisciplinary scholarship to examine CSA disclosure among Black children through three interconnected frameworks: Critical Race Theory, Attachment Theory, and Trauma-Informed Care, which illuminate how structural racism, relational dynamics, and trauma shape children's safety, trust, and willingness to seek help. Using a theory-synthesized conceptual framework approach, this paper integrates cultural, systemic, and relational influences to explain how silence surrounding CSA is produced and sustained within Black families, churches, and community institutions. This manuscript also explores facilitators of disclosure, including caregiver responsiveness, culturally grounded education, and trauma-informed practices that validate children's experiences and reduce stigma. Practical implications are offered for mental health professionals, educators, and faith leaders who seek to create safe and supportive environments that promote early disclosure and healing. By situating CSA within its broader sociocultural and historical context, this manuscript advances a culturally responsive framework to guide prevention, community engagement, and survivor-centered interventions. Breaking the silence requires intentional efforts that honor cultural values, address systemic inequities, and empower trusted adults to protect children and support children's recovery and resilience.
To investigate the mechanistic role of Sijunzi decoction (SJZD) in overcoming chemoresistance through the suppression of adaptive metabolic responses in non-small cell lung cancer (NSCLC). Chemical profiling of SJZD-derived components in systemic circulation was conducted using liquid chromatography-tandem mass spectrometry (LC‒MS/MS) in Sprague-Dawley rats. Multiomics integration and network pharmacology were employed to identify convergent targets shared by the bioactive constituents of SJZD and genes associated with cisplatin resistance. In vitro functional assessments using cisplatin-resistant human lung adenocarcinoma (A549/DDP) cells included the following: quantification of cell viability via Cell Counting Kit-8 (CCK-8) assays; evaluation of mitochondrial bioenergetics through targeted metabolomic profiling; and ultrastructural characterization of ferroptotic morphology via transmission electron microscopy (TEM). Cellular redox homeostasis was dynamically monitored using fluorescent probes, including a DCFH-DA probe for reactive oxygen species (ROS) and a C11-BODIPY581/591 probe for lipid peroxidation. siRNA-mediated gene silencing and immunohistochemical analysis were performed to elucidate the functional hierarchy of the p62/Keap1/nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant axis. Complementary in vivo validation was performed using BALB/c nude mice bearing A549/DDP xenografts, with longitudinal monitoring of tumor progression under SJZD treatment regimens. Untargeted metabolomics of SJZD-medicated serum revealed 392 differentially abundant metabolites, with pathway enrichment revealing significant dysregulation of glutamine metabolism. Structural validation confirmed 55 bioactive components of SJZD in serum, including glycyrrhizin, ginsenoside Ro, liquiritigenin, and atractylenolide I. Integration of these components with disease targets yielded 355 overlapping genes associated with both SJZD activity and cisplatin-resistant NSCLC, with significant enrichment in oxidative stress response pathways. Experimental assays confirmed that SJZD induced ferroptosis in cisplatin-resistant A549/DDP cells, as evidenced by disrupted iron homeostasis, lipid peroxidation, and characteristic mitochondrial damage. These effects and subsequent cell death were specifically abrogated by the ferroptosis inhibitor ferrostatin-1 (Fer-1) but not by apoptosis inhibition, confirming that ferroptosis is the primary mechanism of cell death. Mechanistically, the inhibition of p62/Keap1/Nrf2 signaling was involved in the modulation of SJZD-induced ferroptosis both in vitro and in vivo. SJZD counteracts metabolic adaptation through ferroptosis mediated by the inhibition of p62/Keap1/Nrf2 in cisplatin-resistant NSCLC.
Predicting clinically significant drug-drug interactions (DDIs) continues to be an unresolved challenge in contemporary pharmacovigilance, primarily due to the inadequacy of current computational frameworks in addressing the nonlinear, multi-scale characteristics of simultaneous drug metabolism. This paper presents the Quantum Graph-Differential (QGD) model an exact mathematical framework that combines quantum-inspired graph theory with a set of interconnected fractional differential equations to describe and forecast pairwise drug-drug interactions (DDIs). The principal component of our construction is the quantum interaction graph [Formula: see text], wherein the vertex set represents distinct drug molecules as quantum states within a finite-dimensional Hilbert space, and the complex-valued edge weights are obtained from the overlap of shared metabolic pathways and transporter affinity profiles.A Schrödinger-type equation on [Formula: see text] governs drug-drug coupling, and the graph Hamiltonian [Formula: see text] is constructed from a novel fractional quantum graph Laplacian [Formula: see text], [Formula: see text]. A hybrid quantum-classical dynamical model is created by coupling the time evolution of the interaction wavefunction [Formula: see text] to a compartmental pharmacokinetic/pharmacodynamic (PK/PD) ordinary differential equation system. Using Banach fixed-point and semigroup theory, we prove existence, uniqueness, and long-time asymptotic stability of solutions. Using the QGD framework on a selected dataset of 7,428 clinically confirmed DDI pairs from DrugBank v5.1, TWOSIDES, and FAERS, our model outperforms five established baselines by 1.5-13.9 percentage points in AUC, with an average precision of 0.948 and an AUC of 0.962. Quantum edge weighting alone explains a 3.7% relative F1 gain over unweighted graph methods, according to ablation experiments. These results show that quantifiable, interpretable improvements in DDI prediction can be obtained by incorporating quantum mechanical concepts into graph-differential frameworks.
Ticks are obligate hematophagous arachnids that parasitize both humans and animals. While considerable research in Malaysia has focused on bacterial detection in ticks, knowledge of tick-borne Anaplasma, Ehrlichia and Brucella in farm ruminants remains limited. In this study, 1,241 ticks comprising of four species (Rhipicephalus microplus, Rhipicephalus haemaphysaloides, Haemaphysalis bispinosa, and Haemaphysalis wellingtoni) were collected from 674 farm ruminants across Peninsular Malaysia. The ticks were pooled and molecularly screened for Anaplasma and Ehrlichia using 16S rRNA gene primers, and Brucella using the BSCP31 gene primer. Out of 130 tick pools, five (3.85%) tested positive for Anaplasma and two (1.54%) for Ehrlichia. No Brucella DNA was detected in all four tick species. All positive pools consisted exclusively of R. microplus, with no pathogens identified in the other three tick species. BLAST analysis revealed that the Anaplasma sequences were identical to Anaplasma marginale, A. platys, and Candidatus "Anaplasma boleense", while the Ehrlichia sequences were identical to Ehrlichia ewingii. This study represents the first screening for Anaplasma, Ehrlichia, and Brucella in ticks infesting farm ruminants in Peninsular Malaysia.
Glycated hemoglobin (HbA1c) is a well-established biomarker reflecting chronic glycemic control in diabetes. It accumulates through non-enzymatic glycation of hemoglobin under sustained hyperglycemia and serves as a surrogate of metabolic memory. Emerging in parallel, glycosylated RNA (glycoRNA), small noncoding RNAs bearing covalently attached N-linked glycans, has revealed unexpected roles in immune signaling and glycoimmunomodulation. While glycation and glycosylation represent distinct biochemical processes, both are modulated by glucose availability and cellular stress. This opinion paper aimed to explore the conceptual parallels between HbA1c and glycoRNA, proposing that hyperglycemia-induced metabolic changes may simultaneously influence both processes. In light of these, glycoRNA represents an emerging biomarker as a functional effector in metabolic disease, mirroring the hyperglycemia-driven immunological dimensions of HbA1c with a further advantage of a defined metabolic sequence, which can deepen diagnostics towards disease progression patterns. Though direct experimental evidence is currently limited, we outline plausible mechanistic intersections and suggest methodological frameworks for future research. Therefore, this perspective aims to stimulate interdisciplinary investigation into glycoRNA biology within the broader context of glycemic dysregulation and immune modulation in diabetes.
What is this plain language review about?Cortisol is a hormone that supports many essential functions. When cortisol remains too high for too long (a condition called hypercortisolism), it has negative effects throughout the body, including on organs and tissues involved with regulating blood sugar (glucose). CATALYST was a large study in adults with type 2 diabetes who didn’t meet blood glucose targets despite taking multiple medications (‘difficult to control type 2 diabetes’).What were the results?The CATALYST study found that about 1 in 4 (24%) of 1,057 adults with difficult-to-control type 2 diabetes had hypercortisolism due to excess cortisol being produced within the body. Additional evaluations confirmed who was eligible to receive treatment in the study. One hundred thirty-six people with difficult-to-control type 2 diabetes and hypercortisolism entered the treatment phase; 91 took mifepristone (Korlym), a medicine that reduces cortisol activity, and 45 took placebo for 24 weeks along with their usual treatments. The main result that the study looked at was HbA1c, a blood test that shows a person’s average blood glucose level over the prior few months.Mifepristone led to a larger decrease in HbA1c (–1.47%) than placebo (–0.15%), and many people taking mifepristone could lower or stop some glucose-lowering medicines like insulin. They also lost about 10 pounds on average and had greater reductions in waist size than people taking placebo. More people stopped mifepristone than placebo (46% vs 18%). The most common reason people stopped mifepristone treatment was because of side effects (26 people who took mifepristone stopped vs 1 person who took placebo). Side effects for people taking mifepristone were typically mild or moderate. Common side effects in people taking mifepristone included low potassium and symptoms of cortisol withdrawal (tiredness, nausea, vomiting, headache, diarrhea, dizziness) that occur when cortisol activity drops quickly after being high for a long time. These side effects were expected with mifepristone, were temporary, were not dangerous, and were manageable with dose changes and education.What do the results mean?The CATALYST results suggest that people with difficult-to-control type 2 diabetes may benefit from being tested for hypercortisolism. For people with hypercortisolism, treatments targeting cortisol overactivity (such as mifepristone) may help them lower their HbA1c and lose weight.[Box: see text][Box: see text]Link to original article here.
Opioid-propofol sedation is standard for gastrointestinal endoscopy but may contribute to postoperative fatigue (POF). This study compared the severity of POF between sufentanil-propofol and alfentanil-propofol sedation in patients undergoing gastrointestinal endoscopy. In this randomized trial, 248 patients scheduled for esophagogastroduodenoscopy and/or colonoscopy received either alfentanil (7.5-10 μg/kg) or sufentanil (0.1-0.2 μg/kg) combined with propofol for deep sedation. The primary outcome was POF severity assessed by the Christensen Fatigue Scale (CFS) 30 min post-procedure. Secondary outcomes included recovery times (awakening and ambulation), incidence of clinically significant fatigue (CFS ≥ 6), and adverse events. At 30 min post-procedure, the alfentanil group had significantly lower CFS scores than the sufentanil group (mean [standard deviation, SD]: 4.7 [1.0] vs. 5.7 [1.0]; mean difference -1.1, 95% CI -1.3 to -0.8; P < 0.001). The proportion of patients with CFS score ≥ 6 was also lower in the alfentanil group (20.8% vs. 35.7%, P = 0.004). Recovery was faster in the alfentanil group for both awakening (3.0 [2.2] vs. 5.5 [2.8] minutes, P < 0.001) and ambulation (12.8 [2.4] vs. 15.7 [3.4] minutes, P < 0.001). Adverse events including dizziness, nausea, and vomiting were less frequent with alfentanil (15.2% vs. 26.0%, P = 0.035; and 4.8% vs. 12.2%, P = 0.036). Compared to sufentanil, alfentanil combined with propofol significantly reduced postoperative fatigue and enhanced recovery in patients undergoing deeply sedated gastrointestinal endoscopy. Name of trial registry: Chinese Clinical Trial Registry. ChiCTR2300071429. URL: https://www.chictr.org.cn/showproj.html?proj=186791.
Sugarcane molasses serves as a vital non-food feedstock for ethanol fermentation, and its efficient utilisation depends on breeding of excellent microbial strains. Therefore, identification of industrial strains for ethanol fermentation is central to improving fermentation efficiency. To identify high-efficiency ethanol-fermenting strains, we developed a method for preparing high-throughput polymerase chain reaction (PCR) templates within 3 min using seven industrial Saccharomyces cerevisiae strains, integrating single-cell morphology and phenotypic variations in ethanol fermentation. Method specificity was confirmed by amplifying and sequencing the internal transcribed spacer region, and the efficiency was validated by extracting genomic DNA using cetyltrimethylammonium bromide (CTAB). Subsequent genetic diversity analysis using random amplified polymorphic DNA (RAPD) with eight effective primers screened from twenty-two random primers revealed genetic similarity coefficients ranging between 0.47 and 0.96. The high-yield strains 1015-04-01 and 1002-03-03 showed the highest similarity (0.96), whereas strain 1015-04-01 and the low-yield strain 1415 exhibited the lowest similarity (0.47). Unweighted pair group method with arithmetic mean (UPGMA) cluster analysis demonstrated that the high-yield strain 1016-02-04, and strains 1415 and 1313 formed a major cluster, and the low-yield strains 1415 and 1313 formed a distinct subcluster; four other high-yield strains constituted a separate cluster, indicating certain genetic differences between high- and low-yield strains, together with partial genetic overlap. The RAPD results exhibited a certain correlation with differences in final ethanol concentration and single-cell morphology, providing preliminary genetic marker references for the rapid identification and screening of high-performance strains used in ethanol fermentation from sugarcane molasses.
A phytochemical study on the 70% ethanol extract of the stem bark of Vietnamese Ceiba pentandra (L.) Gaertn led to the isolation of the three new sesquiterpene alkaloids pentandralactams A (1), B (2), and C (3), along with the six known compounds thespesilactam (4), isohemigossylic acid lactone-2-methyl ether (5), alanense H (6), hibiscolactone A (7), 11-hydroxy-2-O-methylhibiscolactone A (8), and vavain 3'-O-β-D-glucoside (9). Their structures were elucidated through extensive spectroscopic analyses, including HR-ESI-MS, and 1D and 2D NMR. All isolates were tested for their ability to inhibit NO production in LPS-induced RAW 264.7 cells. The sesquiterpene alkaloids pentandralactams A-C (1 - 3) exhibited potent NO inhibition with IC50 values of 8.03, 9.79, and 11.28 µM, respectively. In silico, compound 1 demonstrated the strongest binding affinity with iNOS enzyme with extensive π-π stacking, hydrophobic interactions, and a key hydrogen bond, without any unfavorable contacts. Compound 2 formed multiple hydrogen bonds in addition to π-π interactions, contributing to stable binding, though its broader interaction distribution may slightly affect its specificity. Compound 3 also engaged in essential π-π and hydrophobic contacts but exhibited an unfavorable acceptor-acceptor interaction with ASN370, potentially reducing its efficacy. These results highlight the potential of C. pentandra-derived compounds for further development as anti-inflammatory agents.
The development of dual-functional electrocatalysts with outstanding properties in oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) is of great significance in the field of hydroelectrolysis hydrogen production. Herein, we propose to simultaneously optimize the HER and OER properties of NiFe-LDH-based composite electrocatalysts through cerium doping and RuO2 modification. Benefiting from the synergistic effect of flower-like surface morphology with a large number of fine structures, formation of highly active species as well as RuO2 containing Ru3+ species, RuO2-Ce-NiFe-LDH-0.01/NF only needs low overpotential of 48 and 214 mV for HER and OER to achieve 10 mA cm-2, respectively. More significant, the electrolyzer of RuO2-Ce-NiFe-LDH-0.01/NF//RuO2-Ce-NiFe-LDH-0.01/NF only demands 1.48 V to deliver 10 mA cm-2 and demonstrates robust stability for 100 h. This work opens up a pathway to develop remarkable bifunctional electrocatalysts, demonstrating their enormous potential for industrial applications in water electrolysis.
BackgroundSepsis affects an estimated 166 million people annually. Short-term survival has been the primary focus of research to date, yet individuals who survive acute sepsis face substantial long-term challenges, including chronic illness, physical disability, cognitive impairment, chronic organ dysfunction, cardiovascular events, and psychological disorders. These complications contribute to personal economic hardship, high healthcare utilization, frequent rehospitalization, and significant mortality rates.ObjectivesWe aimed to identify and summarize key interventions for sepsis survivors' post-hospital discharge - including physical rehabilitation, psychological care, provider assessments, monitoring, medication, and education - and to identify gaps in current evidence to elucidate future research priorities.MethodsA systematic scoping review was completed across five databases, supplemented with hand searching. Two reviewers independently screened and extracted data. Eligible studies focused on adult survivors of sepsis, where interventions were implemented after discharge from acute care, and included any research design.ResultsThirteen studies with four follow-up papers were included. Five reported on the impact of simultaneous intervention protocols, four on physical rehabilitation alone, and two on provider assessment and follow-up. The final two focused on psychological care, and pharmacotherapy. Mortality and readmission rates were the most common outcomes measured; satisfaction with care services, mental health outcomes, and cardiovascular event incidence were also evaluated. Qualitative study data was limited. Four studies mentioned intervention costs, but none completed a cost-benefit analysis. Based on a limited pool of evidence, protocolized multi-intervention approaches, provider assessment and follow-up, and physical rehabilitation show some promise in reducing hospital readmissions and improving long-term survival from sepsis. No interventions positively impacted sepsis survivors' mental health. Further, no studies evaluating educational interventions alone were identified.ConclusionsThis review highlights the need for more comprehensive, multidisciplinary post-sepsis care interventions. Future research should focus on patient education, mental health support, and cost-effectiveness analyses to inform evidence-based post-sepsis care strategies.
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Despite evidence that enhanced recovery protocols (ERPs) improve outcomes in adults undergoing surgery, adoption for pediatric populations has lagged. To assess the implementation and clinical effectiveness of a consensus-based ERP for pediatric patients undergoing elective gastrointestinal (GI) surgery. A prospective type 2 hybrid implementation-effectiveness, stepped-wedge, cluster-randomized by entry date into implementation phase, trial of pediatrics patients, 10 to 18 years of age, undergoing elective GI surgery at 18 US sites from September 2019 to June 2024. Sites were randomized into 3 groups, each spending at least 9 months in a control phase, with usual care, followed by an implementation phase at 6-month intervals that included a 21-element ERP supported by a structured Implementation Toolkit, based on 5 Active Implementation Frameworks (5AIFs), and a sustainment phase (12-24 months). Implementation was facilitated by a 1-year, group-based Learning Collaborative curriculum, a repository of tools, ERP adherence feedback, and implementation report cards. Site-level scores were created based on 5AIFs domains. ERP adherence was assessed by ERP elements delivered at patient and site level. The primary effectiveness outcome, postoperative length of stay (LOS), and secondary effectiveness outcomes (including opioid use, time to regular diet, complications, readmission, and patient-reported health-related quality of life [HRQOL]) were evaluated across study phases (baseline, implementation, and sustainability). Correlations between site-level implementation scores and fidelity were estimated. Of the 597 enrolled pediatric patients (median [IQR] age, 15 [13-17] years; 274 [45.9%] female; 323 [54.1%] male), 433 (72.5%) had inflammatory bowel disease. No significant differences were found by study phase in LOS or secondary outcomes, except shorter time to regular diet and decreased opioid use during hospitalization. Patients who received at least 13 ERP elements had shorter median LOS (-1.14 days [95% CI -2.01 to -0.27]) and fewer complications (adjusted odds ratio, 0.48 [95% CI, 0.28-0.82]). Patient-level adherence increased by study phase (number of ERPs: 11 [10-13], 14 [12-15], and 14 [13-15], [P < .001]). ERP integration into order sets and site culture were moderately correlated with fidelity. This stepped-wedge cluster-randomized trial found that despite multifaceted implementation strategies, a pediatric GI surgery ERP did not significantly reduce LOS. However, when accounting for implementation fidelity at the patient level, it resulted in significantly lower LOS and complications. ClinicalTrials.gov Identifier: NCT04060303.
To evaluate the efficacy and safety of Lianxia Xiaopi Granules (LXXP) in treating functional dyspepsia (FD) with combined cold and heat pattern in Chinese medicine (CM). A multicenter, randomized, double-blind, and placebo-controlled trial was conducted at 11 centers between April 1, 2021, and October 24, 2022 in China. Using stratified block randomization at a 2:1 ratio, patients diagnosed with FD were randomly assigned to receive either LXXP (3.5 g/bag, equivalent to 8.337 g of raw herbs) or a placebo (3.5 g/bag) 3 times daily for 8 weeks. The primary outcome was dyspepsia symptom response rate. Secondary outcomes included individual dyspepsia symptom response rate, Chinese medicine syndrome efficacy evaluation scale including reduction rate of CM symptom total score, cure and effective rates, and safety analysis. Subgroup analyses were performed according to postprandial distress syndrome (PDS) or epigastric pain syndrome (EPS) subtypes and Helicobacter pylori (Hp) infection status. A total of 240 participants completed the trial, 160 in the LXXP group and 80 in the placebo group. At week 8, the dyspepsia symptom response rate was significantly higher in the LXXP group than in the placebo group [54.38% (87/160) vs. 32.50% (26/80), P=0.0013]. LXXP significantly improved postprandial fullness, early satiety, and bloating compared with the placebo group (P<0.05). Subgroup analysis showed greater efficacy in PDS and Hp-negative patients (P<0.05). Safety analysis revealed no significant differences in adverse events between the 2 groups. LXXP effectively improves FD symptoms, particularly in PDS and Hp-negative patients, supporting its application in CM-based treatment. (Trial registration No. ChiCTR2100041993).
Escherichia coli constitutively release nano-sized outer membrane vesicles (OMVs) containing numerous virulence factors and immunomodulatory proteins. In this research, we demonstrate that OMVs isolated from the E. coli readily entered Raw 264.7 macrophages and were randomly dispersed within the cytoplasm, and therefore able to deliver their molecular cargos to host cells. With electron microscopy, it can also be observed that OMVs attached to the cell surface or existed in the membrane vesicles of the cell. E. coli-OMVs proved to be non-toxic and had no obvious negative impact on the viability of macrophage cells when the concentration ranged from 1 to 10 µg/mL. The OMVs were targeted to mitochondria of Raw 264.7 macrophage, which was accompanied by elevated intracellular reactive oxygen species levels, activated autophagy, and a marked reduction in intracellular ATP levels-a hallmark of mitochondrial dysfunction. Consistent with this, E. coli-OMVs induced massive and dose-dependent proinflammatory responses in macrophage cells. Altogether, these results indicated that E. coli exploits OMVs to target virulence factors and immunomodulatory proteins to host cells, triggering mitochondrial dysfunction, autophagy, and proinflammatory responses, thus consequently affecting host-pathogen interactions in course of infection.