BACKGROUND: Periprosthetic infections pose a devastating complication in skeletally immature patients treated for an orthopaedic oncological condition. Reconstructive approaches to revision procedures are often limited, and many cases still require amputation. CASE PRESENTATION: In this report, we present our unique experience with the bio-expandable MUTARS® BioXpand prosthesis, utilized during the second stage of a revision surgery in an adolescent female patient. Initially, the patient underwent reconstruction using a conventional endoprosthesis following the resection of a high-grade distal femur osteosarcoma; however, she developed a deep infection six months later. During a two-stage revision procedure, the infection was successfully eradicated at the cost of loss of growth potential at also the site of proximal tibia. The initial 5 cm limb-length discrepancy was restored through the application of bioexpandable endoprosthesis, which allowed for an 8 cm gain in bone stock. At the last follow-up appointment, the patient was fully weight-bearing and demonstrated excellent clinical outcomes, with no evidence of infection or tumor recurrence. CONCLUSION: This successful limb-salvage procedure indicates that bioexpandable endoprosthesis may serve as a viable and effective reconstructive option in revision surgery for skeletally immature individuals.

• MeSH
• Femur * surgery   pathology   MeSH
• Prosthesis-Related Infections * surgery   etiology   MeSH
• Humans MeSH
• Adolescent MeSH
• Femoral Neoplasms * surgery   pathology   MeSH
• Bone Neoplasms * surgery   pathology   MeSH
• Osteosarcoma * surgery   pathology   MeSH
• Prognosis MeSH
• Reoperation MeSH
• Limb Salvage * methods   MeSH
• Plastic Surgery Procedures * methods   MeSH
• Check Tag
• Humans MeSH
• Adolescent MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH

BACKGROUND: Previous research has demonstrated impaired proprioception and poorer responses to tactile deep pressure, visual-tactile integration, and vestibular stimuli in individuals with generalized hypermobility, potentially leading to sensory processing issues. Therefore, we aimed to explore the influence of hypermobility on somatognosia and stereognosia. METHODS: Forty-six participants were assessed using the Beighton score and categorized into three groups: non-hypermobile (n = 20), symptomatic hypermobile (n = 13), and asymptomatic hypermobile (n = 13). Somatognosia was evaluated using the shoulder width test in the vertical plane and pelvic width test in the vertical and horizontal planes. Stereognosia was assessed with Petrie's test. Spearman's rank correlation coefficient was examined the relationship between the Beighton score and measures of somatognosia and stereognosia. An unpaired t-test was used to compare variables between hypermobile (both symptomatic and asymptomatic) and non-hypermobile individuals, while a one-way ANOVA was used to compare data between the three groups. RESULTS: No significant relationship was observed between Beighton scores and measures of somatognosia and stereognosia. The t-test revealed no statistically significant differences between hypermobile and non-hypermobile groups in the shoulder width, two pelvic widths, and Petrie's tests (all p ≥ 0.105). Similarly, one-way ANOVA showed no statistically significant differences between the three groups across these tests (all p ≥ 0.177). CONCLUSIONS: The results indicate that somatognosia and stereognosia are not significantly related to the Beighton score and do not significantly differ between the groups studied. These sensory processing functions are unlikely to contribute to the common complaints reported by hypermobile individuals. CLINICAL TRIAL NUMBER: Not applicable.

• MeSH
• Agnosia * diagnosis   MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Joint Instability * diagnosis   physiopathology   psychology   complications   epidemiology   MeSH
• Proprioception physiology   MeSH
• Stereognosis * physiology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

No study has systematically compared the suitability of DNA methylation (DNAme) profiles in non-invasive samples for the detection of breast cancer (BC). We assess non-tumour DNAme in 1,100 cervical, buccal, and blood samples from BC cases and controls and find that cervical samples exhibit the largest nuber of differentially methylated sites, followed by buccal samples. No sites were significant in blood after FDR adjustment. Deriving DNAme-based classifiers for BC detection in each sample type (WID-buccal-, cervical-, or blood-BC), we achieve validation AUCs of 0.75, 0.66, and 0.51, respectively. Buccal and cervical BC-associated DNAme alterations distinguish between BC cases and controls in both surrogate and breast tissue (AUC > 0.88), yet individual sites and the directionality of methylation changes are not identical between these two sample types, and buccal sample DNAme aligns with breast methylation changes more closely. Pending additional validation, these insights may have the potential to improve non-invasive personalized BC prevention.

• MeSH
• Adult MeSH
• Epigenesis, Genetic * MeSH
• Epigenomics * methods   MeSH
• Middle Aged MeSH
• Humans MeSH
• DNA Methylation * MeSH
• Breast Neoplasms * genetics   diagnosis   MeSH
• Case-Control Studies MeSH
• Mouth Mucosa metabolism   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

An increasing number of studies have characterized the bone as an endocrine organ, and that bone secreted factors may not only regulate local bone remodeling, but also other tissues and whole-body metabolic functions. The precise nature of these regulatory factors and their roles at bridging the bone, bone marrow adipose tissue, extramedullary body fat and whole-body energy homeostasis are being explored. In this study, we report that KIAA1199, a secreted factor produced from bone and bone marrow, previously described as an inhibitor of bone formation, also plays a role at promoting adipogenesis. KIAA1199-deficient mice exhibit reduced bone marrow adipose tissue, subcutaneous and visceral fat tissue mass, blood cholesterol, triglycerides, free fatty acids and glycerol, as well as improved insulin sensitivity in skeletal muscle, liver and fat. Moreover, these mice are protected from the detrimental effects of high-fat diet feeding, with decreased obesity, lower blood glucose and glucose tolerance, as well as decreased adipose tissue inflammation, insulin resistance and hepatic steatosis. In human studies, plasma levels of KIAA1199 or its expression levels in adipose tissue are positively correlated with insulin resistance and blood levels of cholesterol, triglycerides, free fatty acids, glycerol, fasting glucose and HOMA-IR. Mechanistically, KIAA1199 mediates its effects on adipogenesis through modulating osteopontin-integrin and AKT / ERK signaling. These findings provide evidence for the role of bone secreted factors on coupling bone, fat and whole-body energy homeostasis.

• MeSH
• Adipogenesis * physiology   MeSH
• Diet, High-Fat MeSH
• Energy Metabolism * MeSH
• Hyaluronoglucosaminidase MeSH
• Insulin Resistance MeSH
• Humans MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Obesity metabolism   MeSH
• Proteins * metabolism   MeSH
• Adipose Tissue metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

BACKGROUND AND PURPOSE: White matter changes assessed by DTI typically reflect tract functionality. This study aimed to investigate DTI parameter alterations in important regions pre- and postshunt implantation in patients with idiopathic normal pressure hydrocephalus (iNPH), alongside assessing the relationship between DTI parameters and clinical improvement. MATERIALS AND METHODS: Patients with probable iNPH underwent prospective preoperative MRI and comprehensive clinical work-up between 2017-2022. Patients with clinical symptoms of iNPH, positive result on a lumbar infusion test, and/or gait improvement after 120-hour lumbar drainage were diagnosed with iNPH and underwent shunt-placement surgery. Fractional anisotropy and mean diffusivity values for individual regions of interest were extracted from preoperative and postoperative MRI. These values were correlated with the clinical picture of individual patients. RESULTS: A total of 32 patients (73.59 ± 4.59 years) with definite iNPH were analyzed. Preoperative DTI characteristics of internal capsule and corona radiata correlated with the 1-year improvement in the Dutch Gait Scale postoperatively (all P < .036). Cognitive domain improvement after surgery in memory and psychomotor speed correlated with preoperative DTI values of cingulate gyrus (P = .050), uncinate fasciculus (P = .029), superior longitudinal fasciculus (P = .020), or corpus callosum (P < .045). CONCLUSIONS: DTI characteristics of white matter regions reflect clinical improvement after shunt surgery in patients with iNPH. They tend to improve toward physiologic DTI values, thus further accentuating the benefit of shunt surgery in both clinical and radiologic pictures.

• MeSH
• Anisotropy MeSH
• White Matter diagnostic imaging   MeSH
• Middle Aged MeSH
• Humans MeSH
• Hydrocephalus, Normal Pressure * surgery   diagnostic imaging   MeSH
• Prospective Studies MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Cerebrospinal Fluid Shunts * MeSH
• Treatment Outcome MeSH
• Diffusion Tensor Imaging * methods   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Data from surveillance on antibiotic resistance have shown an increasing prevalence of non-enzymatic resistance (β-lactamase-negative ampicillin-resistant) to β-lactam antibiotics among H. influenzae strains in the Czech Republic. Aminopenicillins are recommended agents for non-invasive Haemophilus influenzae infections. The phenomenon of non-enzymatic resistance to β-lactams is complicated by the fact that the phenotypic detection of PBP3 with specific amino acid substitutions (rPBP3) is challenging, since rPBP3 isolates have repeatedly been demonstrated to be split by the epidemiological cut-off values (ECOFF) for aminopenicillins defined by EUCAST. OBJECTIVES: We sought to determine whether the penicillin disc has sufficient detection ability to predict the non-enzymatic mechanism; whether other antibiotics can be used for detection; and what is the agreement between the broth microdilution and disc diffusion methods. METHODS: We undertook susceptibility testing of selected antibiotics according to EUCAST of 153 rPBP3 strains, and sequencing of the ftsI gene to determination amino acid substitutions. RESULTS: For a selected set of rPBP strains: (i) the detection capability for penicillin, ampicillin, cefuroxime and amoxicillin/clavulanate was found to be 91.5%, 94.4%, 89.5% and 70.6%, respectively; (ii) the categorical agreement between the disc diffusion method and the MIC for ampicillin and cefuroxime was 71.1% and 83.8%, respectively. CONCLUSIONS: We observed better recognition of rPBP3 strains by the ampicillin disc than by the penicillin disc. There is frequently a discrepancy in the interpretation of susceptibility results between the methods used.

• MeSH
• Anti-Bacterial Agents * pharmacology   MeSH
• Bacterial Proteins * genetics   MeSH
• beta-Lactam Resistance * MeSH
• beta-Lactams * pharmacology   MeSH
• Phenotype MeSH
• Haemophilus influenzae * drug effects   genetics   isolation & purification   enzymology   MeSH
• Haemophilus Infections microbiology   MeSH
• Humans MeSH
• Microbial Sensitivity Tests methods   MeSH
• Penicillin-Binding Proteins * genetics   MeSH
• Sequence Analysis, DNA MeSH
• Amino Acid Substitution * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH

Accumulating evidence suggests that manganese oxide nanoparticles (NPs) show multiple enzyme-mimicking antioxidant activities, which supports their potential in redox-targeting therapeutic strategies for diseases with impaired redox signaling. However, the systemic administration of any NP requires thorough hemocompatibility testing. In this study, we assessed the hemocompatibility of synthesized Mn3O4 NPs, identifying their ability to induce spontaneous hemolysis and eryptosis or impair osmotic fragility. Concentrations of up to 20 mg/L were found to be safe for erythrocytes. Eryptosis assays were shown to be more sensitive than hemolysis and osmotic fragility as markers of hemocompatibility for Mn3O4 NP testing. Flow cytometry- and confocal microscopy-based studies revealed that eryptosis induced by Mn3O4 NPs was accompanied by Ca2+ overload, altered redox homeostasis verified by enhanced intracellular reactive oxygen species (ROS) and reactive nitrogen species (RNS), and a decrease in the lipid order of cell membranes. Furthermore, Mn3O4 NP-induced eryptosis was calpain- and caspase-dependent.

• MeSH
• Cell Membrane * metabolism   drug effects   MeSH
• Eryptosis * drug effects   MeSH
• Erythrocytes drug effects   metabolism   MeSH
• Hemolysis drug effects   MeSH
• Calpain * metabolism   MeSH
• Caspases * metabolism   MeSH
• Humans MeSH
• Nanoparticles * chemistry   MeSH
• Oxides * pharmacology   chemistry   MeSH
• Reactive Nitrogen Species * metabolism   MeSH
• Reactive Oxygen Species * metabolism   MeSH
• Manganese Compounds * pharmacology   chemistry   MeSH
• Calcium * metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

African trypanosomes are medically important parasites that cause sleeping sickness in humans and nagana in animals. In addition to their pathogenic role, they have emerged as valuable model organisms for studying fundamental biological processes. Protein tagging is a powerful tool for investigating protein localization and function. In a previous study, we developed two plasmids for rapid and reproducible polymerase chain reaction-based protein tagging in trypanosomes, which enabled the subcellular mapping of 89% of the trypanosome proteome. However, the limited selection of fluorescent protein tags and selectable markers restricted the flexibility of this approach. Here, we present an extended set of >100 plasmids that incorporate universal primer annealing sequences, enabling protein tagging with a range of fluorescent, biochemical and epitope tags, using five different selection markers. We evaluated the suitability of various fluorescent proteins for live and fixed cell imaging, fluorescent movies, and we demonstrate the use of tagging plasmids encoding tandem epitope tags to support expansion microscopy approaches. We show that this series of plasmids is functional in other trypanosomatid parasites, significantly increasing its value. Finally, we developed a new plasmid for tagging glycosylphosphatidylinositol-anchored proteins. We anticipate that this will be an important toolset for investigating trypanosomatid protein localization and function.

• MeSH
• Humans MeSH
• Plasmids genetics   MeSH
• Protozoan Proteins * metabolism   genetics   MeSH
• Protein Transport MeSH
• Trypanosoma brucei brucei metabolism   genetics   MeSH
• Trypanosomatina * metabolism   genetics   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

PURPOSE: Surgical mesh, often made from polypropylene, is commonly recommended to enhance hernia repair outcomes in adults. Concerns about polypropylene, as a cause of allergy and/or autoimmune disease prompted this study to evaluate immunological parameters in patients with mesh and healthy controls. METHODOLOGY: A case-control cohort study was conducted at a university hospital. Electronic patient records of hernia repairs using polypropylene mesh (January 2018-April 2022) were analysed. Blood samples from patients and healthy controls were assessed using various methods, including enzyme-linked immunosorbent assay (ELISA), immunofluorescence, immunoblotting, and flow cytometry. RESULTS: The database search identified 1544 participants. After applying the exclusion criteria 33 patients remained in the polypropylene mesh group. Patients with mesh had lower median IgG3 levels (p = 0.02) and Rheumatoid factor (RF) IgM (p = 0.018) compared to the control group. Although both IgG3 and RF IgM levels were in the normal reference range. In addition, 5 patients in the mesh group tested positive for serum ANCA levels compared to none in the control group (p = 0.053). No other differences in immunoglobulins, autoantibodies, complement, or immune cell subtypes were observed. CONCLUSION: Patients with polypropylene mesh exhibited median IgG3 and RF IgM serum levels that were within the normal reference range but slightly lower compared to the control group. Among patients with polypropylene mesh, five displayed positive serum ANCA levels without autoimmune-related symptoms. Overall, no definitive signs of autoimmunity caused by polypropylene mesh. A larger, prospective study is warranted to further explore potential immune responses to polypropylene mesh.

• MeSH
• Surgical Mesh * adverse effects   MeSH
• Adult MeSH
• Immunoglobulin G blood   MeSH
• Immunoglobulin M blood   MeSH
• Cohort Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• Herniorrhaphy * instrumentation   MeSH
• Polypropylenes * adverse effects   MeSH
• Rheumatoid Factor blood   MeSH
• Aged MeSH
• Case-Control Studies MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

IMPORTANCE: Understanding the pathogenic mechanisms of Fuchs endothelial corneal dystrophy (FECD) could contribute to developing gene-targeted therapies. OBJECTIVE: To investigate associations between demographic data and age at first keratoplasty in a genetically refined FECD cohort. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study recruited 894 individuals with FECD at Moorfields Eye Hospital (London) and General University Hospital (Prague) from September 2009 to July 2023. Ancestry was inferred from genome-wide single nucleotide polymorphism array data. CTG18.1 status was determined by short tandem repeat and/or triplet-primed polymerase chain reaction. One or more expanded alleles (≥50 repeats) were classified as expansion-positive (Exp+). Expansion-negative (Exp-) cases were exome sequenced. MAIN OUTCOMES AND MEASURES: Association between variants in FECD-associated genes, demographic data, and age at first keratoplasty. RESULTS: Within the total cohort (n = 894), 77.3% of patients were Exp+. Most European (668 of 829 [80.6%]) and South Asian (14 of 22 [63.6%]) patients were Exp+. The percentage of female patients was higher (151 [74.4%]) in the Exp- cohort compared to the Exp+ cohort (395 [57.2%]; difference, 17.2%; 95% CI, 10.1%-24.3%; P < .001). The median (IQR) age at first keratoplasty of the Exp + patients (68.2 years [63.2-73.6]) was older than the Exp- patients (61.3 years [52.6-70.4]; difference, 6.5 years; 95% CI, 3.4-9.7; P < .001). The CTG18.1 repeat length of the largest expanded allele within the Exp+ group was inversely correlated with the age at first keratoplasty (β, -0.087; 95% CI, -0.162 to -0.012; P = .02). The ratio of biallelic to monoallelic expanded alleles was higher in the FECD cohort (1:14) compared to an unaffected control group (1:94; P < .001), indicating that 2 Exp+ alleles were associated with increased disease penetrance compared with 1 expansion. Potentially pathogenic variants (minor allele frequency, <0.01; combined annotation dependent depletion, >15) were only identified in FECD-associated genes in 13 Exp- individuals (10.1%). CONCLUSIONS AND RELEVANCE: In this multicenter cohort study among individuals with FECD, CTG18.1 expansions were present in most European and South Asian patients, while CTG18.1 repeat length and zygosity status were associated with modifications in disease severity and penetrance. Known disease-associated genes accounted for only a minority of Exp- cases, with unknown risk factors associated with disease in the rest of this subgroup. These data may have implications for future FECD gene-targeted therapy development.

• MeSH
• Genome-Wide Association Study MeSH
• Adult MeSH
• Fuchs' Endothelial Dystrophy * genetics   surgery   epidemiology   diagnosis   MeSH
• Genetic Predisposition to Disease * MeSH
• Polymorphism, Single Nucleotide * MeSH
• Middle Aged MeSH
• Humans MeSH
• Retrospective Studies MeSH
• Risk Factors MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Severity of Illness Index MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Observational Study MeSH