This report describes an especially rare postoperative pseudoaneurysm of the sphenopalatine artery following midface advancement using Le Fort III in an Apert syndrome patient. The Apert patient referenced in this report was a 13-year-old boy with severe midface hypoplasia, significant obstructive sleep apnea, and Angle Class III malocclusion. The patient underwent a low Le Fort III osteotomy, subsequently followed by gradual anterior distraction with an external halo distractor. One month postoperatively, the patient experienced recurrent, massive blood loss due to unilateral epistaxis. In order to immediately address life-threatening hemorrhaging and maintain advanced segment stability, the external distractors were removed, and a custom protraction face mask was applied for retention. A computerized tomography angiography showed a 4×3 mm saccular pseudoaneurysm from a branch of the left sphenopalatine artery in the pterygopalatine fossa near the posterior maxillary sinus wall. Careful microcatheterization and embolization achieved complete occlusion with preservation of adjacent collateral flow, resulting in immediate and sustained cessation of epistaxis, hemoglobin stabilization, and recovery without further complication. After 12 weeks of protraction face mask retention, achieved midface advancement remained stable; there was no recurrent bleeding over the next 6 months, and the patient's occlusion was classified as Angle Class II. This case underscores that recurrent severe postoperative epistaxis occurring after Le Fort III distraction requires immediate computerized tomography angiography to detect pseudoaneurysm and supports endovascular embolization as a safe, minimally invasive, highly effective first-line therapy within a multidisciplinary care model.
Intermaxillary fixation (IMF) is commonly performed following orthognathic surgery, including Le Fort I osteotomy and sagittal split ramus osteotomy, to maintain the planned occlusion. Although perioperative pulmonary complications are rare in healthy young adults, we encountered a case of lung abscess that developed from aspiration pneumonia during the period of IMF. Here, we report the case with a review of the literature. The patient was a 22-year-old man with bilateral cleft lip and palate, presenting with class III malocclusion due to maxillary hypoplasia. Orthognathic surgery (Le Fort I osteotomy and sagittal split ramus osteotomy) was performed to improve facial appearance and occlusion. Postoperatively, he developed a fever, and his oxygen saturation decreased. On postoperative day (POD) 8, chest radiography and CT revealed pneumonia in the left lower lobe, and antibiotic therapy was initiated. Despite treatment, his condition persisted, and a repeat CT on POD 15 showed progression to a lung abscess. A string test-positive Klebsiella pneumoniae (Kp) was identified as the causative organism. Upon switching to broad-spectrum antibiotics, the inflammatory response subsided, and antibiotic treatment was completed on POD 43. Severe aspiration pneumonia is rare in young patients without underlying disease. In this case, IMF and infection with a string test-positive Kp led to abscess formation, complicating treatment. This highlights the importance of early detection and treatment of pneumonia during the period of IMF.
Skin cancer remains one of the most preventable yet prevalent malignancies worldwide, with non-melanoma and melanoma skin cancers ranking among the top 5 and top 20 most common cancers, respectively. Rising incidence rates in countries such as the United States and Australia have been linked to high ultraviolet (UV) radiation exposure and modifiable behavioral risk factors. Public health efforts increasingly emphasize sun safety education to reduce UV exposure and mitigate long-term cancer risk. To summarize the current research landscape of intervention strategies for the primary prevention of skin cancer and the study designs used to evaluate these efforts. We conducted a scoping review following PRISMA-ScR guidelines across PubMed, CINAHL, Embase, Cochrane Library, and PsycInfo. Included studies assessed original sun safety programs implemented in school, community, and healthcare settings, focusing on behavior change, accessibility, and long-term impact. This review highlights the variability in intervention design and underscores the need for comprehensive, evidence-based strategies that integrate education with accessible resources. Strengthening these efforts is essential to improving sun safety practices and reducing the global burden of skin cancer.
Zoonotic diseases are a primary threat to military readiness during deployments in the Asia-Pacific region. To characterize these risks, we conducted a multi-site, multi-year 'One Health' biosurveillance study during the Balikatan (BK) 2024 and 2025 exercises in the Philippines, sampling rodents, ectoparasites, and the environment at four key training locations on Luzon Island. A comprehensive biosurveillance study at four BK training sites revealed distinct, evolving, and site-specific zoonotic disease risks that require tailored health protection strategies. The risk is most acute at Clark Air Base, a critical dual-threat hotspot with an active circulation of several pathogenic strains of Leptospira in environment and rodents near the animal support facility and a direct threat from Rickettsia-positive chiggers. Other sites show escalating vector-borne disease threats including Fort Magsaysay Military Reservation transforming into a high-risk area for rickettsial diseases and Camp Aquino showing an emerging scrub typhus risk on top of its persistent Leptospira circulation. Even limited surveillance at Naval Operating Base Subic confirmed a mixed-threat environment where both Leptospira and rickettsial pathogens are co-circulating. Crucially, the detection of environmental Leptospira during the dry season is a key predictive indicator for a probable surge in transmission risk during the subsequent wet season, demanding proactive mitigation efforts.
Orthognathic surgery is performed to improve facial esthetics and function in patients with dentofacial deformities. This study aimed to evaluate the impact of orthognathic surgery on perceived facial age using an artificial intelligence (AI)-based age-estimation tool and to examine accompanying changes in self-rated flourishing and social appearance anxiety. This retrospective, single-arm, before-and-after study included 27 patients who underwent bilateral sagittal split ramus osteotomy (BSSRO) and/or Le Fort I osteotomy. Preoperative and postoperative standardized frontal photographs were analyzed with the AI-based application "AgeBot: How Old Do I Look?". Participants also completed the Social Appearance Anxiety Scale (SAAS) and the Flourishing Scale (FS; Turkish adaptation by Telef). Both questionnaires were completed at a single postoperative interview-first for the remembered preoperative state and then for the current postoperative state-so the psychosocial pre-post comparisons reflect retrospectively perceived change. Normality was assessed on the paired differences; the primary AI-age outcome was analyzed with the paired t-test (confirmed by the Wilcoxon signed-rank test) and the psychosocial outcomes with the Wilcoxon signed-rank test, with effect sizes reported. A data-informed sensitivity analysis, rather than an a priori power calculation, accompanied the primary outcome. AI-estimated facial age did not change significantly after surgery (mean difference [preoperative-postoperative] 0.11 ± 2.49 years, 95% CI -0.87 to 1.09, p = 0.818; Cohen's dz = 0.04), and the confidence interval excluded the previously reported 1.31-year reduction. Exploratory change-score comparisons showed no significant differences by sex or smoking status. Postoperative SAAS scores were lower than retrospective preoperative scores (median 37 [IQR 24.5-42.0] vs. 51 [43.0-56.0]; Z = -4.07, p < 0.001, r = 0.55), and postoperative FS scores were higher (median 46 [40.0-51.5] vs. 45 [38.5-45.0]; Z = -2.45, p = 0.014, r = 0.37). Orthognathic surgery was not associated with a statistically significant change in AI-estimated facial age in this small cohort. More favorable social appearance anxiety and flourishing scores were observed following treatment, but the retrospective, uncontrolled assessment precludes causal attribution. AI-assisted facial age estimation may complement patient-reported outcomes, but validated, repeatability-tested tools are required before it can serve as a primary outcome measure.
Elephant endotheliotropic herpesvirus (EEHV) is endemic in Asian elephants and can cause fatal hemorrhagic disease (HD) in juveniles, with calves aged 1-8 years being most vulnerable, particularly following the decline of maternal antibodies. Current supportive treatments, which commonly include fluids, plasma infusions, and human anti-herpesvirus drugs, are not consistently effective, highlighting the urgent need for preventative strategies. To address this challenge, we generated an EEHV1A multi-antigen mRNA vaccine targeting four conserved herpesvirus entry proteins (gB, gH, gL, and gO), which elicited robust humoral and cellular immune responses in mice without adverse effects. Based on these preclinical findings, a vaccine trial was conducted in nine Asian elephants, comprising three seropositive and six seronegative individuals. Animals received up to four 400 μg doses intramuscularly 3 weeks apart, with serum samples collected at baseline (day 0), post-booster (day 42), and monthly through day 192. Seropositive elephants demonstrated anamnestic responses with increased antibody levels to all four vaccine antigens individually. Seronegative elephants responded more robustly to gH and gL versus variable responses to gB and gO. Enzyme-linked immunosorbent assays (ELISAs) detecting the gH/gL/gO trimer indicate sustained antibody level increases in both sero-positive and sero-negative groups, persisting up to 192 days post-vaccination in seropositive elephants. Notably, post-vaccine titers against the trimer in some seronegative elephants reached up to 50% of baseline levels observed in EEHV-experienced subadult and adult elephants. These findings represent a critical advancement toward an effective EEHV1A vaccine to reduce HD mortality and support Asian elephant conservation efforts. Elephant endotheliotropic herpesvirus (EEHV) causes fatal hemorrhagic disease in 65% of infected juvenile Asian elephants, critically threatening this endangered species with fewer than 50,000 individuals remaining globally. This study demonstrates the first successful mRNA vaccine application in elephants, targeting EEHV1A glycoproteins essential for viral attachment and entry. The vaccine elicited sustained antibody responses for up to 6 months in both EEHV-naive and previously infected elephants, with post-vaccination levels in some seronegative animals reaching 50% of those in chronically infected adults. These immunological data provide a critical baseline understanding of protective immunity, as demonstrated in a companion case report where two vaccinated elephants from this cohort survived subsequent wild-type EEHV1A infection without hemorrhagic disease. This work establishes mRNA vaccination as a viable conservation strategy, providing a scalable platform adaptable for other EEHV subtypes and representing a crucial advancement toward preventing EEHV mortality in endangered elephants.
To evaluate rates of vision screening failure, eye exam completion, eyeglass prescribing, and follow-up recommendations from a school-based vision program (SBVP). Retrospective cross-sectional analysis. Pre-kindergarten through 5th grade students (ages 4-13) who underwent school-based screening in Fort Worth, Texas in 2022-2024. Students who failed screening were offered school-based eye exams. Parent-reported demographics and school-level economic disadvantage (Free and Reduced-Price Meals; FARM%) were extracted. Mixed-effects logistic regression evaluated associations of grade, gender, race, ethnicity, eyeglass wear at screening, and FARM% for screening failure, eye exam after failure, and eyeglass prescription among exam completers. Associations between ocular diagnoses and follow-up interval, categorized as <6 months or ≥6 months, were tested using chi-square or Fisher's exact tests. Rates of screening failure, eye exam completion, eyeglass prescription, and follow-up interval. Among 41,236 students screened across 81 schools (median FARM%: 93.9%), 64.0% were Hispanic. Overall, 8,682 (21.1%) failed screening; 3,873 (44.6%) completed an eye exam. Hispanic and Black students had higher odds of screening failure (OR 1.35, 95% CI 1.25-1.46; 1.36, 95% CI 1.25-1.48, respectively) compared to non-Hispanic and non-Black students, respectively. After screening failure, Hispanic students had higher odds of completing an eye exam (OR 1.27, 95% CI 1.08-1.48), whereas Black students had lower odds (OR 0.82, 95% CI 0.69-0.97). Students with greater school-level economic disadvantage had higher odds of screening failure (OR 1.17 per 10% FARM increase, 95% CI 1.14-1.21) and completing an exam after failure (OR 1.24 per 10% increase, 95% CI 1.13-1.38). Among 3,767 students examined, 14.2% were recommended follow-up <6 months. Earlier follow-up was more common among those with amblyopia/amblyopia suspect (68.9% vs 6.6%) and strabismus (64.1% vs 13.3%) compared to those without (both p<0.001). In a predominantly Hispanic, economically disadvantaged district, this SBVP identified substantial unmet vision needs with disparities in screening failure and eye exam completion. Earlier follow-up recommendations were more common for high-risk diagnoses. Future work should focus on understanding whether students successfully connect to follow-up care after referral and developing guidelines to support children with ongoing eye care needs beyond SBVPs.
The U.S. Department of Veterans Affairs (VA) has funded intramural research for over 100 years. A growing number of research funders, including VA, have placed an increasing emphasis on engaging patients in the research process and have invested in engagement infrastructure; however, few accounts are available that detail that infrastructure. This article describes the process and outcomes to plan, build, operate, and evaluate an Overdose Prevention Veteran Engagement (VE) Panel. We employed multiple methods to document panel creation and operation, including authors' experiences, polls, and surveys. A nine-member Planning Committee, including both researchers and Veterans, worked over 4 months to establish processes for panel member recruitment, selection, and orientation. Ongoing service practices were created and documented, including researcher recruitment, meeting planning, and continuous improvement efforts. Authors' reflections on contributors to panel success were solicited and shared. A 12-member national VE panel was created. Three orientation sessions prepared members for their responsibilities, helped them feel confident in their roles, and connect with each other. After orientation, the panel met with unique research teams on seven occasions (average meeting attendance, 78%). Both Veterans and researchers reported high satisfaction via post-meeting evaluations. All consultations produced Veteran-inspired changes to researchers' projects. VA partners created an engagement consultation service bringing researchers together with Veteran patients who have both lived experience with drug use and an interest in reducing harms from substance use. Detailed processes and tools used to develop this successful engagement infrastructure may be adapted for use in other settings or with other pressing public health issues. Veterans with lived experience related to overdose prevention collaborated on the design and operation of the patient engagement service described in this work and as co-authors of this article.
Seasonal heat stress (HS) is a pervasive environmental challenge with profound consequences for female reproductive physiology, affecting ovarian function, oocyte maturation, and early embryonic development. At the ovarian level, HS disrupts follicular growth, impairs steroidogenesis, and compromises granulosa cell function, thereby creating a suboptimal microenvironment that reduces oocyte competence. In oocytes, HS induces oxidative stress, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, spindle abnormalities, chromosomal missegregation, and persistent epigenetic alterations. These disruptions extend into early embryonic development, where redox imbalance, apoptosis, ER stress, and altered lineage allocation reduce cleavage and blastocyst formation, compromise trophectoderm and inner cell mass integrity, and impair implantation potential. Maternal heat exposure further exacerbates embryonic vulnerability by altering the oviductal and uterine environment, reducing embryotrophic factors and antioxidant defenses, and ultimately influencing offspring phenotype and fertility, potentially across generations. Accordingly, this review aims to synthesize current knowledge on the physiological and molecular impacts of heat stress on ovarian function, oocyte maturation, and early embryonic development. To this end, we consider studies conducted under both in vivo and in vitro conditions, highlighting shared and distinct mechanisms of thermal stress at the organ and cellular levels to identify potential targets for intervention.
Balloon dilation of the Eustachian tube (BDET) is a safe, effective office-based procedure for treating chronic obstructive and barochallenge-induced Eustachian tube dysfunction. Performed under local anesthesia in minutes, it offers a cost-effective alternative to the operating room. Success depends on careful patient selection, thorough preoperative workup, and appropriate anesthetic protocols, including topical and injectable agents to manage pain, vasovagal responses, and barometric pressure changes. Angled endoscopes improve outcomes by ensuring accurate balloon placement. Complications are generally minor and self-limiting, though rare serious events have been reported. With appropriate technique, BDET can reliably improve both objective and subjective patient outcomes.
Continuous monitoring of climatic variables is essential for precision viticulture and data-driven decision support systems. However, agricultural sensor networks are frequently affected by missing data due to hardware failures, communication issues, or maintenance interruptions. In this work, we propose a spatio-temporal graph-based autoencoder for reconstructing missing temperature and relative humidity time series collected from a five-node vineyard sensor network over a two-year period. The model combines a GRU-based temporal encoder, augmented with a time-decay imputation mechanism applied to the input data, with a GraphSAGE spatial module, enabling the joint exploitation of temporal dynamics and inter-node spatial correlations. Experimental results on real-world data show that the proposed approach achieves accurate reconstruction under controlled missing-data scenarios generated through structured artificial masking. For moderate corruption levels (p=0.3), the model attains reconstruction losses of 0.003 for temperature and 0.005 for humidity using short temporal windows (L = 36~3 h), corresponding to MAE values below 0.03 °C and 0.1%, respectively. Even at higher corruption levels (p=0.7), performance remains stable, with losses below 0.008 and 0.011, and MAE values within 0.05 °C and 0.17%. The results highlight a trade-off between temporal context and reconstruction accuracy: shorter windows yield lower absolute errors under moderate corruption whereas, under extreme data loss (p=0.9), the longer windows (L = 144~12 h) reduce the composite temperature reconstruction loss from 0.027 to 0.021. Additionally, temperature is consistently reconstructed more accurately than humidity, reflecting its smoother dynamics and stronger spatial coherence.
Sleep health is a multi-faceted biopsychosocial concept that affects well-being across the lifespan. Insufficient sleep occurs in large numbers of children and there is emerging evidence for the influence of socioecological factors and adverse childhood experiences (ACEs). The purpose of this study was to determine the influence of adverse childhood experiences on sleep health in preschool age children as mediated by family interaction habits and outdoor play. Our secondary analysis of the 2023 National Survey of Children's Health used the weighted dataset filtered for children ages 3-5 years. Sixty-six percent of parents reported adequate child sleep; nearly 89% of parents reported consistent bedtimes. Seventy-one percent reported no ACEs. Most children had one or more hours of outdoor play each day. Daily family interaction (reading, singing, stories, meals) occurred in approximately half of families. Structural equation modeling results indicated that the negative effects of ACEs on consistent bedtime were mediated by reading aloud and family meals, while adequate sleep duration was mediated by reading aloud and singing/storytelling. These findings represent a promising picture of young children and families, and insight into a window of time during child development when family interaction can positively affect sleep health in spite of adverse childhood experiences.
Workforce shortages, training gaps, and role ambiguity among primary care providers (PCPs) contribute to delays in pediatric autism identification and management. This study's aim is to examine PCPs' beliefs, intentions, behaviors, and capabilities related to pediatric autism care and identify factors associated with workforce readiness. Guided by the Reasoned Action Approach, this cross-sectional survey included 107 PCPs nationwide. The questionnaire assessed Beliefs, Intentions, Behaviors, and Capabilities. Multivariate analyses tested differences by provider type, years in practice, and practice setting, with follow-up analysis of variance used to identify contributing items. Linear discriminant analysis and path modeling examined interdomain relationships. Provider type was the most consistent predictor of differences across domains. Significant multivariate effects were observed for Beliefs and Capabilities, whereas fewer differences emerged for Intentions and Behaviors. Nurse practitioners demonstrated greater alignment across domains compared with physicians and physician assistants but reported lower diagnostic confidence. Practice setting influenced referral behaviors, with rural providers reporting greater reliance on specialists. Path analysis indicated that Capabilities mediated the relationship between Beliefs and both Intentions and Behaviors. Primary care providers readiness for autism care varied primarily by provider type, with additional influence from practice setting and limited effects of years in practice. Although nurse practitioners demonstrated a consistent readiness profile, gaps in diagnostic confidence may constrain independent management. Targeted training, decision-support tools, and tiered diagnostic models may strengthen PCP capacity and support earlier autism identification and management in primary care.
There is evidence that nitric oxide deficiency occurs in mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and may result in impaired blood perfusion in small blood vessels, contributing to stroke-like episodes (SLEs). The primary aim of this phase one study was to estimate the maximum tolerated dose (MTD) of L-citrulline in adults with MELAS. The primary safety outcome was the occurrence of a dose limiting toxicity (DLT) in the first eight weeks after treatment initiation. Secondary outcomes included changes in cerebral blood flow (CBF), cerebrovascular reactivity (CVR), and plasma citrulline, arginine, and ornithine levels from baseline to end of treatment (week four). Plasma guanidino compounds were assessed from baseline to week one for potential arginine toxicity and plasma lactate and alanine from baseline to end of treatment as pharmacodynamic biomarkers. Ten consecutive patients were screened, enrolled and assigned to the following doses: 10 g (n = 1), 20 g (n = 1), 30 g (n = 2), and 40 g (n = 6). There were no DLTs observed with any of the doses. However, analysis of plasma guanidino compounds demonstrated analyte outliers (Z-scores >2) with higher doses of L-citrulline (30 and 40 g). CBF increased from baseline in seven study participants, six of whom were on the highest dose. The highest CBF increase was observed in the occipital region. With the highest dose of L-citrulline, substantial increases in plasma arginine and citrulline were observed at week four when compared to baseline. While no DLTs were observed, the increase of guanidino compounds with 30 g and 40 g of L-citrulline needs to be further interrogated with serial measurements in a future study to ensure safety of these doses and determine whether the increase is sustained long term. A randomized placebo-controlled trial will be required to evaluate the efficacy of L-citrulline in individuals with MELAS.
Elevated low-density lipoprotein cholesterol (LDL-C) is a modifiable risk factor for cardiovascular disease, the leading cause of premature death worldwide. Assessing the LDL-C-related burden is critical for guiding prevention and treatment strategies. To estimate the global, regional, and national burden of ischemic heart disease and ischemic stroke attributable to elevated LDL-C (relative to 35-54 mg/dL) from 1990 to 2023 and to quantify the contributions of population growth, aging, risk-deleted burden, and exposure changes to burden trends. This comparative risk assessment, part of the Global Burden of Disease Study 2023, estimated population-level LDL-C exposure and associated health loss in 204 countries and territories. Mean LDL-C levels were estimated using spatiotemporal gaussian process regression based on 806 studies across 161 countries. Relative risks were derived from meta-analyses of 38 randomized clinical trials. Population-attributable fractions for deaths and disability-adjusted life-years (DALYs) were estimated by age and sex for adults aged 25 years or older from 1990 to 2023, with 95% uncertainty intervals. Population-level LDL-C concentrations. Population-attributable fractions, counts, and rates (all ages and age standardized per 100 000) of LDL-C-attributable deaths and DALYs from ischemic heart disease and ischemic stroke, with uncertainty intervals. In 2023, elevated LDL-C accounted for 3.6 million deaths (95% uncertainty interval, 2.2-5.4 million; 6.0% of global mortality) and 90.7 million DALYs (95% uncertainty interval, 58.9-123.3 million; 3.2% of DALYs). Although global all-ages rates remained stable, age-standardized death and DALY rates decreased by 45.6% and 39.5%, respectively, since 1990. In 2023, age-standardized LDL-C-attributable DALY rates were highest in Eastern Europe and lowest in high-income Asia-Pacific. One-third of the global LDL-C burden occurred in India and China. Population growth and aging drove the increasing burden, with notable regional disparities in LDL-C exposure and risk-deleted DALY rates shifting toward middle-sociodemographic settings. Despite declining age-standardized rates, the absolute LDL-C burden has increased since 1990 due to demographic changes and has shifted toward middle-sociodemographic countries. Measurement and surveillance gaps persist. Strengthened prevention, diagnosis, and treatment access strategies are essential to mitigate the health burden of LDL-C.
Future large-scale combat operations, high-impact domestic disasters, and infrastructure-disrupting crises will generate casualty volumes and system stress far exceeding those experienced during the conflicts occurring during the previous two decades. These threats will transcend the traditional distinctions between military and civilian healthcare systems. They will necessitate an integrated national response capable of absorbing sustained casualty surges and preserving access to care for the civilian population. At the 2026 Eastern Association for the Surgery of Trauma Annual Scientific Assembly, a multidisciplinary short course entitled "Forging the Frontlines at Home: Integrating Military-Civilian Systems for National Readiness and Resilience" convened military, civilian, academic, and policy leaders to examine readiness gaps and propose actionable pathways to facilitate military-civilian integration. This article synthesizes key themes from that program across three domains: (1) defining the operational problem space, (2) coordinating a synchronized national response, and (3) understanding the financial and administrative consequences of large-scale casualty care. Together, these perspectives highlight that national casualty readiness for combat casualty care needs to be a core component of domestic resilience.
Routine prophylactic antibiotic use is not recommended following uncomplicated vaginal births because of the global threat of antimicrobial resistance (AMR). The study was conducted to determine the magnitude and underlying reasons for routine antibiotic use following uncomplicated vaginal births. We conducted an explanatory sequential study among women with uncomplicated vaginal births. We interviewed 370 women following facility discharge using interviewer-administered questionnaires. Eight in-depth interviews were conducted among midwives and clinical officers. Descriptive statistics and thematic analysis were used to analyse the data. The study obtained ethical clearance. The median age of the participants was 25 (interquartile range 20-30). Out of the 370 women, 34% (n=127/370) had perineal tears, 19% (n=69/370) had preterm prelabour rupture of membranes and 6% (n=23/370) had preterm labour. Almost all (99%) women with uncomplicated vaginal births were prescribed prophylactic antibiotics during facility discharge. A combination of amoxicillin and metronidazole (49%, n=181/366) and ampiclox and metronidazole (40%, n=147/366) were the commonly prescribed drugs during discharge. Antibiotics were routinely given to prevent puerperal infections. Perineal tears, episiotomies and unsterile environment were additional justification given for antibiotic use. Sterility was seen to be untenable which necessitated antibiotic use to cover for gaps in maintaining infection prevention and control measures. In some cases, antibiotics were considered necessary regardless of the absence of medical indications and the risk of AMR. Healthcare providers had inadequate awareness of the risks of AMR and the guidelines on antibiotic use during discharge. Widespread routine antibiotic use after uncomplicated vaginal births reflected practices of overmedicalisation of childbirth and limited awareness of AMR. Developing local policies, strengthening infection prevention and control measures and innovating antimicrobial stewardship initiatives may be critical in reducing unnecessary antibiotic use after delivery.
Supplements are widely perceived as safe and beneficial; yet in oncology, this assumption is questionable. Clinical trials over the past few decades have often produced disappointing results, raising a critical question: are these agents used correctly, or could they inadvertently cause harm? This review examines supplements frequently used in cancer care-such as oral vitamin C, berberine, N-acetylcysteine, vitamin D, vitamin E, melatonin, polyphenols, alpha-lipoic acid, selenium, and coenzyme Q10-which can act as tumor suppressors or promoters depending on dose, route, and disease stage. We examine their dual antioxidant and pro-oxidant properties, revealing that therapeutic outcomes are shaped not only by the molecule itself, but also by bioavailability, dosing thresholds, and the tumor redox environment. Building on these insights, we propose that four factors may be considered to guide clinical use: ensure that anticancer effects are not overshadowed by antioxidant activity, achieve sufficient bioavailability, confirm pro-oxidant concentrations where possible, and prioritize supplements that target the respiration-supported non-OxPhos pathways. By framing supplements as context-dependent redox modulators rather than universally beneficial agents, this review provides a mechanistically grounded framework for informing future research and safer, more effective integrative oncology strategies.
Background/Objectives: Stem cells with the ability to differentiate into other cell types and self-renewal afford a powerful apparatus for the healthcare system to replace and rejuvenate damaged tissues and organs in the treatment of various diseases. For the last few decades, stem cell therapy (SCT) has evolved from being an experimental approach to a recognized clinical treatment. SCT and regenerative medicine have garnered tremendous attention and become prominent tools, especially in treating chronic and acute disease and addressing organ failures, and in their repair and replacement, which are directly associated with human health, life, and longevity. Methods: In this review, after providing a brief history and need for the SCT, the employed delivery techniques utilizing various biomaterials, as well as recent developments in nanotechnological methods, are presented. It is focused on the current literature for the recent progress of stem cell therapy and tissue engineering for the application fields in neurological, ophthalmological, cardiovascular, orthopedic, and oncology, followed by the challenges associated with their applications. Results: In addition to safety concerns, challenges such as uncontrollable differentiations, genetic and epigenetic instability, limited cell survival and integration, immunological rejections, scaling and manufacturing drawbacks, as well as unpredictable behaviors and clinical limitations were reviewed. Conclusions: Future aspects with respect to regenerative medicine and tissue engineering, gene editing and personalized therapies, immunomodulation and anti-inflammatory applications, as well as neuroregeneration and treatment of neurodegenerative disorders are reflected.
Small interfering RNAs (siRNAs) are important regulators of gene expression with well-established roles in pathogen defense. Yet, their specific roles in antibacterial immunity are not well understood. Here, we identify an siRNA pathway involved in repressing antibacterial innate immunity in Caenorhabditis elegans. We show that genes required for the biogenesis or function of WAGO Argonaute-associated siRNAs, called 22G-RNAs, function in a common genetic pathway with the immune-suppressive transcription elongation and splicing factor TCER-1 to inhibit immunity. Loss of tcer-1 led to reduced levels of 22G-RNAs from a subset of WAGO targets, while mutations in several WAGO 22G-RNA pathway genes phenocopied the enhanced immunoresistance of tcer-1 mutants, suggesting a shared regulatory module. Integrative 22G-RNA-mRNA analyses and molecular genetic studies show that this module does not induce widespread gene silencing, but instead targets a restricted set of immune-relevant effectors, including scrm-4, which encodes a conserved phospholipid translocase that promotes host resistance. Together, our findings establish endogenous WAGO 22G-RNAs as repressors of antibacterial immunity and identify TCER-1 as a physiological regulator that promotes 22G-RNA biogenesis to constrain host defense. The results uncover a previously unrecognized small RNA-dependent mechanism linking transcription, metabolism, and antibacterial innate immunity.