Choline phosphate-based bioactive hydrogel for sustained release of exosomes from adipose-derived stem cells to enhance diabetic wound healing.

Ischemic stroke, the second leading cause of death and a primary source of severe disability in adults worldwide, is associated with high morbidity and mortality rates that correlate closely with the extent of neuronal damage. A critical strategy for improving patient outcomes is the early identification and rescue of the ischemic penumbra, a region at risk but potentially salvageable. However, accurately identifying and visualizing this penumbra poses a significant challenge in treatment and is crucial for predicting patient prognosis. Conventional magnetic resonance imaging (MRI) techniques often fail to delineate viable tissue effectively.Cleaved Caspase-3 (c-Casp3), a key executor of apoptosis, is specifically and highly expressed within the penumbra, making it an ideal molecular target for precise imaging. To address this challenge, we designed and constructed a multifunctional, enzyme-responsive MRI nanoprobe (FGAPT) for the molecular imaging of the ischemic penumbra. This probe capitalizes on the elevated expression of activated Caspase-3 during ischemic neuronal apoptosis, facilitating its specific accumulation and activation at the lesion site. As a result, there is a significant enhancement of the T1-weighted imaging signal, allowing for accurate delineation of the penumbra. This study establishes an imaging strategy for the precise identification of the ischemic penumbra, thereby presenting a paradigm for guiding individualized thrombolytic and neuroprotective interventions in ischemic stroke. The proposed methodology lays a robust imaging foundation for transitioning stroke management from a generalized therapeutic approach to personalized treatment optimization. STATEMENT OF SIGNIFICANCE: The precise delineation of the ischemic penumbra is critical for guiding therapy in acute ischemic stroke, yet remains a challenge for conventional imaging. To address this, we developed an enzyme-responsive magnetic resonance imaging (MRI) nanoprobe, FGAPT, for the molecular visualization of this salvageable tissue. This smart probe is engineered around a MRET mechanism, linking a superparamagnetic quencher (Fe₃O₄) and a paramagnetic enhancer (Gd-DOTA) with a peptide sequence specifically cleaved by activated Caspase-3-a key executor of apoptosis upregulated in the penumbra. Surface conjugation of a brain-targeting aptamer ensures blood-brain barrier penetration. In a rodent stroke model, the probe achieved high-contrast, specific T1-signal enhancement exclusively within the penumbra, as confirmed by spatial colocalization with histologically verified apoptotic cells. This Caspase-3-activated imaging strategy enables accurate differentiation between the infarct core and the ischemic penumbra. By directly visualizing a pivotal molecular determinant of cellular fate, our work provides a novel tool to advance stroke management from a rigid "time window" paradigm toward a precision "tissue window" approach.

To evaluate predictors of postoperative and functional outcomes following salvage oropharyngectomy. In this single-center retrospective study, we included all patients who underwent an oropharyngectomy in an irradiated neck for recurrent or metachronous cancer between 2014 and 2023. We included 94 patients. The rate of complications was 53.2%, and was associated in multivariable analysis with tumor involving the midline (p = 0.001), oral cavity (p = 0.017) or glossotonsillar sulcus (p = 0.037), transcervical approach (p = 0.004), and high body mass index (p = 0.011). In multivariable analysis, high body mass index (p = 0.023), midline-crossing tumor (p = 0.022), and older age (p = 0.061) were associated with a hospital stay longer than 21 days. After a median follow-up of 74.3 months, 59.6% of patients had a gastrostomy. Predictors for this dependency in multivariable analysis were T3/T4 tumors (p = 0.06) and p16-status (p = 0.079). Salvage oropharyngectomy in irradiated neck remains associated with a complex postoperative course and a high morbidity.

Radical cystectomy (RC) has historically been the standard treatment for muscle-invasive bladder cancer (MIBC); nonetheless, it is associated with a high morbidity and mortality, with complication rates often exceeding 60%, a relatively high 90-day mortality rate, as well as a significant impact on quality of life (QoL). This substantial burden has generated increasing interest in effective bladder-sparing alternatives. Among these approaches to bladder preservation, trimodal therapy (TMT), comprising maximal transurethral resection of bladder tumour (TURBT) followed by concurrent chemotherapy and radiotherapy (chemoRT) using radiosensitising agents, has become a guideline accepted alternative to RC in appropriately selected patients with MIBC. Additional bladder-sparing strategies, such as TURBT monotherapy or TURBT followed by systemic therapy and surveillance in those patients achieving a complete clinical response, may be alternatives in select settings, although data are limited. Appropriate surveillance after a bladder-sparing approach is paramount to offer timely salvage RC when needed, occurring in approximately 11-16% of contemporary TMT cohorts. QoL outcomes consistently favour TMT over RC, particularly in preserving urinary and sexual function. Severe treatment-related toxicity with TMT is uncommon, with Grade ≥3 adverse events occurring in <10% of cases. In conclusion, bladder-sparing approaches offer a suitable alternative to RC in appropriately selected patients with MIBC, incorporating multidisciplinary care and a commitment to lifelong surveillance.

Diagnostic accuracy of short-incubation cultures versus standard protocols for bacterial identification and susceptibility testing via VITEK® MS and VITEK®2 XL.

Acute haemorrhagic strokes are most common in people with hypertension, which causes high morbidity and mortality in Bangladesh. In this study, we investigated that whether serum potassium level is associated with risk of haemorrhagic strokes in hypertensive patients or not. We conducted a cross-sectional descriptive study that was carried out in the Department of Medicine and Neurology of Mymensingh Medical College Hospital, Mymensingh from December 2019 to May 2020. Total 100 patients (Mean age: 59.5±15 years, 58% male and 42% female) of hypertension with acute haemorrhagic stroke were enrolled in this study considering inclusion (both sex, CT scan proven stroke) and exclusion criteria (patients with congestive cardiac failure, conn's syndrome and kidney diseases). Our results showed that significant number of patients (34.0%) had potassium imbalance, with hypokalaemia (k+ <3.5) present in 31.0% study patients and hyperkalaemia (k+ >5) found in 3.0% patients. The present study also revealed that majority of patients having potassium imbalance had lower ICH score. From these findings we can conclude that hypokalemia may be responsible for subsequent increase in hemorrahagic stroke incidents in hypertensive patients. However, association between severity of acute hemorrahagic stroke and potassium imbalance was found not significant.

Oral cancer is one of the most common head and neck malignancies and remains associated with high morbidity, mortality, and treatment-related toxicity. Despite advances in surgery, radiotherapy, and chemotherapy, there is still a need for safer adjunctive therapies with better therapeutic potential. Astaxanthin, a natural lipophilic carotenoid, has gained attention because of its antioxidant, anti-inflammatory, and anticancer activities. The available evidence suggests that astaxanthin may suppress oral premalignant and malignant progression by inhibiting inflammation, oxidative stress, proliferation, invasion, angiogenesis, and survival signaling pathways, while promoting apoptosis and reactivating tumor suppressor mechanisms. Preclinical studies also indicate that astaxanthin-based formulations may improve delivery efficiency and enhance antitumor effects in oral cancer models. Overall, astaxanthin appears to be a promising natural candidate for oral cancer prevention and treatment. However, most findings are based on preclinical studies, and further well-designed clinical investigations are required to confirm its efficacy and safety.

Rhodiosin promotes cerebral angiogenesis in mice with ischemic stroke via PI3K/Akt pathway activation.

Sepsis-induced myocardial injury (SIM) is a common complication of sepsis that can cause high morbidity and mortality. However, the molecular mechanisms underlying SIM have still not been fully elucidated. Ferroptosis is a novel form of cell death associated with oxidative stress and is characterised by elevated iron levels. In the present study, mouse cardiomyocytes (H9c2 cells) and C57BL/6 mice were treated with lipopolysaccharide (LPS) to establish an in vitro and an in vivo model of SIM, respectively. RNF113A, a member of the RING finger protein (RNF) family with E3 ligase activity, was downregulated in H9c2 cells treated with LPS compared to untreated cells. Overexpression of RNF113A reduced LPS-induced cardiac injury and ferroptosis both in vitro and in vivo. Mechanistically, RNF113A directly targets Keap1 and promotes its ubiquitination and degradation. This results in the activation of Nrf2 signaling. Our findings suggest that RNF113A directly targets Keap1 to activate Nrf2 signalling, which plays an essential role in the pathogenesis of SIM.

Anorexia nervosa (AN) is a severe psychiatric disorder with high morbidity and increased relative mortality compared to the general population. Involuntary treatment (IT) is implemented after exhausting voluntary treatment options. This study investigates mortality in patients with AN following IT, using IT as an indicator of patient vulnerability. A register-based cohort study including individuals diagnosed with AN (ICD-10: F50.0, F50.1) from 2000 to 2016 at any Danish hospital and with an inpatient admission following their AN diagnosis. The exposure was the first instance of any IT event and categories of IT after AN. IT could be associated with AN or any other diagnosis. The outcome was mortality; all-cause and divided into deaths from diseases and medical conditions, external causes, or suicide. Excess mortality was estimated as hazard ratios (HR) using Cox proportional hazards regression. The model was adjusted for sex, age at AN diagnosis, birth year, prior IT, self-harm, and other psychiatric morbidities. Over the study period 4425 individuals (93.3% female; mean age at diagnosis = 22, SD = 12) were included in the study. Of these, 821 individuals received IT (18.5%) and 206 individuals (4.7%) died. The HRs were elevated for all-cause mortality (HR = 2.21, [95% CI: 1.54-3.17]), external causes (HR = 3.88, [95% CI: 1.94-7.77]), and suicide (HR = 5.30, [95% CI: 2.07-13.54]). The analysis of IT categories only showed an elevated HR for electroconvulsive therapy and somatic concerns (HR = 1.96, [95%CI: 1.04-3.67]). Despite IT primarily being used to safeguard the life of the most vulnerable patients, mortality for those who received IT was elevated. The results indicate that this patient group requires sustained clinical attention.

Contributing Factors to Delay of Adjuvant Postsurgical Radiation for Malignant Brain Tumors: A Single Institution Experience in a Rural State.

Krabbe Disease (KD) is a lysosomal leukodystrophy characterized by the production of psychosine in oligodendrocytes, leading to neurodegeneration and ultimately death. The only treatment modality currently available for this disease is hematopoietic stem cell transplantation (HSCT), a procedure with high morbidity, highlighting the need for further therapies to be developed. In this study, we established and characterized GALC knockout MO3.13 cells, a cell line derived from human oligodendrocytes, as a model for KD. Clonal MO3.13 cells with GALC KO were obtained via CRISPR/Cas9-mediated gene editing. GALC activity was measured by a 4-methylumbellyferyl (4-MU)-based assay, and morphology analyses were performed using light microscopy and transmission electron microscopy. Psychosine was measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The GALC KO cells have elevated levels of psychosine and an increased number of autophagosomes, autolysosomes, and cytoplasmic granules on transmission electron microscopy. Glycogen abundance was decreased in GALC KO cells compared to controls. After administration of BMN-S202, a ceramide galactosyltransferase inhibitor, psychosine levels in GALC KO cells were reduced back to WT levels. In conclusion, we demonstrated that the GALC KO MO3.13 cell line recapitulates the KD phenotype and biochemical response to SRT and may be a useful KD model for mechanistic studies and therapeutic development for KD.

Sex-related differences in infective endocarditis. A retrospective study in a high-volume surgical centre.

Metabolic and bariatric surgery in MAFLD: a meta-analysis of endocrine outcomes, fibrosis remission, and postoperative complications.

Individualized Surgical Management of Brainstem Cavernous Malformations: A Single-Center Experience with 50 Cases and Favorable Long-Term Outcomes.

Arthrofibrosis is a debilitating complication following total knee arthroplasty (TKA), affecting 3 to 13% of primary TKA patients and leading to 10% of revision surgeries. This review evaluates the current management strategies for arthrofibrosis, answering key questions on treatment modalities: (1) nonsurgical interventions, (2) arthroscopic and open surgical approaches, (3) revision procedures, and (4) adjunct and emerging therapies. Nonsurgical treatments, including aggressive physical therapy and continuous passive motion devices, show some improvements in range of motion (ROM), but long-term efficacy remains uncertain. Arthroscopic lysis of adhesions improves knee flexion by 26.7 to 51.2 degrees, with a mean final flexion of 100 to 103 degrees, but carries higher infection and revision risks. Open arthrolysis provides ROM improvements up to 43.4 degrees, with higher morbidity and complications. Revision TKA yields better functional outcomes, with mean flexion improvements of 15 to 25 degrees, but 43% of patients require further care. Emerging therapies, such as low-dose irradiation and pharmacologic agents like celecoxib and dexamethasone, show promise but require further validation. Despite advancements, gaps in high-quality data and standardized protocols persist, underscoring the need for more prospective trials.

Late preterm birth: how big is the problem?

Improving Diagnosis and Management of Infantile-Onset Epilepsies in Resource-Limited Settings (SHIELD Model).

Diabetes Mellitus (DM) is frequently complicated by Diabetic Foot Ulcers (DFUs), which contribute to high morbidity, mortality, and healthcare costs. Regular foot care and clinic follow-up can reduce the incidence of DFUs and related complications, yet adherence to these practices remains poorly described in Sudan. To assess compliance with foot care practices and identify factors associated with compliance and barriers to regular foot care clinic attendance among patients with diabetes attending the Jabber Abo Aliz Diabetes Care Center in Khartoum, Sudan. A cross-sectional descriptive study was conducted from December 2021 to February 2022 involving 120 patients with DM attending foot care clinics. Data were collected using structured questionnaires covering demographic and clinical characteristics, foot care behaviours, and perceived barriers. Compliance was measured using a Likert-based scoring system, with scores ≥ 9/17 classified as compliant. Data were analysed using SPSS version 21.0, applying Chi-square tests and ANOVA where appropriate, with statistical significance set at p < 0.05. Among 120 participants (55% female; mean age 49 ± 11 years), 70% were classified as compliant with foot care. Compliance was significantly associated with female gender (p = 0.043), age < 40 years (p = 0.034), urban residence (p = 0.037), higher socioeconomic status (p = 0.002), and good glycemic control (HbA1c ≤ 7%; p = 0.001). Duration of DM showed no significant association (p = 0.184). Transportation and distance were the most reported barriers to clinic attendance (30%). Most patients attending foot care clinics demonstrated good adherence to foot care practices, particularly those with favourable socioeconomic and clinical profiles. However, geographic and economic barriers continue to limit regular attendance. Strengthening outreach strategies, reducing access barriers, and integrating foot care education into routine diabetes management could improve outcomes and reduce DFU-related complications in Sudan.

Combined resection for tracheal invasion in esophageal cancer is extremely challenging. Tracheal resection with cervical or mediastinal tracheostomy is often performed; however, this procedure has high morbidity rates and results in loss of voice. We present our experience performing a partial-layer tracheal resection, "tracheal shaving," for esophageal cancer with tracheal invasion. We successfully performed tracheal adventitia and tracheal muscle resection in a patient with adventitial invasion, and the shaving area was reinforced by omental covering along with a gastric tube reconstructed through the posterior mediastinum. We believe that our "tracheal shaving" technique may potentially allow curative resection in selected T4 cases while preserving laryngeal function. It may serve as a minimally invasive alternative to conventional tracheal resection, although further evaluation is required.