AQP5 enriches for stem cells and cancer origins in the distal stomach.

LGR5 marks resident adult epithelial stem cells at the gland base in the mouse pyloric stomach1, but the identity of the equivalent human stem cell population remains unknown owing to a lack of surface markers that facilitate its prospective isolation and validation. In mouse models of intestinal cancer, LGR5+ intestinal stem cells are major sources of cancer following hyperactivation of the WNT pathway2. However, the contribution of pyloric LGR5+ stem cells to gastric cancer following dysregulation of the WNT pathway-a frequent event in gastric cancer in humans3-is unknown. Here we use comparative profiling of LGR5+ stem cell populations along the mouse gastrointestinal tract to identify, and then functionally validate, the membrane protein AQP5 as a marker that enriches for mouse and human adult pyloric stem cells. We show that stem cells within the AQP5+ compartment are a source of WNT-driven, invasive gastric cancer in vivo, using newly generated Aqp5-creERT2 mouse models. Additionally, tumour-resident AQP5+ cells can selectively initiate organoid growth in vitro, which indicates that this population contains potential cancer stem cells. In humans, AQP5 is frequently expressed in primary intestinal and diffuse subtypes of gastric cancer (and in metastases of these subtypes), and often displays altered cellular localization compared with healthy tissue. These newly identified markers and mouse models will be an invaluable resource for deciphering the early formation of gastric cancer, and for isolating and characterizing human-stomach stem cells as a prerequisite for harnessing the regenerative-medicine potential of these cells in the clinic.

Safety, efficacy, and survival outcomes of immune checkpoint inhibitors rechallenge in patients with cancer: a systematic review and meta-analysis.

BACKGROUNDS: There is little evidence on the safety, efficacy, and survival benefit of restarting immune checkpoint inhibitors (ICI) in patients with cancer after discontinuation due to immune-related adverse events (irAEs) or progressive disease (PD). Here, we performed a meta-analysis to elucidate the possible benefits of ICI rechallenge in patients with cancer. METHODS: Systematic searches were conducted using PubMed, Embase, and Cochrane Library databases. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and incidence of irAEs were the outcomes of interest. RESULTS: Thirty-six studies involving 2026 patients were analyzed. ICI rechallenge was associated with a lower incidence of all-grade (OR, 0.05; 95%CI, 0.02-0.13, P < .05) and high-grade irAEs (OR, 0.37; 95%CI, 0.21-0.64, P < .05) when compared with initial ICI treatment. Though no significant difference was observed between rechallenge and initial treatment regarding ORR (OR, 0.69; 95%CI, 0.39-1.20, P = .29) and DCR (OR, 0.85; 95%CI, 0.51-1.40, P = 0.52), patients receiving rechallenge had improved PFS (HR, 0.56; 95%CI, 0.43-0.73, P < .05) and OS (HR, 0.55; 95%CI, 0.43-0.72, P < .05) than those who discontinued ICI therapy permanently. Subgroup analysis revealed that for patients who stopped initial ICI treatment because of irAEs, rechallenge showed similar safety and efficacy with initial treatment, while for patients who discontinued ICI treatment due to PD, rechallenge caused a significant increase in the incidence of high-grade irAEs (OR, 4.97; 95%CI, 1.98-12.5, P < .05) and a decrease in ORR (OR, 0.48; 95%CI, 0.24-0.95, P < .05). CONCLUSION: ICI rechallenge is generally an active and feasible strategy that is associated with relative safety, similar efficacy, and improved survival outcomes. Rechallenge should be considered individually with circumspection, and randomized controlled trials are required to confirm these findings.

Transcriptome data-based status of PI3K/AKT/mTOR pathway indicates heterogeneity and immune modulation in patients with pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer with limited treatment options. The PI3K/AKT/mTOR pathway is commonly activated in PDAC and plays a critical role in its progression. METHODS AND RESULTS: In this study, the effect of taselisib (a selective PI3K inhibitor) on PDAC cell proliferation was investigated, and a significant decrease in viability was observed with increasing concentrations of taselisib. Differential analysis on samples from the Genotype-Tissue Expression and The Cancer Genome Atlas databases revealed 24 dysregulated PI3K/AKT/mTOR pathway-related genes (PRGs). Unsupervised clustering-based analysis of transcriptome cohorts revealed two clusters with high consistency between RNA-seq and microarray cohorts. Cluster B had higher enrichment of immune cells, particularly CD8+ T cells, and lower levels of immunosuppressive Treg cells. Moreover, we investigated the relationship between drug sensitivity and different clusters and found that cluster A had a better response to PI3K/AKT/mTOR pathway-related inhibitors and chemotherapy. Finally, cluster A exhibited significant activation of PI3K/AKT/mTOR and related oncogenic pathways, contributing to poor prognosis. The study also developed a risk score based on the expression profiles of PRGs and machine learning, which showed a significant increase in overall survival time among patients in the low-risk group. Importantly, the PI3K/AKT/mTOR pathway could be used to better predict individual risk scores, as evidenced by stratified survival analysis. CONCLUSIONS: These findings suggest that targeting the PI3K/AKT/mTOR pathway may have therapeutic potential in PDAC, and distinct pathway states, immune modulation and tumor microenvironments have prognostic value.

Role of hepatitis B core-related antigen in predicting the occurrence and recurrence of hepatocellular carcinoma in patients with chronic hepatitis B: A systemic review and meta-analysis.

BACKGROUND AND AIM: The purpose of the current study was to investigate the predictive value of hepatitis B core-related antigen (HBcrAg) on the occurrence and recurrence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). METHODS: We searched PubMed, Embase, Scopus, and Web of Science from database inception to April 6, 2023. Pooled hazard ratio (HR) or odds ratio (OR) with 95% confidence interval (CI) was calculated for the occurrence and recurrence of HCC. RESULTS: Of the 464 articles considered, 18 articles recruiting 10 320 patients were included. The pooled results showed that high serum HBcrAg level was an independent risk factor for the occurrence of HCC in CHB patients (adjusted HR = 3.12, 95% CI: 2.40-4.06, P < 0.001, I2 = 43.2%, P = 0.043; OR = 5.65, 95% CI: 3.44-5.82, P < 0.001, I2 = 0.00%, P = 0.42). Further subgroup analysis demonstrated that the predictive ability of HBcrAg for the occurrence of HCC is not influenced by the hepatitis B e antigen (HBeAg) status or the use of nucleoside/nucleotide analogs (NAs). In addition, our meta-analysis also suggests that HBcrAg is a predictor of HCC recurrence (adjusted HR = 1.71, 95% CI: 1.26-2.32, P < 0.001, I2 = 7.89%, P = 0.031). CONCLUSIONS: For patients with CHB, serum HBcrAg may be a potential predictive factor for the occurrence of HCC, regardless of HBeAg status or NA treatment. It may also serve as a novel prognostic biomarker for the recurrence of HCC. More studies are needed to confirm our conclusions.

Evaluation of the microbiological efficacy of cleaning agents for tracheostomy inner cannulas.

PURPOSE: Biofilms are a significant cause of morbidity in patients with indwelling medical devices. Biofilms pose a potential risk with reusable inner cannulas by increasing the risk of infections. Effective decontamination is thus vital in decreasing bioburden. The current guidelines for cleaning inner cannulas are varied, with multiple techniques being recommended, which are not supported by strong evidence. This randomized, controlled, cross-over study attempted to enumerate the bacterial count of inner cannulas used in tracheostomy patients (n = 60) pre-and post-decontamination with detergent (A) or sterile water (B). MATERIALS AND METHODS: The patients were randomly allocated to sequence A > B or B > A in 1:1 fashion. The saline flushing of the inner cannulas was plated on trypticase soy agar with 5 % sheep blood to enumerate the bacterial count. RESULTS: The mean ratio [Log (CFU)post/Log (CFU)pre]A/[Log (CFU)post/Log (CFU)pre]B based on 53 samples was 0.918 ± 0.470, two-sided 90 % confidence interval (CI) 0.812, 1.024. The equivalence criterion was met as the mean ratio after cleaning fell within the equivalence region of 0.8 and 1.25. CONCLUSION: This study demonstrated the microbiological efficacy of both detergent and sterile water in the decontamination of inner cannulas, and that sterile water was not less effective than detergent in reducing the bacterial load for safe re-use of inner cannulas. This has the potential to promote cost savings for patients with tracheostomy, both in the hospital and the community. The study findings may also be relevant in formulating tracheostomy care policies.

Transcriptomic landscape of endothelial cells: Key tumor microenvironment components indicating variable clinical outcomes in pancreatic ductal adenocarcinoma.

Endothelial cells (ECs) present in the tumor microenvironment (TME) exhibit significant diversity that may impact the efficacy of anti-tumor treatments. Thus, our study sought to elucidate the various clusters of ECs present in pancreatic ductal adenocarcinoma (PDAC) and explore their possible interactions and influence on clinical outcomes. We obtained single-cell transcriptome data from 24 PDAC tumors and 11 normal pancreases, minimizing any batch effects between samples. Next, we compared the relative abundance of various ECs clusters across distinct sample types. Pseudo-time analysis was employed to investigate the differentiation origin of ECs. A variety of bioinformatics methods were used to investigate potential communication between ECs and malignant cells, as well as assess metabolic changes, pathway alterations, and immune-related markers expression within distinct EC clusters. Lastly, we investigated the impact of particular ECs clusters on patient prognosis in bulk transcriptome data. Our study identified seven distinct clusters of ECs, denoted as CA4+ ECs, MMP2+ ECs, SPP1+ ECs, MT1F+ ECs, CCL5+ ECs, RGS5+ ECs, and TYROBP+ ECs. Pseudo-time analysis suggested that the loss of CA4+ ECs and MT1F+ ECs may promote malignant progression. Cell communication elucidated that MT1F+ ECs exhibited the strongest outgoing interaction strength, whereas RGS5+ ECs displayed the strongest incoming interaction strength. Furthermore, TYROBP+ ECs exhibited greater metabolic activity, and notably, CCL5+ ECs displayed increased expression of immune-related molecules. Lastly, across cohorts of bulk transcriptome levels, CA4+ ECs, MT1F+ ECs, and RGS5+ ECs consistently demonstrated prognostic indicative effects. PDAC patients exhibit the presence of seven distinct EC clusters, each demonstrating significant metabolic and immunological heterogeneity. Targeted therapeutic approaches directed toward CA4+ ECs and MT1F+ ECs may prove advantageous in addressing challenges associated with PDAC treatment. Additionally, variations in the relative abundance of CA4+ ECs, MT1F+ ECs, and RGS5+ ECs were indicated as predictive of patient prognosis.

Combination of tibial tubercle transfer, medial patellofemoral ligament reconstruction, trochleoplasty and lateral release for patellofemoral instability provides good middle- to long-term outcomes in adolescents.

PURPOSE: There are limited studies that have reported the middle- to long-term outcomes of combined procedures consisting of more than two procedures for patellofemoral instability. The current study aims to investigate and report the middle- to long-term outcomes of a combination procedure of tibial tubercle transfer, medial patellofemoral ligament reconstruction, trochleoplasty and lateral release for patellofemoral instability in patients aged 18 years and below. METHODS: In the cohort study, all patients aged 18 years old or younger who underwent a combination procedure of tibial tubercle transfer, medial patellofemoral ligament reconstruction, trochleoplasty and lateral release for recurrent patellofemoral instability were included. RESULTS: A total of 21 patients were included in the study. All patients had no further patellofemoral dislocation, pain and apprehension following the 4-in-1 surgery (p < 0.01). There was a significant improvement in the Kujala score from 36.1 (SD 12.9) pre-operatively to 93.1 (SD 3.6) post-operatively (p < 0.001). The patients also had a statistically significant improvement in their radiological factors, including the patellar tilt angle (p < 0.001), sulcus angle (p = 0.001), trochlear groove depth (p = 0.041), tibial tubercle-trochlear groove distance (p < 0.001) and Caton-Deschamps index (p = 0.001). CONCLUSION: A combination procedure of tibial tubercle transfer, medial patellofemoral ligament reconstruction, trochleoplasty and lateral release leads to good middle- to long-term subjective, functional and radiographic outcomes for patients with recurrent patellofemoral instability and underlying predisposing factors of increased TT-TG distance of more than 20 mm, Dejour B or D trochlear dysplasia and medial patellofemoral ligament rupture. LEVEL OF EVIDENCE: IV.

Efficacy and safety of immune checkpoint inhibitors for hepatocellular carcinoma patients with macrovascular invasion or extrahepatic spread: a systematic review and meta-analysis of 54 studies with 6187 hepatocellular carcinoma patients.

BACKGROUND AND AIMS: The impacts of macrovascular invasion (MVI) or extrahepatic spread (EHS) on the efficacy and safety of immune checkpoint inhibitors (ICIs) among hepatocellular carcinoma (HCC) patients remain unclear. Thus, we conducted a systematic review and meta-analysis to clarify whether ICI therapy is a feasible treatment option for HCC with MVI or EHS. METHODS: Eligible studies published before September 14, 2022, were retrieved. In this meta-analysis, the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and occurrence of adverse events (AEs) were outcomes of interest. RESULTS: Fifty-four studies involving 6187 individuals were included. The findings indicated that the presence of EHS in ICI-treated HCC patients may indicate an inferior ORR (OR 0.77, 95% CI 0.63-0.96), but may not significantly affect the PFS (multivariate analyses: HR 1.27, 95% CI 0.70-2.31) and OS (multivariate analyses: HR 1.23, 95% CI 0.70-2.16). Additionally, the presence of MVI in ICI-treated HCC patients may not have significant prognostic impact on ORR (OR 0.84, 95% CI 0.64-1.10), but may indicate inferior PFS (multivariate analyses: HR 1.75, 95% CI 1.07-2.84) and OS (multivariate analyses: HR 2.03, 95% CI 1.31-3.14). The presence of EHS or MVI in ICI-treated HCC patients may not significantly impact the occurrence of any serious immune-related adverse events (irAEs) (grades ≥ 3) (EHS: OR 0.44, 95% CI 0.12-1.56; MVI: OR 0.68, 95% CI 0.24-1.88). CONCLUSION: The presence of MVI or EHS in ICI-treated HCC patients may not significantly impact the occurrence of serious irAEs. However, the presence of MVI (but not EHS) in ICI-treated HCC patients may be a significant negative prognostic factor. Therefore, ICI-treated HCC patients with MVI warrant more attention.

MALAT1/ mir-1-3p mediated BRF2 expression promotes HCC progression via inhibiting the LKB1/AMPK signaling pathway.

BACKGROUND: The long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been reported to play a vital role in the occurrence and development of various tumors. However, the underlying mechanism of MALAT1 in hepatocellular carcinoma (HCC) has not been thoroughly elucidated. METHODS: The expression levels of MALAT1 in HCC tissues and different cell lines were detected by qRT-PCR. Antisense oligonucleotides (ASO)-MALAT1 transfected cells were used to explore the biological effects of MALAT1 in HCC cells by cell counting kit 8 (CCK-8), colony formation, transwell, wound healing, and flow cytometry analysis. Western blotting was performed to measure AMPK and apoptosis-related protein levels. Dual-luciferase reporter assay was performed to verify the relationship between MALAT1 and its specific targets. RESULTS: We found that MALAT1 was upregulated in HCC, and MALAT1 knockdown in HCC cells inhibited cell proliferation, migration, and invasion and inhibited apoptosis in vitro. Further studies demonstrated that MALAT1 positively regulated the expression of transcription factor II B­related factor 2 (BRF2), which was associated with tumor recurrence, large tumor size, and poor prognosis in HCC. Mechanistically, MALAT1 was found to act as a competitive endogenous RNA to sponge has-miR-1-3p, which upregulated BRF2 expression. Knockdown of BRF2 inhibited the progression of HCC by activating the LKB1/AMPK signaling pathway. Overexpression of BRF2 reversed the inhibitory effect of MALAT1 knockdown on HCC cell viability. Moreover, ASO targeting MALAT1 inhibited the growth of xenograft tumors. CONCLUSIONS: Our results demonstrate a novel MALAT1/miR-1-3p/BRF2/LKB1/AMPK regulatory axis in HCC, which may provide new molecular therapeutic targets for HCC in the future.

The Differences in Structure and Function of the Cerebellum Between Cantonese-Mandarin Bilinguals and Mandarin Monolinguals: a Multi-model MRI Study.

The effects of the long-term bilingual experience on structure and function of the cerebellum remain unclear. To explore whether there are differences in cerebellar gray matter structure between Cantonese-Mandarin bilinguals and Mandarin monolinguals and whether these different cerebellar structures have different resting-state functional connectivity (RSFC) with the cerebrum between the two groups, 30 Cantonese-Mandarin bilingual and 30 Mandarin monolingual college students were scanned by the T1-weighted magnetic resonance imaging (MRI) and resting-state functional MRI. Voxel-based morphology (VBM) analysis and RSFC analysis were used to analyze the cerebellar gray matter volume (GMV) and cerebellar-cerebro functional connectivity, respectively. Correlation analysis was performed between GMV/RSFC and the rapid automatized naming (RAN) and cognitive control. Compared to Mandarin monolinguals, Cantonese-Mandarin bilinguals showed larger GMV in bilateral cerebellar inferior posterior lobe (including bilateral VIIIa, VIIIb,IX, and right X, Vermis VIIIb, and Vermis IX) and a significant increase in RSFC coupling of the right inferior cerebellar posterior lobe with orbital part of left inferior frontal gyrus (IFG). In addition, there was a positive correlation between average response time (RT) of Mandarin alphanumeric RAN and RSFC between the right inferior posterior lobe of cerebellum and left IFG of all participants. The long-term Cantonese-Mandarin bilingual experience can increase the GMV of the bilateral cerebellar inferior posterior lobe and the RSFC between the right inferior cerebellar posterior lobe with orbital part of left inferior frontal gyrus (IFG).

Measuring health equity in the ASEAN region: conceptual framework and assessment of data availability.

BACKGROUND: Existing research on health equity falls short of identifying a comprehensive set of indicators for measurement across health systems. Health systems in the ASEAN region, in particular, lack a standardised framework to assess health equity. This paper proposes a comprehensive framework to measure health equity in the ASEAN region and highlights current gaps in data availability according to its indicator components. METHODS: A comprehensive literature review was undertaken to map out a core set of indicators to evaluate health equity at the health system level. Secondary data collection was subsequently conducted to assess current data availability for ASEAN states in key global health databases, national health accounts, and policy documents. RESULTS: A robust framework to measure health equity was developed comprising 195 indicators across Health System Inputs and Processes, Outputs, Outcomes, and Contextual Factors. Total indicator data availability equated to 72.9% (1423/1950). Across the ASEAN region, the Inputs and Processes sub-component of Health Financing had complete data availability for all indicators (160/160, 100%), while Access to Essential Medicine had the least data available (6/30, 20%). Under Outputs and Outcomes, Coverage of Selected Interventions (161/270, 59.63%) and Population Health (350/350, 100%) respectively had the most data available, while other indicator sub-components had little to none (≤ 38%). 72.145% (384/530) of data is available for all Contextual Factors. Out of the 10 ASEAN countries, the Philippines had the highest data availability overall at 77.44% (151/195), while Brunei Darussalam and Vietnam had the lowest data availability at 67.18% (131/195). CONCLUSIONS: The data availability gaps highlighted in this study underscore the need for a standardised framework to guide data collection and benchmarking of health equity in ASEAN. There is a need to prioritise regular data collection for overlooked indicator areas and in countries with low levels of data availability. The application of this indicator framework and resulting data availability analysis could be conducted beyond ASEAN to enable cross-regional benchmarking of health equity.

Comparison of BACTEC versus conventional enrichment medium for peritoneal dialysate fluid culture.

BACKGROUND: Bacterial peritonitis remains a significant cause of mortality in patients on peritoneal dialysis (PD). Early detection of causative organisms and targeted antimicrobial treatment allow for better clinical outcomes. This study compares bacterial growth results from peritoneal dialysate in the BACTEC blood culture system vs. conventional culture. MATERIALS AND METHODS: We conducted a prospective study on 46 patients with 63 consecutive episodes of suspected PD peritonitis between August 2020 and August 2021. PD dialysate was simultaneously sent to the laboratory in both BACTEC and sterile bottles. BACTEC bottles were incubated in the BD BACTEC FX system for 5 days. PD effluent transported from the sterile bottles was centrifuged at 3,000 rpm for 15 minutes; the supernatant was inoculated into cooked-meat broth for enrichment. Both incubation methods were extended to 14 days if microorganisms were seen on the Gram-stained smear. Recovery of isolated micro-organisms and time to detection (TTD) were compared. RESULTS: 26 episodes of suspected PD peritonitis based on clinical criteria were identified during the study period. The sensitivity of the BACTEC and the conventional culture methods was 50% and 42.3%, respectively (p = 0.45). Seven samples had partial concordance or discordant results. McNemar's χ2-test revealed no statistical difference between either method (p = 0.45). TTD was 18.9 ± 24.4 hours via the BACTEC method vs. 37 ± 16.5 hours in conventional cultures (p = 0.014). CONCLUSION: The comparable sensitivities and similar yield in identifying pathogens could be due to the enrichment medium and prolonged incubation period. The shorter TTD for the BACTEC method could facilitate earlier confirmation of bacteriological diagnosis and subsequent treatment strategies.

HSF1 Alleviates Brain Injury by Inhibiting NLRP3-Induced Pyroptosis in a Sepsis Model.

Background: Sepsis, which could cause a systemic inflammatory response, is a life-threatening disease with a high morbidity and mortality rate. There is evidence that brain injury may be related to severe systemic infection induced by sepsis. The brain injury caused by sepsis could increase the risk of mortality in septic patients, which seriously affects the septic patient's prognosis of survival. Although there remains a focus on sepsis research, clinical measures to prevent and treat brain injury in sepsis are not yet available, and the high mortality rate is still a big health burden. Therefore, it is necessary to investigate the new molecules or regulated pathways that can effectively inhibit the progress of sepsis. Objective: NLR family pyrin domain-containing 3 (NLRP3) increased in the procession of sepsis and functioned as the key regulator of pyroptosis. Heat shock factor 1 (HSF1) can protect organs from multiorgan dysfunction syndrome induced by lipopolysaccharides in mice, and NLRP3 could be inhibited by HSF1 in many organs. However, whether HSF1 regulated NLRP3 in sepsis-induced brain injury, as well as the detailed mechanism of HSF1 in brain injury, remains unknown in the sepsis model. In this research, we try to explore the relationship between HSF1 and NLRP3 in a sepsis model and try to reveal the mechanism of HSF1 inhibiting the process of brain injury. Methods: In this study, we used wild-type mice and hsf1 -/- mice for in vivo research and PC12 cells for in vitro research. Real-time PCR and Western blot were used to analyze the expression of HSF1, NLRP3, cytokines, and pyrolytic proteins. EthD-III staining was chosen to detect the pyroptosis of the hippocampus and PC12 cells. Results: The results showed that HSF1 is negatively related to pyroptosis. The pyroptosis in cells of brain tissue was significantly increased in the hsf1 -/- mouse model compared to hsf1 +/+ mice. In PC12 cells, hsf1 siRNA can upregulate pyroptosis while HSF1-transfected plasmid could inhibit the pyroptosis. HSF1 could negatively regulate the NLRP3 pathway in PC12 cells, while hsf1 siRNA enhanced the pyroptosis in PC12 cells, which could be reversed by nlrp3 siRNA. Conclusion: These results imply that HSF1 could alleviate sepsis-induced brain injury by inhibiting pyroptosis through the NLRP3-dependent pathway in brain tissue and PC12 cells, suggesting HSF1 as a potential molecular target for treating brain injury in sepsis clinical studies.

Polyphenol Profile, Antioxidant Activity, and Hypolipidemic Effect of Longan Byproducts.

Longan, a popular fruit in Asia, has been used in traditional Chinese medicine to treat several diseases for centuries. Recent studies have indicated that longan byproducts are rich in polyphenols. The aim of this study was to analyze the phenolic composition of longan byproduct polyphenol extracts (LPPE), evaluate their antioxidant activity in vitro, and investigate their regulating effect on lipid metabolism in vivo. The results indicated that the antioxidant activity of LPPE was 231.350 ± 21.640, 252.380 ± 31.150, and 558.220 ± 59.810 (mg Vc/g) as determined by DPPH, ABTS, and FRAP, respectively. UPLC-QqQ-MS/MS analysis indicated that the main compounds in LPPE were gallic acid, proanthocyanidin, epicatechin, and phlorizin. LPPE supplementation prevented the body weight gain and decreased serum and liver lipids in high-fat diet-induced-obese mice. Furthermore, RT-PCR and Western blot analysis indicated that LPPE upregulated the expression of PPARα and LXRα and then regulated their target genes, including FAS, CYP7A1, and CYP27A1, which are involved in lipid homeostasis. Taken together, this study supports the concept that LPPE can be used as a dietary supplement in regulating lipid metabolism.

Morbidities and prognostic factors after tibial pilon fracture: impact on patients.

INTRODUCTION: This study aims primarily to characterize the sequelae and morbidity associated with tibial pilon injuries from the patients' perspectives in terms of multiple surgical interventions, duration of hospital stay, downtime from work, loss of productivity and impact on patients' lives. The secondary aim is to review the associated risk factors for these morbidities. MATERIALS AND METHODS: All patients with surgically treated tibial pilon fractures from 1st July 2007 to 30th June 2017 were included. The morbidities reviewed focused on delay to surgery, numbers of surgeries, limb amputation, length of stay (LOS), readmissions, duration of medical leave (ML), follow-up and number of outpatient visits. RESULTS: There were 102 patients included in the review and up to 70% of them had an average 7 days delay to definitive surgery. They also required an average hospital LOS of at least 2 weeks extending up to 3 more weeks if soft tissue reconstruction was necessitated. Up to a third of patients were readmitted with 15% of them needing further treatment. These patients required a notable period of downtime from work as shown in the long ML (mean 152.6 days [S.D. = 110.7]). Multiple conditional regression models showed AO/OTA classification (B and C) and open fracture as independent predictors of delay to surgery. Predictors for increased LOS were high velocity mechanism of injury at 4 days longer and patients who needed soft tissue reconstruction at 21 days longer. In terms of downtime from work, only work injury has been identified as an independent predictor of ML at 88.5 days longer. CONCLUSION: Tibial pilon fractures leads to significant morbidities with profound negative impact on patients' lives in terms of multiple surgical interventions required, prolonged hospital stay, need for readmissions and prolonged downtime from work. These morbidities from patients' perspective should be emphasized to patients and employers to manage their expectations and potential limitations.

Generational effect on nurses' work values, engagement, and satisfaction in an acute hospital.

BACKGROUND: The present nursing workforce comprises four generational of nurses working side-by-side. While such a generation blend adds invaluable diversity to the workforce, it also brings added complexity. The study aimed to describe and summarise work values and attitudes of four nursing generations, namely Baby boomers, Generation X, Y and Z. METHOD: A cross-sectional questionnaire study was adopted. A total of 778 nurses from an acute hospital in Singapore completed the online questionnaire. The Work Value and Attitude scale measuring seven constructs (Work Centrality, Non-compliance, Technology Challenge, Work life balance, leadership, Power, and Recognition) was employed for data collection. RESULTS: The Cronbach's alpha was 0.714 for the overall instrument. Statistically significant differences amongst the four generations of nurses emerged in the Work Value and Attitude scale in the construct of non-compliance (p = 0.007), technology challenge (p = 0.027), work-life balance (p < 0.001), and recognition (p < 0.001). No statistically significant differences were noted for the rest of the constructs. DISCUSSION AND CONCLUSION: The findings of this study highlight that differences in work values and attitudes exist among nurses of different generations. Generation X are less likely to challenge the conventional norm and supervisors. Generation Y and Z are the most tech-savvy generations and can adapt quickly to new technology. There is also a greater emphasis on work-life balance as the generation gets younger. Generation Y and Z nurses perceived that younger nurses do not get due respect and recognition from their colleagues. Acknowledging the generational differences in work values and attitudes can facilitate nursing management to tailor strategies to improve individual and organisation performance while creating a work environment that enhances intergeneration harmony and teamwork.

An AR-ERG transcriptional signature defined by long-range chromatin interactomes in prostate cancer cells.

The aberrant activities of transcription factors such as the androgen receptor (AR) underpin prostate cancer development. While the AR cis-regulation has been extensively studied in prostate cancer, information pertaining to the spatial architecture of the AR transcriptional circuitry remains limited. In this paper, we propose a novel framework to profile long-range chromatin interactions associated with AR and its collaborative transcription factor, erythroblast transformation-specific related gene (ERG), using chromatin interaction analysis by paired-end tag (ChIA-PET). We identified ERG-associated long-range chromatin interactions as a cooperative component in the AR-associated chromatin interactome, acting in concert to achieve coordinated regulation of a subset of AR target genes. Through multifaceted functional data analysis, we found that AR-ERG interaction hub regions are characterized by distinct functional signatures, including bidirectional transcription and cotranscription factor binding. In addition, cancer-associated long noncoding RNAs were found to be connected near protein-coding genes through AR-ERG looping. Finally, we found strong enrichment of prostate cancer genome-wide association study (GWAS) single nucleotide polymorphisms (SNPs) at AR-ERG co-binding sites participating in chromatin interactions and gene regulation, suggesting GWAS target genes identified from chromatin looping data provide more biologically relevant findings than using the nearest gene approach. Taken together, our results revealed an AR-ERG-centric higher-order chromatin structure that drives coordinated gene expression in prostate cancer progression and the identification of potential target genes for therapeutic intervention.

Association between lack of dental service utilisation and caregiver-reported caries in Australian Indigenous children: A national survey.

AIM: To investigate the association between the lack of dental service utilisation and dental caries in Australian Indigenous children. METHODS: Data from the Longitudinal Study of Indigenous Children, which is a longitudinal population-based cross-sectional study in Australia were analysed. A total of 1258 children were included, consisting of the baby cohort and the child cohort at Wave 7. Logistic regression analysis was conducted to examine the association between caregiver-reported child dental caries and dental service utilisation. Multiple imputation using the fully conditional specifications approach was used to account for missing data. RESULTS: Around one tenth (12.3%) of Indigenous children did not see a dentist when required. Lack of dental service utilisation was associated with an increased likelihood of caregiver-reported dental caries (odds ratio (OR) 2.4; 95% confidence interval (CI) 1.5-3.8) and teeth removed due to dental caries (OR 2.3; 95% CI 1.1-4.7). These associations remained after adjusting for confounders (caregiver-reported dental caries OR 2.3; 95% CI 1.3-3.8; teeth removed due to dental caries OR 2.1; 95% CI 1.0-4.4). The reasons reported for not utilising dental services when required were the lack of an available dentist (31.4%), difficulties with physical access (19.8%), long waiting times (13.9%), financial issues with cost (5.8%) and feeling that 'they could cope' (4.6%). CONCLUSIONS: Lack of dental service utilisation was associated with dental caries and extraction due to caries in Australian Indigenous children.

Physical Characterization, Nutrient, Phenolic Profiles and Antioxidant Activities of 16 litchi Cultivars Grown in the Upper Yangtze River Region.

Litchi grown in the upper Yangtze River region have the advantage of being late-maturing owing to the geographical location. This study aimed to evaluate the physical characteristics, nutritional values, phenolic composition and antioxidant activities of 16 litchi cultivars grown in the upper Yangtze River region. Litchi grown in this region had total soluble solid and ascorbic acid contents comparable with those of cultivars grown in other locations. The total polyphenol contents were determined using the Folin-Ciocalteu assay, and the phenolic profiles were determined using UPLC-QqQ-MS/MS. Nine phenolic compounds were identified and quantified in this study. Naringin, rutin and p-coumaric acid were the major phenolic compounds in all the litchi cultivars. Statistical analysis of all the physiochemical results was performed using principal component analysis. Our results indicated that litchi grown in the upper Yangtze River region not only showed the late-maturity characteristic but were also good dietary sources of phenolic compounds and antioxidants. In particular, 'Fei Zi Xiao' and 'Jing Gang Hong Nuo', characterized by high polyphenol contents and high antioxidant capacities, were of superior comprehensive quality. This study provides important information for the development of late-maturing litchi industry.

Predictive Scoring for Recurrent Patellar Instability After a First-time Patellar Dislocation.

PURPOSE: Patellofemoral instability is a common acute knee injury seen in the pediatric population. First-time patellar dislocations usually undergo conservative management, but ~15% to 80% of patients experience recurrent instability. This study aims to develop a prediction model using radiographic parameters of the patellofemoral joint seen on computed tomography scans in different degrees of knee flexion, to determine the risk of recurrence after the first episode of patellofemoral instability. METHODS: A 12-year retrospective case-control study was performed. All patients in a single institution aged 18 years or younger who had a computed tomography patellar tracking scan performed for patellar instability were included. Predictors included in the score were determined through backward logistic regression and compared using receiver operating characteristic curve analysis. RESULTS: This study revealed that recurrent dislocation in first-time patellofemoral dislocation could be accurately predicted using the prediction score that consisted of age, tibial tubercle-trochlear groove distance and congruence angle at 10- and 20-degree flexion. The sensitivity of the score was 100% and specificity was 73.3%. Three diagnostic zones were identified and used to categorize patients into low-, intermediate-, and high-probability groups. CONCLUSION: This study presented a scoring system that incorporated radiographic knee kinematics in the risk assessment for recurrent patellofemoral instability for patient stratification. The scoring system could guide the decision for early surgical intervention after the first-episode patellofemoral dislocation for patients at high risk of recurrent patellofemoral dislocation.