Different Drug Mobilities in Hydrophobic Cavities of Host-Guest Complexes between ß-Cyclodextrin and 5-Fluorouracil at Different Stoichiometries: A Molecular Dynamics Study in Water.

Cyclodextrins (CDs) are cyclic oligosaccharides able to form noncovalent water-soluble complexes useful in many different applications for the solubilization, delivery, and greater bioavailability of hydrophobic drugs. The complexation of 5-fluorouracil (5-FU) with natural or synthetic cyclodextrins permits the solubilization of this poorly soluble anticancer drug. In this theoretical work, the complexes between ß-CD and 5-FU are investigated using molecular mechanics (MM) and molecular dynamics (MD) simulations in water. The inclusion complexes are formed thanks to the favorable intermolecular interactions between ß-CD and 5-FU. Both 1:1 and 1:2 ß-CD/5-FU stoichiometries are investigated, providing insight into their interaction geometries and stability over time in water. In the 1:2 ß-CD/5-FU complexes, the intermolecular interactions affect the drug's mobility, suggesting a two-step release mechanism: a fast release for the more exposed and hydrated drug molecule, with greater freedom of movement near the ß-CD rims, and a slow one for the less-hydrated and well-encapsulated and confined drug. MD simulations study the intermolecular interactions between drugs and specific carriers at the atomistic level, suggesting a possible release mechanism and highlighting the role of the impact of the drug concentration on the kinetics process in water. A comparison with experimental data in the literature provides further insights.

A Multicenter Experience of Three Different "Iliac Branched" Stent Grafts for the Treatment of Aorto-Iliac And/Or Iliac Aneurysms.

BACKGROUND: The aim of study was to assess the safety and effectiveness of 3 different commercial iliac branch devices (IBDs): the Zenith Branch Iliac Endovascular Graft; the Gore Excluder Iliac Branch System and the E-liac Stent Graft System for the treatment of aorto-iliac or iliac aneurysms. METHODS: From January 2017 to February 2020, a retrospective reviewed was conducted on a total of 96 patients. Primary endpoint was IBD instability rate at 24 months. Secondary endpoints included onset of any endoleaks, buttock claudication, IBD-related reintervention and all-death rates, postoperative acute kidney, and changes in maximum diameter from baseline of the aortic aneurysmal sac. RESULTS: At 24 months, the branch instability rate was similar among the 3 IBDs employed [Jotec 1/24 (4.1%), Gore 1/12 (8.3%), Cook 6/47 (12.7%), P-value = 0.502]. As well, no statistical difference in terms of branch occlusion and branch-related endoleaks was observed. The Jotec group showed a significant decrease in maximum diameter from the baseline of the aortic aneurysmal sac when compared to the Gore group alone. No other differences were found relevant to the onset of any endoleaks, reinterventions, and all-death rates. At 24 months, the Kaplan-Meier estimate of survival freedom from any branch instability was 95.8%, 91.6%, and 86.8% for Jotec, Gore and Cook groups, respectively. CONCLUSIONS: The use of IBDs represents a safe method for preserving patency of the IIA during treatment of aorto-iliac or iliac aneurysms providing a low rate of IBD instability.

Care of suspected long bone fractures in the emergency department: Families' perspectives and priorities.

OBJECTIVE: Despite growing interests in patient-reported outcomes, youth and families are rarely involved in designing quality improvement measures. Few quality indicators exist for the care of children with injuries in the Emergency Department (ED) and extremity fractures are among the most common injuries in children. This study's aim was to identify both parents' and youth's perspectives about ED care in the context of a suspected long-bone fracture. METHODS: Youth (10-18 years old) and their parents were surveyed prospectively during their ED visit. Participants were asked: 1) to identify their main concerns, 2) to identify quality measures that were most important to them, and 3) to evaluate the ED care they received. Descriptive analyses present participants' responses. Continuous data was analyzed using a Student t-test and categorical data using a Chi-square test. RESULTS: Over 15 months, 350 families met eligibility criteria and were approached to participate, of which 300 participants consented and 249 surveys were completed (71% response rate): 148 parents and 101 youth (median age: 12) completed their respective surveys. Participants placed a high importance on several themes: pain management, short length of stay, and quality interactions with ED clinicians. Youth as a group prioritized their overall wellbeing and the ED environment (e.g., waiting room comfort, signage), while parents focused on accurate diagnoses and treatments. The following items were less prioritized: that radiology be close to the ED, to see the radiograph, to have access to a wheelchair, to know the identities of clinicians on the team, and to have access to entertainment. Parents and youth within the same family often did not share the same priorities. Ninety-two percent of parents reported their child's pain was treated, while 81% and 63% of youth reported their pain was treated sufficiently and quickly, respectively. CONCLUSIONS: Parents and youth can identify their priorities for ED care and should be engaged in efforts to improve and report on the quality of care in the ED. Youths' and parents' perspectives are complimentary and may not align, even within families. The priorities identified in this study can help inform quality improvement initiatives and personalized patient care.

SOMAscan Proteomics Identifies Novel Plasma Proteins in Amyotrophic Lateral Sclerosis Patients.

Amyotrophic lateral sclerosis (ALS) is a complex disease characterized by the interplay of genetic and environmental factors for which, despite decades of intense research, diagnosis remains rather delayed, and most therapeutic options fail. Therefore, unravelling other potential pathogenetic mechanisms and searching for reliable markers are high priorities. In the present study, we employ the SOMAscan assay, an aptamer-based proteomic technology, to determine the circulating proteomic profile of ALS patients. The expression levels of ~1300 proteins were assessed in plasma, and 42 proteins with statistically significant differential expression between ALS patients and healthy controls were identified. Among these, four were upregulated proteins, Thymus- and activation-regulated chemokine, metalloproteinase inhibitor 3 and nidogen 1 and 2 were selected and validated by enzyme-linked immunosorbent assays in an overlapping cohort of patients. Following statistical analyses, different expression patterns of these proteins were observed in the familial and sporadic ALS patients. The proteins identified in this study might provide insight into ALS pathogenesis and represent potential candidates to develop novel targeted therapies.

Antibacterial and Cytotoxic Silica-Polycaprolactone-Chlorogenic Acid Hybrids by Sol-Gel Route.

Organic-inorganic hybrid materials were synthesized by a sol-gel route, using silicon alkoxide together with low molecular weight polycaprolactone and caffetannic acid. The synthesized hybrids were characterized by scanning Fourier-transform infrared (FTIR) spectroscopy, and their surface morphology was acquired by scanning electron microscopy (SEM) analysis. The hybrids were investigated for their antiradical capacity using the DPPH and ABTS tests, while the Kirby-Bauer test was used to evaluate their effects on the growth of Escherichia coli and Enterococcus faecalis. Furthermore, a biologically active hydroxyapatite layer has been observed to form on the surface of intelligently synthesized materials. The MTT direct test showed that the hybrid materials are biocompatible with NIH-3T3 fibroblast cells, while they were cytotoxic towards colon, prostate, and brain tumor cell lines. These results shed new light on the suitability of the synthesized hybrids in the medical field, thus affording knowledge on the features of the bioactive silica-polycaprolactone-chlorogenic acid hybrids.

Antibacterial and Chemical Characterization of Silica-Quercetin-PEG Hybrid Materials Synthesized by Sol-Gel Route.

This paper aims to synthesize, via the sol-gel method, a biomaterial usable in the medical field. Here, the silica-PEG-quercetin system was evaluated in relation to the different concentrations of PEG (0, 6, 12, 24, 50 wt%) and quercetin (0, 5, 10, 15 wt%), respectively. In addition, Fourier Transform-Infrared spectroscopy (FT-IR), Scanning Electron Microscopy (SEM), and Kirby-Bauer analyses were performed. FT-IR was used to evaluate the hybrid formation and the influence of both PEG and Quercetin in the hybrid synthesized materials, SEM was used to evaluate the morphological properties, while the Kirby-Bauer test was used to understand the ability of the materials to inhibit the growth of the assayed bacterial strains (Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis, and Staphylococcus aureus).

A cross-sectional study evaluating hospitalization rates for chronic limb-threatening ischemia during the COVID-19 outbreak in Campania, Italy.

The expansion of coronavirus disease 2019 (COVID-19) prompted measures of disease containment by the Italian government with a national lockdown on March 9, 2020. The purpose of this study is to evaluate the rate of hospitalization and mode of in-hospital treatment of patients with chronic limb-threatening ischemia (CLTI) before and during lockdown in the Campania region of Italy. The study population includes all patients with CLTI hospitalized in Campania over a 10-week period: 5 weeks before and 5 weeks during lockdown (n = 453). Patients were treated medically and/or underwent urgent revascularization and/or major amputation of the lower extremities. Mean age was 69.2 ± 10.6 years and 27.6% of the patients were women. During hospitalization, 21.9% of patients were treated medically, 78.1% underwent revascularization, and 17.4% required amputations. In the weeks during the lockdown, a reduced rate of hospitalization for CLTI was observed compared with the weeks before lockdown (25 vs 74/100,000 inhabitants/year; incidence rate ratio: 0.34, 95% CI 0.32-0.37). This effect persisted to the end of the study period. An increased amputation rate in the weeks during lockdown was observed (29.3% vs 13.4%; p < 0.001). This study reports a reduced rate of CLTI-related hospitalization and an increased in-hospital amputation rate during lockdown in Campania. Ensuring appropriate treatment for patients with CLTI should be prioritized, even during disease containment measures due to the COVID-19 pandemic or other similar conditions.

Management and outcomes of paediatric ileocolic intussusception at a paediatric tertiary care hospital: A retrospective cohort study.

BACKGROUND: Rapid reduction of ileocolic intussusception is important to minimize the compromise in blood flow to the affected bowel segment. This study aimed to quantify the potentially modifiable time between diagnosis and initiation of pneumatic reduction, identify factors associated with delays, and characterize the outcomes of pneumatic reduction in a recent cohort. METHODS: This retrospective observational study occurred at a tertiary care paediatric hospital with a consecutive sample of all children with ileocolic intussusception September 2015 through September 2018. The primary outcome was the time between ultrasound diagnosis of intussusception and the beginning of pneumatic reduction. Independent variables were age of the patient, time of day of arrival, transfer from another facility, and intravenous access prior to ultrasound. Outcomes of pneumatic reduction were expressed as proportions. RESULTS: There were 103 cases of ileocolic intussusception (among 257,282 visits) during the study period. The median time between diagnostic confirmation and initiation of reduction was 36 minutes. This was shorter for transferred patients and children with intravenous access prior to ultrasound. One perforation was identified at the beginning of reduction, without hemodynamic instability. Six children (5.8%) underwent either open (n=4) or laparoscopic surgery (n=2) for reduction failure. CONCLUSION: The median delay between diagnosis and initiation of reduction at this paediatric hospital was short, especially among patients transferred with a suspicion of intussusception and children with intravenous access prior to diagnosis. Complications from pneumatic reduction were infrequent.

Impact of wait time during a first pediatric emergency room visit on likelihood of revisit in the next year.

OBJECTIVE: Pediatric emergency departments (ED) develop strategies to decrease wait time. Yet, lowering wait times may incite patients to come back, and increase patient volume. We aim to determine if wait time in a first visit influenced the likelihood of a revisit to the same setting. METHODS: We performed a retrospective cohort study of children with a first visit to a single pediatric ED between November 1st 2016, and October 31st 2017. First visit was defined as no visit in the same ED in the previous 12 months. The primary outcome was the occurrence of a revisit at the same ED within 12 months of the first visit. Our main predictor was the wait time at the first visit for primary evaluation by a physician. We used multivariable logistic regression models to adjust for potential risk factors (age, triage level, day of visit and disposition). RESULTS: Among 85,844 ED visits during the study period, 36,844 were first visits and fulfilled inclusion/exclusion criteria. Median wait time was 101 min (interquartile range: 56-177 min). Among those with a first visit, 11,351 (30.8%) had a revisit within 12 months. In multivariable analysis, each one hour increase in wait time was associated with a lower probability of revisit (OR: 0.92; 95% CI: 0.91-0.94). CONCLUSIONS: Shorter wait time was associated with higher likelihood of a revisit to the same ED in the following 12 months. Strategies to reduce wait times should take into consideration possible concomitant increase in patient volume.

Motor neuron degeneration, severe myopathy and TDP-43 increase in a transgenic pig model of SOD1-linked familiar ALS.

Amyotrophic Lateral Sclerosis (ALS) is a neural disorder gradually leading to paralysis of the whole body. Alterations in superoxide dismutase SOD1 gene have been linked with several variants of familial ALS. Here, we investigated a transgenic (Tg) cloned swine model expressing the human pathological hSOD1G93A allele. As in patients, these Tg pigs transmitted the disease to the progeny with an autosomal dominant trait and showed ALS onset from about 27 months of age. Post mortem analysis revealed motor neuron (MN) degeneration, gliosis and hSOD1 protein aggregates in brainstem and spinal cord. Severe skeletal muscle pathology including necrosis and inflammation was observed at the end stage, as well. Remarkably, as in human patients, these Tg pigs showed a quite long presymptomatic phase in which gradually increasing amounts of TDP-43 were detected in peripheral blood mononuclear cells. Thus, this transgenic swine model opens the unique opportunity to investigate ALS biomarkers even before disease onset other than testing novel drugs and possible medical devices.