Search Results (6,019)

Background: Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is a rare X-linked lysosomal storage disorder caused by pathogenic variants in the iduronate-2-sulfatase gene, leading to progressive multisystem involvement. Although international management guidelines exist, challenges in their implementation across different healthcare systems remain insufficiently addressed. This study aimed to establish a national expert consensus in Türkiye on the treatment and management of MPS II, aligning local practice with international standards. Methods: A modified Delphi methodology was conducted using two rounds of online surveys supported by three steering committee meetings. The process involved 10 experienced clinicians and a scientific committee of six professors. Based on international guidelines and country-specific clinical challenges, 72 consensus statements and 84 exploratory questions were developed. Statements achieving ≥ 80% agreement were accepted as consensus. Results: Consensus supported initiating enzyme replacement therapy (ERT) in both severe and attenuated MPS II, guided by functional and cognitive status. Severe cognitive impairment was not considered an exclusion criterion for ERT, given its somatic benefits. Experts agreed on continuing ERT into adulthood with individualized discontinuation decisions. Routine evaluations every 6–12 months, including respiratory, cardiac, and neurocognitive assessments, were recommended. Additional consensus areas included individualized premedication strategies, structured transition to adult care, selective home infusion, annual patient-reported outcome assessments, and the establishment of a national MPS II registry. Hematopoietic stem cell transplantation was not endorsed. Conclusions: This Delphi study demonstrates strong expert consensus on MPS II management in Türkiye, providing a practical framework to guide clinical practice, support alignment with international recommendations, and inform future policy and research priorities. Full article

Early-onset infection caused by Streptococcus agalactiae (Group B Streptococcus, GBS) may occur during gestation or delivery and can lead to severe neonatal sepsis, meningitis, or pneumonia. Discordant GBS infections in twin gestations are rare. We report a fatal case of early-onset GBS infection in dichorionic–diamniotic twins conceived via IVF and delivered by caesarean section at 32 weeks’ gestation due to discordant fetal growth and abnormal Doppler indices in Twin A (Umbilical Artery PI = 1.4; Middle Cerebral Artery PI = 1.5). Twin A had Apgar scores of 3, 5, and 5 and rapidly developed tachycardia, respiratory distress, and systemic infection, while Twin B, with Apgar scores of 7, 8, and 9, remained clinically stable. Both infants were admitted to the NICU and underwent routine blood, urine, and cerebrospinal fluid testing. Despite the prompt initiation of parenteral ceftriaxone and respiratory support, Twin A deteriorated rapidly and died within 28 h. GBS was isolated from Twin A’s blood culture, and maternal placental tissue and high vaginal samples collected before antibiotic administration also grew GBS, with all isolates demonstrating identical antimicrobial resistance profiles. Molecular analysis revealed matching rib1 and alp2/3 gene patterns in isolates from the mother and Twin A. Maternal anovaginal immunochromatography at delivery was positive, whereas screening cultures obtained at 29 weeks’ gestation were negative. This case highlights the limitations of culture-based GBS screening in high-risk pregnancies and preterm deliveries and underscores the potential value of molecular assays and point-of-care testing to improve detection of S. agalactiae throughout pregnancy and the peripartum period. Emerging preventive strategies, including modulation of the genital microbiome and maternal vaccination aligned with WHO recommendations, may further reduce the burden of neonatal GBS disease. Full article

A male castrated Shih Tzu was evaluated for recurrent nocturnal episodes of acute respiratory distress accompanied by hemoptysis and transient erythrocytosis. The dog was clinically normal between episodes, but each nighttime event was severe and prompted repeated emergency visits. During each emergency presentation, thoracic radiographs revealed severe diffuse interstitial-to-alveolar pulmonary infiltrates, and packed cell volume showed marked but reversible increases. A stepwise diagnostic evaluation, including serial indirect blood pressure measurement, coagulation assessment, echocardiography, and bronchoscopy with bronchoalveolar lavage, progressively excluded typical infectious, cardiac, structural, and coagulopathic causes of hemoptysis and acute respiratory distress. Given the stereotyped pattern of near-acute crises with diffuse pulmonary infiltrates and hemoptysis, mechanisms analogous to noncardiogenic pulmonary edema or exercise-induced pulmonary hemorrhage were considered. Therapeutic trials with sildenafil and furosemide failed to prevent further nocturnal recurrences. Considering concurrent transient PCV surges and the proposed role of catecholamine-driven splenic contraction as a rapidly mobilizable erythrocyte reservoir, a sympathetically mediated process was suspected, and α₁-adrenergic blockade with prazosin was initiated. Following prazosin therapy, sustained clinical remission was achieved, with no further emergency episodes over a 15-month follow-up period. The response may have reflected multiple pharmacological effects of prazosin, including attenuation of sympathetically mediated splenic α₁-adrenergic activity, systemic vasodilation, and reduction in venous return. This unique case suggests that dysregulation of the sympathetic nervous system may have contributed to the recurrent hemoptysis and acute respiratory distress and highlights adrenergic modulation as a potential therapeutic consideration in similar cases. Full article

Pulmonary diseases such as Chronic obstructive pulmonary disease (COPD), asthma, pulmonary fibrosis, and acute respiratory infections remain a major global health challenge due to their complex pathophysiology and limited therapeutic options. Conventional 2D cultures and animal models have provided foundational insights; however, they often fail to accurately replicate the human lung’s intricate architecture, immune interactions, and patient-specific variability. Recent advances in vitro technologies have transformed pulmonary research, enabling the generation of physiologically relevant and translational disease models. The review highlights the progression of lung research platforms from traditional monolayer cultures to advanced systems such as air–liquid interface models and 3D lung organoids. These cutting-edge models more effectively mimic the biochemical, mechanical, and spatial microenvironment of the respiratory system, enhancing the fidelity of disease modelling and drug screening. In parallel, the integration of computational modelling and artificial intelligence (AI) has emerged as a powerful synergistic approach. AI-driven analytics facilitate high-throughput imaging, biomarker discovery, and patient-stratified therapeutic prediction, while computational tools simulate disease networks, mechanobiological interactions, and pharmacological responses. The convergence of these technologies supports a deeper understanding of pulmonary disease progression and accelerates the development of precision therapeutics. Collectively, this review underscores the transformative potential of combining in vitro lung models with advanced computational and AI methodologies. This synergy not only improves translational relevance and reduces reliance on animal testing but also paves the way for personalised interventions that better address the complexity of human pulmonary disease. Full article

Mining activities are characterised by a multiplicity of inherent occupational hazards. Exposure to mineral dust such as silica, asbestos, and coal dust is common in mining, leading to pneumoconiosis. Exposure to respirable silica-containing dust is one of the common respiratory hazards associated with adverse health effects such as silicosis, lung cancer, renal failure, scleroderma, systemic lupus erythematosus (SLE) and chronic obstructive pulmonary disease (COPD), to mention but just a few. In southern Africa, there is a rising epidemic of silicosis, human immunodeficiency virus (HIV) and tuberculosis (TB). Excessive exposure to silica-containing dust exacerbates the TB and silicosis epidemic in mining areas. There is poor control of dust exposure and a lack of occupational hygiene assessments of silica dust in mining in southern Africa. In southern Africa, there remains a persistent knowledge gap regarding the extent of occupational exposures to respirable chemical substances, such as silica dust. Consequently, occupational hygiene air monitoring was conducted in mining companies across four low-income Southern Africa Development Community (SADC) countries, Lesotho, Mozambique, Malawi and Zambia, to provide a baseline exposure dataset. The hazardous nature of work associated with mining activities still persists in these low-income countries, with 53% (n = 72) of quarries and 20% (n = 19) of coal mines having respirable quartz exposures exceeding the reference occupational exposure limit (OEL) of 0.1 milligrams per cubic meter (mg/m³). The highest exposure ranges for quartz were recorded in surface aggregate quarries, with the maximum concentration recorded at 2.739 mg/m³. The highest number of air samples (93%, n = 111), which were in compliance with the OEL of 3 mg/m³ for respirable dust, were recorded in the copper, diamond, ruby, cement quarry and gold mines. This exploratory study confirms the variable extent of mineworker exposure to respirable dust and corresponding quartz fractions emanating from different mining activities. The collected exposure data provides a baseline overview of exposures within the mining industry in the SADC region. It also serves as a vital input for future regional exposure surveillance databases, as well as preliminary data for directing future research towards regional exposure prevention initiatives. Full article

The C-terminal binding protein 1 (CTBP1) is a transcriptional corepressor with a major role in nervous system growth and development. There are only 20 published cases with CTBP1 mutations, displaying a phenotype of Hypotonia, Ataxia, Developmental Delay and Tooth enamel defect Syndrome (HADDTS). Histochemical evidence of decreased mitochondrial respiratory chain activity has been previously reported, but comprehensive data on the metabolic phenotype assessed by various cellular respiration parameters are still missing. We present a 10-year-old female with typical HADDTS features, harboring the most reported de novo heterozygous CTBP1 mutation c.991C>T. To elucidate her metabolic phenotype, we quantified mitochondrial respiration in peripheral blood mononuclear cells (PBMCs) utilizing an analyzer for assessing mitochondrial function (Seahorse XFp). Real-time metabolic assays revealed profound mitochondrial dysfunction with significantly attenuated maximal respiration and spare respiratory capacity compared to neurotypical controls. Following mitochondria-targeted nutritional support for one-year measurable bioenergetic improvements and reduced number of respiratory infections were registered. However, neurological recovery and new skill acquisition were not observed. We present a novel case of CTBP1-related neurodevelopmental disorder and demonstrate, for the first time, the application of non-invasive, real-time mitochondrial functional assessment in this setting, providing additional evidence for mitochondrial dysfunction in HADDTS. Full article

Background/Objectives: The emergence of SARS-CoV-2 variants and breakthrough infections underscores the need for next-generation vaccines capable of protecting from natural infection and/or preventing virus transmission. Intranasal vaccination offers a promising approach by eliciting local immune responses in the nasal mucosa, the primary site of infection and reservoir for transmissible virus. We evaluated two live-attenuated, respiratory syncytial virus-vectored vaccines in which the RSV F and G surface glycoproteins were replaced with a chimeric SARS-CoV-2 Spike protein from the ancestral USA/WA-1/2020 strain (MV-014-212) or the Delta variant (MV-014-212-delta). Methods: K18-hACE2 mice and LVG Syrian hamsters were vaccinated with a single intranasal dose of MV-014-212 or MV-014-212-delta. Systemic and mucosal immunity were assessed following vaccination, and protection was evaluated following Delta SARS-CoV-2 challenge. In vaccinated hamsters, morbidity, viral shedding, and lung inflammation and injury were also assessed following natural exposure to infected cagemates. Results: A single intranasal dose of either vaccine elicited systemic and mucosal immunity in K18-hACE2 mice, including serum neutralizing antibodies, Spike-specific memory B cells and plasmablasts, and Spike-specific CD8⁺ lung-resident memory T cells. Although MV-014-212-delta vaccination provided the best protection against the Delta variant virus challenge, both vaccines decreased viral loads in nasal discharge, lung, and brain, and reduced weight loss and mortality. In naturally acquired infection studies, vaccinated hamsters exposed to infected cagemates exhibited minimal weight loss, limited viral replication within the nasal mucosa, and attenuated lung pathology. Conclusions: Intranasal RSV-vectored vaccines can elicit broad protective respiratory immunity, suggesting that this platform could be leveraged for other respiratory pathogens. Full article

The ATP-dependent inhibition of cytochrome c oxidase (CytOx, complex IV of the electron transport chain) is the second mechanism of respiratory control adjusting mitochondrial respiration in order to prevent excessive electron flow and reactive oxygen species (ROS) production. Here, we investigate how tricarboxylic acid (TCA) cycle metabolites and the subsequent complex I or complex II activities influence this regulatory mechanism. Therefore, CytOx activity was assessed by the oxygen consumption rate after cytochrome c (Cyt c) titration to stimulate complex IV activity in isolated rat heart mitochondria (RHM) and permeabilized AC16 cells. Mitochondrial membrane potential (Δψm) and ROS formation were analysed by flow cytometry. Our results show that TCA cycle intermediates differed in their impact on CytOx activity and subsequent ROS formation. NADH-linked substrates such as α-ketoglutarate, glutamate and malate increased respiratory capacity, but preserved ATP-dependent control of CytOx, indicating that elevated electron supply alone does not necessarily abolish ATP sensitivity. In contrast, succinate, which feeds electrons directly into complex II, strongly increased respiration causing the loss of ATP-dependent respiratory control in both model systems. Despite this strong respiratory effect, succinate induced only modest changes in mitochondrial membrane potential in isolated mitochondria, whereas permeabilized cardiomyocytes exhibited reduced polarization accompanied by increased superoxide formation. Together, these findings demonstrate that the effectiveness of ATP-dependent CytOx inhibition is influenced by TCA cycle activity and depends on the site of electron entry into the respiratory chain. Thus, substrate-dependent modulation of respiratory control links metabolite availability to mitochondrial redox regulation in cardiac cells. Full article

The growing prevalence of chronic diseases, population aging, and the shift toward preventive and personalized care under Healthcare 5.0 have increased the need for continuous health monitoring beyond clinical settings. While wearable devices enable remote monitoring, their long-term use is often limited by user compliance, comfort issues, battery dependence, and disruption of daily routines. To address these limitations, unobtrusive home-based health monitoring systems have emerged, integrating sensing technologies into domestic environments and everyday objects. This review provides a system-level analysis of unobtrusive health monitoring technologies for smart homes. It examines seven major sensing approaches, including camera-, laser-, radar-, infrared-, mechanical-, bioelectrical-, and optical-based sensors, and their integration into four home environments: living areas, bathrooms, bedrooms, and home offices. For each sensing modality, the operating principles, monitored physiological parameters, representative applications, and key advantages and limitations are discussed. Overall, existing solutions reveal trade-offs among measurement accuracy, robustness in real home conditions, energy autonomy, privacy preservation, and user acceptance. Heart rate and respiratory rate are the most commonly monitored parameters, while multimodal and clinically validated systems remain limited. Although unobtrusive sensing technologies show strong potential for proactive and personalized healthcare, challenges related to accuracy, interoperability, privacy, and cost continue to hinder large-scale adoption. Full article

Inhalation injury (II) exacerbates burn mortality via obstructive fibrin casts. We evaluated a protocol combining scheduled flexible bronchoscopy (FOB) with nebulized heparin and N-acetylcysteine (NAC). This single-center, randomized controlled trial enrolled 76 mechanically ventilated adult burn patients with bronchoscopically confirmed II. The intervention (n = 38) comprised a 7-day protocol of scheduled FOB with alternating nebulized heparin (5000 IU) and 20% NAC every 4 h. Controls (n = 38) received standard care with on-demand FOB. Primary outcomes were 28-day mortality and day-7 Lung Injury Score (LIS). Unadjusted 28-day mortality was lower in the intervention group (57.9% vs. 81.6%; p = 0.025), alongside a decreased median day-7 LIS (1.0 vs. 1.38; p = 0.021). Respiratory mechanics improved significantly, demonstrating reduced driving pressure and increased static compliance (p < 0.001). However, in multivariable Cox regression, baseline injury severity independently predicted mortality, while the intervention indicated a non-significant hazard reduction trend (aHR = 0.66, 95% CI: 0.36–1.23). No systemic anticoagulation occurred. In conclusion, scheduled FOB with nebulized heparin and NAC improves respiratory mechanics and attenuates lung injury in II. Although unadjusted mortality decreased, baseline severity remains the primary mortality driver, suggesting this protocol is a physiologically beneficial adjunct requiring further multicenter validation. Trial registration: Thai Clinical Trials Registry, TCTR20260408001 (retrospectively registered). Full article

Antimicrobial resistance (AMR) is one of the most significant threats to healthcare systems, particularly in low- and middle-income nations where infection prevention and control, antimicrobial stewardship, and laboratory surveillance might not be optimal. Acinetobacter baumannii is a high-risk nosocomial pathogen that has a strong capacity to develop extreme resistance phenotypes. Still, the degree to which extensively drug-resistant (XDR) and pandrug-resistant (PDR) phenotypes reflect the cumulative impact of antimicrobial pressure at unit and system levels in Iraqi hospitals is not fully described. This was a cross-sectional surveillance study that was a laboratory-based investigation done in public hospitals in the Governorate of Kirkuk between January 2024 and January 2025. The BD Phoenix system identified 80 non-duplicate A. baumannii isolates that were obtained in high-risk hospital units. The interpretation of antimicrobial susceptibility testing was done according to CLSI guidelines. Internationally recognized definitions were adjusted to local therapeutic availability to classify isolates as XDR or PDR. Unadjusted odds ratios and Fisher’s exact test were used to assess the associations between the PDR phenotype and the chosen clinical or unit-level variables. Among the 80 isolates, 60 (75%) were XDR and 20 (25%) were PDR. Burn units and wound-related infections were disproportionately represented by PDR isolates. There were significant associations between the PDR phenotype and burn unit admission, wound infection, exposure to invasive devices, long hospitalization (greater than 14 days), and previous exposure to broad-spectrum antibiotics. ICU admission and respiratory infection were not significantly related. Cefepime had in vitro activity only in a subset of XDR isolates. Extreme resistance phenotypes can be used as convenient sentinel measures of cumulative antimicrobial pressure and system-level stress in resource-limited environments. There is an urgent need to strengthen infection prevention and control, antimicrobial stewardship, and laboratory surveillance to preserve the remaining therapeutic options. Full article

Preserved ratio impaired spirometry (PRISm) is increasingly recognized as a clinically important non-obstructive spirometric phenotype associated with excess all-cause, respiratory, and cardiovascular mortality. PRISm is variably defined across studies and should be distinguished from pre-COPD and restrictive spirometric pattern, particularly in LMIC settings where diagnostic context may differ. Although most evidence has been generated in high-income settings, PRISm may be especially relevant in low- and middle-income countries (LMICs), where the phenotype appears to arise within a markedly different exposure environment. Rather than reflecting predominantly the smoking–obesity–metabolic profile commonly described in wealthier populations, PRISm in LMICs may more often emerge from the cumulative effects of tuberculosis, household biomass smoke, ambient particulate air pollution, poverty-related undernutrition, impaired lung growth, and other adverse life-course exposures. These factors may contribute both to low-volume lung-function impairment and to increased cardiovascular risk through shared pathways of chronic low-grade inflammation, immune activation, oxidative stress, endothelial dysfunction, and metabolic dysregulation. In this context, PRISm may represent a measurable interface between environmental and infectious lung injury, social disadvantage, and systemic vascular vulnerability. The emerging literature further suggests that PRISm in LMICs may include distinct leaner, poverty-related, and infection-linked phenotypes that differ from the obesity-associated patterns more often described in high-income cohorts. This perspective has important clinical implications, as PRISm may identify individuals at elevated risk of cardiometabolic comorbidity, heart failure, stroke, and cardiovascular death who may otherwise remain unrecognized within current respiratory care pathways. Although direct causal evidence remains limited, the convergence of epidemiological, mechanistic, and clinical data supports the view that PRISm in LMICs should be considered a meaningful cardiopulmonary risk state rather than a benign spirometric abnormality. Further LMIC-focused longitudinal, mechanistic, and implementation research is needed to refine phenotyping, clarify causal pathways, and inform integrated prevention strategies. Full article

Chronic exposure to ionizing radiation from uranium legacy sites remains a significant public health concern in Northern Kazakhstan. This review evaluates epidemiological, clinical, and environmental evidence published between 2000 and 2025, with particular emphasis on studies conducted during 2014–2023 in the Stepnogorsk region among populations residing near former uranium mining sites. Residents were exposed to annual external gamma doses of approximately 1.0–3.5 mSv and radon-related doses of up to 1.2 mSv. Cancer registry analyses revealed 1913 malignancy cases in the exposed group (vs. 358 controls), with digestive (29%) and respiratory (17%) cancers predominating. Early signs of chronic radiation syndrome (CRS) were consistently observed, including olfactory dysfunction, immunosuppression, vestibular disturbances, hematologic anomalies, and elevated chromosomal aberrations (1.3–1.5× baseline). Non-cancer morbidity was also elevated, including hypertension (32% vs. 24%), chronic bronchitis (14% vs. 8%), and reduced forced expiratory volume in one second (FEV₁; −9.7%), indicating broader systemic effects. These results underscore the need for targeted public health strategies incorporating CRS biomarker screening, cancer surveillance, personal dosimetry, and environmental remediation in uranium-impacted communities. Full article

Sleep disorders, such as insomnia, obstructive sleep apnea (OSA), narcolepsy, REM sleep behavior disorder, and circadian rhythm disturbances, represent a rapidly expanding global health burden that is strongly associated with cardiovascular, metabolic, neurological, and psychiatric diseases. Advancements in wearable sensing technologies and Internet of Medical Things (IoMT) infrastructures have expanded the possibilities for continuous, home-based sleep assessment beyond conventional polysomnography laboratories. These Sleep Health Internet of Things (S-HIoT) systems combine multimodal physiological sensing (EEG, ECG, SpO₂, respiratory effort and actigraphy) with wireless communication and cloud-based analytics for automated sleep-stage classification and disorder detection. Nonetheless, the digitization of sleep medicine brings about significant cybersecurity concerns. The constant transmission of sensitive biomedical information makes S-HIoT networks open to anomalous traffic flows, signal manipulation, replay attacks, spoofing, and data integrity violation. Existing studies mostly focus on analyzing physiological signals and network intrusion detection independently, resulting in a systemic vulnerability of cyber–physical sleep monitoring ecosystems. With the aim of addressing this empirical deficiency, this review integrates emerging advances (2022–2026) in the AI-assisted categorization of sleep phases and IoMT anomaly detector designs on the finer analysis of CNN, LSTM/BiLSTM, Transformer-based systems, and a component part of federated schemes and the lightweight, edge-deployable intruder assessor models available. The aim of this study is to uncover a gap in the literature: integrated architectures to trade off audiences of faithfulness of physiological modeling with communication-layer security. To counter it, we present a single framework to include CNN-based spatial feature extraction, Bidirectional Long Short-Term Memory (BiLSTM)-based temporal models and Random Forest-based ensemble classification using a dual task-learning approach. We propose a multi-objective optimization framework to jointly optimize the performance of sleep-stage prediction and that of network anomaly detection. Performance on publicly available datasets (Sleep-EDF and CICIoMT2024) confirms that hybrid integration can be tailored to achieve high accuracy [99.8% sleep staging; 98.6% anomaly detection] whilst being characterized by low inference latency (<45 ms), which is promising for feasibility in real-time deployment in view of targeting edge devices. This work presents a comprehensive framework for developing secure, intelligent, and clinically robust digital sleep health ecosystems by bridging chronobiological signal modeling with cybersecurity mechanisms. Furthermore, it highlights future research directions, including explainable AI, federated secure learning, adversarial robustness, and energy-aware edge optimization. Full article

Garrya flavescens S. Wats. (GF) has been traditionally used to treat gastrointestinal spasms, yet its bioactivity within the central nervous system remains unexplored. This study aimed to characterize the bioactive constituents of GF and evaluate its anti-inflammatory and metabolic regulatory effects in lipopolysaccharide-activated microglia. Phytochemical profiling using LC-HRMS and HPLC identified rutin as a primary bioactive component, present at an exceptionally high concentration (9309 μg/g). In BV-2 microglial and RAW 264.7 cells, GF treatment significantly suppressed the expression of pro-inflammatory cytokines and mediators in a dose-dependent manner. Mechanistic studies revealed that GF specifically modulated the ERK signaling pathway. Furthermore, Seahorse XF analysis demonstrated that GF restored mitochondrial homeostasis by reducing basal respiration and proton leak while significantly enhancing spare respiratory capacity. Finally, conditioned medium from GF-treated microglia improved the viability of N2A neuronal cells. These findings highlight GF as a potent botanical source with significant neuroprotective potential, offering a promising candidate for functional food or nutraceutical applications targeting neuroinflammatory disorders. Full article