Robin sequence (RS) is a rare congenital condition characterized by retrognathia, glossoptosis, and upper airway obstruction, with highly variable respiratory severity at birth. Prenatal measurement of the inferior facial angle (IFA) is used to support diagnosis, but its prognostic value for respiratory outcomes remains uncertain. This study assessed whether fetal MRI-measured IFA predicts early respiratory status in infants with RS. We conducted a retrospective monocentric study including consecutive infants with prenatal suspicion and postnatal confirmation of RS who underwent fetal MRI between 2009 and 2021. Respiratory status was assessed at delivery and at 6 months and categorized as room air breathing, noninvasive respiratory support, or intubation/tracheostomy. Five blinded operators independently measured the IFA and the anteroposterior skull size (APSS) on median sagittal MRI slice. Interobserver agreement was evaluated using intraclass correlation coefficients. Potential predictors of respiratory outcomes were analyzed using ordinal logistic regression. Among 43 infants, 72% required respiratory support at birth. More than half required ongoing respiratory assistance during early infancy. IFA values did not differ across respiratory outcome categories and were not associated with respiratory status at birth or during follow-up. Interobserver reliability was poor for IFA measurements, whereas APSS showed excellent agreement. In multivariable analyses, higher gestational age at birth was the only factor associated with reduced respiratory morbidity during the first 6 months.  These findings indicate that, although IFA is useful for diagnosing RS, it lacks reproducibility and prognostic value for respiratory outcomes, highlighting the need for delivery in specialized centers. • In Pierre Robin sequence, no reliable prenatal predictor of respiratory status at birth exists. Although the inferior facial angle is used for prenatal diagnosis, its ability to predict neonatal respiratory severity is unknown. • The inferior facial angle in prenatal fetal MRI shows limited predictive value for respiratory status at birth and during early infancy in infants with Robin sequence, with substantial measurement variability reducing its reliability as an isolated prognostic imaging marker.
Postural collapse and increased reliance on accessory respiratory muscles during meals can compromise ventilatory efficiency, particularly in individuals with respiratory impairment. Forward elbow-supported sitting is commonly used to unload the upper limbs; however, this posture often induces trunk flexion and cervical extension, which may adversely affect respiratory mechanics. To date, the effects of lateral armrest support on posture and respiratory function during seated eating have not been quantitatively investigated. To examine the effects of lateral armrest support on thoracic alignment, cervical posture (cervical inclination angle), shoulder muscle stiffness (upper trapezius and middle deltoid), vital capacity, and subjective comfort during seated eating in healthy young adults, compared with unsupported sitting and anterior elbow-supported sitting. Forty healthy young adults completed three randomized sitting conditions: (A) unsupported sitting, (B) anterior elbow-supported sitting, and (C) lateral armrest-supported sitting using a side-mounted armrest. Thoracic kyphosis index, cervical inclination angle, muscle stiffness of the upper trapezius and middle deltoid, vital capacity (VC), and subjective comfort were assessed. Data were analyzed using Friedman tests, with post-hoc pairwise comparisons performed using the Durbin-Conover test with Bonferroni correction. Thoracic kyphosis index differed significantly across conditions (p = .002), with both forward elbow-supported and lateral armrest-supported sitting showing lower values than unsupported sitting. Cervical inclination angle also differed significantly (p < .001), with forward elbow-supported sitting demonstrating greater cervical extension than the other conditions. Upper trapezius muscle stiffness was significantly reduced in the lateral armrest-supported condition compared with unsupported and forward elbow-supported sitting (both p < .01). Vital capacity was significantly greater in the lateral armrest-supported condition than in unsupported sitting (p = .003). Subjective comfort ratings were highest in the lateral armrest-supported condition (p < .001). Lateral armrest support demonstrated biomechanical advantages in healthy young adults, including improved spinal alignment, reduced shoulder girdle loading, and greater vital capacity compared with unsupported sitting. These findings provide preliminary mechanistic insight and may inform future investigations in clinical populations; however, direct extrapolation to individuals with respiratory or neurological impairment requires further study.
Occupational exposure to respiratory sensitizers is a major cause of allergic asthma. Although miRNAs are increasingly linked to asthma pathogenesis, their specific role in allergic asthma remains poorly defined. This study aims to assess a human-based 3D in vitro model to investigate the possible role of miRNAs in allergic asthma. Calu-3 cells cultured in ALI were exposed to three respiratory sensitizers: hexamethylen diisocyanate (HDI), ammonium hexachloroplatinate (HClPt), and trimellitic anhydride (TMA) using VITROCELL® Cloud Alpha 6 System. In addition, 2,4-dinitrochlorobenzene (DNCB) as skin sensitizer and the irritant sodium dodecyl sulphate (SDS) were tested. Cytotoxicity was assessed by MTT and LDH assays, while epithelial barrier integrity was evaluated by TEER. MiRNA profiling was performed, followed by targeted analysis. Cytokine release (IFN-γ, IL-4, IL-5, IL-6, IL-8, IL-10, IL-17, IL-18, IL-33, MCP-1, MIP-1α, TGF-β and TSLP) was quantified, and miRNAs involvement was investigated using miRNA mimics and inhibitors. HMOX gene expression was assessed. MiRNA profiling revealed several miRNAs consistently downregulated across all respiratory sensitizers, including miR-26b-5p, miR-34a-5p, miR-125b-5p, miR-148a-3p, and miR-200a-3p. HClPt induced a significant increase in IL-6 release and HMOX expression, whereas HDI and TMA caused a significant reduction. To understand the possible link, specific miRNA mimic and inhibitor conditions were used. Results indicate that miR-18b-5p, miR-135b-5p and let-7a-5p regulated IL-6 release and HMOX expression. Respiratory sensitizers from different chemical classes were able to induce distinct miRNA-dependent regulatory mechanisms affecting IL-6 and HMOX expression. These findings support the relevance of human cell-based in vitro models for investigating allergic asthma.
Chronic hypoventilation is common in individuals with neuromuscular disease (NMD). Nocturnal noninvasive home mechanical ventilation (NIHMV) reduces daytime PaCO2, but the underlying mechanism remains unclear. To evaluate the impact of NIHMV on central respiratory drive in individuals with NMD whose daytime PaCO2 decreases following ventilation. A prospective, longitudinal observational study was conducted in adults with NMD and chronic hypoventilation receiving usual clinical care. Central respiratory drive was assessed using CO₂ rebreathing and compared with healthy controls. Airway occlusion pressure (P0.1) was related to PETCO₂ during rebreathing to calculate the P0.1/PETCO₂ slope. Recruitment reflected real-world clinical practice, and data were analyzed post hoc. P0.1/PETCO₂ slopes were obtained in all 20 individuals at the six-month post-NIHMV evaluation; eight individuals subsequently completed a third CO₂ rebreathing assessment at 24 months. Baseline PaCO₂ (55.1 ± 8.2mmHg) normalized post-NIHMV (p < 0.001), whereas the P0.1/PETCO₂ slope remained unchanged (p = 0.338). The median slope in the NMD group was 0.011 (0.004-0.030), compared with 0.187 (0.150-0.244) in controls (p < 0.001). Breath-holding time was prolonged in 17 individuals and remained stable throughout the follow-up. Consistent with previous studies, NIHMV can normalize daytime PaCO₂ in individuals with NMD. In those who achieved PaCO₂ normalization, no improvement in central respiratory drive was observed. The unchanged P0.1/PETCO₂ slope indicates that daytime PaCO₂ normalization is unlikely to be mediated by enhanced central chemosensitivity. Further studies are needed to clarify the physiological mechanisms responsible for hypercapnia correction with NIHMV.
Dexmedetomidine (DEX) is increasingly used for neonatal sedation, but safety data remain limited. We conducted a single-center retrospective study including neonates receiving continuous DEX infusion. Cardiorespiratory events were extracted from bedside monitoring during the 8 h before and the 24 h after initiation. Hemodynamic and clinical parameters were analyzed, and autonomic activity was assessed using Newborn Infant Parasympathetic Evaluation (NIPE) monitoring in a subgroup. Thirty-seven infants (18 preterm, 19 term) were included; 86% received concomitant morphine. Bradycardia episodes increased after DEX initiation, particularly in preterm infants (p < 0.05). In contrast, hypotension, lactate levels remained unchanged, while urine output varied over time without a clinically meaningful reduction. Hypoxemic events decreased, while oxygen requirements remained stable. In the NIPE subgroup, heart rate decreased, with a trend toward increased NIPE values. DEX was associated with increased bradycardia without clear evidence of impaired hemodynamic or respiratory tolerance. These findings suggest an overall reassuring short-term safety profile and suggest a physiologically mediated sedative effect. What is Known: • Dexmedetomidine is increasingly used for sedation in preterm and term neonates, but cardiorespiratory safety data remain limited. • Bradycardia is the most frequently reported adverse effect. What is New: • Continuous monitor-derived data show increased bradycardia after dexmedetomidine initiation, without hypotension or impaired perfusion, while hypoxemic events decreased. • Autonomic monitoring (NIPE) suggests a trend toward increased parasympathetic activity, which may reflect modulation of autonomic balance under dexmedetomidine.
Respiratory syncytial virus (RSV) remains a major cause of severe acute respiratory infections across the life course, particularly in infants, older adults, and immunocompromised individuals. For decades, clinical management relied almost exclusively on supportive care, while ribavirin, the only licensed antiviral, offered limited therapeutic benefit. The recent introduction of prefusion F (pre-F)-based vaccines and long-acting monoclonal antibodies has reshaped RSV prevention and represents the most significant advance since the discovery of the virus. Nevertheless, effective pharmacological treatment of established infection continues to be an unmet need, and the burden of RSV-associated hospitalizations and mortality persists worldwide. This review critically synthesizes current and emerging RSV therapeutic strategies from a pharmacological and translational perspective, integrating approved interventions with emerging antiviral pipelines. Licensed vaccines and monoclonal antibodies have demonstrated high efficacy in preventing lower respiratory tract disease; however, their impact is constrained by limited access and uptake, as well as the absence of complementary direct-acting antivirals (DAAs). Investigational agents targeting the fusion protein and the N/L replication complex have shown potent antiviral activity, but clinical trials have highlighted challenges related to the timing of administration, host immunity, and resistance selection. Advances in structural biology, air-liquid interface models, high-throughput screening, and artificial intelligence are accelerating the identification of new molecular targets and host-directed strategies. Overall, RSV control will require an integrated therapeutic framework in which vaccines and monoclonal antibodies prevent severe disease, while early-administered DAAs and resistance-aware combination strategies treat established infection and reduce breakthrough disease in high-risk populations.
Influenza A, Influenza B, SARS-CoV-2, Respiratory Syncytial Virus and other respiratory pathogens are an ongoing public health concern. Rapid identification of these viruses early in infection is essential for effective treatment and outbreak control. The AMDI™ Fast PCR Mini Respiratory Panel (MRP) integrates sample preparation and real-time RT-PCR to detect Flu A, Flu B, SARS-CoV-2 and RSV from anterior nasal swab specimens in <10 min at the point of care. We established the analytical performance characteristics of the Fast PCR MRP and determined that the limit of detection (LoD) is 250 copies/mL for Flu A and RSV, and 500 copies/mL for Flu B and SARS-CoV-2. A reproducibility study at 3 clinical sites demonstrated ≥ 98.2% positivity for targets in a weak positive sample, ≥99.6% positivity for targets in a moderate positive sample and ≥99.3% negativity for a negative sample. Fast PCR MRP had 100% analytical reactivity for all strains tested (23 Flu A, 6 Flu B, 8 SARS-CoV-2 and 6 RSV) ≥ 98% predicted in silico inclusivity and no cross-reactivity to 40 microorganisms, nor interference from 15 endogenous and exogenous substances. The Fast PCR MRP delivers excellent analytical performance comparable to high complexity laboratory assays, at the point of care.
The optimal protocol for clinical liver 31P-magnetic resonance spectroscopy (MRS) remains unclear. Single-voxel 31P-MRS using image-selected in vivo spectroscopy (ISIS) employs respiratory-triggering (RT) or free-breathing (FB) acquisition. RT provides robust data but prolongs scan duration; FB allows faster acquisition but may suffer from low signal-to-noise ratio (SNR). Yet, direct comparison using a regulatory-approved coil in a clinical setting has not been reported. To compare 31P-MRS data stability and robustness between RT and FB. Prospective. 24 volunteers (19 male/5 female). 3 T MRI; single-voxel 31P-MRS using ISIS (free induction decay-based) with approved 31P coil. 31P-MRS was performed using RT and FB techniques (128 and 192 signal averages, respectively; expected scan duration ~13 min each). Spectra were analyzed using jMRUI. SNR and peak areas for PME, Pi, PDE, α-ATP, and NADPH, normalized using γ-ATP, were compared. PME/PDE and NADPH/(PME + PDE) ratios were also compared. Paired t-tests and Bland-Altman analysis were used. A p value < 0.05 was considered significant. Scan duration was significantly longer for RT (15 min 44 s) than FB (12 min 56 s). No significant differences were observed for SNR (p = 0.570), NADPH/(PME + PDE) (p = 0.931), PME/γ-ATP (p = 0.556), Pi/γ-ATP (p = 0.931), α-ATP/γ-ATP (p = 0.332), or NADPH/γ-ATP (p = 0.394). Significant differences were noted for PDE/γ-ATP (RT 1.68 vs. FB 1.35, p = 0.003) and PME/PDE (RT 0.434 vs. FB 0.489, p = 0.046). Bland-Altman analysis showed near-zero fixed biases and no proportional bias, with limits of agreement from -0.53 to 0.62 (PME), -0.30 to 0.30 (Pi), -0.41 to 1.07 (PDE), -0.45 to 0.43 (α-ATP), and -0.80 to 0.90 (NADPH). 31P-MRS of the liver showed equivalent stability and robustness for RT and FB. FB yielded comparable data within a shorter, predictable scan duration. 2. 1. The liver plays a central role in the body's metabolism, and phosphorus magnetic resonance spectroscopy (31P‐MRS) is a noninvasive technique that can measure liver energy and membrane metabolism without a biopsy. A recently approved commercial coil now makes it possible to perform 31P‐MRS on standard clinical MRI systems at any facility. However, the optimal acquisition protocol for obtaining stable, high‐quality data within a clinically acceptable scan time has not yet been established. This study compared two approaches in 24 healthy volunteers, both designed to complete within approximately 13 min: respiratory triggering and free breathing. Both methods produced equivalent measurements of key liver metabolites, but free breathing consistently delivered a fixed, predictable scan duration, making it more practical for routine clinical use.
Respiratory epidemics often place substantial pressure on intensive care units (ICU), which are continuously challenged to managing acute and life-threatening conditions under unpredictable workloads. During these periods, ICUs usually exhibit inefficient patient flows, treatment delays, and critical resource shortages. Proactive decision-making and precise interventions are therefore pivotal for patient survival and minimizing long-term sequelae. This paper proposes a robust approach combining Artificial Intelligence (AI), Bayesian Optimization, and Digital Twin (DT) to support ICU patient flow management. An eXtreme Gradient Boosting (XGBoost) algorithm is used to predict the patient transfer probability from the emergency department (ED) to the ICU within the next 24 h. Bayesian optimization is employed for efficient hyperparameter tuning of the XGBoost model. Then, the transfer predictions are inserted into a DT to verify ICU capacity for timely care and design interventions for process mismatches. A case study from a European healthcare group validates the proposed approach. The specificity of the prediction XGBoost model was 94.90% (CI 95% 91.72% - 97.11%), whereas the sensitivity was 81.55% (CI 95% 72.70% - 88.51%). Finally, the median ICU bed waiting time decreased to between 66.74 and 69.38 h after implementing a patient transfer policy with a partner hospital having available ICU beds. This study demonstrates the effectiveness of AI-DT in predicting the probability of ICU transfers, assessing the operational response of emergency wards and intensive care units, and crafting practical scenarios for enhancing patient flow management.
Increasing frequency and intensity of marine heatwaves pose growing challenges to intertidal bivalves. This study investigated the effects of gradual temperature elevation on respiratory metabolism and associated physiological responses in the clam Mactra veneriformis. Oxygen consumption rate (OCR), ammonia excretion rate (AER), gill histology, Na+/K+-ATPase activity, and metabolomic profiles were examined at 17-28 °C. OCR increased significantly with temperature (p < 0.05), suggesting elevated aerobic metabolic demand. In contrast, AER showed a unimodal pattern, increasing to a peak at 26 °C and declining at higher temperatures, possibly reflecting physiological constraints under thermal stress. O:N ratios remained above 7, indicating a mixed utilization of metabolic substrates with a greater contribution of lipids and carbohydrates. Gill structure remained intact at lower temperatures but exhibited looser architecture at 26-28 °C, suggesting structural adjustment. Na+/K+-ATPase activity increased progressively with temperature, indicating higher ion-transport demand. Metabolomic analysis identified 2426 metabolites, with differential metabolites mainly enriched in lipid-related pathways. Overall, gradual warming induced coordinated physiological and metabolic responses in Mactra veneriformis, providing an integrated perspective on its response to thermal stress.
Mitochondria are well established as key supporters of synaptic plasticity, yet the nanoscale spatial distribution of specific mitochondrial membrane proteins during this process remains poorly understood. Using 3D MINFLUX nanoscopy, we investigated their polarized distribution within synapses of cortical neurons undergoing chemical long-term potentiation (cLTP). Upon cLTP induction in DIV17 neurons, we observed an increased mitochondrial occupancy in stimulated synapses. Respiratory complexes of the inner mitochondrial membrane (IMM)-such as COX-IV and SDHA-showed a polarized accumulation near presynaptic sites, as validated by cluster analysis and 3D mapping. By contrast, outer mitochondrial membrane (OMM) proteins, including TOMM20 and VDAC, exhibited no significant polarized distribution. Together, these results demonstrate that cLTP selectively remodels the inner mitochondrial membrane to address localized energy requirements, highlighting the power of 3D MINFLUX for resolving protein organization with subcellular precision.
Previously, young children had limited respiratory support options during interfacility transport. Recently, high-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) have become available for pediatric transport. We hypothesized that the implementation of HFNC and NIV on interfacility transport decreases the rate of intubation in infants and toddlers before and after transport to a tertiary-care pediatric intensive care unit (PICU). We conducted a retrospective chart review of children aged 30 days to < 36 months transported to a tertiary-care PICU from a referring hospital with respiratory distress from 2014 to 2019. Groups were analyzed before (2014-2017) and after the implementation (2017-2019) of HFNC and NIV during transport. NIV was defined as positive pressure ventilation delivered through nasal cannula. The primary outcome was to compare the pre- and postimplementation groups with regard to the rate of intubation before transport and within 48 hours of PICU admission. Secondary outcomes were the association between intubation rate and comorbidities and the comparison of length of respiratory support and hospital length of stay between the pre- and postimplementation groups. A total of 262 patients met criteria, 133 before and 129 after the intervention. The rate of intubation before PICU admission was 44% in the preintervention group versus 36% in patients transported after the implementation of HFNC and NIV, a trend that was not statistically significant (P = .19). The rate of intubation within 48 hours of PICU admission was 8% (before) and 11% (after) with no statistical significance (P = .48). Comorbidities were not associated with an increased rate of intubation before transport (P = .09) or within 48 hours of admission (P = .45). Hospital length of stay and length of respiratory support were not different between pre- and postintervention groups (P = .18 and P = .3, respectively). The availability of HFNC/NIV was associated with a significant decrease in the proportion of patients who received oxygen via nasal cannula or face mask during transport (46% before vs. 13% after the intervention; P < .01). After the introduction of HFNC/NIV during transport to a large tertiary-care hospital in a major metropolitan area, fewer nasal cannula/face masks were used during transport in favor of HFNC/NIV but no significant change in intubation rates was found.
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.
Endotracheal suctioning is a routine procedure in the pediatric ICU (PICU) and can be performed via open or closed systems. Closed-system suctioning has benefits for pressure maintenance in the ventilatory system and oxygen supply during the technique but is less effective. The association of an expiratory pause in closed-system suctioning is an alternative technique. We sought to evaluate the volume of suctioned secretions, respiratory mechanics, and hemodynamic parameters during closed endotracheal suctioning with expiratory pause, compared with conventional closed suctioning. Randomized crossover pilot trial with infants receiving invasive mechanical ventilation >24 h, with neuromuscular blocker, without cough reflex, randomized to define the order of suctioning techniques (T1-technique 1 conventional suctioning without expiratory pause; T2-technique 2: with expiratory pause), performed with a 2-h interval. Evaluated hemodynamic parameters (heart rate, blood pressure, and peripheral arterial oxygen saturation), respiratory mechanics (static and dynamic compliance, inspiratory and expiratory resistance, driving pressure), and suctioning secretion were weighed on a precision balance. Shapiro-Wilk test for normally distributed variables analysis and generalized estimating equation for effect analysis. Ten infants were included with a median age of 2 months (1.0-3.7). The amount of secretions from the technique with expiratory pause was significantly higher compared with conventional suctioning (mean 1.4 g vs 1.1 g; P < .001). Treatment effect was observed in the analysis of driving pressure (P < .001) and inspiratory resistance (P = .02), with an increase in these variables after suctioning with expiratory pause. There were no significant differences in hemodynamic variables. The closed-system suctioning with expiratory pause was more effective in secretion removal compared with conventional closed suctioning. However, driving pressure and inspiratory resistance increased after suctioning with an expiratory pause.
Severe scoliosis with prior corrective spinal surgery poses significant anesthetic challenges in obstetric patients due to altered spinal anatomy and potential respiratory compromise. Conventional neuraxial or general anesthesia may be risky, making alternative approaches necessary for safe cesarean delivery. The Taylor paramedian technique provides an effective option by bypassing distorted midline anatomy. A 35-year-old primigravida (G1P0) at 37±1 week's gestation with surgically corrected thoracolumbar scoliosis and restrictive pulmonary disease, complicated by bronchopneumonia, was admitted for cesarean delivery. Preanesthetic assessment revealed limited cervical mobility, restricted mouth opening, and challenging spinal landmarks. Initial midline puncture at L3-L4 failed, so a paramedian Taylor approach at L5-S1 using anatomical landmarks was performed. Intrathecal 12 mg plain 0.5% bupivacaine with 20 µg fentanyl achieved complete sensory and motor block. Maternal hemodynamics remained stable with normal oxygenation. Cesarean section was completed uneventfully, delivering a healthy neonate weighing 3 kg with Apgar scores 8 and 9. Postoperative recovery was smooth, and the patient was discharged on day 3. Paramedian Taylor spinal anesthesia is a safe and effective alternative in parturients with severe scoliosis and restrictive pulmonary disease. Individualized planning, technical expertise, and careful execution allow complete sensomotor block, minimize respiratory risk, and ensure successful cesarean delivery in high-risk patients.
The impact of bracing on pulmonary function in adolescent idiopathic scoliosis (AIS) remains unclear, with prior studies reporting variable findings. Some report short-term reductions during brace wear, whereas long-term impairment has not been consistently demonstrated. To clarify these effects, we conducted a systematic review and meta-analysis of controlled clinical trials. PubMed, Web of Science, and Scopus were searched from inception to 15 October 2025, following PRISMA 2020 guidelines, along with screening of reference lists. Eligible studies were controlled trials evaluating the effects of bracing on pulmonary parameters in AIS. Two reviewers independently screened and extracted data, evaluated methodological quality using the Cochrane Risk of Bias tool, and performed pooled analyses. Fourteen studies met the inclusion criteria, involving 548 participants. Pooled findings indicated short-term reductions in several pulmonary measures. Immediate decreases were observed in total lung capacity (SMD = - 0.83, p = 0.01) and functional residual capacity. FVC and FEV1 showed significant short-term reductions at 1 month (SMD = - 0.68 to - 0.76, p < 0.001), followed by normalization at 2 months, and again a moderate decline at 6 months (SMD = - 0.62, p = 0.007). The FEV1/FVC ratio was significantly reduced at 6 months (SMD = - 1.05, p = 0.007). Changes in peak expiratory flow and maximum voluntary ventilation were also reported across 1-8 months. Many assessments were conducted in‑brace, suggesting that the observed reductions may reflect transient mechanical restriction, rather than persistent physiological impairment. Out‑of‑brace or longer‑term measurements were generally non‑significant. Current evidence indicates that bracing in AIS may lead to short‑term or in‑brace reductions in lung volumes and ventilatory parameters, while persistent or irreversible impairment after brace removal has not been demonstrated. These findings support a mechanical rather than pathological explanation for most observed changes. Incorporating mitigating strategies, such as respiratory muscle training, may help manage short-term respiratory effects during brace treatment.
Achondroplasia (ACH) is the most common skeletal dysplasia characterized by disproportionate short stature due to impaired endochondral ossification. One of the most critical and potentially fatal complications of ACH is foramen magnum and upper cervical canal stenosis. Compression at the cervicomedullary junction may lead to myelopathy, hypotonia, developmental delay, and central sleep apnea. Early detection and timely surgical intervention are essential to prevent permanent neurological injury. This retrospective study evaluated 15 pediatric patients with ACH (9 girls, 6 boys; age range 3-42 months, mean 17.2 months) who underwent foramen magnum decompression and C1 laminectomy at Marmara University Neurosurgery Department between 2016 and 2025. All patients underwent comprehensive neurological and radiological evaluation, including MRI and 3D CT of the craniovertebral junction, and were classified by the Achondroplasia Foramen Magnum Score (AFMS). Nine patients had AFMS level 4 stenosis and six had level 3. The anteroposterior diameter of the foramen magnum ranged from 4.03 to 11.03 mm, with an area between 17.40 and 105.16 mm2. Presenting symptoms included motor delay (n = 4), respiratory disturbances or central apnea (n = 4), and macrocephaly (n = 3). Postoperative imaging confirmed adequate decompression in all patients. Neurological and respiratory improvement occurred in all patients except one with persistent hypotonia. One patient died early postoperatively due to recurrent pneumonia and sepsis. Complications were minimal. Foramen magnum decompression with C1 laminectomy is a safe and effective procedure for infants and children with achondroplasia presenting with cervicomedullary compression. Early radiological and neurological evaluation, particularly with AFMS, facilitates accurate surgical decision-making and improves outcomes.
Current diagnostics for ischemic stroke (IS) lack timeliness and accessibility, highlighting the need for novel molecular diagnostic models. Three gene expression datasets (GSE16561, GSE22255 and GSE58294), encompassing both IS patients and healthy control subjects, were retrieved from a public database. The mitochondrial dysfunction genes retrieve from the intersection of the GeneCards and MitoCarta3.0 databases. The limma and WGCNA package were used to obtain the genes related to IS. Feature genes were screened using LASSO, RF, SVM, and diagnostic models were constructed using NeighborMethod, NeuralNet, and BayesMethod. 3548 differentially expressed genes (DEGs) (1538 upregulated, 2010 downregulated) were identified in IS patients when compared to controls. WGCNA analysis yielded 10 IS-related modules containing 1643 genes. The intersection of DEGs, module genes, and mitochondrial dysfunction genes yielded 100 mitochondrial dysfunction genes associated with IS. These genes collectively regulate biological processes like mitochondrial ATP synthesis coupled electron transport and respiratory electron transport chain, and participate in IS-associated signaling pathways such as reactive oxygen species and oxidative phosphorylation. Further machine learning methods identified 4 feature genes, including MCL1, MRPL46, MTX3 and RNASEH1. These four genes exhibited robust diagnostic potential in the merged dataset (all AUC > 0.7). The machine learning models achieved AUC values of 0.814 (NeighborMethod), 0.852 (NeuralNet), and 0.842 (BayesMethod). External validation using an independent cohort confirmed that all models maintained high diagnostic accuracy (AUC range: 0.730-0.783). This study established a multi-gene diagnostic model for IS, identifying novel molecular biomarkers to improve the timeliness and accessibility of IS diagnosis.
The severe gag reflex (SGR) is an involuntary protective response to foreign substances. SGR presents a significant obstacle to the provision of standard dental care. This retrospective case series study evaluates the clinical outcomes and the feasibility of low-dose (2.5 mg) intranasal midazolam administration on SGR control in uncooperative patients with Gagging Severity Index 5. This retrospective study includes patients who could not receive endodontic treatment due to the severe gag reflex and were referred for general anesthesia. Data from 13 adult patients, one of whom had an intellectual disability, were used. A fixed low-dose (2.5 mg) of intranasal midazolam was administered under the control of an anesthesiologist. Clinical monitoring (vital signs) focused on respiratory effort, skin color, and the maintenance of verbal commands. Endodontic treatment was started with local anesthesia approximately 10 minutes after 2.5 mg midazolam administration, averaging 40 minutes per session. All patients remained conscious, responsive to verbal commands, and cooperative during treatment. One patient received intranasal saline as an ad-hoc clinical observation, but midazolam was later administered due to persistent gagging. SGR was effectively managed in all patients during initial and ongoing sessions of endodontic treatment without side effects. All necessary dental procedures, including root canal treatment and restorations, were performed comfortably. A conservative 2.5 mg dose of intranasal midazolam can safely control severe gag reflex in adult patients during long and complex dental procedures, such as endodontic treatment. Also, it is a practical, less invasive alternative to general anesthesia.
Tuberculosis (TB) remains a significant public health challenge in Northeast Iran, yet longitudinal data evaluating regional transmission patterns following COVID-19 disruptions remain limited. This cross-sectional study, conducted from 2017 to 2023 at Qaem University Hospital, Mashhad, Iran, analyzed 14,572 patients with suspected TB using smear microscopy, culture, and PCR to characterize the test positivity rate (TPR), temporal shifts, and diagnostic challenges. We identified a 10.3% TPR (1,494 out of 14,572), with significant demographic disparities: females accounted for 51.7\% of cases (OR = 0.74, 95\% CI: 0.665-0.824; p < 0.001), although the association strength was weak (Cramér's V = 0.05). Adults aged 65 and older represented 51.6\% of the cases. The COVID-19 pandemic led to a 33.3\% decline in diagnoses from 2019 to 2020, with outpatient recovery lagging behind inpatient services. Time-series analysis identified a significant structural break in March 2020 (p < 0.001), statistically confirming the sharp decline in diagnoses due to the pandemic. Bronchoalveolar lavage showed the highest positivity rate at 54.7\%, identifying 135 smear-negative/culture-positive cases. Seasonal peaks in spring (27.8\%) are hypothesized to result from post-winter Vitamin D troughs and social gatherings during Nowruz. These findings emphasize the importance of geriatric-focused screening, multimodal diagnostic protocols, and pandemic-resilient TB surveillance. Regional policies should focus on integrated respiratory screening and community-based interventions to reduce seasonal transmission.