Jenkinsbusch7511
Angiostrongylus cantonensis L5, parasitizing human cerebrospinal fluid, causes eosinophilic meningitis, which is attributed to tissue inflammatory responses caused primarily by the high percentage of eosinophils. Eosinophils are also involved in killing helminths, using the peroxidative oxidation and hydrogen peroxide (H
O
) generated by dismutation of superoxide produced during respiratory burst. In contrast, helminthic worms have evolved to attenuate eosinophil-mediated tissue inflammatory responses for their survival. In previous study, we demonstrated the extracellular function of Acan-Gal-1 in inducing the apoptosis of macrophages. Here, the intracellular functions of Acan-Gal-1 were investigated, aiming to further reveal the mechanism involved in A. cantonensis L5 worms surviving inflammatory responses in the human central nervous system.
In this study, a model organism, Caenorhabditis elegans, was used as a surrogate to investigate the intracellular functions of Acan-Gal-1 in protecting the worm rvous system.The global COVID-19 pandemic has affected the world's population by causing changes in behavior, such as social distancing, masking, restricting people's movement, and evaluating existing medication as potential therapies. Many pre-existing medications such as tocilizumab, ivermectin, colchicine, interferon, and steroids have been evaluated for being repurposed to use for the treatment of COVID-19. None of these agents have been effective except for steroids and, to a lesser degree, tocilizumab. Ivermectin has been one of the suggested repurposed medications which exhibit an in vitro inhibitory activity on SARS-CoV-2 replication. The most recommended dose of ivermectin for the treatment of COVID-19 is 150-200 µg/kg twice daily. As ivermectin adoption for COVID-19 increased, the Food and Drug Administration (FDA) issued a warning on its use during the pandemic. However, the drug remains of interest to clinicians and has shown some promise in observational studies. This narrative reviews the toxicological profile and some potential therapeutic effects of ivermectin. Based on the current dose recommendation, ivermectin appears to be safe with minimum side effects. However, serious questions remain about the effectiveness of this drug in the treatment of patients with COVID-19.
The development of accurate urinary biomarkers for non-invasive and cost-effective detection of primary and recurrent bladder tumours is recognized as one of the major clinical needs in bladder cancer diagnostics. The purposes of this study were (1) to validate the results of a previous technical comparison by determining the diagnostic performance of nine methylation markers in urine pellet compared to full void urine, and (2) to validate the diagnostic performance of the optimal marker panel GHSR/MAL from a previous exploratory study in a preclinical setting.
Urine samples of 108 patients with bladder cancer and 100 age- and gender-matched controls were prospectively collected for methylation analysis. Urinary methylation levels of the markers FAM19A4, GHSR, MAL, miR-129, miR-935, PHACTR3, PRDM14, SST and ZIC1 were determined with quantitative methylation-specific PCR in urine pellet. Area under the curves (AUCs) were determined for individual markers and the marker panel GHSR/MAL. click here The diagnostic perforer cancer. Subsequent preclinical validation confirmed the diagnostic potential of GHSR/MAL. These findings underline the diagnostic potential of the marker panel GHSR/MAL for future bladder cancer diagnostics.
This technical validation supports the robustness of DNA methylation analysis in urine pellet and full void urine for the non-invasive detection of bladder cancer. Subsequent preclinical validation confirmed the diagnostic potential of GHSR/MAL. These findings underline the diagnostic potential of the marker panel GHSR/MAL for future bladder cancer diagnostics.
Upper limb impairment affects activity and participation in children with unilateral cerebral palsy (UCP). Pressure garment therapy (PGT) using compressive dynamic Lycra
garments is an innovative intervention proposed for the management of cerebral palsy consequences. The PROPENSIX study aims to evaluate the efficacy of a therapy using a Lycra
sleeve as compared to a placebo sleeve to improve bi-manual performance measured by the Assisting Hand Assessment (AHA) in children with unilateral cerebral palsy.
The PROPENSIX trial is a multicenter, prospective, placebo-controlled, double-blinded, randomized study. One hundred children with UCP, aged from 5 to 10, are randomly assigned as soon as they are recruited in a 11 ratio to perform usual daily activities, especially activities involving bimanual performances, with Lycra
sleeve or placebo sleeve during 6 months. The primary endpoint is the change in bimanual performance from inclusion to 6 months, evaluated by AHA. The secondary endpoints evaluate chh unilateral cerebral palsy.
ClinicalTrials.gov NCT02086214 . Retrospectively registered on March 13, 2014 TRIAL STATUS Study start data December 2012. Recruitment status completed. Primary completion date April 2021. Estimated study completion date December 2022. Protocol version 10 (date February 2018).
ClinicalTrials.gov NCT02086214 . Retrospectively registered on March 13, 2014 TRIAL STATUS Study start data December 2012. Recruitment status completed. Primary completion date April 2021. Estimated study completion date December 2022. Protocol version 10 (date February 2018).
Depression is one of the commonest mental disorders in primary care but is poorly identified. The objective of this review was to determine the level of detection of depression by primary care clinicians and its determinants in studies from low- to middle-income countries (LMICs).
A systematic review and meta-analysis was conducted using PubMed, PsycINFO, MEDLINE, EMBASE, LILAC, and AJOL with no restriction of year ofpublication. Risk of bias within studies wasevaluated with the Effective Public Health Practice Project (EPHPP). "Gold standard" diagnosis for the purposes of this review was based on the 9-item Patient Health Questionnaire (PHQ-9; cutoff scores of 5 and 10), other standard questionnaires and interview scales or expert diagnosis. Meta-analysis was conducted excluding studies on special populations. Analyses of pooled data were stratified by diagnostic approaches.
A total of 3159 non-duplicate publications were screened. Nine publications, 2 multi-country studies, and 7 single-country studies, making 12 country-level reports, were included. Overall methodological quality of the studies was good. Depression detection was 0.0% in four of the twelve reports and < 12% in another five. PHQ-9 was the main tool used the pooled detection in two reports that used PHQ-9 at a cutoff point of 5 (combined sample size = 1426) was 3.9% (95% CI = 2.3%, 5.5%); in four reports that used PHQ-9 cutoff score of 10 (combined sample size = 5481), the pooled detection was 7.0% (95% CI = 3.9%, 10.2%). Severity of depression and suicidality were significantly associated with detection.
While the use of screening tools is an important limitation, the extremely low detection of depression by primary care clinicians poses a serious threat to scaling up mental healthcare in LMICs. Interventions to improve detection should be prioritized.
PROSPERO CRD42016039704 .
PROSPERO CRD42016039704 .
Cholestatic liver injury can lead to serious symptoms and prognoses in the clinic. Currently, an effective medical treatment is not available for cholestatic liver injury. Human menstrual blood-derived stem cells (MenSCs) are considered as an emerging treatment in various diseases. This study aimed to explore the treatment effect of MenSCs in cholestatic liver injury.
The treatment effect of MenSCs on chronic cholestatic liver injury was verified in 3,5-diethoxycarbonyl-1,4-dihydroxychollidine (DDC)-induced C57/BL6 mice. Pathological, fibrosis area in the liver tissue and serum liver enzymes were tested. Proteomics and western blot were used to explore the related targets and molecular mechanisms. Adeno-associated virus (AAV) 9-infected mice were applied for verification.
MenSCs markedly improved the survival rate of the DDC-treated mice (60% vs. 100%), and decreased the mouse serum aspartate aminotransferase (AST) (169.4 vs. 108.0 U/L, p < 0.001), alanine aminotransferase (ALT) (279.0 vs. 228.9 U/L, p < 0.01), alkaline phosphatase (ALP) (45.6 vs. 10.6 U/L, p < 0.0001), direct bilirubin (DBIL) (108.3 vs. 14.0μmol/L, p < 0.0001) and total bilirubin (TBIL) (179.2 vs. 43.3μmol/L, p < 0.0001) levels as well as intrahepatic cholestasis, bile duct dilation and fibrotic areas (16.12 vs. 6.57%, p < 0.05). The results further indicated that MenSCs repaired the DDC-induced liver tight junction (TJ) pathway and bile transporter (OATP2, BSEP and NTCP1) injury, thereby inhibiting COL1A1, α-SMA and TGF-β1 activation by upregulating liver β-catenin expression.
MenSC transplantation could be an effective treatment method for cholestatic liver injury in mice. MenSCs may exhibit therapeutic effects by regulating β-catenin expression.
MenSC transplantation could be an effective treatment method for cholestatic liver injury in mice. MenSCs may exhibit therapeutic effects by regulating β-catenin expression.
Skeletal muscle-derived stem cells (SC) have become a promising approach for investigating myogenic differentiation and optimizing tissue regeneration. Muscle regeneration is performed by SC, a self-renewal cell population underlying the basal lamina of muscle fibers. Here, we examined the impact of hypoxia condition on the regenerative capacity of SC either in their native microenvironment or via isolation in a monolayer culture using ectopic differentiation inductions. Furthermore, the effect of low oxygen tension on myogenic differentiation protocols of the myoblasts cell line C2C12 was examined.
Hind limb muscles of wild type mice were processed for both SC/fiber isolation and myoblast extraction using magnetic beads. SC were induced for myogenic, adipogenic and osteogenic commitments under normoxic (21% O
) and hypoxic (3% O
) conditions. SC proliferation and differentiation were evaluated using histological staining, immunohistochemistry, morphometric analysis and RT-qPCR. The data were statisticaoxic culture. Combining the differentiation medium with dexamethasone under hypoxia improves the efficiency of the myogenic differentiation protocol of C2C12 by increasing the length of the myotubes.
Hypoxia exposure increases cell resources for clinical applications and promotes SC multipotency and thus beneficial for tissue regeneration.
Hypoxia exposure increases cell resources for clinical applications and promotes SC multipotency and thus beneficial for tissue regeneration.The prognosis of pancreatic ductal carcinoma (PDAC) with peritoneal metastasis remains dismal. Systemic chemotherapy alone may not be effective, and the combination of intraperitoneal chemotherapy with systemic chemotherapy is expected to prolong the overall survival in patients with peritoneal metastasis. We have designed a randomized phase III trial to confirm the superiority of intravenous (i.v.) and intraperitoneal (i.p.) paclitaxel (PTX) with S-1 relative to gemcitabine plus nab-PTX (GnP), which is the current standard therapy for patients with metastatic PDAC. A total of 180 patients will be accrued from 30 institutions within 3 years. Patients will be randomly assigned in a 11 ratio to receive either i.v. and i.p. PTX with S-1 or GnP (target of 90 patients per group). The primary endpoint is overall survival; secondary endpoints are progression-free survival, response rate, proportion with negative peritoneal washing cytology during chemotherapy, proportion requiring conversion surgery, and adverse event profiles.