Barriers and characteristics for successful transition to adult healthcare for individuals with cerebral palsy: a systematic review

Abstract

Background: Cerebral palsy (CP) is a common childhood disability. However, these individuals are now living longer lives, participating in adult roles, and seeking healthcare services. The transition from pediatric to adult healthcare for adolescents with CP is a challenging yet significant time. Adolescents experience several barriers during transition.

Objectives: To utilize the environmental and personal dimensions of the ICF model in order to explore barriers when transitioning to adulthood as well as discuss characteristics and physical therapy implications needed to succeed within transition.

Methods: Electronic searching of PubMed, CINAHL, ERIC, Scopus, ProQuest, and the Cochrane Library databases was concluded on January 9, 2019 for studies including transition between pediatric and adult healthcare in individuals diagnosed with CP. Two independent reviewers agreed upon inclusion, eligibility, and quality assessment of each study using the Mixed-Methods Appraisal Tool (MMAT).

Results: Seven studies were included in the systematic review. Results for each study were separated based on the personal and environmental contextual factors of the ICF model and solutions to the barriers were then discussed.

Conclusions: Research has provided proposed solutions to select barriers, however, other barriers have yet to be addressed. More research is needed to address these barriers and provide a model program that can be implemented within the healthcare systems to promote a successful transition for adolescents with CP from pediatric to adult services.     

Anti-goat antibodies as a rare cause of high gonadotropin levels during menopausal transition

Abstract

Objective: To understand the origin of extremely high gonadotropin levels in a perimenopausal woman.

Methods: A 52-year-old woman with a 2?months of amenorrhea followed spontaneous menstrual cycles recovery was referred to our outpatient clinic with elevated follicle-stimulating hormone (FSH, 483 mUI/ml), luteinizing hormone (LH, 475 mUI/ml) and prolactin (PRL, 173?ng/ml). She was known to take levosulpiride. The gonadotropin levels did not fit with the clinical features.

Results: A gonadotroph tumor was ruled out. Further analysis confirmed constantly high FSH, LH and PRL levels. The measurements were repeated using different analytical platforms with different results. After serial dilutions, nonlinearity was present suggesting an immunoassay interference. After post-polyethylene glycol recovery, hormone levels appeared in the normal range. Anti-goat antibodies were recognized in the serum of the patient.

Conclusions: This case report shows a case of falsely abnormal high gonadotropin and PRL levels in a woman during menopause transition. In the clinical practice the evaluation of gonadotropin profile is not recommended at this age, but the abnormal levels stimulated further evaluation. An interference in the assay due to anti-goat antibodies resulted in abnormally high level of FSH and LH. A strict collaboration between clinicians and the laboratory is needed, when laboratory findings do not correspond to clinical findings.     

Profilin 1, negatively regulated by microRNA-19a-3p,serves as a tumor suppressor in human hepatocellular carcinoma

Profilin 1 (PFN1) is a critical actin-regulatory protein; however, its functional role in hepatocellular carcinoma (HCC) progression remains to be further elucidated. In the present study, we observed that the expression levels of PFN1 were significantly decreased in HCC tissues and cell lines. Low PFN1 expression was significantly correlated with aggressive clinicopathological characteristics and poor prognosis of HCC patients. Further in vitro experiments demonstrated that overexpression of PFN1 remarkably inhibited the proliferation, migration, invasion and EMT of HCC cells. Moreover, we also found that PFN1 was a direct target gene of miR-19a-3p, and in HCC tissues, and there was a significantly inverse correlation between PFN1 mRNA and miR-19a-3p expression. Collectively, our results showed that PFN1 functions as a tumor suppressor in HCC, and might serve as a diagnostic and therapeutic target for HCC patients.     

Helicobacter pylori induces epithelial-mesenchymal transition in gastric carcinogenesis via the AKT/GSK3β signaling pathway

Helicobacter pylori (H. pylori) is a main risk factor for gastric cancer (GC). Epithelial-mesenchymal transition (EMT) is involved in the development and progression of H. pylori-associated GC. However, the exact molecular mechanism of this process remains unclear. The AKT/GSK3β signaling pathway has been demonstrated to promote EMT in several types of cancer. The present study investigated whether H. pylori infection induced EMT, and promoted the development and metastasis of cancer in the normal gastric mucosa, and whether this process was dependent on AKT activation. The expression levels of the EMT-associated proteins, including E-cadherin and N-cadherin, were determined in 165 gastric mucosal samples of different disease stages by immunohistochemical analysis. The expression levels of E-cadherin, N-cadherin, AKT, phosphorylated (p-)AKT (Ser473), GSK3β and p-GSK3β (Ser9) were further determined in H. pylori-infected Mongolian gerbil gastric tissues and cells co-cultured with H. pylori by immunohistochemical analysis and western blotting. The results indicated that the expression levels of the epithelial marker E-cadherin were decreased, whereas the expression levels of the mesenchymal marker N-cadherin were increased during gastric carcinogenesis. Their expression levels were associated with H. pylori infection. Furthermore, H. pylori infection resulted in downregulation of E-cadherin expression and upregulation of N-cadherin expression in Mongolian gerbils and GES-1 cells. In addition, an investigation of the associated mechanism of action revealed that p-AKT (Ser473) and p-GSK3β (Ser9) were activated in GES-1 cells following co-culture with H. pylori. Furthermore, following pretreatment of the cells with the AKT inhibitor VIII, the expression levels of E-cadherin, N-cadherin, p-AKT and p-GSK3β did not show significant differences between GES-1 cells that were co-cultured with or without H. pylori. The levels of p-AKT and p-GSK3β were increased in H. pylori-infected Mongolian gerbils. In conclusion, the present study demonstrated that H. pylori infection activated AKT and resulted in the phosphorylation and inactivation of GSK3β, which in turn promoted early stage EMT. These effects were AKT-dependent. This mechanism may serve as a prerequisite for GC development.     

探讨绝经过渡期、育龄子宫肌瘤患者异常阴道出血相关因素分析

目的: 探讨育龄、绝经过渡期子宫肌瘤患者异常阴道出血危险因素，为异常阴道出血临床精准诊断、治疗提供理论依据。方法： 选取2017年06月—2020年06月于内蒙古医科大学附属医院住院行手术治疗的子宫肌瘤患者。实验组设为非月经期异常阴道出血的子宫肌瘤患者，对照组为无异常阴道流血子宫肌瘤患者。根据第9版教科书年龄18-43岁定为育龄组；44-54岁定为绝经过渡期组（我国妇女平均绝经年龄为49.5岁，80%在44-54岁之间〔1〕）。 应用Excel双录入，核对无误后进行统计分析。计数资料的比较用R×C列联表卡方检验、四格表卡方检验及两独立样本秩和检验。非条件Logistic回归模型用于子宫肌瘤阴道异常出血危险因素的分析，并分别得到OR值与相应95%的可信区间。在此模型中，OR值＞1认为是危险因素，OR值＜1认为是保护因素。统计学显著性水平设定为双侧p≤0.05，即认为差异有统计学意义。全部统计分析选用SPSS19.0软件进行统计学分析。结果：1.将与子宫肌瘤阴道异常出血相关的33项临床指标纳入单因素分析得出，月经周期异常、肌瘤位置（子宫颈肌瘤）、肌瘤直径≥9cm、血红蛋白异常、子宫内膜癌、核分裂像＞5个差异有统计学意义（P≤0.05），均是子宫肌瘤阴道异常出血的危险因素；2.子宫肌瘤异常阴道出血核分裂像＞5个与子宫内膜病理性改变和异常阴道出血差异有统计学意义（P=0.019）。结论：1. 子宫内膜发生病理改变是子宫肌瘤患者引起异常阴道出血的原因之一。2.月经周期异常、子宫颈肌瘤、肌瘤直径≥9cm、血红蛋白异常、子宫内膜病理改变均是子宫肌瘤阴道异常出血的危险因素；子宫肌瘤核分裂像＞5个是子宫平滑肌瘤出现异常阴道出血的独立高危因素；3.子宫肌瘤核分裂像＞5与阴道出血、子宫内膜病理改变有统计学意义。进行单因素分析后得知，月经周期、肌瘤位置、肌瘤大小、血红蛋白、子宫内膜病理变化均子宫肌瘤阴道异常出血的发生有关。 关键词育龄；绝经过渡期；子宫平滑肌瘤；异常阴道出血；危险因素     

Biopharmaceutics classification and intestinal absorption of chikusetsusaponin IVa

The objective of this study was to investigate the absorption behavior of chikusetsusaponin IVa (CHS‐IVa) in the rat intestine using single‐pass intestinal perfusion (SPIP) and to classify CHS‐IVa into the biopharmaceutics classification system (BCS). The equilibrium solubility of CHS‐IVa was determined by the shaker method. The absorption mechanism of CHS‐IVa in the intestine was studied by comparing the P_eff of different concentrations of CHS‐IVa. The intestinal site dependence of CHS‐IVa absorption was studied by comparing the P_eff of the same concentration of CHS‐IVa in different intestinal segments. The relationship between CHS‐IVa and intestinal efflux protein was studied by perfusion with an efflux protein inhibitor. The permeability of CHS‐IVa was investigated by comparing the P_eff of CHS‐IVa and the reported value. The solubility of CHS‐IVa over the pH range 1.0–7.5 was 14.4 ± 0.29 to 16.9 ± 0.34 mg/ml. The P_eff of CHS‐IVa in the duodenum was 1.76 × 10^?3 to 2.00 × 10^?3 cm/min. The P_eff of CHS‐IVa in the jejunum was 1.26 × 10^?3 to 1.39 × 10^?3 cm/min. The P_eff of CHS‐IVa in the ileum was 1.25 × 10^?3 to 1.31 × 10^?3 cm/min. The P_eff of CHS‐IVa in the colon was 1.02 × 10^?3 to 1.08 × 10^?3 cm/min. There was no statistical difference of the P_eff in the four segments at different CHS‐IVa concentrations. The P_eff of CHS‐IVa (0.07, 0.7 and 7.0 mg/ml) were all notably smaller than the reported P_eff (3.00 × 10^?3 cm/min) in the jejunum. The P_eff of CHS‐IVa was not influenced by verapamil (P‐gp inhibitor), indomethacin (MRP inhibitor) and pantoprazole (BCRP inhibitor). CHS‐IVa was classified as high solubility, low permeability and BCS III. The main absorptive tracts were the upper intestinal tracts and the rank order of intestinal permeability was duodenum > jejunum ≈ ileum > colon. The transport mechanism of CHS‐IVa in all intestinal segments might be primarily passive transport. CHS‐IVa was not a substrate of P‐gp, MRP and BCRP.     

Emerging from their burrow: Hedgehog pathway inhibitors for cancer

Introduction: Cancer treatment is moving away from conventional cytotoxic drugs and towards agents that target specific proteins and mechanisms important to cancer development or survival. The Hedgehog Pathway (HhP) is a signal transduction pathway and its constitutive activation is tumorigenic in basal cell carcinoma (BCC). The HhP enables phenotypic flexibility, and channels tumor-stroma interactions. As a result, it is over-expressed in numerous cancers as well as in the tumor microenvironment and may represent a promising therapeutic target.

Areas covered: In this article, we review the rationale for targeting HhP and its role as an oncogenic driver, in tumor epithelial-to-mesenchymal transition (EMT), and in the tumor microenvironment and describe the results of preclinical and clinical studies involving HhP inhibitors.

Expert opinion: HhP activation plays an important role in both the tumor microenvironment and tumor EMT which can lead to treatment resistance for a number of different malignancies. In addition to standard use in BCC, several HhP inhibitors are in preclinical, early, and mid-stage clinical development for other solid and hematologic malignancies.     

Rescue of the Cold Preserved Rat Liver by Hypothermic Oxygenated Machine Perfusion

The aim of the study was to investigate whether hypothermic oxygenated liver perfusion after cold liver preservation resuscitated metabolic parameters and whether this treatment had a benefit for liver viability upon reperfusion.
We preserved rat livers either by cold storage (UW) for 10 h, or by perfusion for 3 h (oxygenated modified UW) after 10 h cold storage. We assessed viability of livers after preservation and after ischemic rewarming + normothermic reperfusion ex vivo . Ten hour cold storage reduced mitochondrial cytochrome oxidase and metabolically depleted the livers. Oxygenated perfusion after cold storage resulted in uploaded cellular energy charge and oxidized mitochondrial cytochrome oxidase. Reperfusion after 10 h cold storage increased formation of superoxid anions, release of cytosolic LDH, lipid peroxidation, caspase activities and led to disruption of sinusoidal endothelial cells. In contrast, reperfusion after 10 h cold storage + 3 h hypothermic oxygenated perfusion resulted in no changes of lipid peroxidation, bile flow, energy charge, total glutathione, LDH release and of caspase activation, as compared to fresh resected livers.
This study demonstrates, that a metabolically depleted liver due to cold storage can be energy recharged by short-termed cold machine perfusion. The machine perfused graft exhibited improved viability and functional integrity.