Theoretical study of Gibbs free energy and NMR chemical shifts, of the effect of methyl substituents on the isomers of (E)-1-(α,Ꞵ-Dimethylbenzyliden)-2,2-diphenylhydrazine.

A theoretical analysis of free Gibbs Energy and NMR 1H 13C chemical shifts of the effect of introduce methyl groups on diphenyl rings, to produce different isomers of (E)-1-(α,Ꞵ-dimethylbenzylidene)-2,2-diphenylhydrazine, is presented. IR vibrational frequencies, Mulliken charges, molecular electrostatic potential (MEP), Gibbs free energy (G) and 1H- and 13C-NMR chemical shifts were obtained by theoretical calculations. In this analysis it was found that the position of the methyl group affects the values of the 1H- and 13C-NMR chemical shifts and the ∆G and ∆H thermodynamic properties of formation and reaction, these properties vary with the same trend, for the isomers studied. Gibbs free energy calculations show that the theoretical (E)-1-(3,4-Dimethylbenzylidene)-2,2-diphenylhydrazine isomer is the most stable, which explains the success of the experimental synthesis of this compound among the other isomers. For this molecule, the C of the HC=N group is the most nucleophilic and the H is the least acidic. The 1H-NMR chemical shifts of protons show a strong correlation with the C=N distance. It was also observed that methyl affects the ν(C=N) frequencies, the C=N distance increases when the inductive effect of the methyl groups is in the structure.

Scedosporium aurantiacum: First isolation in Argentina from a previously healthy patient after traumatic inoculation.

Scedosporium/Lomentospora species are widely distributed in nature. They are generally saprophytes, but can cause opportunistic infections in immunocompromised patients and occasionally in immunocompetent patients that are difficult to treat due to high levels of antifungal resistance. The distribution of Scedosporium/Lomentospora species shows regional differences. Scedosporium boydii and Scedosporium apiospermum are the most frequently isolated species in our region, whereas Scedosporium aurantiacum is more common in other regions. We describe the first isolation in Argentina of S. aurantiacum in a vitreous humor infection from a previously healthy patient after traumatic injury in her left eye. Due to the suspicion of fungal endophthalmitis, a mycological study of the vitreous humor was performed. The culture allowed the isolation of S. aurantiacum. The patient was treated with voriconazole with favorable clinic evolution.

Continuous renal replacement therapy in COVID-19-associated AKI: adding heparin to citrate to extend filter life-a retrospective cohort study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) may predispose patients to thrombotic events. The best anticoagulation strategy for continuous renal replacement therapy (CRRT) in such patients is still under debate. The purpose of this study was to evaluate the impact that different anticoagulation protocols have on filter clotting risk. METHODS: This was a retrospective observational study comparing two different anticoagulation strategies (citrate only and citrate plus intravenous infusion of unfractionated heparin) in patients with acute kidney injury (AKI), associated or not with COVID-19 (COV + AKI and COV - AKI, respectively), who were submitted to CRRT. Filter clotting risks were compared among groups. RESULTS: Between January 2019 and July 2020, 238 patients were evaluated: 188 in the COV + AKI group and 50 in the COV - AKI group. Filter clotting during the first filter use occurred in 111 patients (46.6%). Heparin use conferred protection against filter clotting (HR = 0.37, 95% CI 0.25-0.55), resulting in longer filter survival. Bleeding events and the need for blood transfusion were similar between the citrate only and citrate plus unfractionated heparin strategies. In-hospital mortality was higher among the COV + AKI patients than among the COV - AKI patients, although it was similar between the COV + AKI patients who received heparin and those who did not. Filter clotting was more common in patients with D-dimer levels above the median (5990 ng/ml). In the multivariate analysis, heparin was associated with a lower risk of filter clotting (HR = 0.28, 95% CI 0.18-0.43), whereas an elevated D-dimer level and high hemoglobin were found to be risk factors for circuit clotting. A diagnosis of COVID-19 was marginally associated with an increased risk of circuit clotting (HR = 2.15, 95% CI 0.99-4.68). CONCLUSIONS: In COV + AKI patients, adding systemic heparin to standard regional citrate anticoagulation may prolong CRRT filter patency by reducing clotting risk with a low risk of complications.

Simple Phenotypic Tests To Improve Accuracy in Screening Chromosomal and Plasmid-Mediated Colistin Resistance in Gram-Negative Bacilli.

CLSI and EUCAST recommend that only broth microdilution (BMD) should be used for routine colistin susceptibility testing; however, this technique can be difficult to perform in resource-poor settings. The purpose of this study was to evaluate the accuracy of a colistin agar spot test (COL-AS) and a colistin drop test (COL-DT) compared to BMD. COL-AS and COL-DT were assessed with a collection of 271 Gram-negative bacilli clinical isolates: 195 Enterobacterales (including 63 mcr-1 positive strains), 37 Acinetobacter spp., and 39 Pseudomonas aeruginosa For COL-AS, 3.0 µg/ml (final concentration) of colistin was added to a Mueller-Hinton agar plate and subsequently swabbed with a 0.5 McFarland standard suspension of the tested strain within a 1 cm2 spot. For COL-DT, 10 µl of a 16 µg/ml colistin solution was dripped on the surface of a Mueller-Hinton agar plate, previously inoculated with a lawn of the tested strain (0.5 McFarland standard). Colistin solution was made either by dissolving powder or by disk elution in cation-adjusted Mueller-Hinton broth (CA-MHB). Overall, 141/271 (52%) isolates were categorized as colistin resistant by reference BMD. COL-AS yielded a categorical agreement (CA) of 95.5% compared to BMD, with 0.7% very major errors and 3.8% major errors. COL-DT yielded a CA of 96.2% compared to BMD, with 0.7% and 0% very major errors and 3.1% and 3.8% major errors, for colistin powder and disk elution solutions, respectively. Most major errors occurred for mcr-1 strains with MICs that fluctuated from 2 to 4 µg/ml according to the method used. In conclusion, we developed and validated methods suited to the systematic screening of resistance to colistin in Gram-negative bacilli.

The Heterogeneity of Global Pediatric Surgery: Defining Needs and Opportunities Around the World.

BACKGROUND: The global burden of pediatric surgical conditions continues to remain inadequately addressed, particularly in low- and middle-income countries. Among the many factors contributing to this gap are a lack of access to care secondary to resource shortages and inequitable distribution, underfinancing of healthcare systems, poor quality of care, and contextual challenges such as natural disasters and conflict. The relative contribution of these and other factors varies widely by region and even with countries of a region. METHODS: This review seeks to discuss the heterogeneity of global pediatric surgery and offer recommendations for addressing the barriers to high-quality pediatric surgical care throughout the world. RESULTS: There is significant heterogeneity in pediatric surgical challenges, both between regions and among countries in the same region, although data are limited. This heterogeneity can reflect differences in demographics, epidemiology, geography, income level, health spending, historical health policies, and cultural practices, among others. CONCLUSION: Country-level research and stakeholder engagement are needed to better understand the heterogeneity of local needs and drive policy changes that contribute to sustainable reforms. Key to these efforts will be improved financing, access to and quality of pediatric surgical care.

Novel topical formulation for ischemic chronic wounds. Technological design, quality control and safety evaluation.

Ulceration of the foot in diabetes is common and disabling, and frequently leads to amputation of the leg. The pathogenesis of foot ulceration is complex, clinical presentation variable and management requires early expert assessment. Despite treatment, ulcers readily become chronic wounds. Chronic wounds are those that remain in a chronic inflammatory state failing a normal healing process patterns. This is partially caused by inefficient eradication of opportunistic pathogens like Pseudomonas aeruginosa. We propose its control or eradication will promote wound healing. Lactobacillus plantarum cultures supernatants (LAPS) shows antipathogenic and pro-healing properties. The main objective was to design two pharmaceutical dosage forms by using LAPS as active pharmaceutical ingredient and to perform its quality control, in vitro activity conservation tests and human trials (safety evaluation). Both selected formulations reach the technological quality expected for 120 days, shows adequate occlusive characteristics and proper adhesion to human skin. From the in vitro release assays were found that LAPS shows adequate release from matrix and maintain its antimicrobial and anti-biofilm activity. First human trials were developed and neither edema nor erythema on healthy skin voluntaries was found. We conclude that C80 and C100 are adequate for their use in future clinical trials to demonstrate a comprehensive therapeutic effectiveness in ischemic chronic wounds.

Equipment and method for in vitro release measurements on topical dosage forms.

CONTEXT: In countries where research budgets are meager as Argentina, the tendency to innovation and improvements in the designs prototypes "made in Argentina" marks a growing trend adopted by researchers. This article presents a diffusion cell of original design, for release studies of Active Pharmaceutical Ingredient (API) from classical topical dosage forms, also includes the methodology for its optimization and validation. The objective was to evaluate and validate a system designed and to compare it to the Franz cells system. METHODS: Parameters, reproducibility and robustness were performed included factors as, stirring conditions, membrane stabilization treatment and temperature variation. Release and retention on membrane assay were performed using two different API and formulations. RESULTS: The method is reproducible and robust for the parameters tested. Release assays show that no significative difference with the Franz Cells system. Our system allows the simultaneous measurement of different parameters, representing an innovation on these methodologies. The LMC was used for assays of in vitro retention on membrane and the values obtained were reproducible and coincident whit values obtained for other authors. CONCLUSIONS: The system designed and the methodology employed, are acceptable for in vitro release studies. The device and method has the characteristics required.

Characteristics of hemolytic uremic syndrome in patients from a pediatric hospital in Peru, 2010-2020. / Características del síndrome urémico hemolítico en pacientes de un hospital pediátrico de Perú, 2010-2020.

OBJECTIVES.: Motivation for the study. There are few studies in Peru on hemolytic uremic syndrome. Main findings. Between the years 2010 to 2020, the age at diagnosis has not changed; however, more patients presented oliguria and required more renal replacement therapy (peritoneal dialysis) compared to previous years. Implications. This syndrome is an important cause of renal damage in children; therefore, its surveillance and notification are necessary. In addition, measures of prevention and early recognition of the disease must be implemented, since this condition is generally caused by consumption of contaminated food.

Single-fraction low-energy electronic brachytherapy for conjunctival lymphoma.

PURPOSE: Conjunctival lymphoma represents an uncommon tumor, accounting for 5-10% of total extranodal lymphomas. Although radiotherapy is a frequent treatment option, limited capacities and lack of specialized centers are common problems in Peru, forcing radiation oncologists to apply short courses of radiotherapy. Here, we report a case series of patients treated with a novel single-shot scheme. Additionally, we present a literature review of the current short-course irradiation strategies. CASES PRESENTATION: Three cases of conjunctival marginal zone (B-cell) lymphoma (marginal zone lymphoma [MZL]/mucosa-associated lymphoid tissue [MALT]) of the fornix are presented. Following biopsy and sonographic assessment of the lesion thickness, we applied a focused single dose of 14 Gy kilovoltage brachytherapy (prescribed to the maximum thickness of the lesion). Follow-up was scheduled in quarterly intervals. After 28, 31, and 40 months of follow-up, none of the three patients treated exhibited acute or chronic toxicities and remained local or distant disease-free. CONCLUSIONS: Single dose kilovoltage brachytherapy was effective and safe in this small cohort of patients. Based on the literature, there is an evidence that local treatment in short-course radiotherapy is effective and should be considered amongst therapeutic options for these patients; however, this novel approach should be evaluated prospectively in a larger cohort.

Intraoperative radiotherapy for glioblastoma: an international pooled analysis.

PURPOSE: To report the results of the first international pooled analysis of patients with glioblastoma treated with intraoperative radiotherapy (IORT) in addition to standard of care therapy. METHODS: Data from 51 patients treated at five centers in Germany, China and Peru were analyzed. All patients underwent tumor resection followed by a single application of IORT (10-40 Gy, prescribed to the applicator surface) with low-energy X-rays. Thereafter, standard adjuvant radiochemotherapy and maintenance chemotherapy were applied. Factors of interest were overall survival (OS), progression-free survival (PFS), local PFS (L-PFS; defined as appearance of new lesions ≤1 cm to the cavity border) and distant PFS (D-PFS; lesions >1 cm). The same endpoints were estimated at 1-, 2- and 3-years using the Kaplan-Meier method. Additionally, rates and severity (as per Common Terminology Criteria for Adverse Events Version 5.0) of radionecrosis (RN) were analyzed. RESULTS: The median age was 55 years (range: 16-75) and the median Karnofsky Performance Status was 80 (20-100). At a median follow-up of 18.0 months (2-42.4), the median OS, PFS, L-PFS and D-PFS were 18.0 months (95% CI: 14.7-21.3), 11.4 months (95%CI: 7.58-15.22), 16 months (95%CI: 10.21-21.8) and 30.0 months (95%CI: 18.59 - 41.41), respectively. The estimated 1-, 2- and 3-year OS, PFS, L-PFS and D-PFS were 79.5%, 38.7% and 25.6%; 46.2%, 29.4%, and 5.9%; 60.9, 37.9%, and 12.6%; and 76.7%, 65.0%, and 39.0% respectively. First progression occurred locally in only 35.3% of cases. Grade 1 RN was detected in 7.8% and grade 3 in 17.6% of the patients. No grade 4 toxicity was reported and no treatment-related deaths occurred. CONCLUSION: Compared to historical data, this pooled analysis suggests improved efficacy and safety of IORT with low-energy X-rays for newly diagnosed glioblastoma. Prospective data is warranted to confirm these findings.