/Purpose: To achieve the World Health Organization goal of eliminating viral hepatitis by 2030, a key strategy in resource-limited areas is to identify the areas with high prevalence and to ...prioritize screening and treatment intervention. We hypothesized that a hospital-based laboratory database could be used to estimate the township- and village-specific anti-hepatitis C virus (HCV) prevalence.
Yunlin County Public Health Bureau has been collecting anti-HCV test data from eight major hospitals. Township- and village-specific screening testing rates and anti-HCV prevalence were calculated for residents 40 years or older. A township with a wide range of anti-HCV prevalence rates was selected for outreach universal screening and for validating the village-specific prevalence of anti-HCV in the analysis of the data from the hospitals.
The overall anti-HCV screening testing rate in Yunlin County was 30.4 %, whereas the anti-HCV prevalence rate for persons 40 years or older was 15.4 %. The village-specific anti-HCV prevalence rates ranged from 3.8 % to 85.8 %. Community-based screening was conducted in Kouhu Township. The village-specific anti-HCV prevalence rates ranged from 0 % to 18.8 %. Three of the four villages had the highest village-specific anti-HCV prevalence in the community-based study and the hospital-based study. Additionally, 95.8 % of the new HCV cases detected by universal screening received anti-HCV therapy.
The hospital-based database provided a framework for identifying the villages with high anti-HCV prevalence. Additionally, community-based universal screening should be prioritized for villages with high prevalence in hospital-based databases.
The aberrant activation of signaling pathways contributes to cancer cells with metabolic reprogramming. Thus, targeting signaling modulators is considered a potential therapeutic strategy for cancer. ...Subcellular fractionation, coimmunoprecipitation, biochemical analysis, and gene manipulation experiments revealed that decreasing the interaction of kirsten rat sarcoma viral oncogene homolog (KRAS) with p110α in lipid rafts with the use of naringenin (NGN), a citrus flavonoid, causes lipid raft-associated phosphatidylinositol 3-kinase (PI3K)−GTP-ras-related C3 botulinum toxin substrate 1 (Rac1)−protein kinase B (Akt)-regulated metabolic dysfunction of glycolysis and mitochondrial oxidative phosphorylation (OXPHOS), leading to apoptosis in human nasopharyngeal carcinoma (NPC) cells. The use of lethal-7g (let-7g) mimic and let-7g inhibitor confirmed that elevated let-7g resulted in a decrease in KRAS expression, which attenuated the PI3K−Rac1−Akt−BCL-2/BCL-xL-modulated mitochondrial energy metabolic functions. Increased let-7g depends on the suppression of the RNA-specificity of monocyte chemoattractant protein-induced protein-1 (MCPIP1) ribonuclease since NGN specifically blocks the degradation of pre-let-7g by NPC cell-derived immunoprecipitated MCPIP1. Converging lines of evidence indicate that the inhibition of MCPIP1 by NGN leads to let-7g upregulation, suppressing oncogenic KRAS-modulated PI3K–Rac1–Akt signaling and thereby impeding the metabolic activities of aerobic glycolysis and mitochondrial OXPHOS.
MicroRNAs (miRNAs) can regulate the expression of genes involved in the establishment of the window of implantation (WOI) in the endometrium. Recent studies indicated that cell-free miRNAs in uterine ...fluid and blood samples could act as alternative and non-invasive sample types for endometrial receptivity analysis. In this study, we attempt to systematically evaluate whether the expression levels of cell-free microRNAs in blood samples could be used as non-invasive biomarkers for assessing endometrial receptivity status. We profiled the miRNA expression levels of 111 blood samples using next-generation sequencing to establish a predictive model for the assessment of endometrial receptivity status. This model was validated with an independent dataset (
= 73). The overall accuracy is 95.9%. Specifically, we achieved accuracies of 95.9%, 95.9%, and 100.0% for the pre-receptive group, the receptive group, and the post-respective group, respectively. Additionally, we identified a set of differentially expressed miRNAs between different endometrial receptivity statuses using the following criteria:
-value < 0.05 and fold change greater than 1.5 or less than -1.5. In conclusion, the expression levels of cell-free miRNAs in blood samples can be utilized in a non-invasive manner to distinguish different endometrial receptivity statuses.
Quantum criticality emerges when a many-body system is in the proximity of a continuous phase transition that is driven by quantum fluctuations. In the quantum critical regime, exotic, yet universal ...properties are anticipated; ultracold atoms provide a clean system to test these predictions. We report the observation of quantum criticality with two-dimensional Bose gases in optical lattices. On the basis of in situ density measurements, we observe scaling behavior of the equation of state at low temperatures, locate the quantum critical point, and constrain the critical exponents. We observe a finite critical entropy per particle that carries a weak dependence on the atomic interaction strength. Our experiment provides a prototypical method to study quantum criticality with ultracold atoms.
Mutations in genes involved in the production, migration, or differentiation of cortical neurons often lead to malformations of cortical development (MCDs). However, many genetic mutations involved ...in MCD pathogenesis remain unidentified. Here we developed a genetic screening paradigm based on transposon-mediated somatic mutagenesis by in utero electroporation and the inability of mutant neuronal precursors to migrate to the cortex and identified 33 candidate MCD genes. Consistent with the screen, several genes have already been implicated in neural development and disorders. Functional disruption of the candidate genes by RNAi or CRISPR/Cas9 causes altered neuronal distributions that resemble human cortical dysplasia. To verify potential clinical relevance of these candidate genes, we analyzed somatic mutations in brain tissue from patients with focal cortical dysplasia and found that mutations are enriched in these candidate genes. These results demonstrate that this approach is able to identify potential mouse genes involved in cortical development and MCD pathogenesis.
Bone loss induced by hypoxia is associated with various pathophysiological conditions, however, little is known about the effects of hypoxia and related signaling pathways on osteoblast ...differentiation and bone formation. Because bone marrow-derived mesenchymal stem cells (MSCs) survive under hypoxic conditions and readily differentiate into osteoblasts by standard induction protocols, they are a good in vitro model to study the effects of hypoxia on osteoblast differentiation.
Using human MSCs, we discovered TWIST, a downstream target of HIF-1α, was induced under hypoxia and acted as a transcription repressor of RUNX2 through binding to the E-box located on the promoter of type 1 RUNX2. Suppression of type 1 RUNX2 by TWIST under hypoxia further inhibited the expression of BMP2, type 2 RUNX2 and downstream targets of RUNX2 in MSCs.
Our findings point to the important role of hypoxia-mediated signalling in osteogenic differentiation in MSCs through direct regulation of RUNX2 by TWIST, and provide a method for modifying MSC osteogenesis upon application of these cells in fracture healing and bone reconstruction.
Biocompatible bacterial cellulose pellicle (BCP) is a candidate for biomedical material such as wound dressing. However, due to lack of antibacterial activity, to grant BCP with the property is ...crucial for its biomedical application. In the present study, BCP was modified by 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO)-mediated oxidation using TEMPO/NaClO/NaBr system at pH 10 to form TEMPO-oxidized BCP (TOBCP) with anionic C6 carboxylate groups. The TOBCP was subsequently ion-exchanged in AgNO3 solution and silver nanoparticles (AgNP) with diameter of ∼16.5 nm were in situ synthesized on TOBC nanofiber surfaces by thermal reduction without using a reducing agent. Field emission scanning electron microscopy, X-ray diffraction, X-ray photoelectron spectra, Fourier transform infrared spectroscopy, and thermogravimetric analysis were carried out to confirm morphology and structure of the pellicles with AgNP. The AgNP continuously released Ag+ with a rate of 12.2%/day at 37 °C in 3 days. The TOBCP/AgNP exhibited high biocompatibility according to the result of in vitro cytotoxicity test (cell viability >95% after 48 h of incubation) and showed significant antibacterial activities of 100% and 99.2% against E. coli and S. aureus, respectively. Hence, the highly biocompatible and highly antibacterial TOBCP/AgNP prepared in the present study is a promising candidate for wound dressing.
Background and Objectives
In patients with lymphedema, the disruption of the lymphatic network increases skin turgor and fibrosis of subcutaneous tissue, delays wound healing, causing recurrent ...ulcerations and infections. In these cases, management of ulcers can be challenging.
Methods
Between January 2016 and June 2018, patients presenting with lymphedema were enrolled at our Institution. We selected patients with severe lymphedema and ulcers of lower limbs and we performed a surgical approach, involving free gastroepiploic lymph nodes and omentum flap, harvested through laparoscopy.
Results
We enrolled 135 patients presenting for lymphedema. Among them, 10 eligible cases underwent excision of the ulcer and reconstruction with omentum flap. Mean age was 57.8 years and average follow‐up 24.1 months. Circumferences and skin tonicity significantly decreased from the preoperative period. Lymphoscintigraphy showed improvement of the lymphatic drainage and restoration of lymphatic network. No episodes of infection were recorded in the postoperative period.
Conclusions
Our combined procedure merges free flap techniques and lymphedema surgery: omentum covers the defect while providing a new source of lymph nodes, improving the lymphatic networks of the affected limb. This technique can highly increase the quality of life of the patient in a single‐stage operation with fast recovery and low donor site morbidity.
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