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e the effects of local laboratory capacity. There are implications in increasing GBS screening participation in resource-limited settings.
Human mesenchymal stem cells (MSCs) have the ability to differentiate into bone-forming osteoblasts. The aim of this study was to elucidate if MSCs from patients with OP show a senescent phenotype and explore their bone-forming ability in vivo.
MSCs from patients with OP and controls with osteoarthritis (OA) were implanted into the subcutaneous tissue of immunodeficient mice for histological analysis and expression of human genes by RT-PCR. The expression of senescence-associated phenotype (SASP) genes, as well as p16, p21, and galactosidase, was studied in cultures of MSCs.
In vivo bone formation was evaluated in 103 implants (47 OP, 56 OA). New bone was observed in 45% of the implants with OP cells and 46% of those with OA cells (p=0.99). The expression of several bone-related genes (collagen, osteocalcin, alkaline phosphatase, sialoprotein) was also similar in both groups. There were no differences between groups in SASP gene expression, p16, and p21 expression, or in senescence-associated galactosidase activity.
Senescence markers and the osteogenic capacity in vivo of MSCs from patients with OP are not inferior to that of cells from controls of similar age with OA. This supports the interest of future studies to evaluate the potential use of autologous MSCs from OP patients in bone regeneration procedures.
Senescence markers and the osteogenic capacity in vivo of MSCs from patients with OP are not inferior to that of cells from controls of similar age with OA. This supports the interest of future studies to evaluate the potential use of autologous MSCs from OP patients in bone regeneration procedures.Introduction Nilotinib is a second-generation tyrosine kinase inhibitor (TKI) targeting BCR/ABL, which is used for the first-line treatment of newly diagnosed chronic myeloid leukemia (CML) patients and the second-line treatment of most CML patients who are resistant or intolerant to prior therapy that includes imatinib. In addition to common adverse reactions, long-term use of nilotinib shows some toxicities that are different from those of occurring during other BCR/ABL TKI treatments, such as cardiovascular toxicity. It is life-threatening, which would affect not only the choice of initial treatment of CML patients but also the safety of long-term medication.Areas covered Through searching literature and reports from PubMed and clinical trials, here we review a profile of the adverse effects induced by nilotinib. We also discuss the potential molecular toxicological mechanisms and clinical management, which may provide strategies to prevent or intervene the toxicity associated with nilotinib.Expert opinion Severe adverse effects associated with nilotinib limit its long-term clinical application. However, the exact mechanisms underlying these toxicities remain unclear. Future research should focus on the developing strategies to reduce the toxicities of nilotinib as well as to avoid similar toxicity in the development of new drugs.
Gestational diabetes mellitus is common during pregnancy, impacting maternal health and fetal development. The aim of this study was to identify potential long non-coding RNAs (lncRNAs) and mRNAs in gestational diabetes mellitus.
The placenta tissues from four women patients with gestational diabetes mellitus and three healthy pregnant women were used for RNA sequencing. Differentially expressed lncRNAs and mRNAs were obtained. Then, interaction networks of lncRNA-nearby targeted mRNA and lncRNA-co-expressed mRNA were constructed, followed by functional annotation of co-expressed mRNAs. Third, GSE51546 dataset was utilized to validate the expression of selected co-expressed mRNAs. In addition,
experiment was applied to expression validation of lncRNAs and mRNAs. Finally, GSE70493 dataset was utilized for diagnostic analysis of selected co-expressed mRNAs.
A total of 78 differentially expressed lncRNAs and 647 differentially expressed mRNAs in gestational diabetes mellitus were obtained. Several interaction pairs of lncRNA-co-expressed mRNA including LINC01504-CASP8, FUT8-AS1-TLR5/GDF15, GATA2-AS1-PQLC3/KIAA2026, and EGFR-AS1-HLA-G were identified. Endocytosis (involved HLA-G) and toll-like receptor signaling pathway (involved TLR5 and CASP8) were remarkably enriched signaling pathways of co-expressed mRNAs. It is noted that CASP8, TLR5, and PQLC3 had a significant prognosis value for gestational diabetes mellitus.
Our study identified several differentially expressed lncRNAs and mRNAs, and their interactions, especially co-expression, may be associated with gestational diabetes mellitus.
Our study identified several differentially expressed lncRNAs and mRNAs, and their interactions, especially co-expression, may be associated with gestational diabetes mellitus.Orthopedic device related infections (ODRI's) represent a difficult to treat situation owing to their biofilm based nature. Biofilm infections once established are difficult to eradicate even with an aggressive treatment regimen due to their recalcitrance towards antibiotics and immune attack. The involvement of antibiotic resistant pathogens as the etiological agent further worsens the overall clinical picture, pressing on the need to look into alternative treatment strategies. The present review highlightes the microbiological challenges associated with treatment of ODRI's due to biofilm formation on the implant surface. Further, it details the newer anti-infective modalities that work either by preventing biofilm formation and/or through effective disruption of the mature biofilms formed on the medical implant. The study, therefore aims to provide a comprehensive insight into the newer anti-biofilm interventions (non-antibiotic approaches) and a better understanding of their mechanism of action essential for improved management of orthopedic implant infections.This study aimed to investigate the expression of Fos proto-oncogene, AP-1 transcription factor subunit (c-Fos) in the genital tubercle (GT) of rats with di(2-ethylhexyl) phthalate (DEHP)-induced hypospadias and in the prepuce of patients with hypospadias compared with unaffected controls. Pregnant rats were given 750 mg/kg/day DEHP orally from gestational days 12-19. Western blotting showed that c-Fos expression was increased in DEHP-induced hypospadiac male offspring. In addition, 30 prepuce tissue specimens obtained during hypospadias repair surgery were divided into 2 groups the mild hypospadias group (n = 15) and the severe hypospadias group (n = 15). Fifteen normal prepuce tissue specimens were harvested during elective circumcision as normal controls. Real-time quantitative polymerase chain reaction, western blotting and immunohistochemistry analyses were used to assess c-Fos expression. c-Fos protein levels were higher in the GT of DEHP-induced rats than in that of control rats. c-Fos mRNA and protein levels were also higher in the hypospadias groups than in the control group (p less then 0.05, p less then 0.001), and c-Fos protein levels were significantly higher in the severe hypospadias group than in the mild hypospadias group (p less then 0.01). The expression of c-Fos was increased in both the GT of DEHP-induced hypospadiac rats and the prepuce of hypospadias patients. LY2109761 Thus, c-Fos overexpression might contribute to hypospadias.Abbreviations DEHP di(2-ethylhexyl) phthalate; c-Fos Fos proto-oncogene, AP-1 transcription factor subunit; Mafb the masculinization-regulatory gene v-maf musculoaponeurotic fibrosarcoma oncogene family, protein B; GT genital tubercle; ED embryonic day; AGD anogenital distance; AGI anogenital distance index; ED embryonic day.
A 68-year-old male patient underwent a resection of a DDL (T2 N0 M0, FNCLCC grade 2, stage IIIA) in the retroperitoneum. Three months after this first surgery, a recurrence occurred, and was treated with neoadjuvant and adjuvant doxorubicin plus ifosfamide and surgery (resection). A second recurrence-11 months after the second surgery-was treated with surgery and radiotherapy. The patient then began to undergo VAE treatment (0.2 mg-2 mg, subcutaneously, thrice a week). After the VAE treatment was initiated, the patient reported improved quality of life. A third recurrence-12 months after the third surgery-was treated with surgery, radiotherapy, and with an increased dose of VAE (20 mg). Sixty-nine months (5.8 years) after the fourth surgery a fourth recurrence occurred. It was again treated with surgery, along with a month of intravenous VAE infusions and subsequent subcutaneous VAE (20 mg) treatment. Finally, a fifth recurrence-5 months after the fifth surgery-was treated with subcutaneous and intravenous al of VAE-treated patients with other types of tumors, the adjunct VAE treatment is presumed to have contributed to the favorable outcome. Regarding the clinical relevance of VAE treatment, further investigations are needed.
Evaluate health-related quality-of-life (HRQoL) measures in noncommunicative, neurologically impaired, developmentally delayed (NCNIDD) children compared to normally developing children (ND) who undergo cochlear implantation (CI).
Cross-sectional survey of parents of NCNIDD and ND children who underwent CI.
Two tertiary care medical centers.
Questions comprising the Children With Cochlear Implants Parental Perspectives survey were used in analysis. Average responses were calculated within 8 domains (communication, general functioning, self-reliance, well-being and happiness, social relationships, education, effects of implantation, and support the child). Groups were compared using Wilcoxon rank-sum test. Impact of individual and collective socioeconomic/family covariates was assessed using analysis of variance.
Surveys were returned from 17 of 42 (40%) patients with NCNIDD and 35 of 131 (27%) patients with ND. There were no statistically significant differences between groups in survey response ratpture benefits that may not be apparent in this study.How does belief in controversial ideas persist? I study a community of parents and practitioners who contend that autism spectrum disorder is caused by harmful environmental exposures - notably, early childhood vaccinations - and that there are worthwhile alternative or experimental treatments. Despite objections from dominant experts, these actors maintain their disputed ideas. This study identifies a set of strategies that help maintain internal legitimacy. In particular, actors protect internal legitimacy through professional alignment and contrastive boundary work. Professional alignment mobilizes resemblances to conventional counterparts (i.e. mainstream doctors) to defend unorthodox practices. Meanwhile, contrastive boundary-work performances convey the defining values and strengths that actors associate with their knowledge community and concomitantly, the weaknesses they ascribe to competing groups. Through these activities, actors respond to perceived threats and construct a distinct group identity anchored in shared knowledge, ways of knowing and practice.
Vestibular/ocular motor dysfunction can occur in pediatric concussions, which can impair reading, learning, and participation in athletics. This study evaluated 3 clinical tools for identifying postconcussion vestibular/ocular motor dysfunction (1) Post-Concussion Symptom Scale (PCSS), (2) Convergence Insufficiency Symptom Survey (CISS), and (3) Vestibular/Ocular Motor Screening (VOMS).
Evaluating vestibular/ocular motor dysfunction with multiple clinical tools will capture more symptomatic patients than any 1 tool alone.
Cross-sectional data from a prospective cohort study.
Level 4.
Patients were between 8 and 17 years old and seen in a tertiary care pediatric sports medicine clinic between August 2014 and February 2018. Data were collected from initial visit and included VOMS, PCSS, and CISS. Descriptive statistics, Pearson's correlations, and logistic regressions were used to describe relationships between clinical tools.
Of the 156 patients (55.1% female; 14.35 ± 2.26 years old) included, this study identified 129 (82.