Phylogenetic Analysis and Comparative Genomics of Brucella abortus and Brucella melitensis Strains in Egypt.

Brucellosis is a notifiable disease induced by a facultative intracellular Brucella pathogen. In this study, eight Brucella abortus and eighteen Brucella melitensis strains from Egypt were annotated and compared with RB51 and REV1 vaccines respectively. RAST toolkit in the BV-BRC server was used for annotation, revealing genome length of 3,250,377 bp and 3,285,803 bp, 3289 and 3323 CDS, 48 and 49 tRNA genes, the same number of rRNA (3) genes, 583 and 586 hypothetical proteins, 2697 and 2726 functional proteins for B. abortus and B. melitensis respectively. B. abortus strains exhibit a similar number of candidate genes, while B. melitensis strains showed some differences, especially in the SRR19520422 Faiyum strain. Also, B. melitensis clarified differences in antimicrobial resistance genes (KatG, FabL, MtrA, MtrB, OxyR, and VanO-type) in SRR19520319 Faiyum and (Erm C and Tet K) in SRR19520422 Faiyum strain. Additionally, the whole genome phylogeny analysis proved that all B. abortus strains were related to vaccinated animals and all B. melitensis strains of Menoufia clustered together and closely related to Gharbia, Dameitta, and Kafr Elshiek. The Bowtie2 tool identified 338 (eight B. abortus) and 4271 (eighteen B. melitensis) single nucleotide polymorphisms (SNPs) along the genomes. These variants had been annotated according to type and impact. Moreover, thirty candidate genes were predicted and submitted at GenBank (24 in B. abortus) and (6 in B. melitensis). This study contributes significant insights into genetic variation, virulence factors, and vaccine-related associations of Brucella pathogens, enhancing our knowledge of brucellosis epidemiology and evolution in Egypt.

Safety and effectiveness of disease-modifying therapies after switching from natalizumab.

INTRODUCTION: One strategy to mitigate progressive multifocal leukoencephalopathy (PML) risk is to switch to other highly effective disease-modifying therapies (DMTs). However, the optimal switch DMT following natalizumab (NTZ) discontinuation is yet to be determined. OBJECTIVE: The objective of the study is to determine the most effective and tolerable DMTs to switch to following NTZ discontinuation due to John Cunningham virus (JCV) antibody positivity. METHODS: This is a multicenter observational cohort study that included all stable relapsing-remitting multiple sclerosis (MS) patients who were treated with NTZ for at least 6 months before switching therapy due to JCV antibody positivity. RESULTS: Of 321 patients, 255 switched from NTZ to rituximab/ocrelizumab, 52 to fingolimod, and 14 to alemtuzumab, with higher annualized relapse rate (ARR) in fingolimod switchers (0.193) compared with rituximab/ocrelizumab or alemtuzumab (0.028 and 0.032, respectively). Fingolimod switchers also had increased disability progression (p = 0.014) and a higher proportion developed magnetic resonance imaging (MRI) lesions compared with rituximab/ocrelizumab (62.9% vs. 13.0%, p < 0.001, and 66.6% vs. 24.0%, p < 0.001, respectively). Mean drug survival favored rituximab/ocrelizumab or alemtuzumab over fingolimod (p < 0.001). CONCLUSION: Our study shows superior effectiveness of rituximab/ocrelizumab and alemtuzumab compared with fingolimod in stable patients switching from NTZ due to JC virus antibody positivity.

Improving possible serious bacterial infection (PSBI) management in young infants when referral is not feasible: lessons from embedded implementation research in Ethiopia and Kenya.

BACKGROUND: Sepsis is a leading cause of neonatal mortality, despite the availability of effective treatment of possible serious bacterial illness (PSBI), including when referral to a hospital is not feasible. Gaps in access and delivery worsened during COVID-19. We conducted embedded implementation research in Ethiopia and Kenya aimed at mitigating the impact of COVID-19 and addressing various implementation challenges to improve PSBI management. METHODS: The implementation research projects were implemented at the subnational level in Ethiopia and Kenya between November 2020-June 2022 (Ethiopia) and December 2020-August 2022 (Kenya). Guided by the implementation research frameworks, both projects conducted mixed formative quantitative and exploratory research from April to May 2021, followed by summative evaluations conducted between June and July 2022. Frameworks encompassed Consolidated Framework for Implementation Research (CFIR), Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM), as well as health systems framework that incorporates cascades of care and World Health Organization Health Systems Building Blocks. Results were synthesized across the projects through document review and sharing cross-project measures and strategies through a project community of practice. RESULTS: Despite differences in settings across the projects, cross-cutting facilitators included community health worker program and support, and existence of guidelines for PSBI management at primary care levels. Barriers included community attitudes towards seeking care for sick newborns, COVID-19 risks and fear, and lack of health care worker competence. Country-specific contextual barriers included supply chain issues, civil conflict (Ethiopia), and labor strikes (Kenya). Strategies chosen to mitigate barriers and support implementation and sustainability in both settings included leveraging community health workers to address resistance to care-seeking, health workers' training, COVID-19 infection prevention measures, stakeholder engagement, and advocacy to integrate PSBI management into existing programs, policies, and training. Other strategies addressing emerging project-specific barriers, included improving follow-up through a community health desk and PSBI mobile app (Kenya) and supply chain strengthening (Ethiopia). Both projects improved PSBI management coverage, increased adoption and uptake, and informed national policy changes supporting potential for sustainability. CONCLUSIONS: Pragmatic embedded implementation research effectively supports the identification of barriers and mapping to strategies designed to increase effective coverage of PSBI management when referral is not feasible during the COVID-19 pandemic. Despite differences in context, cross-cutting strategies identified could inform broader scale-up in the region, including during future health system shocks.

Endoscopic callosotomy as a minimally invasive approach to treat paediatric refractory epilepsy: case series.

BACKGROUND: Endoscopic callosotomy has emerged as a promising and minimally invasive technique for the treatment of refractory epilepsy. This paper aims to review the clinical outcomes and advancements associated with endoscopic callosotomy as a therapeutic option. MATERIALS AND METHODS: This study includes 14 Paediatric patients diagnosed and managed at Al-azhar university hospitals. Those 14 patients were studied over 2 years. All patients underwent a corpus callosotomy using the bimanual endoscopic technique. RESULTS: Endoscopic anterior corpus callosotomy was done in 13 patients while one case underwent endoscopic complete callosotomy. The most frequent complication was transient disconnection syndrome followed by transient Urinary incontinence and one case had minor CSF leak. As regard seizure freedom outcome (Engel's Outcome Scale): 4 cases (28.6%) became seizure free (Engle class I), 5 cases (35.7%) with Engle class II, 1 case (7.1%) with Engle class III and 4 cases (28.6%) classify as Engle class IV. CONCLUSION: As a minimally invasive technique with a favorable impact on cognitive function, less complications and a significant reduction in seizure frequency and severity in the majority of paediatric patients, endoscopic corpus callosotomy offeres substantial benefits in managing refractory epilepsy in paediatric.

An ultrasensitive green synchronous factorized spectrofluorimetric approach for the simultaneous determination of Favipiravir and Molnupiravir: Application to pharmaceutical, environmental, and biological matrices.

During the pandemic, Favipiravir (FVP) and Molnupiravir (MPV) have been widely used for COVID-19 treatment, leading to their presence in the environment. A green synchronous spectrofluorimetric method was developed to simultaneously detect them in environmental water, human plasma, and binary mixtures. Maximum fluorescence intensity was achieved at pH 8, with MPV exhibiting two peaks at 300 and 430 nm, and FVP showing one peak at 430 nm. A fluorescence subtraction method effectively removed interference, enabling direct determination of MPV at 300 nm and FVP at 430 nm. The method showed linearity within 2-13 ng/mL for FVP and 50-600 ng/mL for MPV, with recoveries of 100.35% and 100.12%, respectively. Limits of detection and quantification were 0.19 and 0.57 ng/mL for FVP and 10.52 and 31.88 ng/mL for MPV. Validation according to ICH and FDA guidelines yielded acceptable results. The method demonstrated good recoveries of FVP and MPV in pharmaceuticals, tap water and Nile water (99.62% ± 0.96% and 99.69% ± 0.64%) as per ICH guidelines and spiked human plasma (94.87% ± 2.111% and 94.79% ± 1.605%) following FDA guidelines, respectively. Its environmental friendliness was assessed using Green Analytical Procedure Index (GAPI) and the Analytical Greenness Metric (AGREE) tools.

Dermoscopy of subclinical nail involvement in patients with diabetes mellitus: a case-control study.

BACKGROUND: Diabetes mellitus (DM) is a chronic disease characterized by elevated blood glucose levels that can lead to serious complications. Nails are a mirror for general health so changes in nails can be an indicator of disease progression in patients with DM. AIM: To detect subclinical nail changes in patients with DM using dermoscopy. METHODS: In total, 100 participants were recruited, all of them from outpatient clinics, made up of a group with DM (n = 50) and an age- and sex-matched control group without DM (n = 50). All patients had clinically apparently normal nails. In both groups, dermoscopic examinations were conducted and compared. RESULTS: It was found that 33 patients in the DM group (66%) had dermoscopic nail findings in the form of microhaemorrhage (26%), longitudinal striations (24%), distal subungual onychomycosis (24%), superficial pitting (20%), distal onycholysis (18%), splinter haemorrhage (14%), subungual hyperkeratosis (12%), dilated vessels (10%) and distal yellowish discoloration (8%). CONCLUSION: Nail examination can be accomplished with the help of dermoscopy to detect subclinical nail changes in patients diagnosed with DM and, therefore, can give us an idea about disease progression and help with control of DM and treatment plans.

Dermabrasion Versus Microneedling in Transplantation of Autologous Noncultured Melanocyte-Keratinocyte Cell Suspension in Patients With Vitiligo.

BACKGROUND: Autologous noncultured melanocyte-keratinocyte transplantation is one of the procedures used to treat stable vitiligo with varying reported results. Recipient site preparation is one of the variables that could affect repigmentation outcomes. OBJECTIVE: To assess the effectiveness of transplanting autologous melanocyte-keratinocyte suspension in patients with stable vitiligo and to compare recipient site preparation using dermabrasion versus microneedling. METHODS: From March 2020 to September 2022, this randomized comparative study included 40 patients with 40 stable vitiligo lesions managed by suspension transplants of melanocytes. Patients were divided into 2 groups: group A, where the recipient site was prepared using dermabrasion, and group B, which was done by microneedling. The assessment was performed 3 months after the treatment based on the degree of repigmentation (excellent, ≥90%; good, 50%-89%; fair, 20%-49%; and poor response, <20%). RESULTS: Both modalities resulted in effective repigmentation, but the dermabrasion group showed a statistically significant improvement and a satisfactory repigmentation rate. CONCLUSION: Autologous melanocyte transplantation is a safe and effective treatment method for stable vitiligo lesions that have not responded to other therapies. When compared with microneedling, dermabrasion produced better outcomes for recipient site preparation.

Repurposing FIASMAs against Acid Sphingomyelinase for COVID-19: A Computational Molecular Docking and Dynamic Simulation Approach.

Over the past few years, COVID-19 has caused widespread suffering worldwide. There is great research potential in this domain and it is also necessary. The main objective of this study was to identify potential inhibitors against acid sphingomyelinase (ASM) in order to prevent coronavirus infection. Experimental studies revealed that SARS-CoV-2 causes activation of the acid sphingomyelinase/ceramide pathway, which in turn facilitates the viral entry into the cells. The objective was to inhibit acid sphingomyelinase activity in order to prevent the cells from SARS-CoV-2 infection. Previous studies have reported functional inhibitors against ASM (FIASMAs). These inhibitors can be exploited to block the entry of SARS-CoV-2 into the cells. To achieve our objective, a drug library containing 257 functional inhibitors of ASM was constructed. Computational molecular docking was applied to dock the library against the target protein (PDB: 5I81). The potential binding site of the target protein was identified through structural alignment with the known binding pocket of a protein with a similar function. AutoDock Vina was used to carry out the docking steps. The docking results were analyzed and the inhibitors were screened based on their binding affinity scores and ADME properties. Among the 257 functional inhibitors, Dutasteride, Cepharanthine, and Zafirlukast presented the lowest binding affinity scores of -9.7, -9.6, and -9.5 kcal/mol, respectively. Furthermore, computational ADME analysis of these results revealed Cepharanthine and Zafirlukast to have non-toxic properties. To further validate these findings, the top two inhibitors in complex with the target protein were subjected to molecular dynamic simulations at 100 ns. The molecular interactions and stability of these compounds revealed that these inhibitors could be a promising tool for inhibiting SARS-CoV-2 infection.

Genetic analysis of yield traits in Egyptian cotton crosses (Gossypium barbdense L.) under normal conditions.

To generate high-yielding cultivars with favorable fiber quality traits, cotton breeders can use information about combining ability and gene activity within a population to locate elite parents and potential F1 crosses. To this end, in the current study, twelve cotton parents (eight genotypes as female parents and four testers) and their F1 crosses obtained utilizing the linex tester mating design were evaluated for their general and specialized combining abilities (GCA and SCA, respectively) of yield traits. The findings showed that for all the investigated variables, variances owing to genotypes, parents, crosses, and parent vs cross showed extremely significant (P ≤ 0.01) differences. Additionally, throughout the course of two growing seasons, the mean squares for genotypes (parents and crosses) showed strong significance for all the variables under study. The greatest and most desired means for all the examined qualities were in the parent G.94, Pima S6, and tester G.86. The best crossings for the qualities examined were G.86 (G.89 × G.86), G.93 × Suvin, and G.86 × Suvin. The parents' Suvin, G89x G86 and TNB were shown to have the most desired general combining ability effects for seed cotton yield/plant, lint yield/plant, boll weight, number of bolls/plants, and lint index, while Suvin, G.96 and pima S6 were preferred for favored lint percentage. For seed cotton yield, lint percentage, boll weight, and number of bolls per plant per year, the cross-G.86 x (G.89 × G.86) displayed highly significant specific combining ability impacts. The crosses G.86 × Suvin, Kar x TNB, G.93 × Suvin, and G.93 × TNB for all the studied traits for each year and their combined were found to have highly significant positive heterotic effects relative to better parent, and they could be used in future cotton breeding programs for improving the studied traits.

Endorsement and phylogenetic analysis of some Fabaceae plants based on DNA barcoding.

BACKGROUND: DNA barcoding have been considered as a tool to facilitate species identification based on its simplicity and high-level accuracy in compression to the complexity and subjective biases linked to morphological identification of taxa. MaturaseK gene (MatK gene) of the chloroplast is very vital in the plant system which is involved in the group II intron splicing. The main objective of this study is to determine the relative utility of the "MatK" chloroplast gene for barcoding in 15 legume as a tool to facilitate species identification based on their simplicity and high-level accuracy linked to morphological identification of taxa. METHODS AND RESULTS: MatK gene sequences were submitted to GenBank and the accession numbers were obtained with sequence length ranging from 730 to 1545 nucleotides. These DNA sequences were aligned with database sequence using PROMALS server, Clustal Omega server and Bioedit program. Maximum likelihood and neighbor-joining algorithms were employed for constructing phylogeny. Overall, these results indicated that the phylogenetic tree analysis and the evolutionary distances of an individual dataset of each species were agreed with a phylogenetic tree of all each other consisting of two clades, the first clade comprising (Enterolobium contortisiliquum, Albizia lebbek), Acacia saligna, Leucaena leucocephala, Dichrostachys Cinerea, (Delonix regia, Parkinsonia aculeata), (Senna surattensis, Cassia fistula, Cassia javanica) and Schotia brachypetala were more closely to each other, respectively. The remaining four species of Erythrina humeana, (Sophora secundiflora, Dalbergia Sissoo, Tipuana Tipu) constituted the second clade. CONCLUSION: Moreover, their sequences could be successfully utilized in single nucleotide polymorphism or as part of the sequence as DNA fragment analysis utilizing polymerase chain reaction in plant systematic. Therefore, MatK gene is considered promising a candidate for DNA barcoding in the plant family Fabaceae and provides a clear relationship between the families.

Is there variation in utilization of preoperative tests among patients undergoing total hip and knee replacement in the US, and does it affect outcomes? A population-based analysis.

STUDY OBJECTIVE: To describe recent practice patterns of preoperative tests and to examine their association with 90-day all-cause readmissions and length of stay. DESIGN: Retrospective cohort study using the New York Statewide Planning and Research Cooperative System (SPARCS). SETTING: SPARCS from March 1, 2016, to July 1, 2017. PARTICIPANTS: Adults undergoing Total Hip Replacement (THR) or Total Knee Replacement (TKR) had a preoperative screening outpatient visit within two months before their surgery. INTERVENTIONS: Electrocardiogram (EKG), chest X-ray, and seven preoperative laboratory tests (RBCs antibody screen, Prothrombin time (PT) and Thromboplastin time, Metabolic Panel, Complete Blood Count (CBC), Methicillin Resistance Staphylococcus Aureus (MRSA) Nasal DNA probe, Urinalysis, Urine culture) were identified. PRIMARY AND SECONDARY OUTCOME MEASURES: Regression analyses were utilized to determine the association between each preoperative test and two postoperative outcomes (90-day all-cause readmission and length of stay). Regression models adjusted for hospital-level random effects, patient demographics, insurance, hospital TKR, THR surgical volume, and comorbidities. Sensitivity analysis was conducted using the subset of patients with no comorbidities. RESULTS: Fifty-five thousand ninety-nine patients (60% Female, mean age 66.1+/- 9.8 SD) were included. The most common tests were metabolic panel (74.5%), CBC (66.8%), and RBC antibody screen (58.8%). The least common tests were MRSA Nasal DNA probe (13.0%), EKG (11.7%), urine culture (10.7%), and chest X-ray (7.9%). Carrying out MRSA testing, urine culture, and EKG was associated with a lower likelihood of 90-day all-cause readmissions. The length of hospital stay was not associated with carrying out any preoperative tests. Results were similar in the subset with no comorbidities. CONCLUSIONS: Wide variation exists in preoperative tests before THR and TKR. We identified three preoperative tests that may play a role in reducing readmissions. Further investigation is needed to evaluate these findings using more granular clinical data.

Ocular changes of non-segmental vitiligo: A case-control study.

BACKGROUND/OBJECTIVES: Vitiligo is a skin disorder in which the melanocytes are destroyed. Melanocytes can be destroyed anywhere in the body, compromising the function of the organs where they are found. Melanocytes in the epidermis and the uveal tract share a common embryological origin in addition to physiological and morphological similarities. Our aim was to detect ocular changes in non-segmental vitiligo patients. METHODS: This study included 40 non-segmental vitiligo patients and 40 healthy volunteers as a control. Visual acuity testing, slit lamp examination and optical coherence tomography were performed on all patients as well as controls. RESULTS: Patients with non-segmental vitiligo had a considerably greater incidence of ocular alterations than controls, although there was no significant difference in visual acuity. CONCLUSIONS: Vitiligo is a systemic condition that can affect the activity of melanocytes in organs besides the skin. The depigmentation process can influence ocular melanocytes. Ocular problems may be closely connected to vitiligo. Because ocular melanocytes aren't involved in the detection or transmission of visual pathway, there is no vision impairment.

Conceptual Frameworks of Postoperative Recovery: A Scoping Review.

OBJECTIVE: We conducted a scoping review to identify existing conceptual frameworks of postoperative recovery (PR) and assess their content. BACKGROUND: PR is increasingly recognized by providers and third-party payers as a multidimensional phenomenon. Efforts to optimize PR and reduce complications and readmissions continue to evolve through changes in care (i.e., enhanced recovery protocols) and financial incentives. Delineating all factors affecting PR using a conceptual framework should aid in the design of effective interventions. METHODS: Web of Science and PubMed were queried to identify articles, between January 1980 and August of 2019, about conceptual frameworks of PR, using the search terms: "concept," "model," "framework," "recovery after surgery," "conceptual framework" "postoperative," "surgery," and "children." Articles considering PR as a concept rather than an outcome were included. Articles were examined in accordance with Walker and Avant's method for the concept analysis. Concepts identified across articles were classified as domains and subdomains of PR. RESULTS: The search yielded 183 unique articles; 8 met inclusion/exclusion criteria. Most articles defined PR as a period of days to weeks (n = 7) rather than days (n = 1). PR was mostly conceptualized as a process involving the patient and the health care system (n = 4) rather than the patient alone (n = 2). Physiological recovery (n = 8), activities of daily living (n = 8), pain (n = 5), cognitive/psychological recovery (n = 4), social recovery (n = 2), and patient perspective (n = 1) were the identified domains. Existing patient-reported outcome measures were used to assess most PR domains; however, definitions of domains and subdomains differed. None of the PR conceptual frameworks included were specific to children. CONCLUSIONS: There are few conceptual frameworks of PR in adults, and the definitions of PR differ. No framework was specific to children. Consensus on a conceptual framework of PR in adults and development of a conceptual framework of PR specific to children are needed.

Synchronous Spectrofluorimetry Coupled with Third-Order Derivative Signal Processing for the Simultaneous Quantitation of Telmisartan and Chlorthalidone Drug Combination in Human Plasma.

This study is the first to develop and optimize a method for the simultaneous determination of chlorthalidone (CLT) and telmisartan (TEL) in, human plasma samples as well as in their newly released pharmaceutical tablet form, (Telmikind-CT 40®). The method is based on measuring fluorescence intensity, employing synchronous fluorescence mode coupled to third-order derivative signal processing, 0.5% w/v cetyl trimethyl ammonium bromide was used as cationic surfactant to enhance the fluorescence signal intensity and improve method sensitivity. The third-order derivative synchronous spectra of CLT and TEL are well separated with two zero-crossing points which allowed for the determination of CLT and TEL at 362 nm and 351 nm, respectively. Different experimental parameters were carefully investigated and optimized, calibration curves were constructed over concentration ranges of 20-1200 ng.mL-1 and 5-800 ng.mL-1 for CLT and TEL respectively. The developed method is simple and rapid, analytical parameters were validated according to ICH guidelines and high sensitivity was achieved as represented by limits of detection (LOD) of 4.69 and 1.58 ng.mL-1 for CLT and TEL respectively.

Simultaneous determination of citalopram and tadalafil by the second derivative synchronous fluorescence method in biological fluids; application of Box-Behnken optimization design.

This is the first study focusing solely on that determination of tadalafil in the presence of citalopram as an antidepressant drug. The determination in biological fluids of a co-administered antidepressant drug and a sexual stimulation drug is a very critical and important step for psychotic and ischaemic heart disease patients, especially in cases of emergency and this requires therapeutic drug monitoring. A sensitive, efficient and rapid assay was selected satisfactorily and applied for simultaneous determination of citalopram and tadalafil either in their pure forms, in tablet dosage forms or in spiked human plasma. There was a large overlap for both drugs, forming the broad band found in conventional fluorescence spectra and their related synchronous fluorescence intensity. Therefore, the development of a highly sensitive second derivative synchronous fluorescence method was demonstrated that removed this overlap. The proposed method depended on measuring the amplitudes of the second derivative of synchronous fluorescence intensity at suitable wavelengths of 301 nm and 367 nm for citalopram and tadalafil at Δλ = 60 nm, respectively. Box-Behnken design as a response surface methodology was used to fit models and create an optimization process encompassing a set of factors and resulting in an optimum response value specifically designed for this method. Under optimum conditions, the linear dynamic ranges for citalopram and tadalafil estimation were 20-900 and 5-400 ng ml-1 with detection limits of 5.40 and 1.43 ng ml-1 , respectively.

Experimental and Established Oximes as Pretreatment before Acute Exposure to Azinphos-Methyl.

Poisoning with organophosphorus compounds (OPCs) represents an ongoing threat to civilians and rescue personal. We have previously shown that oximes, when administered prophylactically before exposure to the OPC paraoxon, are able to protect from its toxic effects. In the present study, we have assessed to what degree experimental (K-27; K-48; K-53; K-74; K-75) or established oximes (pralidoxime, obidoxime), when given as pretreatment at an equitoxic dosage of 25% of LD01, are able to reduce mortality induced by the OPC azinphos-methyl. Their efficacy was compared with that of pyridostigmine, the only FDA-approved substance for such prophylaxis. Efficacy was quantified in rats by Cox analysis, calculating the relative risk of death (RR), with RR=1 for the reference group given only azinphos-methyl, but no prophylaxis. All tested compounds significantly (p ≤ 0.05) reduced azinphos-methyl-induced mortality. In addition, the efficacy of all tested experimental and established oximes except K-53 was significantly superior to the FDA-approved compound pyridostigmine. Best protection was observed for the oximes K-48 (RR = 0.20), K-27 (RR = 0.23), and obidoxime (RR = 0.21), which were significantly more efficacious than pralidoxime and pyridostigmine. The second-best group of prophylactic compounds consisted of K-74 (RR = 0.26), K-75 (RR = 0.35) and pralidoxime (RR = 0.37), which were significantly more efficacious than pyridostigmine. Pretreatment with K-53 (RR = 0.37) and pyridostigmine (RR = 0.52) was the least efficacious. Our present data, together with previous results on other OPCs, indicate that the experimental oximes K-27 and K-48 are very promising pretreatment compounds. When penetration into the brain is undesirable, obidoxime is the most efficacious prophylactic agent already approved for clinical use.

Psychodermatology knowledge and awareness: A cross-sectional Egyptian perspective.

The merging of psychiatry and dermatology has resulted in a relatively newer emerging field known as psychodermatology (PD). The aim of this cross sectional study was to assess knowledge, attitudes, and practice patterns of Egyptian dermatologists towards psychodermatology. A cross sectional study was designed and data were collected using structured self-administered online questionnaires. A total of 212 dermatologists completed the full questionnaire. Those with incomplete or partially answered responses were excluded. 171 (81.1%) were females and 40 (18.9%) were males. The majority (n = 109;51.4%) of dermatologists completing the survey were between 30 and 40 years age group while those between 40 and 50 years of age accounted for 48 (22.6%). The vast majority of respondent dermatologists never referred (n = 87; 41%) or very rarely referred (n = 58; 27.5%) any psychocutaneous patients to a psychiatrist. Almost 75% of responding dermatologists were not aware of available community or educational resources for PD and 157 (74.1%) expressed interest in receiving continuing medical education (CME) programs. In conclusion, psychodermatology training among dermatologists shall enhance and improve their approach to psychocutaneous conditions.

Myocardial Protection by Blood-Based Del Nido versus St. Thomas Cardioplegia in Cardiac Surgery for Adults and Children.

BACKGROUND: St. Thomas (ST) and Del Nido (DN) cardioplegic solutions are widely used for myocardial protection during cardiac surgery. In 2016, our university hospital shifted from modified St. Thomas to Del Nido solution for both adult and pediatric cardiac surgery. This retrospective study was conducted to compare ST and DN solutions regarding surgical workflow and clinical outcome in pediatric and adult patients undergoing cardiac surgery. METHODS: We reviewed 220 patients who underwent cardiac surgery requiring cardioplegic arrest. Patients were categorized in 2 groups: ST (n = 110) and DN (n = 110). Each group included 60 pediatric and 50 adult patients. Demographic, intraoperative, and postoperative variables were collected. RESULTS: In pediatric patients, no significant difference was found between the 2 groups regarding clamping time, bypass time, need for defibrillation, inotropic score, postoperative ejection fraction (EF), period of mechanical ventilation, intensive care unit stay, or postoperative arrhythmias. One patient in the ST group required mechanical support by extracorporeal membrane oxygenation. We had 5 cases of pediatric mortality (3 in DN and 2 in ST, P = .64). In adult patients, significantly fewer patients in the DN group needed defibrillation than in the ST group. No significant difference was found regarding clamping time, inotropic score, or intraaortic balloon pump use. Mortality in adult patients was 6 cases (4 in ST group and 2 in DN group). CONCLUSION: DN cardioplegia solution is as safe as ST solution in pediatric and adult cardiac surgery. It has comparable results of myocardial protection and clinical outcome, with superiority regarding uninterrupted surgery and lower rate of defibrillation.

Combined Pre- and Posttreatment of Paraoxon Exposure.

AIMS: Organophosphates (OPCs), useful agents as pesticides, also represent a serious health hazard. Standard therapy with atropine and established oxime-type enzyme reactivators is unsatisfactory. Experimental data indicate that superior therapeutic results can be obtained when reversible cholinesterase inhibitors are administered before OPC exposure. Comparing the protective efficacy of five such cholinesterase inhibitors (physostigmine, pyridostigmine, ranitidine, tacrine, or K-27), we observed best protection for the experimental oxime K-27. The present study was undertaken in order to determine if additional administration of K-27 immediately after OPC (paraoxon) exposure can improve the outcome. METHODS: Therapeutic efficacy was assessed in rats by determining the relative risk of death (RR) by Cox survival analysis over a period of 48 h. Animals that received only pretreatment and paraoxon were compared with those that had received pretreatment and paraoxon followed by K-27 immediately after paraoxon exposure. RESULTS: Best protection from paraoxon-induced mortality was observed after pretreatment with physostigmine (RR = 0.30) and K-27 (RR = 0.34). Both substances were significantly more efficacious than tacrine (RR = 0.67), ranitidine (RR = 0.72), and pyridostigmine (RR = 0.76), which were less efficacious but still significantly reduced the RR compared to the no-treatment group (paraoxon only). Additional administration of K-27 immediately after paraoxon exposure (posttreatment) did not further reduce mortality. Statistical analysis between pretreatment before paraoxon exposure alone and pretreatment plus K-27 posttreatment did not show any significant difference for any of the pretreatment regimens. CONCLUSIONS: Best outcome is achieved if physostigmine or K-27 are administered prophylactically before exposure to sublethal paraoxon dosages. Therapeutic outcome is not further improved by additional oxime therapy immediately thereafter.

Oximes as pretreatment before acute exposure to paraoxon.

Organophosphates, useful agents as pesticides, also represent a serious danger due to their high acute toxicity. There is indication that oximes, when administered before organophosphate exposure, can protect from these toxic effects. We have tested at equitoxic dosage (25% of LD01 ) the prophylactic efficacy of five experimental (K-48, K-53, K-74, K-75, K-203) and two established oximes (pralidoxime and obidoxime) to protect from mortality induced by the organophosphate paraoxon. Mortalities were quantified by Cox analysis and compared with those observed after pretreatment with a strong acetylcholinesterase inhibitor (10-methylacridine) and after the FDA-approved pretreatment compound pyridostigmine. All nine tested substances statistically significantly reduced paraoxon-induced mortality. Best protection was conferred by the experimental oxime K-48, reducing the relative risk of death (RR) to 0.10, which was statistically significantly superior to pyridostigmine (RR = 0.31). The other oximes reduced the RR to 0.13 (obidoxime), 0.20 (K-203), 0.21 (K-74), 0.24 (K-75) and 0.26 (pralidoxime), which were significantly more efficacious than 10-methylacridine (RR = 0.65). These data support the hypothesis that protective efficacy is not primarily due to cholinesterase inhibition and indicate that the tested experimental oximes may be considered promising alternatives to the established pretreatment compound pyridostigmine.