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Depression is a prevalent mental health issue among older adults, often exacerbated by chronic illness, social isolation, and age-related cognitive changes. Standard treatments (e.g., pharmacotherapy and cognitive behavioral therapy) may not always be effective, acceptable, or accessible for this population. Mindfulness-Based Cognitive Therapy (MBCT) integrates mindfulness practices with cognitive therapy and may offer a scalable, non-pharmacological approach to late-life depression. To evaluate the effectiveness of MBCT on depressive symptoms in adults aged ≥60 years. Secondary outcomes were anxiety symptoms and quality-of-life indicators when reported. We searched PubMed (MEDLINE) and Scopus for randomized controlled trials (RCTs) comparing MBCT with control conditions in adults aged ≥60 years. Random-effects meta-analyses were conducted using standardized mean differences (Hedges g) for depressive symptom severity across scales. Because fewer than 10 studies were available per outcome, publication bias was not formally assessed. Three RCTs (total n = 178) met inclusion criteria. Two RCTs (n = 121) contributed data to the post-intervention meta-analysis of depressive symptoms. MBCT was associated with significantly lower depressive symptom severity than control conditions (pooled Hedges g = -0.92, 95% CI -1.30 to -0.55; I2 = 0%). Evidence for anxiety and quality-of-life outcomes was limited and could not be pooled; no eligible trials reported relapse/recurrence outcomes. MBCT may reduce depressive symptoms in older adults compared with control conditions, but the evidence base remains small and heterogeneous in measures and comparators. Larger, methodologically rigorous trials with standardized outcomes and longer follow-up are needed to clarify effectiveness for anxiety, quality of life, and durability of effects.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) represent a major advancement in obesity treatment, offering robust efficacy in weight loss and metabolic regulation. Beyond these effects, emerging evidence indicates that GLP-1 RAs also modulate appetite, reward sensitivity, and self-regulation, domains that intersect with behavioral and psychological functioning. This review adopts a biopsychosocial perspective to examine how GLP-1 RAs interact with eating behavior, mood, identity, and self-regulation, particularly in individuals with binge eating disorder (BED) or other psychiatric comorbidities. A clinical framework is proposed to integrate pharmacotherapy with lifestyle and psychological interventions. The temporary reduction in appetite and food reward may create a "low-drive window" in which behavioral strategies such as self-monitoring or stimulus control become more effective. However, high emotional eating, mood symptoms, or identity conflicts may moderate treatment response. Given the high prevalence of psychiatric comorbidities, structured screening using tools like the Patient Health Questionnaire-9 (PHQ-9) or Binge Eating Scale (BES) is recommended. A stepped-care approach from brief digital interventions to formal psychotherapy may help address varying support needs. Crucially, weight regain after discontinuation is common. The review discusses behavioral, psychological, and social mechanisms of relapse and highlights strategies for long-term stabilization. These include emotion regulation, body image work, and maintenance-focused behavioral interventions. GLP-1 RAs should therefore be seen not as standalone treatments but as facilitators of self-directed, sustainable change within integrated care models. Future research should define composite outcomes, explore digital tools for relapse prevention, and develop adaptive pathways tailored to individual psychological profiles.

Fast-track and outpatient surgery have significantly reduced postoperative hospital stays across many surgical specialties. As a result, patients are increasingly discharged with strong opioid prescriptions, contributing to the global opioid crisis. Careful follow-up and opioid tapering are essential. While multidisciplinary Transitional Pain Services (TPS), involving pain specialists, psychologists, and physiotherapists, have shown promise, their widespread implementation is limited by costs and complexity. To address these barriers, we implemented a nurse-led TPS, supervised by a pain specialist and embedded within a multidisciplinary pain clinic. The aim of this study was to evaluate its effectiveness in clinical practice, including a mechanism-based treatment approach to postsurgical pain aimed at opioid tapering and optimizing the use of adjuvant analgesics. This observational cohort study included postoperative patients discharged with >20 mg oral oxycodone equivalents and/or those experiencing or at risk for neuropathic pain. Referred patients received telephone consultations by a nurse practitioner (NP) one to two weeks post-discharge. Each consultation included assessment of pain severity, neuropathic characteristics (using the first two items of the DN4 questionnaire), current analgesic use, and willingness to taper opioids. Patient education and motivational interviewing techniques were employed to support opioid tapering. Descriptive statistics and paired t-tests were used to analyze the data. Between June 2019 and July 2025, 243 patients were enrolled in the TPS. Following nurse-led counseling, 73 % of patients discontinued opioid use entirely, 23 % significantly tapered their dosage (from mean 101-43 mg oral oxycodone equivalent), and 4 % continued at the same dose. Anti-neuropathic medications were initiated in 22 % of patients. A nurse-led Transitional Pain Service is a feasible and effective approach to support opioid tapering in postoperative patients. In addition, early screening for neuropathic pain allows for targeted treatment. This model offers a scalable alternative to traditional multidisciplinary TPS programs.

Targeted delivery of drugs and hyperthermia in cardiovascular disease demand the accurate delivery of nanoparticles in complex arterial geometries. This paper introduces combined hybrid computational model that concomitantly examines the combined impact of nanoparticle radius and interparticle spacing on the thermal and mass transport characteristics of ternary bio-nanofluid flow under magnetohydrodynamic (MHD) effect. The ternary fluid is composed of blood fluid with suspended nanoparticles such as gold (Au), silver (Ag) silica (SiO2). The mathematical model accounts for geometric properties of nanoparticles such as nanoparticles radius and interparticle spacing for their practical utility for several medical interventions. The numerical analysis is based on hybrid computational strategy, where the solutions are determined through the bvp4c numerical solver and then a novel supervised multi hidden layers Artificial neural network (ANN) is integrated. The proposed model has a high predictive capability with an exceptionally high accuracy with the lowest Mean squared error and ideal regression coefficient MSE=9.6327×10-11, Gradient=9.5681e-08, Mu=1e-09, and R2=1.0. Some of the main findings indicate that less spacing between particles (h=0.1) leads to continuous networks of thermal percolation, which enhance the thermal conductivity by up to 35% to improve the efficiency of hyperthermia, whereas the larger nanoparticles (radius ≥1.5) offer a higher drug-loading capacity, yet the rate of heat transfer decreases by 15-20%. Optimization of the magnetic parameter (M=0.1-0.7) also decreases flow velocity by 28% and extends the nanoparticle residence time at the stenosis by 35% which allows sustained drug delivery, results directly applicable to clinical-strength (1.5-3T) MRI-guided interventions. Radiation parameter (Rd=0.5-2.5) increases temperature of the arteries by 15-20% giving controllable thermal modulation to applications of hyperthermia. The proposed model predicts that optimal nanoparticle preparations (50 nm radius, 20 nm spacing) have to potential to lower the rate of restenosis by 30-40% in relation to traditional drug-eluting stents. The purpose of such an integrated computational-machine learning systems is to give quantitative advice to stent coating design, nanoparticle formulation, and optimization of treatment protocols, and has been directly used in biomedical interventions. The results can be used to offer practical advice to stent manufactures, interventional radiologist and pharmaceutical developers to create evidence-based cardiovascular therapy of the next generation.

Cancer cells undergo intense metabolic reprogramming to provide fast proliferation, persistence, immune evasion, and resistance to therapy. Malignant cells often rely on exogenous lipids and maintaining strict metabolic regulation. Cancer cells stimulate de novo lipogenesis, lipid uptake, and storage pathways even in nutrient-limited microenvironments. This review combines current knowledge of cancer types, highlights vital enzymatic regulators and translational prospects. A comprehensive literature review was conducted, focusing on the complex relationship between lipid metabolic pathways and oncogenesis. This review focuses on de novo fatty acid synthesis, lipid uptake mechanisms, and cholesterol regulation in cancer. Important therapeutic targets, including Acetyl-CoA carboxylase (ACC), ATP citrate lyase (ACLY), fatty acid synthase (FASN), and sterol regulatory element-binding proteins (SREBPs) were evaluated. It also emphasizes the role in resistance to chemotherapy, radiotherapy, and specific targeted therapies. Several studies have revealed that dysregulated lipid metabolism contributes to tumour growth, immune evasion, and treatment resistance. Evidence from preclinical and clinical studies revealed that treatments targeting small-molecule inhibitors of FASN, ACLY, SREBPs and CD36, show promising outcomes. Alterations in lipid metabolic pathways serve as critical nodes in oncogenic networks and immune modulation. The inclusion of dietetaey modifications and nanoparticle-conjugated drug delivery provides encouraging results against tumour development. This review combines the roles of key regulators, therapeutic targets, and biomarker approaches that can update future therapies. However, challenges persist, including drug-induced toxicity, metabolic changes, and tumour heterogeneity.

Multiple myeloma (MM) is best understood as a dynamically evolving genomic ecosystem shaped by inherited susceptibility, early oncogenic events, and continuous selective pressures. We propose an evolutionary genomics framework integrating germline risk, disease initiation, clonal diversification, and therapeutic adaptation into a unified model of MM biology. Polygenic risk burden, rare predisposing variants, and alterations in DNA repair and telomere pathways create a permissive background that influences precursor states and immune interactions. Primary cytogenetic events, particularly immunoglobulin heavy chain (IgH) translocations and hyperdiploidy, establish biologically distinct founding clones and constrain subsequent evolutionary trajectories. Disease progression is driven by secondary chromosomal alterations, copy number changes, MYC activation, TP53 loss, and structural rearrangements, promoting genomic instability and transcriptional plasticity. Longitudinal studies reveal branching clonal architectures shaped by treatment-driven selection. Integrating germline and somatic landscapes within an evolution-aware precision framework may improve risk stratification, anticipate high-risk trajectories, and support adaptive strategies to achieve more durable disease control. While polygenic risk scores (PRS) provide insight into inherited susceptibility, they are not yet clinically actionable for risk stratification or screening in MM and currently remain research tools. This framework provides a clinically oriented basis for applying genomic biomarkers to risk stratification, treatment selection, and longitudinal monitoring.

Antimicrobial resistance (AMR) is a major global public health threat, undermining the efficacy of commonly used antibiotics. Resistance patterns differ across bacterial taxa, including Enterobacteriaceae, non-fermenting Gram-negative bacilli, and Gram-positive cocci. This study aimed to provide a comparative analysis of antimicrobial susceptibility among reference strains with defined susceptible and resistant phenotypes, alongside selected clinical isolates, to evaluate the preservation of phenotypic traits and the impact of antibiotic use. Reference susceptibility strains exhibited high susceptibility across most antibiotics, whereas resistant reference strains demonstrated multidrug resistance. Among Enterobacteriaceae, reference strains harboring ESBL and AmpC mechanisms displayed resistance to penicillins, cephalosporins, and carbapenems. Non-fermenters, including Pseudomonas aeruginosa and Acinetobacter baumannii, showed both intrinsic and acquired resistance to multiple classes, particularly carbapenems and fluoroquinolones. Gram-positive cocci largely retained susceptibility to glycopeptides and linezolid, while MRSA, high-level aminoglycoside-resistant enterococci, and penicillin-resistant Streptococcus pneumoniae posed significant therapeutic challenges. Comparative analysis revealed that antimicrobial susceptibility is influenced not only by bacterial taxonomy but also by patterns of uncontrolled or inappropriate antibiotic use. Clinical strains of Klebsiella pneumoniae and Streptococcus pneumoniae displayed reduced and more variable susceptibility compared to the predictable profiles of reference strains. These findings highlight the importance of continuous surveillance, strict adherence to antimicrobial stewardship, and the use of standardized reference strains to ensure reliable susceptibility testing. Early detection of emerging resistance patterns is essential to guide effective therapy and mitigate the public health impact of multidrug-resistant pathogens.

Seizures exist on a clinical spectrum, and providers must adopt a nuanced yet assertive treatment approach, as the transition from benign to life-threatening can occur rapidly. Critical care transport teams are moving these patients more frequently as neuro-specialty care continues to concentrate at quaternary centers and rural health facilities face resource challenges. Patients with seizures can have a variety of physical and physiologic symptoms, and transport crews must be aware of the more subtle symptoms as to intervene appropriately. The priority in seizure management is stopping the seizure, starting with benzodiazepine administration and then escalating to second-line anti-epileptics if benzodiazepines are ineffective. The longer seizure activity continues, the more difficult it is to stop, and the risk of permanent neuronal damage increases. Additional priorities include patient safety/positioning and airway management. Critical care transport crews should be prepared to perform advanced airway management in patients who present in status epilepticus and should get the patient to a facility with magnetic resonance imaging, electroencephalography, and neurocritical care resources. The unique environment of air transport makes management and assessment of these patients especially challenging, and we provide updated guidance to consider.

In Norway, helicopter emergency medical services (HEMS) are dispatched for suspected cerebral stroke if intravenous thrombolysis may be administered within 4.5 hours of symptom onset, and it reduces time of transport by ≥30 minutes compared with basic emergency medical services (EMS). However, cerebral stroke presents with heterogeneous symptoms; therefore, identification by emergency dispatchers can be difficult. The primary outcome was the positive predictive value for stroke among patients with suspected stroke for whom HEMS was dispatched. Secondary outcomes included rates of prehospital interventions, quality indicator fulfillment, and rates of selected in-hospital interventions within time limits. We conducted a retrospective cohort study using aggregated prehospital and in-hospital data from an electronic patient journal. It included 161 primary missions from the HEMS base in Trondheim, where HEMS was deployed on the index criterion of cerebral stroke set by the Emergency Medical Coordination Center between 2022 and 2024. Of all primary missions, 14% (n = 162) were because of suspected stroke. A total of 75 patients (47%) were diagnosed with having stroke, whereas 12 (7%) were diagnosed with having transient ischemic attack. In 7% of cases, an advanced intervention that requires a physician was performed. A total of 40 patients (25%) received intravenous thrombolysis and/or endovascular thrombectomy. Stroke was confirmed in 47% of HEMS dispatches for suspected stroke. HEMS likely reduced transport time by ≥30 minutes for most patients, whereas prehospital advanced interventions were rarely performed. Further studies on index use and comparative studies of HEMS and EMS dispatches could help strengthen patient selection and optimize resource utilization.

Trivalent chromium is an essential trace element involved in carbohydrate and lipid metabolism. The widespread global prevalence of metabolic syndrome and its close association with cardiovascular diseases and type 2 diabetes mellitus have increased scientific interest in the potential metabolic effects of chromium. However, currently available evidence regarding its clinical significance remains inconsistent. This narrative review describes the role of trivalent chromium in the context of metabolic syndrome. A systematic literature search was conducted in the Scopus and Web of Science databases for studies published between 2015 and 2025. The review included randomized controlled trials, observational studies, experimental studies, systematic reviews, and meta-analyses that investigated chromium intake, supplementation, or the association between chromium levels and components of metabolic syndrome. The reviewed studies reported heterogeneous findings regarding the effects of trivalent chromium on components of metabolic syndrome. While some studies demonstrated improvements in glucose metabolism, insulin sensitivity, and lipid profiles, other studies reported no clear or statistically significant effects. The inconsistency of results has been attributed to differences in study design, studied populations, types and dosages of chromium supplementation, and duration of interventions. The lack of uniform research methodologies, limited sample sizes, and the absence of standardized protocols for chromium supplementation hinder the comparability of results. In addition, the heterogeneity of the studied populations limits the reliability of the available data. Available evidence does not support the widespread clinical use of trivalent chromium. Therefore, further large-scale studies are required to determine its efficacy and safety.

Visual impairment affects over 2.2 billion people worldwide and the major causes include age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy. For research in these areas, although animal models offer a more physiologically complex system than in vitro approaches, their use raises ethical considerations, and species-specific differences such as variations in protein sequences and signaling pathways. This can limit the direct translatability of the outcomes. Traditional 2-D cell cultures, in contrast, lack the multicellular organization and dynamic microenvironment necessary to replicate human retinal complexity. Retinal organoids (ROs), three-dimensional tissue constructs derived from pluripotent stem cells, have emerged as a promising model due to their human origin and complex cellular interactions that cannot be achieved in conventional 2-D/3-D co-culture models. In this review, we provide a brief overview of the evolution from 2-D to 3-D retinal models, highlight the structural and functional features of ROs including the presence of layered retinal architecture, photoreceptor outer segment formation, and light-responsive electrophysiological activity and summarize their applications in disease modeling, drug discovery, and gene and cell therapy. ROs represent a significant advancement over traditional models by enabling the recapitulation of human-specific retinal development, facilitating the study of patient-derived disease phenotypes, and providing a platform for personalized therapeutic screening. Their development has deepened understanding of pathological mechanisms in conditions such as retinitis pigmentosa and AMD, while enabling preclinical testing of targeted interventions like CRISPR-based gene editing and photoreceptor cell replacement. Nonetheless, challenges remain in fully replicating retinal vascularization, long-term functional maturation, and synaptic connectivity, underscoring the need for continued refinement and integration with complementary model systems.

Serious fungal diseases are significant yet long neglected public health problem in India, setting an estimated 4.1% of the population and with the mortality from invasive fungal diseases approaching 50%, surpassing several nationally prioritised conditions. The emergence and spread of drug resistant pathogens such as Candida auris, azole resistant Aspergillus fumigatus, and Trichophyton indotineae together with COVID-19 associated mucormycosis epidemic, expose critical gaps in preparedness prevention and care despite the presence of a WHO collaborating centre and an Indian Council of Medical Research (ICMR) mycology Advanced Mycology Diagnostic and Research Centre network, major deficiencies persist in surveillance, diagnostics, antifungal access, stewardship, workforce, capacity and coordinated research OBJECTIVES: The Indian Fungal Infection National Declaration (I- FIND) seeks to catalyse a structured, time bound national response that elevates fungal diseases to a recognised public health priority and measurably reduces morbidity, mortality, and fungal resistance. Its objectives are to identify and target key at risk populations (including those with immunosuppression, critical illnesses, chronic lung disease and poorly controlled diabetes, to acknowledge major community mycoses such as chronic dermatophytosis, vulvovaginal candidiasis, and fungal keratitis, and to define clear domains for action across governance, surveillance, diagnostics, clinical management, research, workforce development, public awareness, One Health, and accountability. I- FIND identifies 9 core domains, including governance, surveillance, diagnostics, clinical management, research, workforce development, public awareness, One Health measures, and accountability. Proposals cover creating a National Task Force, issuing a five-year fungal disease control strategy, integrating mycology network, setting diagnostic standards, incorporating stewardship and prioritizing translational research funding. The declaration is supported by major Indian and international professional societies guides formal adoption and implementation across India.

Glioblastoma (GBM) is one of the most aggressive and treatment-resistant brain tumors, largely due to the restrictive nature of the blood-brain barrier (BBB). This barrier significantly limits the efficient delivery of therapeutic agents to the tumor site, thereby reducing treatment efficacy. This review evaluates the potential of dextran (Dex)-based nanoparticles (NPs) as an advanced platform for enhancing BBB penetration and enabling targeted GBM therapy. Dex, a biocompatible and biodegradable polysaccharide, offers key advantages including ease of functionalization, high drug-loading capacity, and improved systemic stability. Recent studies demonstrate that Dex-based nanocarriers enhance drug transport across the BBB via receptor-mediated and adsorptive transcytosis mechanisms, resulting in improved accumulation at tumor sites. Furthermore, surface engineering strategies facilitate active targeting of GBM cells, thereby increasing therapeutic efficacy while reducing systemic toxicity. Comparative evidence indicates that Dex-based nanocarriers outperform conventional delivery systems in terms of targeting efficiency, biocompatibility, and tailored drug release. These systems also show potential for co-delivery of multiple therapeutic agents, supporting combination treatment approaches for improved clinical outcomes. Emerging preclinical studies highlight improved survival outcomes and enhanced pharmacokinetic profiles associated with Dex-based nanocarriers, reinforcing their therapeutic relevance. Despite these promising findings, challenges related to large-scale manufacturing, reproducibility, and regulatory approval remain significant barriers to clinical translation. Future research should focus on clinical validation, scalable synthesis approaches, and long-term safety assessment to facilitate successful translation into clinical practice. Overall, Dex-based NPs represent a versatile and highly promising strategy to overcome existing limitations in GBM treatment and advance targeted nanomedicine approaches for brain cancer therapy.

This prospective open-label comparative study evaluated the efficacy of various conservative treatments for acute anal fissure (AAF) in accelerating epithelialization and reducing pain. A total of 120 patients with symptom duration &#x2264;6 weeks were randomized into four groups: control (hygiene only), dietary therapy (fiber-rich diet + psyllium), monotherapy with a sphincter relaxant (0.2% nitroglycerin ointment), and combined therapy (diet + nitroglycerin). The primary outcome was time to complete epithelialization; secondary outcomes included pain dynamics on the Visual Analog Scale (VAS) and incidence of chronic fissure. Results demonstrated that combined therapy achieved the shortest epithelialization time (10.5&#xb1;1.5 days), which was significantly shorter than both monotherapy groups and the control (p<0.01). The combined regimen also produced the most pronounced pain reduction from day 3 onward and completely prevented the development of chronic fissure. Dietary modification and nitroglycerin alone improved outcomes but were inferior to the combined approach. In conclusion, the combination of dietary intervention and topical nitroglycerin represents the most effective conservative strategy for AAF, promoting faster healing, superior pain control, and prevention of chronicity.

In the current study, an optimum formulation of alginate-functionalized and PEGylated niosomes (Nio) co-encapsulated with letrozole (Let) and berberine (Ber) was observed for potential preclinical treatment of breast cancer to combat multidrug resistance and reduce drug doses. The incorporation of alginate (AL) and polyethylene glycol (PEG) enabled tunable network architecture, improved colloidal stability, and sustained release behavior of the formulated system. Nio-Let/Ber@PEG and Nio-Let/Ber@AL formulations showed desired entrapment efficiencies of 86.12 and 91.34 for Let and 71.32 and 75.12 for Ber, respectively. Drug release profiles showed that sustained and slower release rates were observed for coated niosomes (Nio-Let/Ber@PEG and Nio-Let/Ber@AL) compared to uncoated niosomes (Nio-Let/Ber). MTT assay showed the IC50 of coated niosomes was much lower than the uncoated formulation and free drugs for MCF-7 and MDA-MB-231 breast cancer cell lines. Moreover, coated niosomal formulations significantly increased the rate of apoptosis induction and cell cycle arrest compared to uncoated niosomes. Also, gene expressions of Bax and caspase 3/8/9 increased while the gene expression of Bcl2 (anti-apoptotic) decreased after treatment with coated niosomes compared to uncoated ones. Taken together, this preliminary research indicated that the co-delivery of Let and Ber through coated niosomal formulations (Nio-Let/Ber@PEG and Nio-Let/Ber@AL) was an efficient controlled dual-drug delivery system to increase the effectiveness of breast cancer therapy.

To examine associations between physical activity (PA) characteristics and psychosocial outcomes - quality of life (QoL) and fear of hypoglycemia (FH) - in children, adolescents, and young adults with type 1 diabetes (T1D). In this cross-sectional study, 100 insulin pump-treated outpatients T1D completed 7-day PA logs capturing timing, type, intensity, and volume. QoL and FH were assessed using age-appropriate validated instruments. General linear models evaluated associations between PA characteristics and psychosocial outcomes, accounting for age group and, in sensitivity analyses, sex and HbA1c. In pooled analyses (N&#x2009;=&#x2009;82 complete cases), age group was significantly associated with both QoL (p&#x2009;=&#x2009;0.037) and FH (p&#x2009;<&#x2009;0.001), with a large effect size observed for FH. In sensitivity analyses adjusting for sex and HbA1c, the age-group effect on FH remained robust, whereas associations with QoL were attenuated. Exercise timing was associated with FH (p&#x2009;=&#x2009;0.047), with higher adjusted FH scores observed among individuals reporting evening exercise. However, pairwise comparisons were not significant after correction. No significant AgeGroup&#xd7;Timing interactions were detected. Preferred exercise type and intensity were not independently associated with psychosocial outcomes. In sensitivity analyses adjusted for sex and HbA1c (N&#x2009;=&#x2009;62), the age-group effect on FH remained robust, whereas timing showed borderline significance. Developmental stage appears to be a major determinant of fear of hypoglycemia in youths with T1D. Exercise timing may contribute modestly to perceived hypoglycemia risk, particularly for evening activity, although findings were attenuated after adjustment. These cross-sectional associations highlight the importance of developmentally tailored exercise counselling, while longitudinal studies are needed to clarify directionality.

A 3-year-old male passenger developed acute respiratory distress approximately 30 minutes after takeoff during an international flight from the United States to Addis Ababa. Despite multiple rounds of nebulized albuterol and escalating oxygen therapy, his respiratory status progressively deteriorated. A multidisciplinary team of onboard physicians administered epinephrine and hydrocortisone from the emergency medical kit while coordinating with ground medical control. The aircraft was subsequently diverted to Athens, Greece, where the child was handed over to emergency services and later stabilized. This case highlights the challenges of managing pediatric respiratory distress in-flight and the critical importance of prompt coordination, adequate medical supplies, and crew preparedness.

Glioblastoma is an aggressive primary brain tumor marked by rapid growth, invasiveness, poor prognosis, and an over 90&#x202f;% tumor recurrence rate. Current radiation and chemotherapy treatments are limited by non-selectivity and toxicity, creating a need for safer complementary treatments. Historically, natural health products (NHPs) have been used medicinally across cultures for their anti-inflammatory and antioxidant effects. More recently, they have gained recognition for their selective, non-toxic properties in cancer treatment, suggesting their potential as adjuncts to conventional therapies. Black maitake (Grifola frondosa) extract, a well-tolerated NHP with known immunomodulatory properties, has demonstrated anticancer effects in breast cancer models. This study investigates the ability of Black Maitake Odaira Extract&#xa0;-&#xa0;Prothera (BMOE; a trade name of the extract manufactured by Shogun Maitake Canada, London, ON) to induce cell death in the U-87 MG glioblastoma cell line using 2D and 3D models, alone and in combination with the standard chemotherapy: temozolomide (TMZ). Apoptosis was assessed via Hoechst 33,342, annexin V, and propidium iodide staining, along with morphological analyses. Mitochondrial depolarization was measured using TMRM, cell migration was assessed via wound-healing assays, and structural integrity was evaluated using 3D spheroids. BMOE, alone and with TMZ, induced dose-dependent apoptosis, mitochondrial depolarization, and impaired glioblastoma cell migration. BMOE also disrupted 3D spheroid structures and promoted nuclear condensation, consistent with apoptotic processes. Most notably, BMOE significantly enhanced the anti-cancer effects of&#xa0;TMZ. These findings support the potential of BMOE as a complementary therapy that enhances the efficacy of current glioblastoma treatments.

Second generation tyrosine kinase inhibitors (TKIs) have improved response rates in patients with chronic phase chronic myeloid leukaemia (CP-CML). Phase 2 trials demonstrated increased deep molecular response rates when combining second generation TKIs with pegylated interferon alfa (Peg-IFN). This trial aimed to evaluate the efficacy and the safety of combining nilotinib with Peg-IFN alfa-2a in patients with newly diagnosed CP-CML. In PETALs, this open-label, randomised, multicentre phase 3 trial, we enrolled patients with newly diagnosed CP-CML from 27 French academic institutions via a centrally-generated electronic system in a 1:1 ratio to two groups: 300 mg oral nilotinib alone twice a day (the nilotinib only group) or 300 mg nilotinib twice a day combined with subcutaneous Peg-IFN (30 &#x3bc;g per week for the first month of treatment and 45 &#x3bc;g per week thereafter) for a maximum of 2 years. The randomly allocated patients were stratified by their Sokal index and European Treatment and Outcome Study long-term survival index. Eligible patients had major BCR::ABL1 transcripts, an Eastern Cooperative Oncology Group performance score of two or lower, who had never received TKIs, and were aged between 18 and 65 years. The primary endpoint was the cumulative rate of molecular response 4&#xb7;5 (MR4&#xb7;5; defined as BCR::ABL1 international scale [IS] of 0&#xb7;0032% and lower), analysed in the intention-to-treat population (n=200). This trial is registered at ClinicalTrials.gov, NCT02201459, and is completed. 205 patients were enrolled between Aug 6, 2014, and Sept 29, 2016, after which five patients were declared ineligible and excluded, resulting in 200 patients being randomly allocated (99 to the nilotinib group and 101 to the combination group). The median age at diagnosis was 45 years (IQR 36-55); 130 patients (65%) were male and 70 (35%) were female. Median follow-up in this cohort was 67 months (IQR 32&#xb7;6-70&#xb7;6). The primary objective was met, with higher rates of MR4&#xb7;5 in the combination group (24% [95% CI 16&#xb7;0-34&#xb7;1] vs 15% [8&#xb7;6-24&#xb7;2], p=0&#xb7;048) at month 12. There were equivalent grade 3-4 haematological side effects in the both groups (14 vs 14) with a predominance for grade 3-4 thrombocytopenia without haemorrhages (six in the combination group vs five in the nilotinib group). Psychiatric grade 3-4 events occurred in six (6%) patients in the combination group (including three unsuccessful suicide attempts) compared with five (5%) in the nilotinib group (including one unsuccessful suicide attempt). Six vascular events also occurred in six patients in the combination group and seven vascular events in five patients in the nilotinib group (all grades 3-4). In this setting, Peg-IFN combined with nilotinib induced higher initial rates of MR4&#xb7;5 compared to TKI monotherapy, despite additional side effects. The onset of psychiatric events might promote immediate cease of Peg-IFN and psychiatrist advice Whether this early molecular response translates into sustained treatment-free survival should be studied in a randomised trial sufficiently powered for this outcome. Novartis Pharma.