BACKGROUND Systemic lupus erythematosus (SLE) patients are admitted to the intensive care unit (ICU) for disease flares and infections, both of which carry a high mortality risk. Studies characterizing the outcome predictors of SLE are few in the Asian continent. This study characterized the clinical profile, treatment, and outcome predictors of ICU admissions with SLE. AIM To ascertain the reasons for ICU admission among SLE patients and to explore outcome predictors in these patients. The primary outcome was ICU mortality. Secondary outcomes included need for ventilation, inotropes, renal replacement therapy, and length of ICU and hospital stay. METHODS A retrospective study of 77 SLE patients was conducted in the medical ICU of a tertiary care teaching hospital in India. Clinical features, treatment, and outcomes of patients admitted between January 2018 and December 2022 were recorded. Factors associated with mortality were explored using bivariate and multivariate logistic regression analysis and reported as adjusted odds ratios with 95% confidence intervals. RESULTS The mean (SD) age was 31.1 (10.3) years; 83.1% were female. The median (interquartile) duration of SLE before admission was 12 (1-60) months; SLE was newly diagnosed in the current admission in 23.4%. The median Acute Physiology and Chronic Health Evaluation II score was 16.3 (14.5-18.2) and similar among survivors and non-survivors; 32 had evidence of disease flare, 44 had an infection, and one patient had an intracranial bleed. ICU admission was for respiratory failure (46.7%), hemodynamic instability (32.5%), and status epilepticus (14.3%). Twenty-nine patients (37.7%) had autoimmune hemolytic anemia, and 11 (14.3%) had diffuse alveolar hemorrhage. Immunomodulation included corticosteroids (96.1%), cyclophosphamide (33.8%), mycophenolate (23.4%), plasma exchange (13%), and immunoglobulins (11.7%). All patients received broad-spectrum antibiotics. Respiratory support, inotropes, and renal replacement therapy were required in 93.5%, 51.7%, and 32.5%, respectively. ICU mortality was 50.7% (95% confidence interval: 39%-62%). The mean ± SD hospital length of stay was 18.9 ± 14.3 days. On multivariate analysis, only shock (P = 0.004) was independently associated with mortality. CONCLUSION Intercurrent infection and disease flare are common reasons for ICU admission in SLE patients. Despite multimodal therapy, mortality is high. Shock was independently associated with mortality.

For trips to the suburban area, passengers who do not own a vehicle typically use either a bus or a suburban railway. The main purposes of such trips are usually work, education, tourism and leisure, medical treatment or healthcare services, visiting relatives and friends, and similar activities. In most cases, passengers plan their trip before departure, which includes choosing the mode of transportation, departure and arrival times, trip duration, transportation costs, and other factors. All these factors differently influence the passenger's final choice of transportation mode. This study investigates the impact of tariffs on the passengers' choice of suburban transportation mode under conditions with an equivalent road and railway connection from the departure point to the destination. During the study, the tariffs were compared for transportation by road and railway suburban transport for different travel distances within the suburban area. The main task of the research is to identify the primary factors that passengers consider when selecting a mode of transport and to establish the conditions under which passengers are more likely to choose suburban railway transport. The article also determines the ratio of travel costs by road and rail modes of transport within suburban traffic and calculates the change in this ratio with increasing travel distance. Furthermore, the influence of other factors on passengers' choices was determined through surveys. The research results allow for more effective setting of transportation tariffs, rational use of strategies for the developing the transportation enterprise, and more accurate forecasting of transportation revenue. Choosing the optimal tariff promotes an increase in demand for railway transport, helps maintain competitiveness in the transportation market, and provides an opportunity to attract new users. The organization of a rational pricing policy ensures effective management of the carrier's income and considers the opportunities and interests of passengers and the transportation company.

Vipassana meditation (VM), a mindfulness-based practice, has been known to promote good health all the way. Global chronic diseases such as cardiovascular diseases, diabetes, and hypertension often bring physical and mental pain together. Through developing emotional regulation and helping to reduce stress, VM can be used as an alternative medicine in combination with the conventional therapies now used for treating this condition. The aim of the study was to evaluate how VM alters key health measures, including body weight, blood pressure and sugar levels, pulse rate, body mass index (BMI), and emotional state. It also sought to identify changes in emotional spectrum of reactions, such as fear, expectations, and concern before/after the 10-day VM camp. A pre-experimental study was done at Khadavli Vipassana Center, from which time it admitted 156 first-time participants. After excluding four participants, the final sample size was 152. Health indices were assessed before and after the meditation using standard tools, while the emotional spectrum was ascertained with a unstructured questionnaire. Paired samples t-tests and analysis of the content of emotional responses were conducted on the data. There were significant improvements in physical health: the participants' mean weight decreased by 0.8 kg, BMI dropped 0.3 kg/m², and their systolic and diastolic readings were slightly reduced. This was accompanied with reduced random blood sugar (by 8.8 mg/dl). Oxygen saturation (SpO2) increased by 0.92%. Emotional responses demonstrated a marked reduction in fear and a corresponding increase in positive affect, including enhanced feelings of peace and well-being, observed upon completion of the 10-day intervention period. People said that they had found peace of mind and taken away stress. VM has a significant impact on the physical health system and psychological health, which suggests that it may be not only useful in relieving chronic illness but also could become an adjunct to standard medical treatment. Randomized controlled trials are needed to confirm these findings.

The reference ranges for biochemical parameters can fluctuate due to factors like altitude, age, gender, and socioeconomic conditions. These values are crucial for interpreting laboratory data and guide clinical treatment decisions. Currently, there is no established set of reference intervals for cord blood biochemical parameters of newborns in India, particularly in Mumbai. To create cord blood biochemical parameters reference intervals specifically for Mumbai, India. A cross-sectional study was conducted in an Indian tertiary care hospital. This study focused on healthy newborns with normal birth weight, born to pregnant mothers without health issues. Cord blood samples, approximately 2-3 mL in volume, were collected from 210 term neonates. These samples were divided into fluoride (glucose) and clot activator (serum) tubes and were subsequently analyzed in the institute's biochemical laboratory. The data obtained from the analysis was then subjected to statistical analysis. The result of the Shapiro-Wilk test suggested non-normality in the data distribution. Consequently, non-parametric statistics were utilized for analysis. The Mann-Whitney U test was utilized to compare parameter distributions among different factors, including the infant's sex, delivery method, maternal age, and obstetric history. A significance level of P < 0.05 was considered to indicate statistical significance. The following represent the median figures and central 95 percentile reference intervals for biochemical parameters in umbilical cord blood of newborns: Serum direct bilirubin = (0.1-0.55) mg/dL, indirect bilirubin = (0.64-2.26) mg/dL, total bilirubin = (0.62-3.14) mg/dL, creatinine = (0.27-0.76) mg/dL, sodium = (128.19-143.26) mmol/L, chloride = (100.19-111.68) mmol/L, potassium = (1.62-9.98) mmol/L and plasma glucose = (24.75-94.23) mg/dL. Statistically significant differences were observed in serum sodium, potassium, and plasma glucose levels when comparing delivery modes. This is the pioneering study in which first time, the biochemical reference intervals in cord blood for newborns are established in western India. The values are applicable for newborns from this area. Larger study throughout the country is required.

(1) Background: The systemic right ventricular (SRV) dysfunction and severe tricuspid regurgitation (TR) remain significant challenges in patients with congenitally corrected transposition of the great arteries (ccTGA) or following atrial switch procedures. Currently, there is no established, evidence-based medical therapy specifically designed for SRV failure, and treatment approaches are largely extrapolated from left ventricular heart failure (HF) guidelines. This therapeutic gap highlights the need for tailored pharmacologic strategies and optimized perioperative management in this unique population. The optimal timing of surgical intervention and the role of modern HF therapy are still under active investigation. (2) Methods: We present a case series of four patients (three adults and one child) with SRV dysfunction and severe TR, who underwent staged treatment consisting of optimized medical therapy followed by surgical tricuspid valve (TV) replacement. Medical therapy included positive inotropes, sacubitril/valsartan, sodium-glucose co-transporter 2 inhibitors (iSGLT2), beta-blockers, mineralocorticoid receptor antagonists (MRAs), and loop diuretics. (3) Results: All patients demonstrated clinical and hemodynamic improvement prior to surgery, with an increase in systemic ventricular ejection fraction (SVEF &gt; 40%) and cardiac index. TV replacement was performed with favorable early postoperative outcomes and preserved ventricular function at mid-term follow-up. No mortality or major adverse events occurred during follow-up. One case of acute cystitis was associated with dapagliflozin. In all patients, postoperative SVEF remained &gt;40%, and no recurrence of significant TR was observed. (4) Conclusions: A stepwise approach combining modern heart failure therapy and elective TV replacement in patients with SRV dysfunction and TR is safe and effective. Preoperative optimization leads to improved ventricular function and may enhance surgical outcomes. These findings support the integration of contemporary pharmacotherapy in the management strategy for SRV failure.

Traditional broad-spectrum antibacterial strategies are known to contribute to the increase in drug-resistant microorganisms and the disruption of microbial ecological balance. To break this stalemate, researchers have begun to explore selective antibacterial strategies that minimize the impact on normal flora and maintain microbial ecological balance. Species-specific antibacterial materials, which can target particular bacterial species or even specific strains, offer innovative perspectives and methodologies for the prevention and treatment of infectious diseases. This review first explores the selective mechanisms that underpin species-specific antibacterial strategies, summarizes the main classifications of species-specific antibacterial strategies, investigates the engineering techniques employed in the development of such materials, and emphasizes the importance of structure-activity relationships in the design of species-specific antibacterial materials. It explores techniques like peptide modification, nanoparticle engineering, and genetic manipulation, highlighting that a thorough understanding of the structure and function of antibacterial materials is essential for improving their efficacy and specificity. Ultimately, it anticipates the potential applications of species-specific antibacterial materials in disease diagnosis and treatment, while addressing the challenges associated with clinical translation. It is expected that this comprehensive review will offer novel perspectives for the development of species-specific antibacterial materials.

Laparoscopic cholecystectomy is the standard treatment for symptomatic cholelithiasis, cholycystitis and other gall bladder diseases. The adoption of robotic-assisted surgery has increased, but its comparative clinical outcomes remain debated. This meta-analysis compares the clinical outcomes of robotic versus laparoscopic cholecystectomy. A comprehensive literature search was conducted in PubMed, Cochrane, Scopus and Embase from inception until August 2025 to identify relevant studies. Risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes with 95% confidence intervals (CI) were calculated using a random-effects model. Heterogeneity was assessed using I2 and X2 statistics. Statistical analysis was performed using RevMan 5.4.1. A p value < 0.05 was considered statistically significant A total of 1,770,300 patients across twenty five included studies were analyzed. Pooled results showed no significant differences between robotic and laparoscopic cholecystectomy in terms of surgical success rate (OR = 1.71, 95% CI: [0.85-3.44]), overall complications (OR = 0.96, 95% CI: [0.89-1.04]), postoperative complications (OR = 0.99, 95% CI: [0.94-1.04]), 30-day readmission (OR = 1.00, 95% CI: [0.93-1.08]), length of hospital stay (MD=-0.02 days, 95% CI: [-0.29 to 0.25]), and major bile duct injury (OR = 1.42,95% CI[0.43-4.66]). Robotic cholecystectomy was associated with a significantly lower conversion to open surgery (OR = 0.35,95% CI: [0.31-0.41], p < 0.00001) but required longer operative time (MD = 12.65min, 95% CI: [6.95-18.35], p < 0.0001). Robotic cholecystectomy is a safe and effective alternative to the laparoscopic approach, demonstrating equivalent success and complication profiles with a distinct advantage in reducing conversions to open surgery. The high heterogeneity for some outcomes suggests careful patient selection is warranted.

Patients with severe acute behavioural disturbance commonly present to the emergency department. Differing expert opinion dominates treatment strategies. We describe an evidence-based approach to parenteral sedation for the management of emergency department patients with severe acute behavioural disturbance. The most common cause of severe acute behavioural disturbance in the emergency department setting is alcohol and drug intoxication, both being relatively short-lived. The goal of parenteral sedation is to provide safe observation until the effect of any intoxication wears off and allow time for further clinical investigation and treatment as required. A validated scoring tool, such as the sedation assessment tool score, is useful to guide objective assessment of behavioural disturbance. We recommend the intramuscular route initially, unless intravenous access is already available (i.e., placed by first responders), as it allows rapid administration and requires less physical restraint. We recommend droperidol, or olanzapine where droperidol is unavailable, as the preferred first-line parenteral agent, due to strong evidence of effectiveness and safety. When rescue therapy is required or in extremely dangerous circumstances, we recommend using ketamine. We do not routinely recommend benzodiazepines, such as midazolam, except for treating specific causes of agitation which respond well to benzodiazepines, such as alcohol withdrawal or stimulant intoxication. We recommend avoiding combination therapy (antipsychotic and benzodiazepine) due to an increased adverse effect profile, without clear evidence for increased effectiveness. Following sedation, we recommend close observation in all patients, including at a minimum regular monitoring of vital signs, level of sedation, and continuous pulse oximetry without supplemental oxygen. End-tidal carbon dioxide monitoring should be used when available. There is a good evidence base to recommend a standardized approach to the management of severe acute behavioural disturbance in the emergency department. We recommend using intramuscular droperidol (or olanzapine if droperidol is not available) as a first-line therapy, which can be repeated at 15 min if effective sedation is not achieved. If rescue sedation is required or in extremely dangerous scenarios when immediate control is required, we recommend ketamine. We do not routinely recommend benzodiazepines as first-line therapy, unless specifically treating a condition likely to benefit from benzodiazepines, such as alcohol (or sedative hypnotic) withdrawal or stimulant intoxication. We do not recommend combination therapy (antipsychotic and benzodiazepines).

Unhealed wounds and persistent perineal sinuses (PPS) may occur in as many as one third of patients after proctectomy for Crohn's disease. The management of these conditions remains a significant challenge, particularly in the context of inflammatory bowel disease (IBD), with existing therapies plagued by high failure rates. This systematic review of the literature assessed the efficacy of medical and surgical therapy for PPS closure in IBD. Secondary aims included review of classification systems used for PPS. A literature search was conducted using Medline, Embase and Cochrane databases on 17 December 2024. The review was registered on PROSPERO (CRD42024622582). Inclusion criteria were adult patients with IBD and PPS or unhealed wounds following proctectomy. We excluded abstract-only publications, case reports, cancer and paediatric cohorts. Two reviewers independently screened abstracts and full texts and extracted data. The primary outcome was clinical healing rate. Secondary outcomes included classification systems used to describe PPS. Risk of bias was assessed. Of 496 records identified, following removal of duplicates, 489 abstracts were screened, and 60 full text articles assessed for eligibility. Of 25 articles included in the final analysis, 23 were case series or retrospective cohort studies, and all were at high risk of bias. No randomised controlled trials were identified. Five articles (including two of the case series) described classification systems for PPS. Interventions included hyperbaric oxygen therapy, Karydakis flap, cleft closure, omentoplasty, skin grafting, gracilis and rectus abdominis flap, platelet-derived growth factor, curettage, lay open and excision of sinuses. Reported healing rates ranged from 30% to 100%. Heterogeneity in the reporting of outcomes, as well as the interventions performed precluded meta-analysis. The published evidence for treatment of PPS in IBD consists of low-quality evidence case series with high risk of bias. There is a need for standardised outcome reporting and high-quality, prospective studies to establish effective treatment algorithms.

Acute lymphoblastic leukemia (ALL) driven by KMT2A rearrangements (KMT2A-r) is an aggressive hematologic malignancy with poor prognosis and a high incidence in infants. While KMT2A fusion proteins drive leukemogenesis through transcriptional dysregulation, recent discoveries have highlighted the pivotal role of non-coding RNAs (ncRNAs) in shaping the molecular and epigenetic landscape of this disease. These key regulators of gene expression influence chromatin dynamics, transcriptional activation, and post-transcriptional control. Circular RNAs (circRNAs) contribute to genome instability and facilitate chromosomal translocations, while some fusion-derived circRNAs (f-circRNAs) sustain oncogenic signaling and promote chemoresistance. Long non-coding RNAs (lncRNAs) orchestrate transcriptional programs that maintain leukemic stem cell properties and reinforce aberrant self-renewal pathways. MicroRNAs (miRNAs) modulate critical oncogenic networks by regulating KMT2A fusion transcripts and downstream effectors, thereby impacting drug resistance, apoptosis, and proliferation. Meanwhile, enhancer RNAs (eRNAs) fine-tune transcriptional activity and epigenetic regulation, influencing KMT2A target gene expression and chromatin accessibility. Collectively, these ncRNAs integrate into the complex regulatory circuits of KMT2A-r ALL, revealing their potential as biomarkers for disease classification, risk stratification, and treatment response prediction. Understanding their interplay with KMT2A fusion proteins not only provides new insights into leukemogenesis but also highlights promising opportunities for therapeutic intervention and precision medicine in this high-risk leukemia subtype.

Prior to the pandemic, malaria showed a global downward trend due to control and surveillance efforts. The COVID-19 pandemic contributed to the disruption of progress in malaria control, leading to an increase in cases and deaths, particularly in Africa. In its bulletin, the World Health Organization (WHO) reported the interruption of essential activities, such as active case finding and mass treatment for diseases like malaria, during the pandemic. This resulted in a setback for disease control efforts, with the recovery of these activities projected by 2030. In Brazil, there are no studies on the impact of the pandemic on malaria transmission. For this reason, the study aims to assess the impacts of the COVID-19 pandemic on the disease's transmission. This is an observational, descriptive, and analytical study with a quantitative approach, which analysed secondary data of reported malaria cases in the state of Pará, Brazil, between 2018 and 2023. Data were obtained from Sivep-Malária (Malaria Epidemiological Surveillance Information System) and the Brazilian Ministry of Health's COVID-19 database. For statistical analysis, the study period was divided into three periods: pre-pandemic (2018-2019), critical period (2020-2021), and less critical period (2022-2023). Comparisons of sociodemographic and occupational variables, parasite species, and case mobility between periods were tested using the Chi-square test. A total of 170,245 malaria cases were reported: 79,125 before the pandemic, 44,830 in the critical period, and 47,502 in the less critical period. Cases among miners increased from 17.2% to 58%. Plasmodium falciparum cases rose from 2.6% to 11.3%. Imported cases from other states accounted for 3813 (2.2%) of the cases. The peaks of autochthonous malaria cases in Pará occurred from August to November between 2018 and 2023. The seasonality of the disease was observed to be maintained at levels similar to the pre-COVID-19 pandemic period. The reduction in the number of malaria cases during the critical period can be attributed to the control actions of the disease control programme in the state of Pará, while the increase was associated with the resumption of social interaction habits and greater internal mobility, facilitated by COVID-19 vaccination.

Leishmaniasis is a vector-borne disease caused by Leishmania protozoa, transmitted through infected female phlebotomine sandflies. Cutaneous leishmaniasis (CL), its most common form, causes considerable morbidity, particularly among Colombian military personnel in endemic areas. Although meglumine antimoniate (MA) remains the first-line treatment, increasing reports of therapeutic failure (TF) raise concerns about its efficacy and highlight the need to identify associated risk factors.The objective of this study was to identify risk factors linked to MA treatment outcomes in Colombian soldiers with CL and to characterise the Leishmania species involved and their geographic distribution.A total of128 soldiers diagnosed with CL (2018-2019) were followed for treatment response. Sociodemographic, clinical and lesion data were collected. Leishmania species were identified through HSP70 and MPI gene barcoding, and geographic origins were mapped. Selected isolates from TF patients underwent in vitro susceptibility testing to MA.The cure proportion was 67.9%, with TF in 32%. Factors significantly associated with TF included previous infections (p = 0.001), prior MA use (p = 0.000), lymphadenopathy (p = 0.008) and lesion type (p = 0.002). Multivariate analysis identified previous treatment (p = 0.000), lesion size and infections acquired in the Orinoquía (p = 0.013) and Pacific (p = 0.014) regions as risk factors. L. (V.) braziliensis predominated, especially in Orinoquía and Amazon regions; L. (V.) panamensis was widespread, and L. (L.) mexicana appeared only in the Andean region. In vitro resistance to MA was not observed in analysed isolates; thus, this factor does not appear related to TF.TF is linked to specific clinical and epidemiological variables, supporting their integration into patient monitoring during MA therapy. Clinical trial number: not applicable.

Background Refractory angina pectoris represents a significant clinical challenge characterized by persistent chest pain despite maximally tolerated medical therapy and optimal revascularization attempts. This study evaluates the efficacy and safety of invasive spinal cord stimulation (SCS) in patients with refractory angina. Methods Twenty-one patients underwent neurostimulation system implantation between 2022 and 2023 (mean age 62.8 ± 7, 12 males) diagnosed with refractory angina. All patients received both chronic continuous stimulation and on-demand stimulation to alleviate anginal pain episodes. The primary endpoint was changes in the Seattle Angina Questionnaire (SAQ-19) scores. Secondary endpoints included changes in the Short Form Health Survey (SF-36), incidence of major adverse cardiovascular events, device-related complications, and nitrate use. Results Eighteen patients completed the final follow-up. No statistically significant improvements were observed in any SAQ-19 domains. However, reductions in pain scores (41% vs. 53%, p = 0.007) and improvements in mental health scores (61% vs. 72%, p = 0.021) and physical functionating (36 vs. 52%, p = 0.017) were noted on the SF-36. Device extraction occurred in three cases (14%)—two due to pocket infection and one at the patient's request. Four lead repositioning procedures were performed (19%). Hospitalization rates significantly decreased over the one-year observation period, from 3.8 to 0.5 hospitalizations per patient ( p = 0.03). Recurrent acute coronary syndrome was noted in one patient, requiring additional coronary stentings. Notably, although no significant reduction in nitrate therapy was achieved, the treatment regimen prevented any new nitrate prescriptions during the study period. Conclusion SCS did not significantly improve the primary endpoint of disease-specific quality of life (SAQ-19). However, treatment was associated with secondary benefits, including improvements in physical functionating, pain and mental health (SF-36) and a significant reduction in hospitalization rates. Complication rates were significant.

Heart failure (HF) imposes a growing public health and macroeconomic burden in low- and middle-income countries (LMICs), yet its long-term economic impact remains unquantified. China, characterized by rapid ageing and escalating cardiovascular risks, provides a critical setting to model HF economic implications. Using data from the Global Burden of Disease Study 2021, China Cardiovascular Association Registry, and national insurance databases, HF macroeconomic burden (2025-35) was projected via a health-augmented macroeconomic model. Three interventions were evaluated: B-type natriuretic peptide (BNP) screening (adults ≥40 years), intensive blood pressure (BP) control (hypertensive patients), and guideline-directed medical therapy (GDMT) optimization for HF with reduced ejection fraction. Costs are reported in 2017 international dollars (INT$). By 2035, HF cases in China will reach 22.7 million [95% uncertainty interval (UI): 9.5-36.9 million], with an age-standardized prevalence of 760.65/100 000 (95% UI: 283.2-1340.8/100 000). The cumulative economic burden (2025-35) is INT$1001.1 billion (95% UI: 733.4-1365.6 billion), representing 0.26% of gross domestic product (95% UI: 0.19%-0.34%), driven by labour force attrition (72.1%; 95% UI: 64.4%-74.8%). Interventions reduced the total burden by 12.5% (95% UI: 10.4%-14.5%): BNP screening (25% coverage) saved INT$78.5 billion (95% UI: 62.8-94.1 billion; 8.10% reduction; cost-benefit ratio 0.49), Intensive BP control saved INT$27.5 billion (95% UI: 25.1-29.9 billion; 2.74% reduction; ratio 0.22), GDMT optimization saved INT$17.0 billion (95% UI: 12.8-22.4 billion; 1.70% reduction; ratio 0.48). HF imposes a substantial and increasing macroeconomic burden in China, largely through workforce productivity losses. Scalable, cost-effective strategies, including primary care-based BNP screening, subsidized hypertension control, and enhanced GDMT adherence, are essential to curb economic losses. These findings inform policy priorities for China and other LMICs confronting demographic transitions.

The present study aimed to evaluate blood redox status and acute phase protein profile throughout two pharmacological treatment protocols for pyometra bitches, employing aglepristone either as a monotherapy or in combination with prostaglandin. A prospective study was conducted in 10 open-cervix pyometra bitches assigned to two groups: aglepristone (n = 5; subcutaneous injections of aglepristone on days 1, 2, and 8 after diagnosis) and aglepristone + prostaglandin (n = 5, aglepristone coupled with daily injections of cloprostenol from days 1 to 7). Blood samples were collected daily for the liver profile (alanine aminotransferase—ALT, alkaline phosphatase, and albumin), acute phase proteins (C-reactive protein-CRP, haptoglobin, and serum amyloid-A), and redox analysis [antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx) and reduced glutathione (GSH), oxidative stress (TBARS), and protein oxidation]. In the aglepristone group, there was increase in albumin concentration and SOD, while protein oxidation and GSH decreased progressively throughout treatment. The aglepristone + prostaglandin group had lower ALT levels but higher lipid peroxidation, GPx, and CRP. In conclusion, the combined use of prostaglandin modified the profile of oxidative markers, antioxidant enzymes, and C-reactive protein, thereby preventing the assessment of treatment efficacy. Conversely, albumin concentration proved a sensitive marker of therapeutic effectiveness in both treatment protocols for pyometra bitches.

Inconsistent reporting can bias suicidality research findings. This study focused on an overlooked pattern-endorsing suicide plans while denying suicidal ideation-and estimated its impact on suicidality prevalence in the Youth Risk Behavior Survey. Publicly available Youth Risk Behavior Survey data from 1993 to 2023 (n = 242,403) were analyzed. Four suicidality indicators were examined: active suicidal ideation, suicide plans, suicide attempts, and post-attempt medical treatment. Statistical analyses included proportion tests and Cohen's h. Overall, 3.1% of respondents reported suicide plans while denying suicidal ideation. Screening out inconsistent reporters systematically impacted the prevalence of suicide plans. By contrast, the prevalence of active suicidal ideation, suicide attempts, and post-attempt medical treatment was only marginally affected. Decisions to include or exclude participants who endorsed suicide plans while denying suicidal ideation should be explicitly justified. Findings underscore the importance of addressing inconsistent reporting and suggest that the suicide plan item may require wording revision to enhance its validity.

Since the discovery of cisplatin's anticancer activity and its clinical approval in 1978, substantial efforts have focused on improving its physiological stability and minimizing off-target toxicity. One promising strategy has been the development of Pt(IV) complexes, which act as redox-activated prodrugs with improved pharmacological profiles compared to Pt(II) drugs. In this study, we present the synthesis of three novel Pt(IV) complexes bearing a pendant deferoxamine (DFO) chelator, designed for theranostic application, combining therapeutic activity with radiometal labeling for positron emission tomography (PET) imaging. Platinum-based drugs are still the gold standard therapy for osteosarcoma but the limited utility and the resistance mechanisms indicate an urgent need for new approaches. In vitro studies demonstrated that these complexes are efficiently internalized by osteosarcoma cells and exhibit minimal toxicity toward healthy MDCK.2 kidney cells, indicating a favorable safety profile. Radiolabeling with Gallium-68 was achieved under mild conditions, yielding stable radiotracers in various biological media after 1 h incubation. This study represents one of the first demonstrations of Pt(IV) theranostic agents suitable for PET imaging, enabling future investigations of Pt(IV) biodistribution profiles that go beyond traditional therapeutic evaluations.

Current clinical treatments for skin scars primarily reduce vascular density in situ. But, outcomes remain unsatisfactory due to limited understanding of scar vascular structure, endothelial cell (EC) heterogeneity, and functional changes. Through dermatoscopy, scanning electron microscopy, and immunofluorescence staining, our study revealed substantial vascular remodeling in scars, including increased neovascularization density, branching complexity, and incomplete vascular wall coverage. Single-cell sequencing constructed an EC atlas of scar patients, identifying upregulated ATP synthesis, decomposition, and oxidative phosphorylation in scar ECs-characteristics resembling tumor vasculature. Notably, a subset of ECs with high neuropilin-1 (NRP1) expression exhibited mesenchymal characteristics. In vitro experiments demonstrated that NRP1 knockdown blocked the transforming growth factor-beta (TGF-β)/SMAD family member 2 (SMAD2) signaling pathway and mitigated endothelial-to-mesenchymal transition (EndMT). Importantly, NRP1 inhibition reduced EndMT, restored normal vascular function and structure, and prevented scar formation in mice. Based on these findings, a functional hydrogel spray was developed using an NRP1-targeting peptide, effectively preventing scar formation by promoting vascular normalization.

Evidence for Clinical Treatment Decisions Without Randomized Data.

Corneal injury remains a significant clinical challenge due to the limited regenerative capacity of the cornea and the difficulties associated with maintaining drug retention at the injury site. This study presents a novel spatiotemporal repair strategy for corneal wounds, utilizing an alkaline phosphatase (ALP)-triggered, lesion-responsive peptide hydrogel that incorporates TB500, a biologically active peptide with the amino acid sequence LKKTETQ, which has not been previously explored for corneal disease treatment. The hydrogel is designed through enzyme-instructed self-assembly (EISA) of a phosphorylated peptide precursor, Nap-YpYY-TB500, which undergoes site-specific dephosphorylation by elevated ALP levels at the wound site, triggering nanofiber formation and gelation in situ. Among three candidate sequences, Nap-YpYY-TB500 exhibited optimal gelation kinetics, nanostructure, and therapeutic efficacy. In vitro, the hydrogel promoted human corneal epithelial cell (HCEC) migration, proliferation, and tight junction recovery, while also enhancing myofibroblastic differentiation and cytoskeletal reorganization of human corneal stromal fibroblasts (HCSFs). In an alkali burn model, the hydrogel significantly accelerated epithelial regeneration, reduced inflammation, and improved corneal barrier function. Our work represents the first ocular application of TB500 and underscores the potential of enzyme-responsive, self-assembling peptide hydrogel as a localized and sustained delivery system for corneal repair.