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Across practice and policy, assistive technologies (ATs) are positioned as a pathway to economic inclusion for graduates with sensory disabilities in South Africa. Still, systemic barriers persist. Developing workable interventions requires in-depth attention to the lived experiences of graduates, which include knowledge on the way devices, systems and attitudes interact in everyday employment seeking and enterprise activities. The study endeavoured to examine how unemployed tertiary-level graduates with sensory disabilities in Gauteng use AT in seeking employment and practising entrepreneurship. Specific enablers and challenges were identified to provide an explanation of variation in economic participation. Interpretive methods guided the study within a qualitative design. Sixteen participants took part in semi-structured interviews: 10 unemployed graduates (with visual or hearing impairments), three human resources professionals and three helping professionals. Coding and analytic development followed Braun and Clarke's six-phase thematic approach. Overall patterns were organised into six themes: (1) discrimination and stigma, (2) accessibility, (3) use and effectiveness of AT, (4) training and support, (5) institutional and government support, and (6) self-initiated strategies and adaptation. Device access proved insufficient. Most constraints operated at the system level, consistent with the social model of disability, as stigma, accessibility failures, limited training and weak enforcement shaped outcomes. Sustained change had to address stigma, accessibility, training and support and accountable policy implementation through coordinated multi-stakeholder action. By centring graduate voices, this article contributed evidence on adaptability and multi-stakeholder lenses relevant to inclusive policy and practice in resource-constrained settings.

Amyotrophic lateral sclerosis (ALS) is traditionally viewed as a late-onset motor neuron disease, yet how cortical dysfunction originates and contributes to pathogenesis remains unresolved. In this study, we reconstruct the developmental trajectory of cultured cortical networks derived from SOD1G93A mouse embryos using a multimodal approach, by combining morphometric, electrophysiological, pharmacological, molecular, computational, and machine-learning techniques. We prove that ALS neurons fail to acquire mature polarization and connectivity, displaying a transient phase of hyperexcitability that precedes a progressive collapse of network organization. Astrocytic dysfunction emerges early and impairs synchronization, establishing a causal link between glial dysfunction and neuronal instability. The analysis of synaptic transmission reveals an excitatory bias followed by maladaptive inhibitory recruitment and GABA/glutamate co-release, causing fragmented and inefficient network topologies. Finally, in silico modelling identified deficient intrinsic adaptation as a key driver of hyperexcitability. Together, our findings position ALS as a developmentally rooted disorder of cultured cortical network homeostasis, driven by glial, synaptic, and intrinsic adaptation failures. By demonstrating that cortical dysfunction is embedded before degeneration, this work provides a unifying framework connecting early network instability to disease progression and establishes electrophysiological network signatures, detected by machine learning classifiers, as candidate biomarkers for early diagnosis and therapeutic screening.

Perinatal HIV transmission is rare when maternal HIV RNA is undetectable, yet transmission can still occur. This report describes an infant diagnosed with HIV at 6 months of age despite the mother's documented viral suppression. Missed opportunities in monitoring and care coordination and proposed solutions to prevent future failures are outlined. This case underscores three key themes: the small but real residual risk of perinatal transmission even with reported suppression, the vulnerability created by lapses in maternal monitoring, and the importance of integrated, multidisciplinary care.

Acrylamide (ACR) is a heat-generated carcinogen, one of the most common toxins, with various effects on the biological system, including oxidative stress and related disorders. Umbelliferone (UMB) is a naturally occurring coumarin derivative that is present in edible fruits, known as an antioxidant, and reported for many other therapeutic effects. In the current study, UMB was evaluated for neuro- and hepatoprotective activity against oxidative stress toxicity induced by a 40 mg/kg daily dose of ACR in a mouse model over 15 days. Also, UMB was used as a ligand for the first time to predict its affinity for the most important proteins involved in neuronal failure. The UMB administration significantly improves liver enzyme elevations, alanine transaminase (ALT) and aspartate transaminase (AST), following ACR injection. Also, UMB treatment reduced elevated total protein (TP) and albumin (ALB) serum levels. In addition, lipid peroxidation levels were significantly reduced by UMB (expressed as malondialdehyde MDA levels), and the levels of total non-enzymatic antioxidant capacity (TAC) were increased in brain tissue homogenate in comparison with brain injury in the ACR group. Furthermore, UMB downregulated the expression of tumor necrosis factor-alpha (TNF-α), an inflammatory marker and caspase-3, an apoptotic marker, while upregulating heme oxygenase-1 (HO-1), an antioxidant enzyme, in both liver and brain tissues. Molecular docking analysis revealed that the compound could form H-bonds and hydrophobic interactions with the target receptors. Results of this study conclude that UMB may be considered a potential pharmaceutical agent to ameliorate ACR-induced toxicity in the liver and brain, due to its anti-inflammatory, antioxidant, and antiapoptotic mechanisms, as well as its moderate affinity for neuronal disease-targeted proteins.

Spinal mucormycosis is an exceptionally rare form of invasive fungal infection, with fewer than 12 confirmed cases reported in the prior literature. Immunocompromised patients are disproportionately affected, and mortality exceeds 50% in this population. Chronic liver disease as a primary predisposing condition is underrepresented in the existing case series. A 54-year-old male with Child-Pugh Grade C chronic liver cirrhosis, diabetes mellitus, and hypothyroidism presented with progressive low back pain and bilateral lower limb weakness of one week duration. Lumbar MRI demonstrated L2-L3 spondylodiscitis with epidural abscess formation, initially attributed to Pott's spine, and antitubercular therapy (ATT) was initiated empirically. Rapid neurological deterioration prompted surgical re-evaluation. The patient underwent an L3 laminectomy with drainage of an L3-L4 anterior epidural abscess. Intraoperative microscopy revealed aseptate ribbon-like hyphae consistent with Mucorales species. Liposomal Amphotericin B (5 mg/kg/day), intravenous micafungin, and oral posaconazole were commenced. Antifungal therapy was complicated by progressive nephrotoxicity and hepatic decompensation requiring repeated dose modifications. The patient developed hepatic encephalopathy with sepsis and died on Postoperative day (POD) 12 from multiorgan failure. This case represents the 12th documented instance of spinal mucormycosis and the first attributable to Child-Pugh Grade C liver disease. In tuberculosis-endemic settings, mucormycosis must be considered in the differential diagnosis of apparent Pott's spine in immunocompromised patients, particularly those with progressive neurological deterioration despite empirical ATT. Concurrent hepatic and renal impairment substantially constrains antifungal options and worsens prognosis. Multidisciplinary coordination and early tissue diagnosis are critical to the management of this rare, life-threatening condition.

Patients with multiple sclerosis (MS) have a higher incidence of heart failure and myocardial infarction. In patients with MS, autonomic dysregulation may cause detrimental hemodynamic instability perioperatively. However, data on outcomes of cardiac surgery in patients with MS are scarce. To describe US nationwide morbidity and mortality in patients with MS undergoing cardiovascular surgery. This cross-sectional study included records of patients who underwent coronary artery bypass grafting, valve, aortic, or combined cardiovascular surgery between 2016 and 2022 in the National Inpatient Sample database. The association between MS and surgical outcomes at admission was evaluated using a balancing-score matched cohort. Data were analyzed between November 1 and 26, 2025. Multiple sclerosis. In-hospital mortality, complications, length of stay, costs, and discharge disposition. Records for 1&#x202f;766&#x202f;170 patients (3605 with MS and 1&#x202f;762&#x202f;565 without) were included. The MS cohort was younger (median [IQR] age, 63 [57-69] years vs 67 [58-70] years) and had a larger proportion of women (2025 [56%] vs 488&#x202f;850 [28%]). Patients with MS, vs those without, exhibited higher frequencies of comorbidities, including chronic lung disease, depression, hypothyroidism, paralysis, psychosis, and valvular disease. In the matched cohorts of 3530 patients, mortality did not differ significantly between patients with MS and those without MS (70 [2.0%] vs 130 [3.7%]; P&#x2009;=&#x2009;.05). The prevalence of a composite complication end point was also comparable between groups (1770 [50%] vs 1810 [51%]; P&#x2009;=&#x2009;.67). This included similarities in prevalence of stroke, acute kidney failure, pulmonary embolism, deep vein thrombosis, gastrointestinal (GI) bleeding, non-GI bleeding, prolonged mechanical ventilation, tracheostomy, pneumonia, surgical site infection, sepsis, blood transfusion, pericardial effusion, fluid overload, and pacemaker requirement. However, discharge disposition differed significantly, with a lower prevalence of routine home discharges in the MS cohort (985 [28%] vs 1265 [36%]; P&#x2009;<&#x2009;.001). Median hospitalization cost ($41&#x202f;285 [IQR, $31&#x202f;508-$56&#x202f;040] vs $40&#x202f;328 [IQR, $30&#x202f;604-$56&#x202f;202]; P&#x2009;=&#x2009;.44) and median length of stay (8 [IQR, 6-12] days in both groups; P&#x2009;=&#x2009;.33) did not differ between cohorts. This cross-sectional study suggests that MS is not associated with increased in-hospital mortality or complications in patients undergoing cardiovascular surgery, although the prevalence of routine home discharges was lower among patients with MS. Surgeons may consider a team approach with neurological experts to optimize perioperative care and increase routine home discharges.

Redo aortic valve replacement after bioprostheses failure carries high risk from friable tissue, pannus ingrowth, and potential root reconstruction. Building on the Surgical Resection of Prosthetic Valve Leaflets Under Direct Vision (SURPLUS) technique for failed transcatheter valves, we describe a novel evolution for failed surgical bioprostheses: Surgical Valve Preservation and Resection of Bioprosthetic Leaflets (SUPERB). In SUPERB, degenerated leaflets are excised while the supporting ring is preserved, permitting deployment of a balloon-expandable prosthesis under direct vision. Between January 2023 and August 2025, 3 high-risk patients with degenerated aortic valves underwent redo replacement at a tertiary center: 2 with failed surgical bioprostheses (SUPERB) and 1 with a failed transcatheter prosthesis (SURPLUS). All were unsuitable for valve-in-valve transcatheter replacement due to low coronary heights, pannus ingrowth, or small annuli. Operative details, perioperative course, and follow-up echocardiography were reviewed. All patients underwent successful leaflet excision with balloon-expandable valve deployment and confirmed coronary patency. Cross-clamp and cardiopulmonary bypass times were minimized vs conventional explantation, and no annular disruption or root replacement was required. Postoperative complications included transient acute kidney injury (n = 2), delirium (n = 1), hypotension (n = 1), and urinary retention (n = 1). All were discharged to rehabilitation. At follow-up, the prostheses remained functional with preserved ventricular performance and no valvular regurgitation. The SUPERB technique extends the SURPLUS concept to failed surgical bioprostheses, providing hybrid alternatives to complete prosthesis explantation. These strategies may reduce operative risk by shortening cross-clamp and bypass times, preserving coronary access, and avoiding root reconstruction. Multicenter evaluation is warranted.

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Sanjad-Sakati syndrome (SSS), also known as hypoparathyroidism-intellectual disability-dysmorphism syndrome, is a rare autosomal recessive disorder caused by a TBCE founder mutation. The full disease spectrum remains poorly understood. To comprehensively analyze growth, phenotype, endocrine manifestations, and mortality in a large multicenter SSS cohort. Clinical and genetic data were collected from 135 individuals across centers in the Gulf region using a REDCap survey. The median age at inclusion was 9.1 years (range: birth-30 years; 50.3% female). The homozygous TBCE founder mutation (c.155_166del; p.Ser52_Gly55del) was detected in all genetically tested individuals (n&#x2009;=&#x2009;68). Intrauterine growth restriction (mean birth weight -3.0 SD, length -3.3 SD) and dysmorphic features were universal. Postnatal growth showed severe failure to thrive during infancy, followed by persistently low height z-scores (-7 to -8). Endocrine features included hypoparathyroidism in all patients, primary hypothyroidism (16.5%), hypoglycemia (27.8%), non-autoimmune insulin-dependent diabetes (1.6%) and pituitary hormone deficiencies. Other findings included developmental delay (100%), hypocalcemic seizures (64.2%), tetany (53.3%), nephrocalcinosis (62.1%), gastroesophageal reflux (29.1%), and recurrent respiratory (63.7%) and bacterial infections (53.8%). Antibiotic prophylaxis was used in 35% of patients. Kaplan-Meier analysis estimated a median survival of 27.2 years, with respiratory failure causing 84% of deaths (21/25). The estimated overall survival at an age of 18 years was 62.4%. This largest reported SSS cohort highlights the high prevalence of associated endocrine, respiratory, and gastrointestinal manifestations, with respiratory failure as the leading cause of death. These data support the need for multidisciplinary care guidelines.

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Inferior vena cava (IVC) filters are used to prevent pulmonary embolism in patients with deep vein thrombosis (DVT). Although generally safe, long-term indwelling filters may cause complications such as fracture, migration, and organ perforation. Cardiac tamponade due to right atrial (RA) perforation is extremely rare, particularly with permanent filters. A 60-year-old woman presented to our institution with sudden epigastric pain. She had undergone permanent IVC filter placement 13 years earlier for DVT and had remained on warfarin thereafter. At the initial hospitalization, electrocardiography (ECG) showed mild ST-segment depression and cardiac biomarkers were slightly elevated. Transthoracic echocardiography and contrast-enhanced CT showed no pericardial effusion, and coronary angiography (CAG) revealed no significant coronary stenosis, although a linear radiopaque structure was incidentally observed near the cardiac silhouette. Vasospastic angina was suspected, and she was discharged after symptom improvement. Three days later, she returned with worsening dyspnea and general fatigue. Transthoracic echocardiography revealed pericardial effusion, and contrast-enhanced CT demonstrated a hyperdense fragment in the RA, additional fragments around the right ventricle (RV), and penetration of the filter into the duodenum. Comparison with CT obtained 4 years earlier showed a newly developed structural defect of the filter, consistent with fracture. Warfarin was discontinued, and no heparin bridging was performed because of the bleeding risk. The patient underwent a sequential open surgical approach consisting of laparotomy followed by median sternotomy, with filter removal and repair of the duodenal perforation performed during the abdominal phase and removal of the migrated fragment and repair of the RA perforation performed under cardiopulmonary bypass during the cardiac phase. Her postoperative course was uneventful, with no recurrent pericardial effusion or IVC obstruction during 2 years of follow-up. Late structural failure may occur even in permanent IVC filters, and migrated filter components can cause life-threatening cardiac tamponade long after implantation.

This study aimed to assess the association between the Model for End-Stage Liver Disease excluding international normalized ratio (MELD-XI) score and heart failure (HF) after isolated mitral valve surgery for degenerative mitral valve regurgitation (dMR). Patients undergoing mitral valve surgery for dMR were divided into groups of high MELD-XI score (>11, n = 28) and low MELD-XI score (&#x2264;11, n = 144). The primary end point was early HF events, defined as operative mortality, use of mechanical circulatory support, and prolonged use of inotropic agents after the surgery. The secondary end point was a composite outcome consisting of all-cause mortality and HF admission. The median follow-up period was 338 (70-789) days. Thirty-day mortality rate was 0.7% in the low MELD-XI score group and 3.6% in the high MELD-XI score group (P = .737). The prolonged use of inotropic agents was significantly higher in the high MELD-XI score group than in the low MELD-XI score group (25.0% vs 6.9%; P = .015). Freedom from composite outcomes was significantly lower in the high MELD-XI score group than in the low MELD-XI score group (log-rank, P < .001). MELD-XI score (odds ratio, 1.10 [95% CI, 1.01-1.19]; P = .023) was identified as a significant risk factor of the early HF events. Multivariate Cox regression analysis found the MELD-XI score (hazard ratio, 1.07 [95% CI, 1.01-1.14]; P = .027) to be a significant risk factor for the composite outcome after surgery. In patients undergoing isolated mitral valve surgery for dMR, elevated preoperative MELD-XI score was associated with an increased risk of early HF events and the composite outcome.

Arrhythmias in childhood are often challenging to diagnose and treat for a pediatrician. Tachyarrhythmias may or may not be associated with underlying structural heart disease or ion channel defects, and may also occur in the post-operative setting. Symptoms vary from excessive crying, irritability and failure to thrive, to palpitations, heart failure and syncope. Knowledge of the normal 12 lead ECG (electrocardiogram) in various stages of life and its transition to adulthood is essential in order to distinguish abnormal ECG from normal variants. Management in acute settings as well as long term medical management and interventional therapies are important. Both, cardiologists as well as pediatricians should be well-versed in the diagnosis and management of tachyarrhythmias in children.

BackgroundAcute liver failure (ALF) is a life-threatening syndrome characterized by abrupt hepatic dysfunction accompanied by systemic inflammatory response and immune dysregulation, resulting in a high susceptibility to infectious complications. In the intensive care unit (ICU) setting, bacterial sepsis and invasive fungal infections represent critical determinants of multiorgan failure, liver transplant eligibility, and patient survival.Main bodyThis narrative review synthesizes current evidence on infectious risk, diagnostic challenges, and antimicrobial management in ALF. The immune response to massive hepatocellular necrosis is initially driven by damage-associated and pathogen-associated molecular patterns, resulting in a sepsis-like hyperinflammatory state. This phase is followed by profound immunoparesis, characterized by impaired innate and adaptive immune responses, which facilitates fbacterial translocation, increases susceptibility to nosocomial infections, and promotes colonization and infection with multidrug-resistant (MDR) pathogens. Infections occur in most ALF patients, yet differentiation between sterile systemic inflammatory response and sepsis remains challenging as fever, leukocytosis, and hemodynamic instability are nonspecific and microbiological cultures frequently yield negative results. Conventional biomarkers primarily reflect hepatocellular injury rather than bacterial infection. Antimicrobial therapy should be individualized based on clinical severity, local epidemiology, and MDR colonization, while accounting for profound pharmacokinetic alterations associated with hepatic failure. In liver transplant candidates and recipients, short-course perioperative prophylaxis and judicious interpretation of MDR screening are pivotal to prevent early postoperative infections without promoting antimicrobial resistance.ConclusionsOptimizing infection diagnosis, biomarker-guided decision-making, and individualized antimicrobial dosing in ALF, particularly in the peri-transplant ICU setting, is critical for improving patient outcomes and limiting the emergence of MDR pathogens.

Extracorporeal life support (ECLS) is the most advanced form of life support in existence for patients experiencing acute cardiac and/or pulmonary failure. However, major limitations for the use of ECLS, in both far-forward and transport environments, are the difficulty of its initiation, the need for adjunctive imaging to avoid damage to the heart and great vessels, and difficulty confirming correct cannula placement. We hypothesize that a dual-lumen cannula (DLC) modified for femoral vein placement will make cannula placement by an individual feasible and will overcome constraints of large imaging adjuncts and limited personnel experience. This type of design may lead to a faster, safer, and more reliable delivery of ECLS to the patient. Herein, our objective is to create recommendations for the design of a DLC for femoral vein placement. We present findings from the placement of a femoral DLC using a simulation mannequin and subsequent interviews with hospital, military, and academic personnel.

The heart is a structurally complex organ where function is intimately tied to the precise spatial organization of diverse cell types. While single-cell RNA sequencing (scRNA-seq) has revolutionized cardiovascular research by providing a high-resolution "parts list" of the heart, the requisite tissue dissociation destroys the critical spatial context of intercellular communication and microenvironmental niches. Spatial transcriptomics (ST) has emerged as a transformative technology that bridges this gap, enabling the mapping of gene expression back to its histological coordinates. This review discusses the rapidly evolving landscape of spatial technologies, categorizing them into sequencing-based methods (e.g., Visium, Stereo-seq) which offer transcriptome-wide discovery, and imaging-based methods (e.g., MERFISH, Xenium, CosMx) which provide subcellular resolution with high sensitivity. We highlight recent applications of these tools in uncovering the spatial architecture of the heart at homeostasis and following injury. Furthermore, we explore the next frontier of spatial multi-omics, including simultaneous profiling of the proteome via sequential immunofluorescence (seq-IF) and expansion proteomics (iPEX), as well as chromatin accessibility. We conclude by discussing the computational challenges and future perspectives of integrating these multi-modal datasets to construct comprehensive atlases of the healthy and injured heart.

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Heart failure is a leading cause of morbidity and mortality worldwide, particularly among the growing elderly population. In degenerative aging and autoimmune diseases, the cytoplasmic leak of mitochondrial DNA, resulting from mitochondrial cristae compromise, triggers persistent low-grade cellular inflammation through activation of the cGAS (cyclic GMP [guanosine monophosphate]-AMP [adenosine monophosphate] synthase)-STING (stimulator of interferon genes) pathway and the IFN-I (type I interferon) response. However, how and whether mitochondrial architectural components and cardiomyocyte inflammation drive cardiac aging and failure are not yet well understood. We investigated the function of STMP1 (short transmembrane mitochondrial protein 1), a 47-amino acid nuclear-encoded mitochondrial-localized peptide featuring a distinctive GxxxGxxxG glycine zipper domain. A mouse with cardiomyocyte-specific knockout of Stmp1 (Stmp1-KO) was generated to investigate its role in cardiac function. We profiled the transcriptome, proteome, and metabolome of Stmp1-KO hearts to determine its functional mechanism of action. Electron microscopy was used to assess the impact of STMP1 depletion and functional rescue after adeno-associated virus 9-mediated gene restoration in the Stmp1-KO mouse. STMP1 is downregulated specifically in cardiomyocytes, and not other cardiac cell types, in aged mice and humans. Genetic loss of Stmp1 in cardiomyocytes resulted in heart failure in vivo. STMP1 interacts with components of the cristae organizing complexes MICOS (mitochondrial contact site and cristae organizing complex) and SAM (sorting and assembly machinery). Consequent to Stmp1 loss, mitochondrial cristae were destabilized, mitochondrial DNA was mislocalized to the cytosol, and the cGAS-STING pathway was activated, with ensuing cellular inflammation and cardiomyocyte cell death. Restoration of wild-type Stmp1 or STING inhibition significantly rescued cardiac function in vivo. Our work reveals a mechanism connecting the micropeptide STMP1 to mitochondrial cristae architecture and cardiomyocyte cellular inflammation, both of which are present as potential drivers of heart failure and cardiac aging.

Whether integrated rehabilitation strategies spanning intensive care unit (ICU), hospital, and postdischarge phases improve quality of life after acute respiratory failure is uncertain. To evaluate the effect of an integrated multicomponent telehealth-based rehabilitation intervention on health-related quality of life at 90 days after hospital discharge among adults with acute hypoxemic respiratory failure requiring invasive mechanical ventilation. This stepped-wedge cluster randomized clinical trial in ICUs of 20 public hospitals in Brazil enrolled adults with acute hypoxemic respiratory failure requiring invasive mechanical ventilation between June 2024 and May 2025, with follow-up through September 2025. A multicomponent telehealth-based rehabilitation program integrating an ICU telehealth-based rehabilitation intervention focused on ventilator liberation; a ward telehealth-based rehabilitation intervention targeting risk stratification and initiation of individualized rehabilitation plans; and a postdischarge telehealth-based rehabilitation intervention consisting of a 2-month personalized centralized telerehabilitation program. Health-related quality of life at 90 days after hospital discharge, measured using the EuroQol 5-Dimension 3-Level (EQ-5D-3L) utility score (range, -0.17 [worse than death] to 1 [best health state], with 0 representing death). Among 1916 enrolled patients (mean [SD] age, 60.6 [17.3] years; 43.6% female), 1063 were assigned to the intervention and 853 to usual care per local protocols. At 90 days after hospital discharge, mean (SD) EQ-5D-3L utility scores were higher in the intervention group than in the usual care group (0.16 [0.31] vs 0.12 [0.28]; adjusted difference, 0.049; 95% CI, 0.0002 to 0.098; P&#x2009;=&#x2009;.04) but did not differ among survivors (0.60 [0.32] vs 0.59 [0.32]; adjusted difference, -0.045; 95% CI, -0.138 to 0.045; P&#x2009;=&#x2009;.34). Compared with usual care, the intervention resulted in lower 90-day all-cause mortality (71.8% [676 of 941] vs 78.3% [584 of 746]; adjusted difference, -7.6%; 95% CI, -14.7% to -0.6%; P&#x2009;=&#x2009;.03) and shorter mean (SD) mechanical ventilation duration (9.9 [10.3] vs 15.5 [15.9] days; adjusted difference, -6.2 days; 95% CI, -8.5 to -3.9; P&#x2009;<&#x2009;.001). In this study, an integrated telehealth-based rehabilitation strategy delivered across ICU, hospital, and postdischarge phases improved 90-day health-related quality of life, potentially influenced by reduced mortality. ClinicalTrials.gov Identifier: NCT06343545.