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BACKGROUND: Calcaneal lengthening osteotomy (CLO) is one of the main surgical options for treatment of pediatric idiopathic flexible flatfoot (FFF). Reportedly, calcaneocuboid (CC) joint subluxation occurs after CLO; however, its effect on the midfoot remains unclear. This study aimed to investigate the radiologic midterm results after CLO treatment in pediatric idiopathic FFF. METHODS: We evaluated 23 pediatric patients with idiopathic FFF aged ≥8 years, who underwent CLO from 1999 to 2017 owing to moderate to severe flatfoot deformity (assessed by visual inspection). Patients aged between 8 and 14 years were included (mean follow-up: 6.3 years; range, 3.1-11.4 years). Anteroposterior and lateral weightbearing foot radiographs were assessed for radiologic parameters preoperatively and at the 3-month, 1-year, and final follow-ups postoperatively. RESULTS: All patients had immediate postoperative radiologic correction of the flatfoot deformity, and these improvements were maintained until the final follow-up. The mean allograft length inserted was 9 (range, 8-10) mm. There was increased CC joint subluxation after CLO, but it improved continuously until the final follow-up. A CC joint spur was newly noted in 1 case. There were 24 cases (24/39, 61.5%) of talonavicular (TN) joint spurs at the final follow-up, but 19 of these were already present on the preoperative radiographs (19/24, 79.2%). Further, the new-onset TN joint spurs were not associated with preoperative clinicoradiologic factors. CONCLUSION: In pediatric patients with idiopathic FFF receiving CLO treatment, preoperative radiologic angles improved. CC joint subluxation increased after surgery; however, it gradually reduced without evidence of CC joint arthritic changes over the time period studied in this cohort.
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PURPOSE: Conservative treatment remains the standard approach for first-time patellar dislocations. While risk factors for patellofemoral instability, a common paediatric injury, are well-established in adults, data concerning the progression of paediatric recurrent patellar dislocation remain scarce. A reproducible method was developed to quantitatively assess the patellofemoral morphology and anatomic risk factors in paediatric patients using magnetic resonance imaging (MRI) and machine learning analysis. METHODS: Data were analyzed from a retrospective review (2005-2022) of paediatric patients diagnosed with acute lateral patellar dislocation (54 patients) who underwent MRI and were compared with an age-based control group (54 patients). Patellofemoral, tibial, tibiofemoral and patellar height parameters were measured. Differences between groups were analyzed with respect to MRI parameters. The potential diagnostic utility of the parameters was assessed via machine learning and genetic algorithm analyses. RESULTS: Significant differences were observed between the two groups in six patellofemoral morphological parameters. Regarding patellar height morphological parameters, all methods exhibited significant between-group differences. Among the tibia and tibiofemoral morphological parameters, only the tibial tubercle-trochlear groove distance exhibited significant differences between the two groups. No sex-related differences were present. Significant variations were observed in patellar height parameters, particularly in the Koshino-Sugimoto (KS) index, which had the highest area under the curve (AUC: 0.87). Using genetic algorithms and logistic regression, our model excelled with seven key independent variables. CONCLUSION: KS index and Wiberg index had the strongest association with lateral patellar dislocation. An optimized logistic regression model achieved an AUC of 0.934. Such performance is considered clinically relevant, indicating the model's effectiveness for the intended application. LEVEL OF EVIDENCE: Level â ¢.
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In 2003-2023, amid 5,436 Acinetobacter baumannii isolates collected globally through the Multidrug-Resistant Organism Repository and Surveillance Network, 97 were ST19PAS, 34 of which carbapenem-resistant. Strains (n = 32) sampled after 2019 harboured either bla OXA-23, bla OXA-72, and/or bla NDM-5. Phylogenetic analysis of the 97 isolates and 11 publicly available ST19 genomes revealed three sub-lineages of carbapenemase-producing isolates from mainly Ukraine and Georgia, including an epidemic clone carrying all three carbapenemase genes. Infection control and global surveillance of carbapenem-resistant A. baumannii remain important.
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Infecções por Acinetobacter , Acinetobacter baumannii , Proteínas de Bactérias , Testes de Sensibilidade Microbiana , beta-Lactamases , beta-Lactamases/genética , Acinetobacter baumannii/genética , Acinetobacter baumannii/isolamento & purificação , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/enzimologia , Humanos , Infecções por Acinetobacter/microbiologia , Infecções por Acinetobacter/epidemiologia , Proteínas de Bactérias/genética , Ucrânia/epidemiologia , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Filogenia , Farmacorresistência Bacteriana Múltipla/genética , República da Geórgia/epidemiologia , Tipagem de Sequências MultilocusRESUMO
Purpose: Hereditary diffuse gastric cancer (HDGC) presents a significant genetic predisposition, notably linked to mutations in the CDH1 and CTNNA1. However, the genetic basis for over half of HDGC cases remains unidentified. The aim of this study is to identify novel pathogenic variants in HDGC and evaluate their protein expression. Materials and Methods: Among 20 qualifying families, two were selected based on available pedigree and DNA. Whole genome sequencing (WGS) on DNA extracted from blood and whole exome sequencing (WES) on DNA from formalin-fixed paraffin-embedded tissues were performed to find potential pathogenic variants in HDGC. After selection of a candidate variant, functional validation and enrichment analysis were performed. Results: As a result of WGS, three candidate germline mutations (EPHA5, MCOA2, and RHOA) were identified in one family. After literature review and in silico analyses, the RHOA mutation (R129W) was selected as a candidate. This mutation was found in two gastric cancer patients within the family. In functional validation, it showed RhoA overexpression and a higher GTP-bound state in the RhoaR129W mutant. Decreased phosphorylation at Ser127/397 suggested altered YAP1 regulation in the Rho-ROCK pathway. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses linked RhoAR129W overexpression to changed migration/adhesion in MKN1 cell line. However, this RHOA mutation (R129W) was not found in index patients in other families. Conclusion: The RHOA mutation (R129W) emerges as a potential causative gene for HDGC, but only in one family, indicating a need for further studies to understand its role in HDGC pathogenesis fully.
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Introduction: Various measurement methods and imaging technique are in use to measure patellar height in pediatric patients. However, there is no gold standard as to which measurement method and modality are the most reliable for pediatric patients. Therefore, the aim of this study was to determine the inter-observer reliability, intra-observer reliability, and applicability of various patellar height measurement methods in pediatric knee. Additionaly, we analyzed the reliability across different imaging modalities. Methods: Total 450 pediatric patients (age: 5-18 years) were evaluated using lateral knee radiographs and magnetic resonance imaging (MRI). The patellar height ratios were measured using five methods. Five methods were Insall-Salvati (IS), Koshino-Sugimoto (KS), Blackburne-Peel (BP), modified Insall-Salvati (MIS), and Caton-Deschamps (CD). The patients were categorized into two age groups: P (ages 5-13) and Q (ages 14-18). Each measurement was conducted twice by two raters. The intra-observer reliability, inter-observer reliability and inter-modality reliability were calculated. In addition, applicability was defined as the possibility to apply each measurement method to each age group. Results: The KS method showed the highest inter-observer reliability and intra-observer reliability when using MRI for both age groups. The inter-observer reliability and intra-observer reliability of the IS for lateral knee radiographs was highest among all observers for group Q. The CD method showed the highest inter-observer reliability in group P, while the KS showed the highest intra-observer reliability in group P using lateral radiographs. The KS method showed the highest inter-modality reliability in group P, while the IS showed the highest inter-modality reliability in group Q. The KS method was applicable to all patients when using lateral knee radiography, and the IS method was applicable to all patients when using MRI. Conclusions: Our results show that the reliability of various measurement method and imaging technique differed based on pediatric knee age group when measuring patellar height. Therefore, in the case of pediatric patients, reliability measurement methods and imaging techniques according to the patient's age should be applied.
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BACKGROUND: Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare autosomal recessive disorder caused by loss-of-function mutations of the NTRK1 gene, affecting the autonomic and sensory nervous system. Clinical manifestation is varied and includes recurrent fever, pain insensitivity, anhidrosis, self-mutilating behavior, and intellectual disability. METHODS: Clinical and genetic features were assessed in two males and one female with genetically confirmed CIPA using exome or genome sequencing. RESULTS: CIPA symptoms including recurrent fever, pain insensitivity, and anhidrosis manifested at the age of 1 year (age range: 0.3-8 years). Two patients exhibited self-mutilation tendencies, intellectual disability, and developmental delay. Four NTRK1 (NM_002529.3) mutations, c.851-33T>A (p.?), c.2020G>T (p.Asp674Tyr), c.2303C>T (p.Pro768Leu), and c.574-156_850+1113del (exons 5-7 del) were identified. Two patients exhibited early onset and severe phenotype, being homozygous for c.851-33T>A (p.?) mutations and compound heterozygous for c.851-33T>A (p.?) and c.2020G>T (p.Asp674Tyr) mutation of NTRK1. The third patient with compound heterozygous mutations of c.2303C>T (p.Pro768Leu) and c.574-156_850+1113del (exons 5-7 del) displayed a late onset and milder clinical manifestation. CONCLUSION: All three patients exhibited variable phenotypes and disease severity. This research enriches our understanding of clinical and genetic aspects of CIPA, highlighting variable phenotypes and disease severity.
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Canalopatias , Neuropatias Hereditárias Sensoriais e Autônomas , Hipo-Hidrose , Indóis , Deficiência Intelectual , Insensibilidade Congênita à Dor , Propionatos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Neuropatias Hereditárias Sensoriais e Autônomas/genética , Hipo-Hidrose/genética , DorRESUMO
Background and Objectives: Reducing opioid exposure in common pediatric surgeries is of paramount importance. This study aimed to assess the efficacy of regional nerve blocks in reducing opioid exposure while preserving high success rates. Materials and Methods: We conducted a retrospective matched cohort study (1:1) including patients with elbow fractures < 12 years old who underwent treatment with percutaneous pinning. Patients were divided into general-anesthesia (GA) and GA-followed-by-supraclavicular-brachial-plexus-block (GA-SCB) groups. The primary outcome was the number of patients administered postoperative rescue opioids. The secondary outcomes included intraoperative and postoperative opioid administration, the time to first request for rescue analgesia, pain scores, block success rate, block performing time, and block-related complications. Results: In a total of 478 patients, 363 underwent percutaneous pinning, and 86 were cohort-matched (GA: n = 43, GA-SCB: n = 43). On the first postoperative day, 34 (79.0%) patients in the GA group were administered postoperative rescue opioids, compared with 12 (27.9%) in the GA-SCB group (p < 0.001). All the patients in the GA-SCB group were opioid-free during the intraoperative period. No SCB-associated complications were observed. Total opioid consumption was significantly lower in the GA-SCB group than in the GA group until the first postoperative day (GA vs. GA-SCB, 3.2 ± 3.0 mg vs. 0.9 ± 1.8 mg, p < 0.001). Conclusions: SCB application in pediatric patients who underwent elbow fracture surgery significantly reduced opioid exposure and had a high success rate when performed using ultrasound guidance by an expert. Furthermore, the complication risk and surgical delay were minimal.
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Bloqueio do Plexo Braquial , Fraturas do Cotovelo , Humanos , Criança , Analgésicos Opioides/uso terapêutico , Estudos Retrospectivos , Estudos de Coortes , Dor Pós-Operatória/tratamento farmacológicoRESUMO
The clinical application of growth factors such as recombinant human bone morphogenetic protein-2 (rh-BMP-2), for functional bone regeneration remains challenging due to limited in vivo efficacy and adverse effects of previous modalities. To overcome the instability and short half-life of rh-BMP-2 in vivo, we developed a novel osteogenic supplement by fusing a protein transduction domain (PTD) with BMP-2, effectively creating a prodrug of BMP-2. In this study, we first created an improved PTD-BMP-2 formulation using lipid nanoparticle (LNP) micellization, resulting in downsizing from micrometer to nanometer scale and achieving a more even distribution. The micellized PTD-BMP-2 (mPTD-BMP-2) demonstrated improved distribution and aggregation profiles. As a prodrug of BMP-2, mPTD-BMP-2 successfully activated Smad1/5/8 and induced mineralization with osteogenic gene induction in vitro. In vivo pharmacokinetic analysis revealed that mPTD-BMP-2 had a much more stable pharmacokinetic profile than rh-BMP-2, with a 7.5-fold longer half-life. The in vivo BMP-responsive element (BRE) reporter system was also successfully activated by mPTD-BMP-2. In the in vivo rat tibia distraction osteogenesis (DO) model, micro-computed tomography (micro-CT) scan findings indicated that mPTD-BMP-2 significantly increased bone volume, bone surface, axis moment of inertia (MOI), and polar MOI. Furthermore, it increased the expression of osteogenesis-related genes, and induced bone maturation histologically. Based on these findings, mPTD-BMP-2 could be a promising candidate for the next-generation osteogenesis drug to promote new bone formation in DO surgery. STATEMENT OF SIGNIFICANCE: This study introduces micellized bone morphogenetic protein-2 (mPTD-BMP-2), a next-generation osteogenic supplement that combines protein transduction domain (PTD) and nano-sized micelle formulation technique to improve transduction efficiency and stability. The use of PTD represents a novel approach, and our results demonstrate the superiority of mPTD-BMP-2 over rh-BMP-2 in terms of in vivo pharmacokinetic profile and osteogenic potential, particularly in a rat tibial model of distraction osteogenesis. These findings have significant scientific impact and potential clinical applications in the treatment of bone defects that require distraction osteogenesis. By advancing the field of osteogenic supplements, our study has the potential to contribute to the development of more effective treatments for musculoskeletal disorders.
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Osteogênese por Distração , Pró-Fármacos , Ratos , Humanos , Animais , Tíbia/metabolismo , Osteogênese por Distração/métodos , Pró-Fármacos/farmacologia , Microtomografia por Raio-X , Proteínas Morfogenéticas Ósseas , Proteína Morfogenética Óssea 2/farmacologia , Osteogênese , Proteína Morfogenética Óssea 7/farmacologiaRESUMO
Sterile silicone ring tourniquets (SSRTs) reduce intraoperative bleeding and provide a wide surgical view. Moreover, they reduce the risk of contamination and are cheaper than conventional pneumatic tourniquets. Our study describes the perioperative outcomes of sterile silicone ring tourniquet placement in pediatric patients undergoing orthopedic surgery. We prospectively recruited 27 pediatric patients aged < 18 years who underwent 30 orthopedic surgeries between March and September 2021. Following complete surgical draping, all operations were initiated by placing SSRTs. We investigated the demographic and clinical characteristics of these patients, details of the tourniquet used, and intra- and postoperative outcomes of tourniquet placement. Owing to the narrowness of tourniquet bands and tourniquet placement at the proximal ends of the extremities, wide surgical fields were achieved, without limiting joint range of motion. Bleeding control was effective. Tourniquets were applied and removed rapidly and safely, regardless of limb circumference. None of the patients experienced postoperative pain, paresthesia, skin problems at the application site, surgical site infections, ischemic problems, or deep vein thrombosis. SSRTs effectively reduced intraoperative blood loss and facilitated wide operative fields in pediatric patients with various limb sizes. These tourniquets allow quick, safe, and effective orthopedic surgery for pediatric patients.
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Klebsiella pneumoniae are a leading cause of healthcare-associated infections worldwide. In particular, strains expressing extended-spectrum ß-lactamases (ESBLs) and carbapenemases pose serious treatment challenges, leading the World Health Organization (WHO) to designate ESBL and carbapenem-resistant Enterobacteriaceae as 'critical' threats to human health. Research efforts to combat these pathogens can be supported by accessibility to diverse and clinically relevant isolates for testing novel therapeutics. Here, we describe a panel of 100 diverse K. pneumoniae isolates that are publicly available to assist the research community in this endeavour. Whole-genome sequencing (WGS) was performed on 3878 K. pneumoniae clinical isolates housed at the Multidrug-Resistant Organism Repository and Surveillance Network. The isolates were cultured from 63 facilities in 19 countries between 2001 and 2020. Core-genome multilocus sequence typing and high-resolution single-nucleotide polymorphism-based phylogenetic analyses captured the genetic diversity of the collection and were used to select the final panel of 100 isolates. In addition to known multidrug-resistant (MDR) pandemic lineages, the final panel includes hypervirulent lineages and isolates with specific and diverse resistance genes and virulence biomarkers. A broad range of antibiotic susceptibilities, ranging from pan-sensitive to extensively drug-resistant isolates, are described. The panel collection, and all associated metadata and genome sequences, are available at no additional cost and will be an important resource for the research community and for the design and development of novel antimicrobial agents and diagnostics against this important pathogen.
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Antibacterianos , Klebsiella pneumoniae , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Filogenia , Farmacorresistência Bacteriana Múltipla/genética , PesquisaRESUMO
We report a genome sequence of Wohlfahrtiimonas chitiniclastica strain MUWRP0946, isolated from a hospitalized patient in Uganda. The genome size was 2.08 million bases, and the genome completeness was 94.22%. The strain carries tetracycline, folate pathway antagonist, ß-lactam, and aminoglycoside antibiotic resistance genes.
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BACKGROUND: To evaluate whether insertion of self-biodegradable stent into the pylorus to prevent delayed-gastric emptying after pylorus-preserving gastrectomy is feasible and safe through porcine experiment. METHODS: Self-biodegradable dumbbell-shaped pyloric stents were designed from absorbable suture materials: poly(glycolide-co-caprolactone) (PGCL) or poly-p-dioxanone (PPDO). After gastrotomy on ten pigs, each stent was inserted: two shams, four PGCL stents, and four PPDO stents. Body weight (Bwt), body temperature (BT), complete blood cell (CBC) count, and plain X-ray were evaluated. On postoperative day (POD) 13, euthanasia was performed for histologic evaluation. RESULTS: Operation was successfully performed in all ten pigs. Without tagging suture, both stents migrated before POD 3. The migration was delayed up to POD 13, when the tagging sutures (-t) were applied between stent and stomach wall. Self-degradation of PGCL started from POD 3, and stents were completely excreted from the abdomen by POD 8. Although PPDO were also weakened as self-degradation progressed, its shape was maintained in gastrointestinal tract for 13 days. Unexpected sudden death occurred in the pig with PPDO-t2 on POD 10, which is more likely due to acute volvulus rather than stent-related complication. There was no significant difference between three groups in terms of Bwt, BT, CBC, and histology (sham vs. PGCL vs. PPDO, all p > 0.05). CONCLUSION: The concept of biodegradable stents made of absorbent suture material seems feasible in porcine experiment. Among them, PGCL which has shown rapid absorption, appears to be a more suitable material for transient pyloric absorbable stent when considering safety aspect.
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Piloro , Neoplasias Gástricas , Humanos , Animais , Suínos , Piloro/cirurgia , Piloro/patologia , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Estudos de Viabilidade , Gastrectomia/métodos , Stents , Abdome/patologiaRESUMO
BACKGROUND: Extra-intestinal pathogenic Escherichia coli (ExPEC) are a leading cause of bloodstream and urinary tract infections worldwide. Over the last two decades, increased rates of antibiotic resistance in E. coli have been reported, further complicating treatment. Worryingly, specific lineages expressing extended-spectrum ß-lactamases (ESBLs) and fluoroquinolone resistance have proliferated and are now considered a serious threat. Obtaining contemporary information on the epidemiology and prevalence of these circulating lineages is critical for containing their spread globally and within the clinic. METHODS: Whole-genome sequencing (WGS), phylogenetic analysis, and antibiotic susceptibility testing were performed for a complete set of 2075 E. coli clinical isolates collected from 1776 patients at a large tertiary healthcare network in the USA between October 2019 and September 2020. RESULTS: The isolates represented two main phylogenetic groups, B2 and D, with six lineages accounting for 53% of strains: ST-69, ST-73, ST-95, ST-131, ST-127, and ST-1193. Twenty-seven percent of the primary isolates were multidrug resistant (MDR) and 5% carried an ESBL gene. Importantly, 74% of the ESBL-E.coli were co-resistant to fluoroquinolones and mostly belonged to pandemic ST-131 and emerging ST-1193. SNP-based detection of possible outbreaks identified 95 potential transmission clusters totaling 258 isolates (12% of the whole population) from ≥ 2 patients. While the proportion of MDR isolates was enriched in the set of putative transmission isolates compared to sporadic infections (35 vs 27%, p = 0.007), a large fraction (61%) of the predicted outbreaks (including the largest cluster grouping isolates from 12 patients) were caused by the transmission of non-MDR clones. CONCLUSION: By coupling in-depth genomic characterization with a complete sampling of clinical isolates for a full year, this study provides a rare and contemporary survey on the epidemiology and spread of E. coli in a large US healthcare network. While surveillance and infection control efforts often focus on ESBL and MDR lineages, our findings reveal that non-MDR isolates represent a large burden of infections, including those of predicted nosocomial origins. This increased awareness is key for implementing effective WGS-based surveillance as a routine technology for infection control.
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Infecção Hospitalar , Infecções por Escherichia coli , Humanos , Escherichia coli/genética , Infecções por Escherichia coli/epidemiologia , Infecção Hospitalar/epidemiologia , Filogenia , beta-Lactamases/genética , Genômica , Atenção à Saúde , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genéticaRESUMO
Low fertility rates and an aging society, growing long-term care needs, and workforce shortages in professional, industrial, and care sectors are emerging issues in South Korea and Taiwan. Both governments have pursued economic/industrial growth as productive welfare capitalism and enacted preferred selective migration policies to recruit white-collar migrant workers (MWs) as mobile elites, but they have also adopted regulations and limitations on blue-collar MWs through unfree labor relations, precarious employment, and temporary legal status to provide supplemental labor. In order to demonstrate how multiple policy regulations from a national level affect MWs' precarity of labor in their receiving countries, which in turn affect MWs' im/mobilities, this article presents the growing trends of transnational MWs, regardless of them being high- or low-skilled MWs, and it evaluates four dimensions of labor migration policies-MWs' working and employment conditions, social protection, union rights and political participation, and access to permanent residency in both countries. We found that the rights and working conditions of low-skilled MWs in Korea and Taiwan are improving slowly, but still lag behind those of high-skilled MWs which also affects their public health and well-being. The significant difference identified here is that MWs in Taiwan can organize labor unions, which is strictly prohibited in Korea; pension protection also differs between the nations. Additionally, an application for permanent residency is easier for high-skilled migrant workers compared with low-skilled MWs and both the Korean and Taiwanese immigration policies differentiate the entry and resident status for low-skilled and professional MWs from dissimilar class backgrounds. Policy recommendations for both countries are also discussed.
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Mão de Obra em Saúde , Migrantes , Humanos , Dinâmica Populacional , Demografia , Países em Desenvolvimento , Política Pública , EconomiaRESUMO
Background: The osteogenic capabilities and biodegradability of octacalcium phosphate (OCP) composites make them unique. Despite the excellent characteristics of OCP, their use is limited due to handling difficulties. In this study, we aimed to evaluate and compare three types of OCPs (cemented OCP (C-OCP), C-OCP with collagen (OCP/Col), and synthetic OCP (S-OCP) with alginate (OCP/Alg)) versus commercially available ß-tricalcium phosphate (ß-TCP) regarding their potential to accelerate bone formation in defective rat tibias. Methods: The specimens with OCP composite were manufactured into 5 âmm cubes and inserted into the segmental defects of rat tibias fixed with an external fixator. In addition, 3 âmm-hole defects in rat tibias were evaluated to compare the graft material properties in different clinical situations. Serial X-ray studies were evaluated weekly and the tibias were harvested at postoperative 6 weeks or 8 weeks for radiologic evaluation. Histological and histomorphometric analyses were performed to evaluate the acceleration of bone formation. Results: In the critical-defect model, OCP/Alg showed bone bridges between segmentally resected bone ends that were comparable to those of ß-TCP. However, differences were observed in the residual graft materials. Most ß-TCP was maintained until 8 weeks postoperatively; however, OCP/Alg was more biodegradable. In addition calcification in the ß-TCP occurred at the directly contacted area between graft particles and bony ingrowth was observed in the region adjacent resected surface of tibia. In contrast, no direct bony ingrowth was observed in OCP-based materials, but osteogenesis induced from resected surface of tibia was more active. In the hole-defect model, OCP/Col accelerated bone formation. ß-TCP and OCP/Alg showed similar patterns with relatively higher biodegradability. In histology, among the OCP-based materials, directly contacted new bone was formed only in OCP/Alg group. The new bone formation in the periphery area of graft materials was much more active in the OCP-based materials, and the newly formed bone showed a thicker trabecular and more mature appearance than the ß-TCP group. Conclusions: In this study, OCP/Alg was equivalent to ß-TCP in the acceleration of bone formation with better biodegradability appropriate for clinical situations in different circumstances. Our OCP/Col composite showed fast degradation, which makes it unsuitable for use in mechanical stress conditions in clinical orthopedic settings. The Translational Potential of this Article: In our research, we compared our various manufactured OCP composites to commercially available ß-TCP in critical-defect rat tibia model. OCP/Col showed acceleration in hole-defect model as previous studies in dental field but in our critical-sized defect model it resorbed fast without acceleration of bony union. OCP/Alg showed matched results compared to ß-TCP and relatively fast resorption so we showed market value in special clinical indication depending on treatment strategy. This is the first OCP composite study in orthopaedics with animal critical-sized tibia bone study and further study should be considered for clinical application based on this study.
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Carbapenem-resistant Enterobacterales pose an urgent threat to human health worldwide. Klebsiella pneumoniae sequence type (ST) 14, initially identified in the Middle East and South-Asia and co-harbouring the carbapenemase genes bla OXA-232 and bla NDM-1, is now emerging globally. One such strain was detected in the USA in 2013 from a patient initially treated in India that also carried armA, a 16S rRNA methyltransferase that confers resistance to all clinically relevant aminoglycosides. Genetic and phenotypic changes were observed in 14 serial isolates collected from this chronically infected patient. The index isolate carried five plasmids, including an IncFIB-IncHI1B (harbouring armA and bla NDM-1), an IncFIA (bla CTX-M-15) and a ColE-like (bla OXA-232), and was extensively resistant to antibiotics. Four years later, a subsequent isolate had accumulated 34 variants, including a loss-of-function mutation in romA, resulting in tigecycline non-susceptibility. Importantly, this isolate now only carried two plasmids, including a large mosaic molecule made of fragments, all harbouring distinct toxin-antitoxin systems, from three of the canonical plasmids. Of the original acquired antibiotic resistance genes, this isolate only retained bla CTX-M-15, and as a result susceptibility to the carbapenems and amikacin was restored. Long-read sequencing of a subset of five representative isolates, collected between 2013 and 2017, allowed for the elucidation of the complex plasmid patterns and revealed the role of IS26-mediated plasmid reshuffling in the evolution of this clone. Such investigations of the mechanisms underlying plasmid stability, together with global and local surveillance programmes, are key to a better understanding of plasmid host range and dissemination.
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Klebsiella pneumoniae , Sistemas Toxina-Antitoxina , Amicacina , Antibacterianos/farmacologia , Carbapenêmicos , Humanos , Klebsiella pneumoniae/genética , Metiltransferases/genética , Testes de Sensibilidade Microbiana , Infecção Persistente , Plasmídeos/genética , RNA Ribossômico 16S/genética , Tigeciclina , beta-Lactamases/genéticaRESUMO
Mesenchymal stem cells (MSCs) have been widely applied to the regeneration of damaged tissue and the modulation of immune response. The purity of MSC preparation and the delivery of MSCs to a target region are critical factors for success in therapeutic application. In order to define the molecular identity of an MSC, the gene expression pattern of a human bone marrow-derived mesenchymal stem cell (hBMSC) was compared with that of a human embryonic fibroblast (hEF) by competitive hybridization of a microarray. A total of 270 and 173 genes were two-fold up- and down-regulated with FDR < 0.05 in the hBMSC compared to the hEF, respectively. The overexpressed genes in the hBMSC over the hEF, including transcription factors, were enriched for biological processes such as axial pattern formation, face morphogenesis and skeletal system development, which could be expected from the differentiation potential of MSCs. CD70 and CD339 were identified as additional CD markers that were up-regulated in the hBMSC over the hEF. The differential expression of CD70 and CD339 might be exploited to distinguish hEF and hBMSC. CMKLR1, a chemokine receptor, was up-regulated in the hBMSC compared to the hEF. RARRES2, a CMKLR1 ligand, stimulated specific migration of the hBMSC, but not of the hEF. RARRES2 manifested as ~two-fold less effective than SDF-1α in the directional migration of the hBMSC. The expression of CMKLR1 was decreased upon the osteoblastic differentiation of the hBMSC. However, the RARRES2-loaded 10% HA-silk scaffold did not recruit endogenous cells to the scaffold in vivo. The RARRES2−CMKLR1 axis could be employed in recruiting systemically delivered or endogenous MSCs to a specific target lesion.
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Osteonecrosis (ON) is a serious complication of acute lymphocytic leukaemia (ALL) or lymphoblastic lymphoma (LBL) treatment, and there is little information regarding ON in Korean paediatric and young adult patients. This retrospective cohort study assessed the cumulative incidence of and risk factors for ON using national health insurance claims data from 2008 to 2019 in 4861 ALL/LBL patients. The Kaplan-Meier method was used to estimate the cumulative incidence of ON according to age groups; the Cox proportional hazard regression model was used to identify risk factors related to ON development after diagnosing ALL/LBL. A cause-specific hazard model with time-varying covariates was used to assess the effects of risk factors. Overall, 158 (3.25%) patients were diagnosed with ON, among whom 23 underwent orthopaedic surgeries. Older age, radiotherapy (HR = 2.62, 95% confidence interval (CI) 1.87-3.66), HSCT (HR = 2.40, 95% CI 1.74-3.31), steroid use and anthracycline use (HR = 2.76, CI 1.85-4.14) were related to ON in the univariate analysis. In the multivariate analysis, age and steroid and asparaginase use (HR = 1.99, CI 1.30-3.06) were factors associated with ON. These results suggest that Korean patients with ALL/LBL who used steroids and asparaginase should be closely monitored during follow-up, even among young adult patients.
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Introduction: Various methods based on bony landmarks are used to determine patellar height. This study analyzed five methods for patellar height measurement on lateral knee radiographs, namely, the Insall-Salvati, Koshino-Sugimoto, Blackburne-Peel, modified Insall-Salvati, and Caton-Deschamps methods. Methods: Overall, 425 pediatric participants (221 males, 204 females; age range 5-18 years) were included and were divided equally into three age groups (A, 5-10 years; B, 11-13 years; and C, 13-18 years). For the comparison of the applicability of each method, the applicable probabilities for each age group and sex-based differences were analyzed using logistic regression techniques. Intra-rater reliability and inter-rater variability were analyzed by two trained raters. Results: The Koshino-Sugimoto method was applicable to all patients. The 80% applicable age of female patients was lower than that of male patients for the Blackburne-Peel (male = 11.9, female = 11) and Caton-Deschamps (male = 11.9, female = 11.1) methods. However, in the Insall-Salvati (male = 12, female = 12.1) and modified Insall-Salvati (male = 12.6, female = 13.1) methods, the 80% applicable age in male patients was lower than that in female patients. The Koshino-Sugimoto method showed the highest variability in group B, while the Insall-Salvati showed the highest variability in group C. In terms of intra-observer reliability, the Caton-Deschamps method showed the same reliability as the Insall-Salvati method, in group C. Conclusions: Our results demonstrated differences in the reliability, variability, and applicability of patellar height measurement methods according to age group. The applicability of patellar height measurement methods also differed according to sex. Therefore, based on age group and sex, different methods should be used for patellar height measurement in pediatric patients.
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OBJECTIVES: Pseudomonas aeruginosa is a leading cause of community- and hospital-acquired infections. Successful treatment is hampered by its remarkable ability to rapidly develop resistance to antimicrobial agents, primarily through mutation. In response, WHO listed carbapenem-resistant P. aeruginosa as a Priority 1 (Critical) pathogen for research and development of new treatments. A key resource in developing effective countermeasures is access to diverse and clinically relevant strains for testing. Herein we describe a panel of 100 diverse P. aeruginosa strains to support this endeavour. METHODS: WGS was performed on 3785 P. aeruginosa isolates in our repository. Isolates were cultured from clinical samples collected from healthcare facilities around the world between 2003 and 2017. Core-genome MLST and high-resolution SNP-based phylogenetic analyses were used to select a panel of 100 strains that captured the genetic diversity of this collection. Antibiotic susceptibility testing was also performed using 14 clinically relevant antibiotics. RESULTS: This 100-strain diversity panel contained representative strains from 91 different STs, including genetically distinct strains from major epidemic clones ST-111, ST-235, ST-244 and ST-253. Seventy-one distinct antibiotic susceptibility profiles were identified ranging from pan-susceptible to pan-resistant. Known resistance alleles as well as the most prevalent mutations underlying the antibiotic susceptibilities were characterized for all isolates. CONCLUSIONS: This panel provides a diverse and comprehensive set of P. aeruginosa strains for use in developing solutions to antibiotic resistance. The isolates and available metadata, including genome sequences, are available to industry, academia, federal and other laboratories at no additional cost.