The aim of our study is to compare the markers and parameters obtained from complete blood count between patients diagnosed with missed abortion in the first trimester and a healthy pregnant control group. This descriptive, retrospective, case-control study included 166 patients diagnosed with missed abortion according to ultrasound criteria, and an equal number of healthy pregnant controls, who visited the Gynecology and Obstetrics Clinic at a Training and Research Hospital from January 1, 2018, to July 1, 2023. Participants, with 5 to 14 weeks of gestation, were selected using simple random sampling. Data on age, gravida, parity, gestational week, and hemogram results were retrieved from medical records and compared. Statistical significance was set at p < 0.05. No significant differences were observed between the case and control groups in terms of gravida, parity, age, or gestational week (p > 0.05). Likewise, comparisons of hemogram parameters and derived values, did not show statistically significant differences (p > 0.05). However, the multivariate logistic regression analysis revealed that each unit increase in lymphocyte count was linked to a 2.075 times higher risk of missed abortion (p = 0.040). Our study found no significant differences in complete blood count parameters between the missed abortion and healthy pregnant groups. Although lymphocyte count was significant in the multivariate model, this association should be interpreted with caution, as complete blood count values were obtained at the time of diagnosis. Therefore, it does not indicate predictive value, and prospective studies are needed to determine whether lymphocyte count may serve as a pre-diagnostic marker.
Heart failure (HF) affects over 64 million people worldwide, with prevalence projected to reach 3% by 2030. In advanced stages, when medical therapy fails and transplantation is limited by organ shortages, left ventricular assist devices (LVADs) represent a viable alternative. This retrospective, single-center study reports 10-year outcomes from the first Chilean LVAD program using the HeartWare (HVAD) device. Between 2013 and 2015, nine patients with advanced HF received HVAD implants. The mean age was 42.2 ± 15.8 years, with a left ventricular ejection fraction of 22% ± 4.1%. One-year survival was 77.8%, and 10-year survival for those using LVAD as destination therapy was 62.2%. All patients experienced at least one infection, with driveline infections being most common (55.5%). Bleeding events affected 77.7%, including gastrointestinal bleeding and severe epistaxis (both 22.2%). Neurological complications occurred in 33.3% of patients. Despite these events, four patients remained on LVAD support after 10 years, with no mechanical device failures requiring replacement. This case series highlights the feasibility, durability, and clinical relevance of long-term LVAD support in low-donation settings. Findings support LVADs as a destination therapy in selected patients and emphasize the importance of multidisciplinary care and structured follow-up.
Split-thickness skin grafting (STSG) is commonly used in the treatment of burn injuries and extensive skin defects. However, significant postoperative pain frequently occurs at donor sites and may impair patient recovery and postoperative rehabilitation. Topical analgesic interventions have been proposed as an effective strategy for localized pain management while minimizing systemic adverse effects. To systematically evaluate the efficacy and safety of topical analgesic interventions for pain control at donor sites following STSG in burn patients. A systematic literature search was conducted in PubMed, Embase, Web of Science, and the Cochrane Library from database inception to January 2026. Randomized controlled trials comparing topical analgesic interventions with placebo or standard care for STSG donor-site pain were included. The primary outcome was postoperative pain score. Secondary outcomes included incidence of rescue analgesia, time to first rescue analgesia, anesthetic requirement, and adverse events. Meta-analysis was performed using Review Manager (RevMan) version 5.3. Ten randomized controlled trials were included in the analysis. For the primary outcome, no statistically significant difference was observed in postoperative pain scores between topical analgesic interventions and control treatment (MD = - 1.87, 95% CI: -5.05 to 1.31, P = 0.25). For secondary outcomes, topical analgesic interventions significantly reduced the incidence of rescue analgesia (OR = 0.06, 95% CI: 0.01-0.58, P = 0.02). Time to first rescue analgesia and anesthetic requirement were reported by single studies and should therefore be interpreted cautiously; these outcomes suggested prolonged time to first rescue analgesia (MD = 8.56, 95% CI: 7.67-9.45, P < 0.00001) and reduced anesthetic requirements (MD = - 20.61, 95% CI: -31.91 to - 9.31, P = 0.0004). No statistically significant differences were found in nausea (OR = 1.09, 95% CI: 0.36-3.30, P = 0.88) or vomiting (OR = 0.50, 95% CI: 0.16-1.56, P = 0.23). Topical analgesic interventions did not significantly reduce postoperative pain scores, which was the primary outcome of this meta-analysis. However, they may reduce the need for rescue analgesia without increasing nausea or vomiting. Because some secondary outcomes were based on single studies, these findings should be interpreted with caution. Further well-designed randomized controlled trials are needed to confirm the clinical benefit of topical analgesia for STSG donor-site pain management.
Understanding the rapid adjustments of plants to high-light exposure remains challenging, as multiple excitation and de-excitation pathways are simultaneously activated. In this study, we examined carotenoid pigment conversions at the second-scale in three tree species in parallel with high temporal resolution (<1 s) in vivo fluorescence and absorption spectroscopy. Our results reveal that both β-branch (violaxanthin, antheraxanthin, zeaxanthin) and α-branch (lutein, lutein epoxide) xanthophylls exhibit remarkably fast and oscillating pool dynamics within the first 20 seconds of illumination, reaching even maximal values in that timeframe. Prompt (0-20 s) conversion of the lutein is observed at the expense of both lutein epoxide and α-carotene in certain species, while accumulation of antheraxanthin and zeaxanthin is seen both prompt (0-20 s) and slower (>30 s). Interestingly, mirror trends between whole α- and β-branch carotenoids seem to indicate balancing trends, involving dynamic precursor shifts between α- and β-carotenes. Further, we observe that quick xanthophyll changes match the kinetic trends of fitted Gaussian-modeled absorbance peaks (approx. at 520, 535, 560 nm) within the early seconds. These quick changes in photon absorption are followed by slower-triggered non-photochemical de-excitation through a particular xanthophyll, seen from the dominant 535-nm peak, and likely attributed to antheraxanthin or zeaxanthin. The quick xanthophylls conversion redistributing the excessive excitation energy while quenching fluorescence (EET phase) is shown as one of the first responses to excessive light, before regulated energy dissipation as heat is initiated. These observations invite to interpret the non-steady state conditions and their parametrization more carefully, considering different photoprotective strategies across species.
Breast cancer (BC) has become the most common malignancy worldwide. Our aim was to assess the global diversity of disability due to breast cancer in 204 countries and territories. Using data from the Global Burden of Disease (GBD) 2021 study the diversity of disability due to breast cancer was estimated for 204 countries and territories, and breast cancer incidence, prevalence, mortality, and Years Lived with Disability (YLDs) were further assessed. Absolute number, rate, and age standardized rate with 95% uncertainty intervals (UIs) were used to compare the difference. Data analysis was further stratified by the socio-demographic index (SDI) of the regions, average annual percentage changes (AAPC) and trends were analyzed by the Joinpoint regression procedure. From 1990 to 2021, the global disability-adjusted life years (DALYs) caused by breast cancer showed a trend of first decrease and then increase in 204 countries, especially during the epidemic period of Corona Virus Disease 2019 (COVID-19) from 2019 to 2021, with 63% of countries experiencing an increase in DALYs for three consecutive years, mainly in Africa. During this period, there was a significant increase trend in DALYs caused by breast cancer in low - and middle-income countries, with Turkey having the highest growth rate. High-income countries showed declines, with Denmark, Luxembourg and the United Kingdom experiencing declines of more than 50%. For males, the highest incidence, prevalence, mortality, and DALYs are mainly concentrated in the Eastern Sub-Saharan Africa region. For females, high incidence and prevalence are found in economically developed regions such as Europe and North America, while the highest mortality and DALYs are primarily concentrated in the Oceania region. The DALYs of breast cancer patients in the 15-49 years age group are highest in low-middle SDI countries, approximately 180.86 per 100,000 (95% UI:161.08, 201.32). For the 50-74 years age group, the highest DALYs are found in low SDI countries, about 754.47 per 100,000 (95% UI: ). In the ≥ 75 years age group, the highest DALYs are observed in high SDI countries, approximately 1166.46 per 100,000 (95% UI:952.49, 1296.24). Overall, DALYs showed a slight global increase from 2012 to 2021 but a decrease over the 30-year span from 1990 to 2021. From 1990 to 2021, DALYs due to breast cancer worldwide decreased first and then increased, especially during the COVID-19 pandemic. There is a significant increase in breast cancer DALYs in low - and middle-income countries, while there is a downward trend in high-income countries. In addition, there is a complex relationship between breast cancer indicators and socio-demographic index (SDI) in different countries and regions, indicating the importance of considering multiple factors when analyzing cancer epidemiology and the need to tailor cancer prevention and treatment approaches based on local context and social characteristics.
Postoperative pain, swelling, and limited mobility are major barriers to early functional recovery after knee arthroplasty. Cryotherapy is widely used during postoperative rehabilitation, but evidence regarding its role when combined with standard rehabilitation remains inconsistent. This study examined whether the addition of cryotherapy to a standard rehabilitation protocol was associated with improved early postoperative outcomes after knee arthroplasty. This retrospective, non-randomized cohort study included 100 patients who underwent primary knee arthroplasty between April and July 2024. Patients were allocated to a cryotherapy group (n = 58) or a control group (n = 42) receiving standard rehabilitation alone, based on clinical practice patterns and patient preference. Primary outcomes included Hospital for Special Surgery (HSS) scores, range of motion, and knee circumference. Secondary outcomes included Visual Analog Scale (VAS) pain scores, opioid consumption, length of hospital stay, complications, and patient satisfaction. At 1 week postoperatively, the cryotherapy group had higher HSS scores (P < 0.001), greater knee flexion (P = 0.006), less extension deficit (P = 0.005), and smaller knee circumference (P = 0.003) than the control group. These between-group differences remained significant at 2 weeks (all P < 0.05) but were no longer significant at 6 weeks. VAS pain scores were lower in the cryotherapy group at 1 week (P < 0.001) and 2 weeks (P < 0.001). The cryotherapy group also used fewer opioid analgesics in the first 48 h (P < 0.001), had shorter hospital stays (P = 0.001), and reported higher patient satisfaction at 6 weeks (P = 0.003). No significant between-group difference in complications was observed (P = 0.121), and no cold-related adverse events were reported. Cryotherapy combined with standard rehabilitation was associated with better early postoperative recovery after knee arthroplasty, particularly during the first 2 postoperative weeks. Cryotherapy may serve as a practical adjunct in early postoperative rehabilitation, although further prospective studies are needed to confirm its clinical benefit.
The incremental value of myocardial perfusion imaging (MPI) before coronary angiography (CAG) for suspected or known stable coronary artery disease (SCAD) has not been validated in China. This study investigated the necessity of MPI for these patients regarding improvements in cardiac outcomes and cost-effectiveness in China. The initial cohort comprised 7,437 patients with suspected or known SCAD between 2018 and 2019. After excluding patients with acute coronary syndrome, previous myocardial infarction (MI) and revascularization, enrolled patients were divided into the CAG group and the MPI group according to the initial strategy (CAG or MPI). Then, two groups were matched by propensity score. The cost, revascularization, MI, and all-cause mortality of patients were followed. The MPI and CAG groups each included 130 patients after matching, with similar basic characteristics (P > 0.05). Significantly decreased cardiac events were observed in the MPI group compared to the CAG group (6 vs. 16, P < 0.05). Furthermore, the number of revascularization (5 vs. 12), MI (1 vs. 3), and all-cause mortality (0 vs. 1) in the MPI group was also lower. The Cox model showed that fewer patients in the MPI group had cardiac events (HR 0.27, 95% CI 0.10-0.71). Moreover, patients in the MPI group had fewer first-visit costs ($718 vs. $1389) and fewer downstream costs ($120 vs. $344) than those in the CAG group (P < 0.001). Our findings suggest that an MPI-first strategy is associated with fewer cardiac events and lower costs compared with an initial CAG strategy. Not applicable. This study is a retrospective analysis.
Modified radical mastectomy (MRM) is frequently associated with moderate to severe postoperative pain, which may negatively affect recovery and quality of life. Regional anesthesia techniques such as the erector spinae plane block (ESPB), thoracic paravertebral block (TPVB), and pectoral nerve block (PECS) have been increasingly used as part of multimodal analgesia strategies for breast surgery. However, their comparative effects on analgesic efficacy and quality of recovery remain unclear. The study included 90 female patients undergoing unilateral elective MRM. Patients were randomly allocated into three groups (n = 30 each) to receive ESPB, TPVB, or PECS block preoperatively with 0.25% bupivacaine. All patients subsequently underwent standardized general anesthesia. Postoperative pain was assessed using the Visual Analog Scale (VAS) at 0, 1, 3, 6, 12, and 24 h. The primary outcome was total morphine consumption at 24 h. Secondary outcomes included time to first morphine request, incidence of rescue fentanyl use, postoperative nausea and vomiting, patient satisfaction, and scores. Demographic characteristics and operative durations were comparable among the groups (p > 0.05). Total 24-hour morphine consumption was significantly higher in the ESPB group (median 10 mg) compared with TPVB (9 mg, p = 0.009) and PECS (9 mg, p = 0.018) groups. Kaplan-Meier analysis revealed that the time to first morphine request was significantly shorter in the ESPB group (p < 0.001), while TPVB provided the longest analgesic duration. No significant differences were found in postoperative pain scores, rescue opioid requirements, or nausea-vomiting incidence (p > 0.05). QoR-15 scores were significantly lower in the ESPB group compared with TPVB and PECS groups (p < 0.001). Both PECS and TPVB provided superior postoperative analgesia and better quality of recovery scores compared to ESPB in patients undergoing modified radical mastectomy. These findings support the use of PECS or TPVB as effective components of multimodal analgesia strategies for breast cancer surgery. ISRCTN Registry, ISRCTN17247698.
Sustaining evidence-based HIV prevention interventions remains a challenge, particularly among at-risk youth in Africa. The 4 Youth by Youth (4YBY) sustainment study is a hybrid type 2 cluster randomized controlled trial that evaluates the sustainability and cost-effectiveness of a crowdsourced approach to sustaining a package of evidence-based HIV prevention services. The study will be conducted across 40 community sites, supported by 18 community-based organizations (CBOs) providing HIV prevention services in Nigeria. Given their longstanding engagement with young people, CBOs serve as key partners in assessing long-term sustainability strategies for the 4YBY intervention, which has proven effective in increasing HIV prevention service uptake among youth. This protocol describes a cluster randomized controlled trial that will be conducted across 40 sites, all randomized into two arms. Half of the sites (20) will be assigned to receive the standard 4YBY intervention (4YBY-S), while the other 20 sites will receive the standard 4YBY intervention plus an enhanced sustainability strategy (4YBY-S + 4YBY-E). While the 4YBY-S group will continue implementing core intervention activities, the 4YBY-E group will receive additional sustainability-focused support. The Enhanced Sustainability Strategy in the 4YBY-E arm consists of four key components. First, "People" involves identifying and training sustainability teams within CBOs to champion intervention longevity. Second, "Learning", where bi-weekly collaborative sessions will be established to foster knowledge-sharing and problem-solving among stakeholders. Third, "Adaptation Monitoring" will focus on continuously tracking and modifying intervention strategies to better align with local needs. Finally, "Nurturing Coaches" includes dedicated coaches who will provide technical assistance, conduct audits, and offer feedback to strengthen sustainability efforts. Evaluation will be guided by Youth Participatory Action Research (YPAR), the PEN-3 Cultural Model, Proctor's Implementation Outcomes Framework, and the Consolidated Framework for Implementation Research (CFIR). The study hypothesizes that sites receiving the enhanced sustainability strategy (4YBY-S + 4YBY-E) will exhibit greater sustainability of core intervention components, defined as the continued delivery, adaptation, and integration of the intervention within community-based organizations-compared to sites receiving only the standard 4YBY intervention (4YBY-S). Additionally, the 4YBY-S + 4YBY-E arm is expected to achieve a higher uptake of HIV prevention services at 24 months, reflecting both the intervention's effectiveness and its long-term viability within community settings. This protocol represents one of the first cluster randomized controlled trials evaluating intervention sustainment strategies for a youth-led, evidence-based HIV prevention program in Africa. Findings will advance implementation science by establishing a threshold for sustainable strategies and identifying the key factors that support the long-term integration and continuation of HIV prevention services for at-risk youth. The results critically impact scaling up community-led interventions and shaping policy frameworks to strengthen the global HIV response. The protocol was registered with clinicaltrials.gov under registration NCT07072481.
Postoperative nausea and vomiting (PONV) remain among the most common and distressing complications following general anaesthesia, significantly affecting patient satisfaction, recovery times, and healthcare costs. Although ondansetron at a dose of 4 mg IV has long been considered the gold standard for PONV prophylaxis, emerging literature suggests that higher doses may improve efficacy in select high-risk populations. However, the relationship between ondansetron dose, anaesthetic regimen, and PONV incidence remains poorly defined, particularly when using a combination of propofol induction and sevoflurane maintenance. This prospective observational study aimed to evaluate the incidence of early PONV (within the first two postoperative hours) following pre-induction administration of ondansetron 4 mg in patients receiving propofol-sevoflurane anaesthesia and to assess the influence of demographic and perioperative factors on emesis incidence. One hundred fifty high-risk adult patients aged 18-60 years undergoing elective surgery under general anaesthesia were enrolled. All received ondansetron 4 mg IV during premedication, propofol for induction, and sevoflurane for maintenance. Episodes of nausea and vomiting were recorded at 30, 60, 90, and 120 min postoperatively. Statistical analyses included Mann-Whitney U tests for continuous variables and Fisher's exact tests for categorical data, with significance set at p < 0.05. A total of 150 patients were included in the analysis. The mean age of the cohort was 39.9 ± 13.1 years, with a predominance of female patients (63.3%). The overall incidence of early postoperative nausea and vomiting (within 120 min) was 9.3% (14/150). Most episodes were mild in severity, with only a small proportion of patients experiencing repeated vomiting. No statistically significant associations were identified between PONV and demographic variables such as age, sex, body mass index, smoking status, or prior history of PONV (p > 0.05). However, a higher proportion of PONV was observed among patients undergoing otorhinolaryngological procedures, although this did not reach statistical significance when analysed across all surgical departments. Ondansetron 4 mg IV administered pre-medication, combined with propofol induction and sevoflurane maintenance, effectively reduced early PONV incidence to 9.3% among high-risk adults. A higher incidence of PONV was observed in patients undergoing ENT procedures. These findings support the continued use of 4 mg as a sufficient and safe prophylactic dose for early postoperative periods, while underscoring the need for larger comparative studies evaluating dose-response relationships and late PONV outcomes.
Efficient delivery of genome-editing tools into embryos is essential for the production of gene-edited cattle. Somatic cell nuclear transfer and microinjection are commonly used techniques, but electroporation has recently gained attention owing to its technical simplicity, high-throughput capacity, and suitability for large-scale applications. However, its application has been largely restricted to gene knockout owing to the presence of the zona pellucida and size limitations of deliverable materials. To address these challenges, in this study, we optimized electroporation-mediated knock-in (KI) strategies in bovine embryos using single-stranded oligodeoxynucleotides (ssODNs) and adeno-associated virus (AAV) vectors as donors. Initial experiments using ssODN donors with asymmetric homology arms (10 bp left and 25 bp right) resulted in a KI blastocyst (BL) frequency of 13.9 ± 14.1%, although outcomes varied widely across replicates. By contrast, AAV donors carrying 61 bp cargo flanked by 500 bp homology arms enabled consistent KI events, after optimizing the concentration of AAV and length of homology arm. Using the optimized system, a 2.2 kb human albumin coding sequence was successfully inserted into the bovine albumin locus, yielding KI BL frequency of 55.6 ± 41.6%. Collectively, these findings demonstrate that electroporation combined with AAV-mediated donor delivery represents an efficient strategy for generating transgenic bovine embryos, which is a crucial first step toward producing transgenic cattle as bioreactors for high-value protein production.
The accumulation of pathogenic tau protein is linked to cognitive decline and neuronal loss in Alzheimer's disease (AD), with tau oligomers identified as particularly neurotoxic. The 51 kDa FK506-binding protein (FKBP51) stabilizes these toxic tau oligomers and has been identified as a risk factor for several neurodegenerative diseases. FKBP51 levels increase with age and are especially high in AD brains, suggesting its involvement in disease progression. The development of the selective FKBP51 inhibitor, SAFit2, which can cross the blood-brain barrier, has shown promise in reducing stress hormones, improving stress responses, and mitigating protein-related pathologies in other neurodegenerative models. However, the effects of SAFit2 on tauopathies, such as those seen in AD, have not yet been investigated. Here, the effects of the FKBP51-selective inhibitor, SAFit2, were evaluated in PS19 tau transgenic mice. Mice received a 28-day regimen of SAFit2, followed by comprehensive behavioral, neuropathological, and proteomic analyses. SAFit2 demonstrated effective brain penetrance, with sex-dependent pharmacokinetics. Treatment slowed cognitive decline and depressive-like behavior, with pronounced benefits in male PS19 mice, including improved spatial memory and reduced tau oligomer burden. In females, SAFit2 promoted clearance of AT8-positive tau multimers with some benefit to recognition memory. Proteomic profiling revealed distinct molecular signatures underlying these sex-specific responses: males exhibited upregulation of RNA processing and ribosomal proteins, while females showed restoration of calcium signaling and synaptic drivers. Notably, behavioral recovery occurred independently of widespread neuroinflammation reversal. These findings provide the first in vivo evidence that FKBP51 inhibition by SAFit2 induces sex-specific remodeling of the brain proteome. This study also provides further evidence for the therapeutic benefits of targeting FKBP51 for tauopathies.
Drawing on Critical Data Studies and research on journalistic framing of emerging technologies, this study examines how German print media portray data risks associated with digital health technologies for chronic disease management. Using structural topic modeling of 3,027 articles from 2010 to 2024, we first identify that data protection concerns constitute a distinct and significant topic in chronic disease coverage. Subsequent manual content analysis of 367 articles from this topic reveals five media frames varying in their portrayal of these risks, from dismissive technological optimism to critical market skepticism. Despite these different frames, we found no significant differences between tabloid and quality publications or between daily and weekly newspapers, suggesting consistency in how German journalism approaches healthcare data risks. Our analysis contributes to understanding the role of media in shaping public perception of digital health technologies.
DNA methylation is a crucial epigenetic regulatory mechanism in eukaryotes, and its dysregulation is closely associated with numerous diseases. Recent advances in long-read sequencing (LRS) have transformed the ability to comprehensively characterize the methylation modifications in DNA, including the technically difficult genomic regions. However, the translation of this technological potential into reliable biological insights relies heavily on accurate computational analysis of raw signal data. Currently, a growing number of bioinformatic tools have emerged, demonstrating superior performance in LRS-based methylation detection. Our review first briefly describes the detection principles and technological improvement of LRS, and then provides a comprehensive overview of the existing LRS-based methylation detection tools and related benchmarking studies. We further explore the applications in biomedical research, the current challenges, and the future perspective of LRS-based methylation detection. By highlighting the research progress and key issues in the field, this review aims to provide researchers with an essential framework to advance the further development and application of LRS-based methylation detection.
Reports from several countries suggested increased incidence of type 1 diabetes during the COVID-19 pandemic, but causality has remained unclear. We investigated incident type 1 diabetes related to SARS-CoV-2 infection and vaccination in Swedish children and adults and assessed whether vaccination modified infection-related risk. We assembled a register-based cohort of all residents aged <80 years on 1 January 2020 and births during follow-up (1 January 2020-31 December 2023). Risk windows after infection (and after each vaccine dose) were 0-30 days, 31-180 days, 181-365 days, and 1-2 years. Incident type 1 diabetes was defined by the earliest ICD-10 diagnosis E10 in the National Diabetes Register or in the National Patient Register. Cox regression with calendar time as the timescale was used with time-varying exposures; analyses were stratified by age (children <18 years; adults 18-79 years), with age-appropriate covariate adjustment. Sensitivity analyses for children were restricted to ages 12-17 years. The cohort included 2,650,492 children (3813 incident type 1 diabetes) and 6,870,328 adults (4453 incident type 1 diabetes). SARS-CoV-2 infection was associated with increased type 1 diabetes risk within 2 years in children (hazard ratio [HR] 1.22; 95% confidence interval 1.10, 1.36) and adults (1.10; 1.00, 1.20), driven largely by the 0-30-day window (5.41; 4.34, 6.74 in children, 3.33; 2.69, 4.12 in adults). Vaccination did not modify infection-associated risk (interaction p>0.5). When vaccination was investigated as the exposure, children showed lower HRs (0.77; 0.67, 0.88) within 2 years, but this association was not observed in ages 12-17 (1.00; 0.80, 1.26); adults showed a small excess risk within 0-30 days after dose 1 (1.32; 1.07, 1.62), but not in later windows or doses. Short-term elevations in incident type 1 diabetes diagnoses were observed in the first 30 days after infection and after first vaccination, and did not persist, supporting detection/diagnostic acceleration rather than a sustained causal effect of SARS-CoV-2 infection or vaccination on type 1 diabetes.
Odontomas are the most common odontogenic tumors and are composed of dental tissues such as enamel, dentin and cementum. They are classified into compound and complex types. Compound odontomas usually appear as tooth-like structures in the anterior maxilla, whereas complex odontomas present as irregular masses of dental tissues, most frequently in the posterior mandible. Although odontomas are generally slow-growing and asymptomatic, large lesions can cause jaw expansion, facial asymmetry, and delayed tooth eruption. Various surgical approaches have been described, ranging from intraoral to extraoral incisions, with or without fixation. In the present study, we present a 21-year-old Iranian woman with a large mandibular complex odontoma extending from the first molar to the ramus. The lesion was removed via an intraoral approach without pathological fracture or the need for fixation. At the 4-month follow-up, the patient experienced uneventful healing and no signs of recurrence. This case highlights that even large mandibular odontomas can be managed intraorally without the need for fixation devices, with favorable short-term outcomes.
Orthopedic trauma patients frequently struggle with pain control, prolonged opioid use, and psychiatric co-morbidities, including depression and post-traumatic stress disorder (PTSD). Current treatment strategies inadequately address both pain and psychological recovery. Ketamine, an NMDA receptor antagonist with analgesic and psychotropic properties, has shown promise in surgical and psychiatric populations but has not been evaluated in polytraumatized orthopedic patients. This study evaluates ketamine's effectiveness on postoperative pain measured by the Visual Analog Scale (VAS), opioid consumption converted to morphine milligram equivalents (MME), and psychological recovery assessed with the Patient Health Questionnaire-9 (PHQ-9) and PTSD Checklist for DSM-5 (PCL-5). In this prospective, randomized, single-blind, active comparator study, 90 adults aged 18-65 undergoing operative fixation for orthopedic injuries at a Level I Trauma Center will receive either ketamine (0.5 mg/kg IV bolus) or standard general anesthesia without ketamine. Participants remain blinded to treatment, while surgical, anesthesia, and postoperative clinical care teams are unblinded. Outcomes will be measured at 1-7 days, 2-3 weeks, 6 weeks, 3 months, and 6 months postoperatively. This is the first randomized controlled trial to evaluate intraoperative ketamine for both physical and psychological recovery in orthopedic trauma patients, addressing a critical gap in perioperative trauma care. The www.clinicaltrials.gov identifier is NCT06903819.
The bulb of Fritillaria unibracteata is a valuable traditional Chinese medicinal material whose bioactive compound accumulation is closely linked to carbon metabolism. As a perennial herb, its bulbs undergo multi-year developmental cycles, with starch and sucrose serving as key storage and mobilizable carbohydrates, respectively. However, the age-dependent dynamics of starch-sucrose interconversion during bulb development and its expression patterns remain poorly understood, limiting our comprehension of the carbon allocation dynamics that support biomass accumulation and medicinal metabolite production. Starch content increased progressively from the first to fourth year, peaked in the fourth year, and then significantly declined in the fifth year. By contrast, sucrose levels exhibited an opposite trend, decreasing in the fourth year and rising sharply in the fifth year, indicating a marked shift in carbohydrate allocation during the late developmental stage. Transcriptome analysis identified 21,964 differentially expressed genes, among which the starch and sucrose metabolic pathway was significantly enriched. Notably, key genes involved in starch biosynthesis, including ADP-glucose pyrophosphorylase and soluble starch synthase/granule-bound starch synthase, showed their highest expression levels in the fourth year, coinciding with maximum starch accumulation. Conversely, the expression of genes associated with sucrose biosynthesis, particularly sucrose phosphate synthase, was significantly upregulated from the fourth to fifth year, corresponding to the observed sucrose increase. Enzyme activity assays mirrored these transcriptional patterns. Weighted gene co-expression network analysis further identified modules associated with starch-sucrose metabolic traits, providing evidence for coordinated transcriptional networks in carbon allocation. Collectively, these findings reveal a pronounced metabolic transition from starch accumulation to sucrose synthesis during bulb development. The transition from the fourth to fifth year represents a critical developmental stage, during which the carbon allocation pattern shifts from starch-dominated storage to enhanced sucrose accumulation and mobilization. This study provides evidence for an age-dependent starch-sucrose metabolic pattern during bulb development in F. unibracteata, offering a theoretical basis for understanding carbon allocation dynamics in Fritillaria bulbs.
The rapid expansion of short-form educational video platforms has substantially increased public access to health information; however, the characteristics and quality of videos concerning patent ductus arteriosus (PDA) have not been systematically evaluated. This study aimed to evaluate the quality and reliability of short-form videos related to PDA posted on TikTok and Bilibili. The Chinese keyword "patent ductus arteriosus" was used to retrieve relevant videos from TikTok and Bilibili, yielding 140 videos for the final analysis. Uploaders were classified according to publicly available account information. Professional uploaders were defined as accounts identifying the uploader as a healthcare professional and displaying official platform verification and/or an explicit affiliation with a recognized medical institution. Credentials were verified using publicly visible profile elements, including verification badges, profile descriptions, professional titles, and stated institutional affiliations. All included videos were independently evaluated by two reviewers. Because paired reviewer-level ratings were available for the Global Quality Score (GQS), inter-rater reliability for GQS was assessed before consensus adjudication using the intraclass correlation coefficient (ICC) and quadratic weighted Cohen's kappa. Video quality and reliability were assessed using five established instruments: the Global Quality Score (GQS), Video Information and Quality Index (VIQI), Patient Education Materials Assessment Tool (PEMAT), the JAMA benchmark criteria, and modified DISCERN (mDISCERN). Only the first 100 algorithm-ranked videos from each platform were screened, in order to reflect the content most likely to be encountered by typical users, although this approach may preferentially capture videos favored by platform recommendation systems. No independent clinical subject-matter expert (such as a neonatologist or cardiologist) was separately involved in the formal scoring process; instead, the evaluation focused on quality, reliability, transparency, and understandability using established assessment instruments. Clinical accuracy was not independently assessed or adjudicated in this study. A total of 140 short videos related to patent ductus arteriosus (PDA) were included in the analysis, with 57 from Bilibili and 83 from TikTok. TikTok videos demonstrated significantly higher audience engagement than those on Bilibili, with markedly greater numbers of likes, favorites, shares, and comments. Bilibili videos were slightly longer in duration, and there was no significant difference in posting time between the two platforms. Videos on TikTok also achieved significantly higher scores across all five quality assessment tools-mDISCERN, GQS, VIQI, PEMAT, and the JAMA benchmark-and most high-quality videos were uploaded by professional individuals. In the present study, these professional individuals were defined on the basis of publicly visible healthcare-related identity information and platform verification status. When stratified by uploader type, videos created by professionals consistently outperformed those from non-professional individuals and institutions in both quality scores and engagement metrics. Professional videos were predominantly found on TikTok. Correlation analyses indicated weak to moderate positive associations between most quality indicators and likes, favorites, and shares on both platforms, although the correlation coefficients remained low. Notably, the average JAMA benchmark score was approximately half of the maximum possible score on both platforms. Inter-rater reliability for GQS was acceptable, with a single-measure ICC of 0.632, an average-measure ICC of 0.774, and a quadratic weighted Cohen's kappa of 0.630. The overall quality of PDA-related health information on major Chinese short-video platforms appears to be moderate. TikTok and professional uploaders demonstrated clear advantages in reliability, comprehensibility, and communication effectiveness. Platform attributes and uploader background exert significant influence on video quality and dissemination performance. Future efforts should focus on strengthening platform oversight, encouraging greater involvement of qualified healthcare professionals, and standardizing the disclosure of information sources and conflicts of interest. Such measures are essential for improving the accuracy, quality, and trustworthiness of online cardiovascular health information and for better supporting parents of children with PDA and the general public. These findings should be interpreted as reflecting informational quality, structure, transparency, and understandability rather than independently verified clinical accuracy.
Early recurrence after curative resection remains common in non-small cell lung cancer (NSCLC). We evaluated whether early postoperative trajectories of the prognostic nutritional index (PNI) improve risk stratification. In a single-center prospective cohort of patients undergoing R0 resection for stage I-III NSCLC (2021-2025), 119 were enrolled; 94 who were alive and recurrence-free at 3 months with complete PNI data formed the landmark cohort. PNI was measured preoperatively and during the first 3 postoperative months and calculated as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (/mm3). The primary exposure was 3-month PNI recovery, and the primary endpoint was 2-year recurrence-free survival (RFS) from the 3-month landmark, estimated with Cox models adjusted for stage and adjuvant therapy. Among 94 patients, 51 (54.3%) showed recovered PNI and 43 (45.7%) non-recovered PNI. During follow-up, 27 RFS events occurred, with higher event rates in the non-recovered group (41.9% vs. 17.6%; 2-year RFS 59.2% vs. 82.3%). Non-recovered PNI was independently associated with worse RFS (adjusted hazard ratio 2.3) and improved a clinical model C-index from 0.66 to 0.73. Sensitivity analyses using alternative cutoffs, continuous PNI change, complication adjustment, treatment-timing exclusions, and conservative Cox models were directionally consistent. Failure to recover PNI within 3 months may identify patients at higher risk of recurrence after curative NSCLC resection. Multicenter validation is required before clinical implementation.