articles+ search results

Nanosponges, crosslinker, nanocarrier, cyclodextrin, analgesics, drug efficacy, Therapeutics. Pharmacology, and RM1-950

AbstractCyclodextrin nanosponges are solid nanoparticles, designed by cross-linking of cyclodextrin polymer; it has been used widely as a good delivery system for water insoluble drugs. The aim of this study is to enhance the solubility of Piroxicam (PXM) using β-Cyclodextrin based nanosponges formulations. PXM nanosponge (PXM-NS) formulations were prepared using β-cyclodextrin and carbonyldiimidazole as a cross linker, three ratios of β-cyclodextrin to crosslinker in addition to three drug to nanosponges ratios were tested. Piroxicam nanosponge formulations were characterized for its particle size, zeta potential, physical compatibility and in vitro release. Stability studies at three temperatures (4 °C, 25 °C and 40 °C) were done for optimal formula. Finally, the in vivo analgesic activity and pharmacokinetic parameters of the optimal formula were conducted. The optimized PXM-NS formula (PXM-NS10) showed particle size (362 ± 14.06 nm), polydispersity index (0.0518), zeta potential (17 ± 1.05 mV), and %EE (79.13 ± 4.33). The dissolution study showed a significant increase in the amount of PXM dissolved compared with the unformulated drug. Stability studies confirmed that nanosponge showed accepted stability for 90 days at 4 °C and 25 °C. In vivo analgesic studies verified that there was a significant enhancement in the analgesic response to PXM in mice, and 1.42 fold enhancement in the relative bioavailability of PXM-NS10 as compared to commercial tablets. Nanosponge prepared under optimal conditions is an encouraging formula for increasing the solubility and therefore the bioavailability of Piroxicam.

Background: Toxic alcohol poisoning is regularly encountered in emergency departments and intensive care units (ICUs). Most patients present with an altered level of consciousness, but the subsequent course and spectrum of neurologic complications and outcomes is highly variable.
Methods: We performed a population-based, multicenter retrospective cohort study of critically ill patients with toxic alcohol poisoning admitted to ICUs in Alberta, Canada, between 2007 and 2019 to describe neurologic sequelae, including seizures, coma, neuroimaging abnormalities, persistent cognitive or visual impairment, and mortality. Multivariate analysis was performed to identify predictors of poor outcome.
Results: We identified 104 patients, including 55 (53%) with methanol ingestion, 36 (35%) with ethylene glycol ingestion, and 13 (13%) with isopropanol ingestion. In patients who underwent neuroimaging, abnormalities were detected in 9 of 24 (38%) with methanol toxicity, 5 of 20 (25%) with ethylene glycol toxicity, and 0 of 10 with isopropanol toxicity (p = 0.07). Basal ganglia were commonly involved with both methanol and ethylene glycol poisoning, but prominent subcortical involvement and restricted diffusion were observed only with methanol poisoning. The composite of death, persistent cognitive impairment, or visual loss occurred in 13 (24%) patients with methanol poisoning, compared with one (3%) with ethylene glycol poisoning and none with isopropanol poisoning (p = 0.006). Among patients with methanol toxicity, greater elevation of the anion gap and lower Glasgow Coma Scale score were independent predictors of poor outcome. No patient with an anion gap ≥ 28 at presentation had a favorable recovery. Progression to death by neurologic criteria occurred in 3 of 55 (5%) patients with methanol poisoning and in none with other toxic alcohols.
Conclusions: Methanol overdose is the most common form of toxic alcohol poisoning to result in ICU admission. Poor neurologic outcomes may occur especially with methanol poisoning, with more than one in five patients dying or having persistent cognitive or visual impairment. A wide anion gap independently predicts poor outcome, emphasizing the importance of expeditious recognition and treatment.
(© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Humans, Child, Memory, Short-Term, Diffusion Magnetic Resonance Imaging, Cognition, Memory Disorders, White Matter pathology, and Attention Deficit Disorder with Hyperactivity diagnostic imaging

Introduction: Attention Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder with many functional impairments thought to be underpinned by difficulties in executive function domains such as working memory. The superior longitudinal fasciculus (SLF) plays an integral role in the development of working memory in neurotypical children. Neuroimaging research suggests reduced white matter organization of the SLF may contribute to working memory difficulties commonly seen in ADHD. This study aimed to examine the relationship between white matter organization of the SLF and working memory in children with ADHD.
Methods: We examined the association of tract volume and apparent fibre density (AFD) of the SLF with working memory in children with ADHD (n = 64) and controls (n = 58) aged 9-11years. Children completed a computerized spatial n-back task and underwent diffusion magnetic resonance imaging (dMRI). Constrained spherical deconvolution-based tractography was used to construct the three branches of the SLF bilaterally and examine volume and AFD of the SLF.
Results: Regression analyses revealed children with ADHD exhibited poorer working memory, and lower volume and AFD of the left SLF-II compared to healthy controls. There was also an association between reaction time and variability (RT and RT-V) and the left SLF-II. Further analyses revealed volume of the left SLF-II mediated the relationship between ADHD and working memory performance (RT and RT-V).
Discussion: These findings add to the current body of ADHD literature, revealing the potential role of frontoparietal white matter in working memory difficulties in ADHD.
(Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Several studies have shown increased incidence, recurrence, and severity of Clostridium difficile  infection (CDI) over the last decade. Patients with inflammatory bowel disease (IBD) who develop CDI are more prone to morbidity and mortality than CDI in patients without IBD. This study seeks to evaluate whether IBD patients who use vedolizumab are at increased risk of CDI compared to IBD patients using other therapies.
Methods: This was a retrospective cohort study, and 684 patients with confirmed IBD (228 on vedolizumab, 228 on anti-TNF, and 228 on 5- Aminosalicylates acid therapy) were enrolled from January 2009 to August 2019 at a tertiary referral IBD center at McMaster University Medical Centre (MUMC) in Hamilton, Ontario, Canada. The primary outcome was time to the development of CDI in IBD patients using different therapies. Secondary outcomes included rates of CDI and the association between baseline variables and risk of CDI. A Cox proportional hazards (PH) model was used to evaluate baseline factors and development of CDI.
Result: There was no difference in time to CDI between the three treatment groups (log rank p-value 0.37). CDI occurred in 16 patients (2.3%), specifically four patients (1.75%) in the vedolizumab group, four patients (1.75%) in the anti-TNF group, and eight patients (3.5%) in the 5-ASA group. The Cox PH model found current smoking, older age, and concomitant immunomodulator use as risk factors for CDI, after adjustment for other covariates. Vedolizumab was not associated with increased risk of CDI in the model.
Conclusion: Biologic therapy with vedolizumab or anti-TNF did not impact risk of CDI . Risk factors for CDI in IBD patients included smoking, older age at the onset of medication, and immunomodulator therapy. Clinicians should have high degree of suspicion for CDI in IBD patients presenting with diarrhea, particularly in those with risk factors identified in this study.
Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(© 2023 The Authors.)

Female, Humans, Adult, Middle Aged, Male, Risk, Food Handling, Inflammatory Bowel Diseases epidemiology, Crohn Disease, and Colitis, Ulcerative

Background & Aims: Several studies have been published on the association between food processing and risks of Crohn's disease (CD) and ulcerative colitis (UC), with some variability in results. We performed a systematic literature review and meta-analysis to study this association.
Methods: From PubMed, Medline, and Embase until October 2022, we identified cohort studies that studied the association between food processing and the risk of CD or UC. Risk of bias of the included studies was assessed by the Newcastle-Ottawa scale. We computed pooled hazard ratios (HRs) and 95% confidence intervals (CIs) using random-effects meta-analysis based on estimates and standard errors.
Results: A total of 1,068,425 participants were included (13,594,422 person-years) among 5 cohort studies published between 2020 and 2022. Four of the 5 included studies were scored as high quality. The average age of participants ranged from 43 to 56 years; 55%-83% were female. During follow-up, 916 participants developed CD, and 1934 developed UC. There was an increased risk for development of CD for participants with higher consumption of ultra-processed foods compared with those with lower consumption (HR, 1.71; 95% CI, 1.37-2.14; I 2  = 0%) and a lower risk of CD for participants with higher consumption of unprocessed/minimally processed foods compared with those with lower consumption (HR, 0.71; 95% CI, 0.53-0.94; I 2  = 11%). There was no association between risk of UC and ultra-processed foods (HR, 1.17; 95% CI, 0.86-1.61; I 2  = 74%) or unprocessed/minimally processed foods (HR, 0.84; 95% CI, 0.68-1.02; I 2  = 0%).
Conclusions: Higher ultra-processed food and lower unprocessed/minimally processed food intakes are associated with higher risk of CD but not UC.
(Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

death, Jordan, metastasis, retinoblastoma, survival, Medicine (General), and R5-920

PurposeTo analyze causes and prognostic factors for death among Retinoblastoma (Rb) patients treated at a single specialized tertiary cancer center in Jordan.MethodsWe reviewed the mortality causes for all Rb patients who have been treated at the King Hussein Cancer Center between 2003 and 2019 and were followed for at least 3 years after diagnosis. The main outcome measures included demographics, laterality, tumor stage, treatment modalities, metastasis, survival, and causes of death.ResultsTwenty-four (5%) of the 478 patients died from retinoblastoma and 5-year survival was 94%. The mean age at diagnosis was 15 months (median, 18 months; range, 4–38 months); eight (33%) received diagnoses within the first year of life. Eleven (46%) were boys, 16 (67%) had bilateral disease, and 3 (13%) had a positive family history. The stage for the worst eye was C for 1 (4%) patient, D in 6 (25%) patients, and E (T3) in 15 (63%) patients. Two patients had extraocular Rb at diagnosis, and four of the patients who had intraocular Rb at diagnosis refused treatment and then came back with extraocular Rb. In total, extraocular disease was encountered in six eyes (six patients). After a 120-month median follow-up period, 24 patients (5%) died of second neoplasms (n = 3) or metastases (n = 21). Significant predictive factors for metastasis and death included advanced IIRC tumor stage (p