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Current source inverters (CSIs) have been widely used for renewable energy sources integration with the utility grid. However, traditional CSIs provide only voltage-boost power conversion, which can be considered a limitation for grid-interfacing applications when consistent tracking of a widely varying input voltage is necessary. Hence, an additional front-end converter is usually utilized in an attempt to step down the input source voltage. Nevertheless, adding the dc-dc bucking stage would reduce the system reliability and its overall efficiency, increase the converter cost, and complicate the control scheme. In order to address the aforementioned shortcomings, this paper proposes a novel three-phase single-stage inverter, suitable for low-power applications, called split-source current-type inverter (SSCTI). The proposed converter can achieve high current boosting capability with lower component count and high-quality output current in comparison with other single-stage topologies. In addition, it utilizes the conventional modulation scheme of the CSI, while maintaining low current stresses on the inverter switches. Comprehensive analysis, modelling, and closed-loop control scheme of the proposed converter are developed. Also, a comparison between the proposed topology and several single-stage topologies is carried out. Moreover, an experimental prototype is built to validate the proposed converter analysis under steady-state operation and different transient scenarios.

Brucellosis is a neglected zoonotic disease that has a significant economic and public health impact, especially in endemic countries. This review delves deeply into brucellosis’s current epidemiological situation and potential sources of livestock infection in Egypt during the last two decades. MLVA-16 and Whole Genome Sequencing based on core-genome SNP analyses confirm the presence of different B. abortus and B. melitensis outbreak strains, both older widely disseminated Brucella strains and newly introduced ones. Despite implementing the test-and-slaughter control strategy over forty years, the disease is still endemic, and different Brucella species circulate among several animal species. The raising of mixed animal species in the same households or farms, exposure to aborted animals, and lack of public awareness about brucellosis transmission are among the main risk factors for increasing livestock brucellosis prevalence in Egypt. Young animals’ voluntary vaccination, lack of a nationwide animal identification system, and uncontrolled animal movement stand beyond the ineffectively applied control strategy and may be subdued by applying mass vaccination to decrease disease prevalence dramatically and target imported camels, domestic pigs, and dogs (housed and stray) in the national control surveillance. Increasing awareness through educational campaigns is compulsory to reduce brucellosis transmission risk to livestock/humans.

To investigate the incidence of the virulence genes among predominant Brucella strains in infected cattle, buffaloes, sheep, goats, and camels as well as in humans in Egypt, a total of 263 samples (85 milk, 167 tissue, 11 whole blood samples), yielded 140 (53.2%) Brucella isolates. Confirmation of Brucella isolates was carried out by conventional biotyping and by PCR using IR1/IR2 primers tar-geting Brucella genus showing an amplicon of 839 bp in all Brucella isolates. Conventional bioty¬ping, as well as duplex PCR of the isolated non-repetitive Brucella strains, identified 107 (76.4 %) as B. melitensis with an amplicon of 731 bp and 33 (23.6%) as B. abortus with an amplicon of 498 bp. Out of 87 Brucella strains isolated from cattle, 63 (72.4%) were B. melitensis. No Brucella isolates were obtained from 7 lymph nodes of camels or 11 human blood samples; however, DNA extraction from 7 human sera and 3 camel lymph nodes gave positive PCR yield. All these samples gave PCR products indicating infection with B. melitensis. The distribution of the virulence genes among 33 B. abortus isolates revealed that virB recorded the highest incidence (97%), then followed bvfA, ure, and omp25 (93.9%), wbkA (90.9%), manB (87.9%) and amiC (84.8%). All 107 B. melitensis isolates had the bvfA, virB, and omp25 genes, while the prevalence of ure was 99.1%, that of wbkA: 96.3%, manB: 95.3% and amiC: 94.4%. The obtained results indicated the high incidence of virulence genes among field Brucella strains among farm animals in Egypt.

Background and Aim: Given the rise in stray and imported dogs in Egypt over the past 5 years, it is surprising that no report of Brucella canis infection in dogs or humans has been documented in Egypt's published papers. This study aimed to detect the presence of antibodies against the rough (B. canis) and smooth Brucellae among dogs in Egypt and to characterize the Brucella species circulating in dogs. Materials and Methods: Blood samples (n = 449) were collected from owned and stray dogs in the Greater Cairo region (n = 309) and Damietta governorate (n = 140). The apparent, true, and total seroprevalence of canine brucellosis caused by B. canis infection were calculated using the 2-mercaptoethanol tube agglutination test (2-ME TAT) and rapid slide agglutination test (RSAT). We used the rose Bengal test (RBT) and the buffered acidified plate antigen test (BAPAT) to check the serum samples from dogs for the presence of antibodies against smooth Brucellae. Three polymerase chain reaction (PCR) assays - Bruce-ladder PCR, B. canis species-specific PCR (BcSS-PCR), and Abortus Melitensis Ovis Suis (AMOS)-PCR - were used to determine the Brucella species in the buffy coats of the serologically positive dogs. Results: The overall apparent and true prevalence of B. canis infection in dogs were estimated to be 3.8% and 13.2%. The estimated true prevalence in stray dogs (15%) was higher than in owned dogs (12.5%). The BAPAT and the RBT using smooth antigens revealed that 11 (2.4%) and 9 (2%) were positive. Bruce-ladder PCR targeting eryC, ABC, and Polysaccharide deacetylase genes was able to identify B. canis in nine out of 17 buffy coat samples. AMOS-PCR identified the eight undetermined Brucella species by Bruce-ladder PCR as Brucella abortus (n = 4) and Brucella melitensis (n = 4). To exclude the presence of Brucella suis, a one-step species-specific BcSS-PCR was performed and specifically amplified all B. canis DNA (n = 9) the same as did the Bruce-ladder PCR. Conclusion: To the best of our knowledge, this is the first report of B. canis detection in dogs in Egypt. Molecular identification of B. abortus and B. melitensis in the Egyptian canines highlights the role of stray dogs in brucellosis remerging in Brucellosis-free dairy farms. Brucella canis infection can be diagnosed specifically with the one-step BcSS-PCR. The obtained results set-an-alarm to the veterinary authorities to launch plans to control this disease in dogs.

Abstract Background Brucella suis is a zoonotic pathogen with a serious impact on public health and the pig industry worldwide. Information regarding B. suis in pigs in Egypt is scarce. This study aimed to investigate the prevalence of B. suis in slaughtered domestic pigs at El-Basatin abattoir in Cairo, Egypt. A total of 1,116 domestic pigs slaughtered in 2020 were sampled for Brucella isolation and identification. Identified Brucella isolates were molecularly confirmed at species, and biovar levels using Bruce ladder PCR and Suis ladder multiplex PCR. Additionally, high-risk practices of 16 abattoir workers (4 veterinarians, 10 butchering and evisceration workers, and 2 scalding workers) were investigated using a pre-piloted structured questionnaire. Results Brucella isolates were recovered from 1.3% of examined pigs (n = 14) at consistently low rates (1.1—2.9%) across the year of sampling from February to December 2020. All isolates were confirmed as B. suis biovar (bv) 2. Remarkably, 92.9% (13/14) of isolates showed atypical ability to produce H2S and hence were considered as B. suis bv2 atypical phenotype. The prevalence was higher in males (1.8%) than in females (0.9). However, this difference was not significant (Odds ratio = 1.9; CI 95% 0.7 – 5.7; P = 0.2). No detectable pathological lesions were associated with B. suis bv2 infection in examined pigs. All strains were isolated from cervical lymph nodes, highlighting a potential oral transmission. High-risk practices were recorded among swine abattoir workers in this study: 75% do not wear gloves or disinfect their knives daily, and 18.8% were willing to work with open wound injuries. Conclusions To the best of our knowledge, this is the first isolation of B. suis bv2 in Egypt. Detection of H2S producing B. suis bv2 atypical phenotype is alarming as it may result in misinterpretation of these isolates as highly human pathogenic B. suis bv1 in Egypt and possibly elsewhere. Further epidemiological tracing studies are crucial for the detection of the origin of this biovar. Including pigs in the national surveillance program of brucellosis, and an education program for swine abattoir workers about occupational risk of B. suis is a need in Egypt.

ZigBee is widely used wireless network in Internet of Things (IoT) applications to remotely sensor and automation due to its unique characteristics compared to other wireless networks. According to ZigBee classification of IEEE 802.15.4 standard, the network consists of four layers. The ZigBee topology is represented in second layer, which is the network and security layer. Furthermore, the ZigBee topology consists of three topologies, star, tree and mesh. Also there are many transmission bands allowed in physical layer, such as 2.4 GHz, 915 MHz, 868 MHz, … etc. The study use Riverbed Modeler to evaluates the effect of ZigBee different topologies on different transmission bands regarding the performance of throughput and end to end delay. The results of the study show which topology should be used at each transmission band to obtain maximum throughput or provides lowest end to end delay, which is case sensitive in some IoT applications that required for example minimum delay.

Brucellosis, caused by the bacteria of the genus Brucella, is one of the most neglected common zoonotic diseases globally with a public health significance and a high economic loss among the livestock industry worldwide. Since little is known about the distribution of B. abortus in Egypt, a total of 46 B. abortus isolates recovered between 2012–2020, plus one animal isolate from 2006, were analyzed by examining the whole core genome single nucleotide polymorphism (cgSNP) in comparison to the in silico multilocus variable number of tandem repeat analysis (MLVA). Both cgSNP analysis and MLVA revealed three clusters and one isolate only was distantly related to the others. One cluster identified a rather widely distributed outbreak strain which is repeatedly occurring for at least 16 years with marginal deviations in cgSNP analysis. The other cluster of isolates represents a rather newly introduced outbreak strain. A separate cluster comprised RB51 vaccine related strains, isolated from aborted material. The comparison with MLVA data sets from public databases reveals one near relative from Argentina to the oldest outbreak strain and a related strain from Spain to a newly introduced outbreak strain in Egypt. The distantly related isolate matches with a strain from Portugal in the MLVA profile. Based on cgSNP analysis the oldest outbreak strain clusters with strains from the UK. Compared to the in silico analysis of MLVA, cgSNP analysis using WGS data provides a much higher resolution of genotypes and, when correlated to the associated epidemiological metadata, cgSNP analysis allows the differentiation of outbreaks by defining different outbreak strains. In this respect, MLVA data are error-prone and can lead to incorrect interpretations of outbreak events.

The scientific community has united to raise awareness of Alzheimer's disease (AD) as a critical condition for future generations because recent predictions indicate that it will become common among the elderly within a few years. Nevertheless, the intricacies of the disease's progression demand exhaustive investigations to unravel its potential mechanisms. Only then can clinicians develop more efficacious therapeutic strategies. Cognitive impairment caused by amyloid aggregation, the development of hyperphosphorylated neurofibrillary tangles, and a malfunctioning cholinergic system are the hallmarks of AD. Even after the disease has started, brain tissue integrity may degenerate. The physiological characteristics of the highly selective blood-brain barrier and the electrostatic charge of the nanoporous extracellular matrix have long placed restrictions on the treatment of brain disorders. A prospective revolution in drug delivery for the treatment of AD is the use of nanomedicine. It depends on enhancing the way that medications are distributed pharmacokinetically throughout the central nervous system. Several types of nanoparticles (Nps) are available thanks to nanotechnology, and these Nps could target the brain and have a long half-life with few systemic side effects and motor problems. With the latest technological developments, scientists are working to develop unique approaches for the treatment of AD. To evaluate the prospective uses of medicinal plants, their components, and different nanomedicine techniques, it was determined that this literature study was necessary. To provide an overview of the various challenges and approaches related to using nanoparticles (NPs) to combat Alzheimer's disease (AD), this introductory review article was developed., 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., (© 2025 The Authors.)

Distraction osteogenesis (DO) is a valuable surgical method for limb lengthening and bone defect correction, but its lengthy consolidation phase presents challenges. The accordion technique (AT), involving compression and distraction of bone segments, has shown potential for enhancing healing. This study aimed to investigate the effectiveness of the AT conducted at three different time points (distraction phase, early consolidation phase, or late consolidation phase) compared to conventional DO in a mouse osteotomy model. Healing was evaluated using in vivo microCT, histology, and computational modeling. Results showed that bridging frequency, BV, and callus tissue composition were similar between conventional DO and late consolidation AT. In contrast, distraction phase AT led to delayed healing at day 15 with a 72% reduction in BV compared to DO, but no significant differences by the endpoint. Early consolidation AT showed significantly impaired healing compared to DO, with only 29% of mice achieving bony bridging, and significantly reduced bone marrow area of the endpoint callus. In silico modeling was generally predictive of in vivo findings and suggested that application of the AT during early consolidation results in destruction of newly-formed vascular tissue. Overall, no benefit was observed for the AT compared to conventional DO with the parameters employed in this study., (© 2024. The Author(s).)

Withania (Solanaceae, Solanoideae) is a widespread genus. Comparative macro-, micro-morphological, anatomical, and molecular features of this genus in Egypt were examined using light and scanning electron microscopy to reassess the conflicted taxonomic relationships between the two studied species. The most significant morphological differences that have been found were: the shape of the lamina, apex, anther, and stigma, and the ratio of calyx tube/lobe; anatomical examination of taxonomic interest are as follows: number of vascular bundles, presence of ears and distribution of accessory vascular bundles in petiole and shape of spongy cells, and number of lower parenchyma in the midrib region of the leaf; trichomes of both species showed no significant differences; pollen, and seed characters are of taxonomic significance in differentiation and characterization between them. Protein profiling revealed that W. somnifera has only conserved proteins, while W. obtusifolia possessed both conserved and additional proteins in their SDS-PAGE banding patterns. Eleven starts codon-targeted (ScoT) primers were applied and produced 96 amplicons with an average of 70.83% polymorphism/primer. W. obtusifolia generated more polymorphic bands and maintained monomorphic ones. SDS-PAGE disclosed that both Withania species were 50% related. While Scot-Dendrogram revealed that both Withania species were poorly related. So, protein and molecular analyses showed considerable genetic variations between these two species., (© 2024. The Author(s).)

Background: Osteogenesis imperfecta (OI) is a connective tissue disorder in which the Type 1 collagen is defective. The eye is a structure rich in collagen Type 1 and is heavily impacted by the disease. Many vision-threatening eye diseases have been associated with OI. The onset of these diseases also tend to occur at an earlier age in individuals with OI. Despite the research on these risks, appropriate ophthalmological screening or care guidelines for individuals with OI remain unknown. As such, the purpose of this scoping review was to explore and describe existing ophthalmological screening and care guidelines to orient OI patient care., Main Body: A scoping review based on the Joanna Briggs Institute (JBI) methodology was conducted. A search of databases (PubMed and Medline) was completed in consultation with a research librarian. A total of 256 studies were imported for screening. Primary sources matching the inclusion and exclusion criteria were screened, extracted, and analyzed using Covidence., Conclusion: A total of 12 primary articles met inclusion and exclusion criteria, containing case reports, case series and cohort studies. Despite the risk of blindness associated with the consequences of OI on the eye, the primary literature fails to provide detailed screening and care guidelines aimed at identifying disease early. We provide general recommendations based on the review findings to guide the ophthalmological care of patients with OI and call upon the experts to convene globally to create screening guidelines. Further investigations of ophthalmological screening are warranted to limit these vision-threatening risks with early detection and treatment. Standardized ophthalmological screening guidelines for OI remain an area for research., (© 2024. The Author(s).)

This study aimed to investigate LRTIs in cancer patients, focusing on pathogen distribution, and outcomes based on tumor types and antimicrobial treatments. The study included 110 cancer patients exhibiting symptoms of lower respiratory tract infections (LRTIs), consisting of 67 males and 43 females across a wide age range from under 1 year to over 60 years old. Exclusion of SARS-CoV-2 infection was conducted before admission. In addition to classical microbiological methods, fast-track detection using Multiplex Real-Time PCR was employed, utilizing the FTD-33 test kit. The findings revealed a diverse landscape of infections, notably Klebsiella pneumoniae , Haemophilus influenzae and Staphylococcus aureus . Parainfluenza 3 and 4 viruses, rhinovirus, influenza A subtype H1N1pdm09, influenza B and C viruses, HCoV-229, HCoV-OC43, and HCoV-HKU1 were infrequently detected. Furthermore, the existence of mixed infection highlighted the complexity of disease conditions in cancer patients. An analysis of antimicrobial treatment highlighted significant variations in fatal outcomes for carbapenem and colistimethate sodium. It was concluded that mixed infections were commonly identified as potential causes of LRTIs among cancer patients, while viral infections were less frequently detected. It underscores the complexity of antimicrobial treatment outcomes.

Respiratory tract infections (RTIs) pose a substantial health burden worldwide, especially among immunocompromised groups like cancer patients. The aim of this prospective cohort study was to explore lower respiratory tract infections in cancer patients. We followed 107 cases with clinically or radiologically suspected lower respiratory tract infections until discharge or death, comprising 65 males and 42 females across diverse age groups. Clinical evaluations, including patient history, examination, and malignancy diagnosis, were conducted. Nasopharyngeal swabs (NPSs), sputum samples, and blood samples were collected within 24 h of symptom onset. Multiplex Real-Time PCR allowed for the simultaneous detection of viral, bacterial, and fungal infections, while conventional microbiological culture methods were used for bacterial and fungal analysis. SARS-CoV-2 infection was excluded in all of the enrolled patients using real-time RT-PCR. Hematological and biochemical analyses included hemoglobin, lymphocyte, neutrophil, and platelet counts, along with ALT, AST, creatinine, and CRP levels. Significant differences were noted in clinical presentations, management outcomes, and prognostic markers among patients with different hematological malignancies. Distinct clinical profiles were identified for leukemia, lymphoma, and solid tumors, with variations in age distribution and symptom prevalence. ICU admission rates varied significantly, with solid tumor patients exhibiting higher rates. The hematological and biochemical biomarkers differed across malignancies, with notable associations between lymphopenia, thrombocytopenia, and mortality following respiratory episodes. This study highlights the critical role of rapid pathogen detection and infection control measures in safeguarding vulnerable cancer patients from nosocomial transmission.

Breast cancer is one of the leading causes of death in females, mainly because of metastasis. Oncometabolites, produced via metabolic reprogramming, can influence metastatic signaling cascades. Accordingly, and based on our previous results, we propose that metabolites from highly metastatic breast cancer cells behave differently from less-metastatic cells and may play a significant role in metastasis. For instance, we aim to identify these metabolites and their role in breast cancer metastasis. Less metastatic cells (MCF-7) were treated with metabolites secreted from highly metastatic cells (MDA-MB-231) and the gene expression of three epithelial-to-mesenchymal transition (EMT) markers including E-cadherin, N-cadherin and vimentin were examined. Some metabolites secreted from MDA-MB-231 cells significantly induced EMT activity. Specifically, hypoxanthine demonstrated a significant EMT effect and increased the migration and invasion effects of MCF-7 cells through a hypoxia-associated mechanism. Hypoxanthine exhibited pro-angiogenic effects via increasing the VEGF and PDGF gene expression and affected lipid metabolism by increasing the gene expression of PCSK-9. Notably, knockdown of purine nucleoside phosphorylase, a gene encoding for an important enzyme in the biosynthesis of hypoxanthine, and inhibition of hypoxanthine uptake caused a significant decrease in hypoxanthine-associated EMT effects. Collectively for the first time, hypoxanthine was identified as a novel metastasis-associated metabolite in breast cancer cells and represents a promising target for diagnosis and therapy., (© 2024. The Author(s).)

The Bcl-2 family plays a crucial role in regulating cell apoptosis, making it an attractive target for cancer therapy. In this study, a series of indole-based compounds, U1 - 6 , were designed, synthesized, and evaluated for their anticancer activity against Bcl-2-expressing cancer cell lines. The binding affinity, safety profile, cell cycle arrest, and apoptosis effects of the compounds were tested. The designed compounds exhibited potent inhibitory activity at sub-micromolar IC 50 concentrations against MCF-7, MDA-MB-231, and A549 cell lines. Notably, U2 and U3 demonstrated the highest activity, particularly against MCF-7 cells. Respectively, both U2 and U3 showed potential BCL-2 inhibition activity with IC 50 values of 1.2 ± 0.02 and 11.10 ± 0.07 µM using an ELISA binding assay compared with 0.62 ± 0.01 µM for gossypol, employed as a positive control. Molecular docking analysis suggested stable interactions of compound U2 at the Bcl-2 binding site through hydrogen bonding, pi-pi stacking, and hydrophobic interactions. Furthermore, U2 demonstrated significant induction of apoptosis and cell cycle arrest at the G1/S phase. Importantly, U2 displayed a favourable safety profile on HDF human dermal normal fibroblast cells at 10-fold greater IC 50 values compared with MDA-MB-231 cells. These findings underscore the therapeutic potential of compound U2 as a Bcl-2 inhibitor and provide insights into its molecular mechanisms of action.

Aim: This paper aims to serve as a guide for surgeons to prepare, execute, and perfect anterior hemiepiphysiodesis of the distal tibia (AHDT)., Background: Treatment of persistent or recurrent equinus deformity following multiple conservative and surgical interventions in patients with idiopathic clubfoot or neuromuscular conditions can be challenging, and multiple surgical options are presented in the existing literature. Anterior hemiepiphysiodesis of the distal tibia is an option that seems to be safe and efficient in treating this entity. To the best of our knowledge, there is not yet any detailed description of this surgical technique in the English literature., Technique: The AHDT detailed surgical technique includes patient positioning, careful distal anterior tibial approach, placement of guided growth plates, fixation with epiphyseal and metaphyseal screws under fluoroscopic guidance, meticulous closure, and postoperative measures., Conclusion: This guide can be used pre-operatively to plan the surgery, intra-operatively to aid in smooth and safe step progression, and post-operatively to assist in critical critiquing., Clinical Significance: By understanding the various stages of the surgery as well as the anatomy, pitfalls can be avoided and AHDT can be performed efficiently., How to Cite This Article: Katz A, Dumas É, Hamdy R. Anterior Hemiepiphysiodesis of the Distal Tibia: A Step-by-step Surgical Technique Guide. Strategies Trauma Limb Reconstr 2023;18(3):174-180., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2023; The Author(s).)

Sponges are habitats for a diverse community of microorganisms. Sponges provide shelter, whereas microbes provide a complementary defensive mechanism. Here, a symbiotic bacterium, identified as Bacillus spp., was isolated from a marine sponge following culture enrichment. Fermentation-assisted metabolomics using thin-layer chromatography (TLC) and gas chromatography-mass spectrometry (GC-MS) indicated that marine simulated nutrition and temperature was the optimum in metabolite production represented by the highest number of metabolites and the diverse chemical classes when compared to other culture media. Following large-scale culture in potato dextrose broth (PDB) and dereplication, compound M1 was isolated and identified as octadecyl-1-(2',6'-di-tert-butyl-1'-hydroxyphenyl) propionate. M1, at screening concentrations up to 10 mg/ml, showed no activity against prokaryotic bacteria including Staphylococcus aureus and Escherichia coli, while 1 mg/ml of M1 was sufficient to cause a significant killing effect on eukaryotic cells including Candida albicans, Candida auris, and Rhizopus delemar fungi and different mammalian cells. M1 exhibited MIC 50 0.97 ± 0.006 and 7.667 ± 0.079 mg/ml against C. albicans and C. auris, respectively. Like fatty acid esters, we hypothesize that M1 is stored in a less harmful form and upon pathogenic attack is hydrolyzed to a more active form as a defensive metabolite. Subsequently, [3-(3,5-di-tert-butyl-4-hydroxyphenyl)-propionic acid] (DTBPA), the hydrolysis product of M1, exhibited ~ 8-fold and 18-fold more antifungal activity than M1 against C. albicans and C. auris, respectively. These findings indicated the selectivity of that compound as a defensive metabolite towards the eukaryotic cells particularly the fungi, a major infectious agent to sponges. Metabolomic-assisted fermentation can provide a significant understanding of a triple marine-evolved interaction. KEY POINTS: • Bacillus species, closely related to uncultured Bacillus, is isolated from Gulf marine sponge • Metabolomic-assisted fermentations showed diverse metabolites • An ester with a killing effect against eukaryotes but not prokaryotes is isolated., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Innovative approaches are needed to address the self-management needs of youths with osteogenesis imperfecta (OI) transitioning into adult-oriented health care systems. Using a sequentially phased research approach, the goal is to design, develop, and test the usability of an innovative eHealth program called "Teens Taking Charge: Managing OI Online," hereafter named "Teens OI." This program seeks to optimize self-management, facilitate a successful transition to adult care, and address a critical gap in the quality of care for youths with OI., Objective: The study objectives are to (1) design and develop an English and French version of the Teens OI and (2) test the usability of the Teens OI in terms of efficiency, effectiveness, and satisfaction from the perspectives of youths with OI and their parents., Methods: A user-centered design is presently in progress to design and develop Teens OI. A "Website Design and Development Council" (ie, Council) has been convened, with 20 youths and parent dyads recruited and global experts surveyed at an international meeting. With unanimous support from the Council, usability testing of the Teens OI will ensue in 4 iterative cycles with 32 youth-parent dyads. All sociodemographic and usability metrics will be descriptively analyzed. All recorded interview and focus group data are analyzed using content analysis techniques involving an iterative process of data reduction, data display, conclusion drawing, and verification., Results: As of December 2022, an 8-person, interdisciplinary Teens OI council, comprising 4 health care professionals, 3 youths and young adults with OI, and 1 parent, has been convened to oversee the design and development of Teens OI. Two cycles of interviews have been conducted with 10 youths with OI with or without their parents (n=6) from December 2021 to September 2022. Data analysis has been in progress since April 2022. Aim 2 is ethically approved and will commence following the completion of content development, expected by late July 2023. Preliminary analysis indicates that the following topics need to be prioritized for the youths: mental health, pain, accessibility, medical care, education, community, and parental care., Conclusions: The proposed study will design and develop a self-management and transitional care program for youths with OI in partnership with patients, caregivers, and health care professionals. This study leverages youths' openness to adopt eHealth technologies to meet their needs and has the potential to actively engage them to autonomously manage their lifelong conditions, and facilitate a successful transition to adult health care. Finally, the proposed study will also address a critical gap in the quality of care and the growing concern that the OI population transitioning from pediatric to adult care is at risk of various adverse events associated with the transition., International Registered Report Identifier (irrid): DERR1-10.2196/47524., (©Argerie Tsimicalis, Jennifer Stinson, Kelly Thorstad, Frank Rauch, Reggie Hamdy, Khadidja Chougui, Sofia Addab, Telma Palomo, Mitchell Bernstein, Noemi Dahan-Oliel, Louis-Nicolas Veilleux, Laura Massochin Nunes Pinto, Raissa Passos dos Santos. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 23.06.2023.)

The large-scale dissemination of coronavirus disease-2019 (COVID-19) and its serious complications have pledged the scientific research communities to uncover the pathogenesis mechanisms of its etiologic agent, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Methods of unveiling such mechanisms are rooted in understanding the viral agent's interactions with the immune system, including its ability to activate macrophages, due to their suggested role in prolonged inflammatory phases and adverse immune responses. The objective of this study is to test the effect of SARS-CoV-2-free proteins on the metabolic and immune responses of macrophages. We hypothesized that SARS-CoV-2 proteins shed during the infection cycle may dynamically induce metabolic and immunologic alterations with an inflammatory impact on the infected host cells. It is imperative to delineate such alterations in the context of macrophages to gain insight into the pathogenesis of these highly infectious viruses and their associated complications and thus, expedite the vaccine and drug therapy advent in combat of viral infections. Human monocyte-derived macrophages were treated with SARS-CoV-2-free proteins at different concentrations. The phenotypic and metabolic alterations in macrophages were investigated and the subsequent metabolic pathways were analyzed. The obtained results indicated that SARS-CoV-2-free proteins induced concentration-dependent alterations in the metabolic and phenotypic profiles of macrophages. Several metabolic pathways were enriched following treatment, including vitamin K, propanoate, and the Warburg effect. These results indicate significant adverse effects driven by residual viral proteins that may hence be considered determinants of viral pathogenesis. These findings provide important insight as to the impact of SARS-CoV-2-free residual proteins on the host cells and suggest a potential new method of management during the infection and prior to vaccination., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Mohammad et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Juvenile hallux valgus (JHV) is a forefoot deformity that causes pain and functional limitation. Treatment poses a challenge in terms of the optimal technique and timing of intervention. A systematic review of the literature on the use of growth modulation in treating JHV was conducted., Materials and Methods: The literature review was performed using PubMed and EMBASE searches for articles investigating growth modulation in the treatment of JHV published before December 1st, 2021. Seven articles were included in the final review that matched the inclusion and exclusion criteria. The primary outcomes included the degree of correction of hallux valgus angle and intermetatarsal angle. A qualitative assessment of the articles was done due to the heterogeneity of the growth modulation methods used in these articles., Results: A total of 135 feet from 78 patients were included from the reviewed articles. Growth modulation methods included temporary screw lateral hemiepiphysiodesis of the first metatarsal, lateral drilling hemiepiphysiodesis of the first metatarsal, and a trephine plug removal of the lateral epiphysis followed by cancellous bone graft insertion. The degree of correction of the hallux valgus and intermetatarsal angles were found to be statistically significant in all studies, regardless of the technique., Conclusion: Growth modulation for JHV by lateral hemiepiphysiodesis using minimally invasive techniques produced favourable radiologic outcomes with some evidence of clinical improvement. Larger, prospective and comparative studies with objective clinical outcome measures may further consolidate this surgical approach as a mean to treating this deformity., How to Cite This Article: AlZeedi M, Park JP, Marwan Y, et al . Growth Modulation for the Treatment of Juvenile Hallux Valgus: A Systematic Review of Literature. Strategies Trauma Limb Reconstr 2023;18(1):51-55., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2023; The Author(s).)

Candida infection represents a global threat with associated high resistance and mortality rate. Azoles such as the triazole drug fluconazole are the frontline therapy against invasive fungal infections; however, the emerging multidrug-resistant strains limit their use. Therefore, a series of novel azole UOSO 1-15 derivatives were developed based on a modified natural scaffold to combat the evolved resistance mechanism and to provide improved safety and target selectivity. The antifungal screening against C. albicans and C. auris showed that UOSO 10 and 12-14 compounds were the most potent derivatives. Among them, UOSO 13 exhibited superior potent activity with MIC 50 values of 0.5 and 0.8 μg mL -1 against C. albicans and C. auris compared to 25 and 600 μg mL -1 for fluconazole, respectively. UOSO 13 displayed significant CaCYP51 enzyme inhibition activity in a concentration-dependent manner with an IC 50 10-fold that of fluconazole, while exhibiting no activity against human CYP50 enzyme or toxicity to human cells. Furthermore, UOSO 13 caused a significant reduction of Candida ergosterol content by 70.3% compared to a 35.6% reduction by fluconazole. Homology modeling, molecular docking, and molecular dynamics simulations of C. auris CYP51 enzyme indicated the stability and superiority of UOSO 13. ADME prediction indicated that UOSO 13 fulfils the drug-likeness criteria with good physicochemical properties., Competing Interests: All the authors declare that there is no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Medical procedures cause pain and anxiety in children. Distraction techniques, including virtual reality (VR), may be used in healthcare settings to reduce rates of undertreated procedural pain and anxiety. A mixed-methods, concurrent triangulation design was piloted at a pediatric orthopedic hospital to assess the feasibility, clinical utility, tolerability, and initial clinical efficacy of VR distraction during medical procedures received by patients with complex musculoskeletal conditions. Questionnaire, scale, interview, observation, and focus group data were collected from patients, their parents, and healthcare professionals. Triangulation of key quantitative and qualitative findings produced final themes and meta-themes. A total of 44 patients and their parents undergoing intravenous insertions (n = 30), pin removals (n = 7), blood draws (n = 3), Botox injections (n = 2), dressing change (n = 1), and urodynamic test (n = 1) were recruited along with 11 healthcare professionals performing the medical procedures. The following themes resulted from triangulation of data sources: VR intervention was (a) feasible because VR was easily implemented into the clinical workflow, (b) clinically useful as VR was accepted by stakeholders and easy to use, (c) tolerable as VR caused minimal discomfort, and (d) showed initial clinical efficacy in managing procedural pain and anxiety. These findings will inform policies and procedures for VR use in practice and a sustainable implementation across the [name of hospital removed for peer review] network., (© 2022 The Authors. Paediatric and Neonatal Pain published by John Wiley & Sons Ltd.)

Pediatric patients with Osteogenesis Imperfecta (OI), a heritable connective tissue disorder, frequently suffer from long bone deformations. Surgical correction often results in bone non-unions, necessitating revision surgery with autogenous bone grafting using bone-marrow-derived stem cells (BM-SC) to regenerate bone. BM-SC harvest is generally invasive and limited in supply; thus, adipose tissue's stromal vascular fraction (SVF) has been introduced as an alternative stem cell reservoir. To elucidate if OI patients' surgical site dissected adipose tissue could be used as autologous bone graft in future, we investigated whether the underlying genetic condition alters SVF's cell populations and in vitro differentiation capacity. After optimizing SVF isolation, we demonstrate successful isolation of SVF of pediatric OI patients and non-OI controls. The number of viable cells was comparable between OI and controls, with about 450,000 per gram tissue. Age, sex, type of OI, disease-causing collagen mutation, or anatomical site of harvest did not affect cell outcome. Further, SVF-containing cell populations were similar between OI and controls, and all isolated SVF's demonstrated chondrogenic, adipogenic, and osteogenic differentiation capacity in vitro. These results indicate that SVF from pediatric OI patients could be used as a source of stem cells for autologous stem cell therapy in OI., (© 2022. The Author(s).)

Human serum albumin (HSA) is the frontline antioxidant protein in blood with established anti-inflammatory and anticoagulation functions. Here, we report that COVID-19-induced oxidative stress inflicts structural damages to HSA and is linked with mortality outcome in critically ill patients. We recruited 39 patients who were followed up for a median of 12.5 days (1-35 days), among them 23 had died. Analyzing blood samples from patients and healthy individuals (n=11), we provide evidence that neutrophils are major sources of oxidative stress in blood and that hydrogen peroxide is highly accumulated in plasmas of non-survivors. We then analyzed electron paramagnetic resonance spectra of spin-labeled fatty acids (SLFAs) bound with HSA in whole blood of control, survivor, and non-survivor subjects (n=10-11). Non-survivors' HSA showed dramatically reduced protein packing order parameter, faster SLFA correlational rotational time, and smaller S/W ratio (strong-binding/weak-binding sites within HSA), all reflecting remarkably fluid protein microenvironments. Following loading/unloading of 16-DSA, we show that the transport function of HSA may be impaired in severe patients. Stratified at the means, Kaplan-Meier survival analysis indicated that lower values of S/W ratio and accumulated H 2 O 2 in plasma significantly predicted in-hospital mortality (S/W≤0.15, 81.8% (18/22) vs. S/W>0.15, 18.2% (4/22), p=0.023; plasma [H 2 O 2 ]>8.6 μM, 65.2% (15/23) vs. 34.8% (8/23), p=0.043). When we combined these two parameters as the ratio ((S/W)/[H 2 O 2 ]) to derive a risk score, the resultant risk score lower than the mean (<0.019) predicted mortality with high fidelity (95.5% (21/22) vs. 4.5% (1/22), log-rank χ 2 =12.1, p=4.9×10 -4 ). The derived parameters may provide a surrogate marker to assess new candidates for COVID-19 treatments targeting HSA replacements and/or oxidative stress., Competing Interests: MB, BY, RE, EA, AE, AK, HE, AS, RH, MZ, DA, MH, NE, ME, AA, AE, AH, SA, LD, SA No competing interests declared, (© 2021, Badawy et al.)

A series of 3-(6-substituted phenyl-[1,2,4]-triazolo[3,4-b]-[1,3,4]-thiadiazol-3-yl)-1H-indoles ( 5a - l ) were designed, synthesized and evaluated for anti-apoptotic Bcl-2-inhibitory activity. Synthesis of the target compounds was readily accomplished through a reaction of acyl hydrazide ( 1 ) with carbon disulfide in the presence of alcoholic potassium hydroxide to afford the corresponding intermediate potassium thiocarbamate salt ( 2 ), which underwent cyclization reaction in the presence of excess hydrazine hydrate to the corresponding triazole thiol ( 3 ). Further cyclisation reaction with substituted benzoyl chloride derivatives in the presence of phosphorous oxychloride afforded the final 6-phenyl-indol-3-yl [1,2,4]-triazolo[3,4-b]-[1,3,4]-thiadiazole compounds ( 5a - l ). The novel series showed selective sub-micromolar IC 50 growth-inhibitory activity against Bcl-2-expressing human cancer cell lines. The most potent 6-(2,4-dimethoxyphenyl) substituted analogue ( 5k ) showed selective IC 50 values of 0.31-0.7 µM against Bcl-2-expressing cell lines without inhibiting the Bcl-2-negative cell line (Jurkat). ELISA binding affinity assay (interruption of Bcl-2-Bim interaction) showed potent binding affinity for ( 5k ) with an IC 50 value of 0.32 µM. Moreover, it fulfils drug likeness criteria as a promising drug candidate.

Background: The oral cavity represents a main entrance of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Angiotensin-converting enzyme 2 (ACE-2), neuropilin-1 (NRP-1), and transmembrane serine protease 2 (TMPRSS2) are essential for the entry of SARS-CoV-2 to the host cells. Both ACE-2 and NRP-1 receptors and TMPRSS2 have been identified in the oral cavity. However, there is limited knowledge about the impact of periapical lesions and their metabolites on the expression of these critical genes. This study aims to measure the impact of periapical lesions and their unique fatty acids (FAs) metabolites on the expression of the aforementioned genes, in addition to interleukin 6 (IL-6) gene and hence SARS-CoV-2 infection loads can be estimated., Methods: Gene expression of ACE-2, NRP-1, TMPRSS2, and IL-6 was performed in periapical lesions in comparison to healthy oral cavity. Since FAs are important immunomodulators required for the lipid synthesis essential for receptors synthesis and viral replication, comparative FAs profiling was determined in oral lesions and healthy pulp tissues using gas chromatography-mass spectrometry (GC-MS). The effect of major identified and unique FAs was tested on mammalian cells known to express ACE-2, NRP-1, and TMPRSS2 genes., Results: Gene expression analysis indicated that ACE-2, NRP-1, and TMPRSS2 were significantly upregulated in healthy clinical samples compared to oral lesions, while the reverse was true with IL-6 gene expression. Saturated and monounsaturated FAs were the major identified shared and unique FAs, respectively. Major shared FAs included palmitic, stearic and myristic acids with the highest percentage in the healthy oral cavity, while unique FAs included 17-octadecynoic acid in periapical abscess, petroselinic acid and L-lactic acid in periapical granuloma, and 1-nonadecene in the radicular cyst. Computational prediction showed that the binding affinity of identified FAs to ACE-2, TMPRSS2 and S protein were insignificant. Further, FA-treated mammalian cells showed significant overexpression of ACE-2, NRP-1 and TMPRSS2 genes except with L-lactic acid and oleic acid caused downregulation of NRP-1 gene, while 17-octadecynoic acid caused insignificant effect., Conclusion: Collectively, a healthy oral cavity is more susceptible to viral infection when compared to that complicated with periapical lesions. FAs play important role in viral infection and their balance can affect the viral loads. Shifting the balance towards higher levels of palmitic, stearic and 1-nonadecene caused significant upregulation of the aforementioned genes and hence higher viral loads. On the other hand, there is a reverse correlation between inflammation and expression of SARS-CoV-2 receptors. Therefore, a mouth preparation that can reduce the levels of palmitic, stearic and 1-nonadecene, while maintaining an immunomodulatory effect can be employed as a future protection strategy against viral infection., (© 2021. The Author(s).)

Background: Providers of on-demand care, such as those in urgent care centers, may prescribe antibiotics unnecessarily because they fear receiving negative reviews on web-based platforms from unsatisfied patients-the so-called Yelp effect. This effect is hypothesized to be a significant driver of inappropriate antibiotic prescribing, which exacerbates antibiotic resistance., Objective: In this study, we aimed to determine the frequency with which patients left negative reviews on web-based platforms after they expected to receive antibiotics in an urgent care setting but did not., Methods: We obtained a list of 8662 urgent care facilities from the Yelp application programming interface. By using this list, we automatically collected 481,825 web-based reviews from Google Maps between January 21 and February 10, 2019. We used machine learning algorithms to summarize the contents of these reviews. Additionally, 200 randomly sampled reviews were analyzed by 4 annotators to verify the types of messages present and whether they were consistent with the Yelp effect., Results: We collected 481,825 reviews, of which 1696 (95% CI 1240-2152) exhibited the Yelp effect. Negative reviews primarily identified operations issues regarding wait times, rude staff, billing, and communication., Conclusions: Urgent care patients rarely express expectations for antibiotics in negative web-based reviews. Thus, our findings do not support an association between a lack of antibiotic prescriptions and negative web-based reviews. Rather, patients' dissatisfaction with urgent care was most strongly linked to operations issues that were not related to the clinical management plan., (©Dian Hu, Cindy Meng-Hsin Liu, Rana Hamdy, Michael Cziner, Melody Fung, Samuel Dobbs, Laura Rogers, Monique Mitchell Turner, David André Broniatowski. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 08.10.2021.)