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Background Residents of the Bronx suffer marked health disparities due to socioeconomic and other factors. The coronavirus disease 2019 pandemic worsened these health outcome disparities and health care access disparities, especially with the abrupt transition to online care. Objectives This study classified electronic health literacy (EHL) among patients at an urban, academic hospital in the Bronx, and assessed for associations between EHL levels and various demographic characteristics. Methods We designed a cross-sectional, observational study in adults 18 years or older presenting to the Montefiore Einstein Center for Cancer Care (MECCC) Department of Radiation Oncology or the Montefiore Department of Medicine in the Bronx. We assessed EHL using the eHealth Literacy Scale (eHEALS) survey, a previously validated tool, and our newly developed eHealth Literacy Objective Scale-Scenario Based (eHeLiOS-SB) tool. Results A total of 97 patients recruited from the MECCC and Department of Medicine participated in this study. There was a statistically significant association between age and EHL as assessed by both eHEALS and eHeLiOS-SB, with older adults having lower EHL scores. Additionally, a question designed to assess general attitudes toward digital health technologies found that most participants had a positive attitude toward such applications. Conclusion Many patients, especially older adults, may require additional support to effectively navigate telehealth. Further research is warranted to optimize telemedicine strategies in this potentially-marginalized population and ultimately to create telehealth practices accessible to patients of all ages and demographics.

Liver cirrhosis is a major health problem with multiple associated complications. The presently available drug delivery systems showed moderate site-specific delivery of antifibrotic molecules to the diseased liver; therefore, research on more effective and selective delivery systems in the context of liver cirrhosis remains a necessity in clinical investigation. The aim of the present study was to develop a peptide-based targeted nanocarrier to deliver an oligonucleotide to the hepatic sinusoidal and perivascular regions of the cirrhotic liver. We have synthesized and characterized a conformationally restricted targeted pentapeptide (RΔFRGD), which contains an unnatural amino acid, α,β-dehydrophenylalanine (ΔF). The RΔFRGD self-assembled into spherical nanoparticles (NPs) and was characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Next, we investigated the delivery potential of the pentapeptide-based NPs to make a stable complex with a well-established small interference RNA and studied its site-specific delivery in experimental liver cirrhosis. We used siNR4A1 of the orphan nuclear receptor 4A1 (NR4A1), a well-known regulatory checkpoint for controlling liver fibrosis. Peptide NPs and their complex with siNR4A1 showed high biocompatibility against various mammalian cell lines. Hepatic tissue biodistribution analysis illustrated that targeted NPs predominantly accumulated in the cirrhotic liver compared to normal rats, specifically in sinusoidal and perivascular areas. A significant downregulation of the NR4A1 mRNA expression (-70%) andlower levels of the NR4A1/GAPDH ratio (-55%) were observed in the RΔFRGD-siNR4A1 nanocomplex-treated group in comparison to the RΔFRGD-vehicle group (RΔFRGD-Veh) at the gene and protein levels, respectively. In addition

RationaleCOVID-19 is an acute infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Human surfactant protein D (SP-D) is known to interact with spike protein of SARS-CoV, but its immune-surveillance against SARS-CoV-2 is not known.ObjectiveThis study aimed to examine the potential of a recombinant fragment of human SP-D (rfhSP-D) as an inhibitor of replication and infection of SARS-CoV-2.MethodsrfhSP-D interaction with spike protein of SARS-CoV-2 and hACE-2 receptor was predicted via docking analysis. The inhibition of interaction between spike protein and ACE-2 by rfhSP-D was confirmed using direct and indirect ELISA. The effect of rfhSP-D on replication and infectivity of SARS-CoV-2 from clinical samples was studied by measuring the expression of RdRp gene of the virus using qPCR.Measurements and Main ResultsIn-silico interaction studies indicated that three amino acid residues in the RBD of spike of SARS-CoV-2 were commonly involved in interacting with rfhSP-D and ACE-2. Studies using clinical samples of SARS-CoV-2 positive cases (asymptomatic, n=7 and symptomatic, n=8 and negative controls n=15) demonstrated that treatment with 5μM rfhSP-D inhibited viral replication by ~5.5 fold and was more efficient than Remdesivir (100 μM). Approximately, a 2-fold reduction in viral infectivity was also observed after treatment with 5μM rfhSP-D.ConclusionsThese results conclusively demonstrate that the calcium independent rfhSP-D mediated inhibition of binding between the receptor binding domain of the S1 subunit of the SARS-CoV-2 spike protein and human ACE-2, its host cell receptor, and a significant reduction in SARS-CoV-2 infection and replication in-vitro.

Gut lymphatic vessels (LVs) are crucial for maintaining gut immunity and abdominal fluid homeostasis. In experimental liver cirrhosis with ascites, gut LVs are dilated and dysfunctional with impaired gut immune response. Therapy with pro-lymphangiogenic factor, vascular endothelial growth factor-C (VEGF-C) promotes functional LVs growth and attenuates inflammation. However, therapeutic role of VEGF-C in cirrhosis has not been explored. Here we developed a nanoformulation comprising of recombinant human VEGF-C loaded reverse micelles (E-VEGF-C) and delivered it orally in rat models of liver cirrhosis to specifically target mesenteric LVs (mLVs). E-VEGF-C treated cirrhotic rats displayed an increased density of gut LVs, improved functional drainage and reduced abdominal fluid/ascites and portal pressures without any adverse events. E-VEGF-C also enhanced the proliferation of LVs in the mesenteric lymph nodes, triggering active immune responses, which helped to contain the spreading of bacteria to other organs preventing systemic infection. At molecular level, E- VEGF-C treatment upregulated the expression of cell adhesion and permeability markers, VE-cadherin and VCAM1 in the mesenteric lymphatic endothelial cells. Collectively, oral delivery of E-VEGF-C in cirrhotic rats ameliorates drainage of gut LVs, ascites formation and immunity and thus represents a potential treatment to manage ascites and immune dysfunction in cirrhosis.

Extracellular vesicles (EVs) are nanoscopic packages that are heterogeneous and bona fide players in hepatic physiology and pathology as they are involved in intercellular communication. EVs carrying bioactive cargoes rich in lipids, proteins or nucleic acids are implicated in the onset and progression of liver diseases. Liver pathology using liver biopsy has been assessed for several intricate conditions such as viral hepatitis, alcoholic and non-alcoholic fatty liver disease, hepatic malignancies and drug-induced liver injury. The lacunae, however, lie in early diagnosis and timely treatment of the above conditions, underscoring the need for non-invasive, accurate diagnostic tools that could replace the gold standard method of tissue biopsy. In this regard, EVs have emerged as promising candidates that could serve as potential biomarkers. In the last two decades, EVs, owing to their multifaceted charm in bringing out cell-free therapeutic responses and the ability of their cargoes to be applied to novel biomarkers, have drawn the great attention of researchers with the advancement and clinical application of liquid biopsy. In this review, we recapitulate the role of EVs and provide insights into the promising role of these small packages as biomarkers in liver pathology.

In vitro models of liver (patho)physiology, new technologies, and experimental approaches are progressing rapidly. Based on cell lines, induced pluripotent stem cells or primary cells derived from mouse or human liver as well as whole tissue (slices), such in vitro single- and multicellular models, including complex microfluidic organ-on-a-chip systems, provide tools to functionally understand mechanisms of liver health and disease. The International Society of Hepatic Sinusoidal Research commissioned this working group to review the currently available in vitro liver models and describe the advantages and disadvantages of each in the context of evaluating their use for the study of liver functionality, disease modeling, therapeutic discovery, and clinical applicability.

Introduction: Racial and ethnic minorities have a higher burden of type 2 diabetes in part due to limited access to health-promoting resources and self-management tools. We developed and implemented a patient-centric mobile application, DiabetesXcel, to provide guideline-based education (via animated videos) and adherence support via goal setting and tailored push notifications. Methods: Patients provided verbal or e-consent via REDCap generated e-mail links virtually (in-light of COVID-19) and completed baseline sociodemographic and e-health literacy (EHL) surveys (eHEALs) ; and DQoL (Diabetes quality of life) , DSMQ (Diabetes Self-Management Questionnaire) and DKQ-24 (Diabetes Knowledge Questionnaire) . Participants were guided on downloading the app and its functionality was explained in detail. Laboratory data were obtained by chart review from the Epic EHR. Results: Of the 50 patients, mean age was 46.9 (± 9.2) years, 70% were female, and 82% identified as Blacks and Hispanics. Overall, the cohort, with an average 13.1 ± 8.3 years since diagnosis, had high prevalence of complications (60%) , and poor glycemic control (HbA1C > 7.5, 58%) . At baseline, scores of satisfaction (22.6 ± 6.9) , worry (10.9 ± 8.4) , impact (15.5 ± 5.2) and total DQoL scores (48.9 ± 15.6) indicated low quality of life (QoL) . DSMQ (21.8 ± 6.9) and DKQ (18.4 ± 3) were low across patients with and without complications (p= 0.5 and 0.8, respectively) . Interestingly, 88% had moderate-good EHL scores. Conclusion: Most patients in our cohort demonstrated good e-health literacy scores. We expect that our mobile health application will promote diabetes education and self-management skills in our underserved minority community and favorably impact clinical outcomes. We eventually plan to disseminate the app and promote its uptake across marginalized populations on the national level. Disclosure S.Kaur: None. L.Mahali: None. E.Cosar: None. S.Jariwala: None. Funding New York Regional Center for Diabetes Translation Research

HSP27, also known as HSPB1, was first discovered with a molecular weight 27kDa belonging to the four member gene family. Elevated levels of HSP27 are seen when different unfavorable conditions prevail such as increase in temperature and oxidative stress or exposure to heavy metals or organic solvents. They possess ATP-independent chaperone like activity which helps in maintaining protein homeostasis. It can also form large oligomers (300-600 kDa) containing different numbers of subunits. It is composed of total 205 amino acids. HSP27 undergoes post-translational modifications i.e. phosphorylation thereby converting large oligomers into dimers. It can act as an anti-apoptotic and antioxidant molecule during oxidative stress. The elevated form of HSP27 is also seen in some cancer belongs to breast, ovary, prostate, brain, colorectal, hepatocellular carcinoma, lung, liver, and cervical regions. Keeping in view of molecular roles of HSP27 signaling in various pathways, we have proposed their translational values in different diseases. In addition, we have also reported the existing scientific data on the HSP27 as the potential cancer biomarker and their therapeutic targets for improved prognosis and treatment in different diseases.

AIM: An impaired hepatocyte proliferation during severe liver injury causes the proliferation of hepatic progenitor cells (HPCs), also called as the ductular reaction (DR). In the present study, we studied the role of key angiogenic factors in HPC-mediated DR in nonalcoholic steatohepatitis (NASH). METHODS: Liver biopsies from patients with NASH (n = 14) were included in the study. Patients with NASH were divided in two groups, early and late fibrosis (based on fibrosis staging). Biopsies were used to analyze the gene expression by quantitative real-time polymerase chain reaction and immunohistochemical (IHC) staining for two markers of DR, viz, CK19 and epithelial cell adhesion molecule (EpCAM). Cocultures were performed between steatotic human umbilical vein endothelial cells (HUVECs) and LX2 and Huh7 cells. Enzyme-linked immunosorbent assays were performed to measure levels of vascular endothelial growth factor (VEGF) in coculture studies. Next, Huh7 cells were treated with VEGF, and proliferation was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assays. The number of EpCAM-positive cells was analyzed by flow cytometry. RESULTS: Of all the angiogenic factors, the gene expression of VEGF and angiopoietin 2 (Ang2) was significantly different between patients with NASH in the early and late fibrosis groups (P

Background and Aims: Hepatitis B virus X protein (HBx) play a key role in pathogenesis of HBV-induced hepatocellular carcinoma (HCC) by promoting epithelial to mesenchymal transition (EMT). In this study, we hypothesized that inhibition of HBx is an effective strategy to combat HCC. Methodology and Results: We designed and synthesized novel HBx gene specific single guide RNA (sgRNA) with CRISPR/Cas9 system and studied its in vitro effects on tumor properties of HepG2-2.15. Full length HBx gene was excised using HBx-CRISPR that resulted in significant knockdown of HBx expression in hepatoma cells. HBx-CRISPR also decreased levels of HBsAg and HBV cccDNA expression. A decreased expression of mesenchymal markers, proliferation and tumorigenic properties was observed in HBx-CRISPR treated cells as compared to controls in both 2D and 3D tumor models. Transcriptomics data showed that out of 1159 differentially expressed genes in HBx-CRISPR transfected cells as compared to controls, 70 genes were upregulated while 1089 genes associated with cell proliferation and EMT pathways were downregulated. Conclusion: Thus, targeting HBx by CRISPR/Cas9 system effectively downregulates HBx gene expression, HBsAg production and mesenchymal characteristics of HBV-HCC cells and holds potential as a therapeutic approach for HBV-HCC.

The lymphatic vascular system runs parallel to the blood vascular system, comprising a network of lymphatic vessels and secondary lymphoid organs. The intestinal lymphatic capillaries (lacteals) and the associated collecting vessels in the mesentery form the gut lymphatic system. The gut lymphatic vasculature comprises the longest-studied lymphatic vessel bed and plays a significant role in the uptake and transport of dietary fat, abdominal fluid balance, and gut immunosurveillance. Gut is closely connected to liver through the portal circulation. In several experimental and clinical studies, the “gut-liver-axis” has been demonstrated to contribute to the pathogenesis of portal hypertension, liver cirrhosis, and its complications. Given a significant impact of gut health on the liver, in the current review, we highlight “gut-liver axis” in context to the circulatory physiology of gut lymphatic vessels. Despite their paramount importance in maintaining fluid and immune homeostasis in the gut, gut lymphatic vessels remain one of the most understudied physiological systems in liver disease pathology. In the current review, we delineate the connections of gut lymphatics with abdominal fluid homeostasis and bacterial translocation in the pathogenesis of liver cirrhosis and portal hypertension. We describe mechanisms and factors that drive gut lymphangiogenesis and lymphatic vessel dysfunction during inflammation. The review also underscores the role of gut lymphatic endothelial cells in regulating gut and liver immunity. We finally discuss the prognostic and therapeutic prospects of studying gut lymphatic vessels in advanced liver cirrhosis.

The purpose of the present study was to evaluate the effects of vascular endothelial growth factor (VEGF) on tumorigenic properties in two-dimensional (2D) and three-dimensional (3D) cultures of hepatoma cells. The proliferation and invasion of hepatoma cells was assessed using wound healing, chemotaxis Transwell, invasion, tube-forming and hanging drop assays in both 2D and 3D cultures. The expression levels of epithelial-mesenchymal transition (EMT) and stemness markers were analysed using reverse transcription-quantitative PCR (RT-qPCR) for mRNA expression and immunofluorescence assay for protein expression. To validate the role of VEGF in tumour growth, a VEGF receptor (VEGFR) inhibitor (sorafenib) was used. The results demonstrated that the hepatoma cells formed 3D spheroids that differed in size and density in the absence and presence of the growth factor, VEGF. In all spheroids, invasion and angiogenesis were more aggressive in 3D cultures in comparison to 2D conditions following treatment with VEGF. Mechanistically, the VEGF-mediated increase in the levels of EMT markers, including Vimentin, N-cadherin 2 (Cadherin 2) and Thy-1 Cell Surface Antigen was observed in the 2D and 3D cultures. Sorafenib treatment for 24 h culminated in a marked reduction in cell migration, cell-cell adhesion, spheroid compaction and EMT gene expression in 3D models as compared to the 2D models. On the whole, the findings of the present study suggested that as compared to the 2D cell cultures, 3D cell cultures model may be used as a more realistic model for the study of tumour growth and invasion in the presence of angiogenic factors, as well as for tumour inhibitor screening.

Background: Runt-related transcription factor (RUNX1) regulates inflammation in non-alcoholic steatohepatitis (NASH). Methods: We performed in vivo targeted silencing of the RUNX1 gene in liver sinusoidal endothelial cells (LSECs) by using vegfr3 antibody tagged immunonano-lipocarriers encapsulated RUNX1 siRNA (RUNX1 siRNA) in murine models of methionine choline deficient (MCD) diet-induced NASH. MCD mice given nanolipocarriers-encapsulated negative siRNA were vehicle, and mice with standard diet were controls. Results: Liver RUNX1 expression was increased in the LSECs of MCD mice in comparison to controls. RUNX1 protein expression was decreased by 40% in CD31-positive LSECs of RUNX1 siRNA mice in comparison to vehicle, resulting in the downregulation of adhesion molecules, ICAM1 expression, and VCAM1 expression in LSECs. There was a marked decrease in infiltrated T cells and myeloid cells along with reduced inflammatory cytokines in the liver of RUNX1 siRNA mice as compared to that observed in the vehicle. Conclusions: In vivo LSEC-specific silencing of RUNX1 using immunonano-lipocarriers encapsulated siRNA effectively reduces its expression of adhesion molecules, infiltrate on of immune cells in liver, and inflammation in NASH.

International audience; Modeling the microstructural evolution of metal and alloys, specifically under irradiation, is essential to predict the aging properties of materials. Many models are based on a transition rate matrix describing the jump frequencies of defects and involve a master equation governing the time evolution of a state probability vector. Here, we present non-stochastic numerical techniques to characterize the motion of individual defects migrating over long distances prior to recombining or being absorbed by another defect, resorting to the theory of absorbing Markov chains. These important events are fully determined by their first-passage time distribution to distant locations, no-passage distribution ,and walker fluxes to the sinks. We show that these functions can be efficiently computed using a method combining Krylov subspace projection and eigenvalue deflation. For a model system describing the absorption of a vacancy by a cavity in aluminum, the use of a small Krylov subspace deflated by the unique eigenmode corresponding to the quasi-stationary distribution is sufficient to capture the kinetics of the defect absorption faithfully. This method can be used in kinetic Monte Carlo simulations to perform stochastic non-local moves or in cluster dynamics simulations to compute sink strengths.

Background and AimLymphatic vessels (LVs) are crucial for maintaining abdominal fluid homeostasis and immunity. In liver cirrhosis, mesenteric LVs (mLVs) are dilated and dysfunctional. Given an established protective role of VEGF-C in LVs, we hypothesized that VEGF-C treatment could improve functions of mLVs in cirrhosis.MethodIn this study, we developed a nanoformulation comprising LV-specific growth-factor, recombinant human VEGF-C(Cys156Ser) protein(E-VEGF-C) and delivered it orally in rat models of liver cirrhosis to target mLVs. Nanoformulation without VEGF-C served as vehicle. Drainage of mLVs was analyzed using tracer dye. Portal and systemic physiological assessments and computed-tomography were performed to measure portal pressures and ascites. Gene expression of mesenteric lymphatic endothelial cells (LyECs) was studied. Immune cell subsets in mesenteric lymph nodes (MLNs) were quantified by flow-cytometry. Gut bacterial translocation to MLNs was examined using GFP-labelled bacteria.ResultsIn cirrhotic rats, mLVs were dilated and leaky with impaired drainage. Treatment with E-VEGF-C induced proliferation of VEGFR3+ mLVs, reduced their diameter and improved functional drainage. Ascites and portal pressures were significantly reduced in E-VEGF-C treated rats compared to vehicle. At molecular level, E-VEGF-C treatment upregulated the expression of cell adhesion and permeability genes (VCAM1, VE-Cad) in LyECs. In MLNs of E-VEGF-C rats, there was an increased percentage of CD8+CD134+ T-cells and decreased CD25+Treg-cells. Bacterial translocation was also limited to MLNs only in E-VEGF-C treated rats with reduced levels of endotoxins in ascites in comparison to vehicle.ConclusionE-VEGF-C treatment ameliorates mesenteric lymph drainage, portal pressure, and strengthens cytotoxic immune responses in MLNs in experimental cirrhosis. It may thus serve as a promising therapy to manage ascites and portal pressure and reduce gut bacterial translocation in patients with cirrhosis.Lay SummaryA human recombinant pro-lymphangiogenic growth factor, VEGF-C, was encapsulated in nanolipocarriers (E-VEGF-C) and orally delivered in rat models of decompensated liver cirrhosis to facilitate its gut lymphatic vessel uptake. E-VEGF-C administration significantly increased mesenteric lymphatic vessel proliferation and improved lymph drainage, attenuating abdominal ascites and portal pressures in the animal models. E-VEGF-C treatment limits bacterial translocation to MLNs only with reduced gut bacterial load and ascitic endotoxins. E-VEGF-C therapy holds the potential to manage ascites and portal pressure and reduce gut bacterial translocation in patients with decompensated cirrhosis.Graphical Abstract

Importance Data on the efficacy of hydroxychloroquine for the treatment of coronavirus disease 2019 (COVID-19) are needed. Objective To determine whether hydroxychloroquine is an efficacious treatment for adults hospitalized with COVID-19. Design, Setting, and Participants This was a multicenter, blinded, placebo-controlled randomized trial conducted at 34 hospitals in the US. Adults hospitalized with respiratory symptoms from severe acute respiratory syndrome coronavirus 2 infection were enrolled between April 2 and June 19, 2020, with the last outcome assessment on July 17, 2020. The planned sample size was 510 patients, with interim analyses planned after every 102 patients were enrolled. The trial was stopped at the fourth interim analysis for futility with a sample size of 479 patients. Interventions Patients were randomly assigned to hydroxychloroquine (400 mg twice daily for 2 doses, then 200 mg twice daily for 8 doses) (n = 242) or placebo (n = 237). Main Outcomes and Measures The primary outcome was clinical status 14 days after randomization as assessed with a 7-category ordinal scale ranging from 1 (death) to 7 (discharged from the hospital and able to perform normal activities). The primary outcome was analyzed with a multivariable proportional odds model, with an adjusted odds ratio (aOR) greater than 1.0 indicating more favorable outcomes with hydroxychloroquine than placebo. The trial included 12 secondary outcomes, including 28-day mortality. Results Among 479 patients who were randomized (median age, 57 years; 44.3% female; 37.2% Hispanic/Latinx; 23.4% Black; 20.1% in the intensive care unit; 46.8% receiving supplemental oxygen without positive pressure; 11.5% receiving noninvasive ventilation or nasal high-flow oxygen; and 6.7% receiving invasive mechanical ventilation or extracorporeal membrane oxygenation), 433 (90.4%) completed the primary outcome assessment at 14 days and the remainder had clinical status imputed. The median duration of symptoms prior to randomization was 5 days (interquartile range [IQR], 3 to 7 days). Clinical status on the ordinal outcome scale at 14 days did not significantly differ between the hydroxychloroquine and placebo groups (median [IQR] score, 6 [4-7] vs 6 [4-7]; aOR, 1.02 [95% CI, 0.73 to 1.42]). None of the 12 secondary outcomes were significantly different between groups. At 28 days after randomization, 25 of 241 patients (10.4%) in the hydroxychloroquine group and 25 of 236 (10.6%) in the placebo group had died (absolute difference, −0.2% [95% CI, −5.7% to 5.3%]; aOR, 1.07 [95% CI, 0.54 to 2.09]). Conclusions and Relevance Among adults hospitalized with respiratory illness from COVID-19, treatment with hydroxychloroquine, compared with placebo, did not significantly improve clinical status at day 14. These findings do not support the use of hydroxychloroquine for treatment of COVID-19 among hospitalized adults. Trial Registration ClinicalTrials.gov:NCT04332991

Ionizing Radiation (IR), especially at high doses, induces cellular senescence in exposed cultures. IR also induces &ldquo, bystander effects&rdquo, through signals released from irradiated cells, and these effects include many of the same outcomes observed following direct exposure. Here, we investigate if radiation can cause senescence through a bystander mechanism. Control cultures were exposed directly to 0, 0.1, 2, and 10 Gy. Unirradiated cells were treated with medium from irradiated cultures or with exosomes extracted from irradiated medium. The level of senescence was determined post-treatment (24 h, 15 days, 30 days, and 45 days) by &beta, galactosidase staining. Media from cultures exposed to all four doses, and exosomes from these cultures, induced significant senescence in recipient cultures. Senescence levels were initially low at the earliest timepoint, and peaked at 15 days, and then decreased with further passaging. These results demonstrate that senescence is inducible through a bystander mechanism. As with other bystander effects, bystander senescence was induced by a low radiation dose. However, unlike other bystander effects, cultures recovered from bystander senescence after repeated passaging. Bystander senescence may be a potentially significant effect of exposure to IR, and may have both beneficial and harmful effects in the context of radiotherapy.

A micron scale alginate based 3D platform embedded with a carbon dot pH sensor, that enables continuous growth monitoring of encapsulated cells in real time is reported. The alginate based 3D micro-scaffold closely mimics a tumor microenvironment by providing a spatial demarcation and making it possible to encapsulate different cells in close proximity. The micro-scaffold contains carbon dot based nanosensors that enable real time monitoring of pH change in the tumor microenvironment avoiding the need for end-point assays for studying cellular growth. The micro-scaffolds have heterogeneous architecture and a hypoxic core region can be observed in as less as 96 h of culture. In this completely synthetic platform, there also exist the flexibility of artificially modifying the porosity of the micro-scaffold as per the requirement of the studies where a denser ECM mimic is required. The micro-scaffolds were conducive for cell growth as suggested by the enhanced functional profile of hepatocellular carcinoma cells and positively influence the genetic expression of the cell specific markers. Additionally, similar to a 3D tumor, non-homogeneous diffusion of molecules is also observed making this an ideal platform for cancer modelling and drug screening.

In the present study, we investigated the relationship between an important 27 bp repeat polymorphism in intron 4 of eNOS and numbers of circulating EPCs in presence of cardiovascular disease (CVD) risk factors in a group of healthy human volunteers. The study comprised of 45 healthy subjects (30–50 years). These subjects had various degrees of CVD risk but no history of CVD. The repeat polymorphism of eNOS was detected by polymerase chain reaction and EPC levels were analyzed by flow cytometry. We observed a good association between the intronic 4 mutant a/b genotype and the combined Framingham risk factor score in our subjects (χ(2) = 3.2, P = 0.07). EPC numbers in subjects with mutant eNOS a/b genotype were also less than those observed in subjects with normal eNOS b/b genotype (P = 0.06). Interestingly, subjects with eNOS a/b genotype showed a significant inverse correlation between framingham risk score and EPC numbers (R = −0.57, P

Given the important role of angiogenesis in liver pathology, the current study investigated the role of Runt-related transcription factor 1 (RUNX1), a regulator of developmental angiogenesis, in the pathogenesis of non-alcoholic steatohepatitis (NASH). Quantitative RT-PCRs and a transcription factor analysis of angiogenesis-associated differentially expressed genes in liver tissues of healthy controls, patients with steatosis and NASH, indicated a potential role of RUNX1 in NASH. The gene expression of RUNX1 was correlated with histopathological attributes of patients. The protein expression of RUNX1 in liver was studied by immunohistochemistry. To explore the underlying mechanisms, in vitro studies using RUNX1 siRNA and overexpression plasmids were performed in endothelial cells (ECs). RUNX1 expression was significantly correlated with inflammation, fibrosis and NASH activity score in NASH patients. Its expression was conspicuous in liver non-parenchymal cells. In vitro, factors from steatotic hepatocytes and/or VEGF or TGF-β significantly induced the expression of RUNX1 in ECs. RUNX1 regulated the expression of angiogenic and adhesion molecules in ECs, including CCL2, PECAM1 and VCAM1, which was shown by silencing or over-expression of RUNX1. Furthermore, RUNX1 increased the angiogenic activity of ECs. This study reports that steatosis-induced RUNX1 augmented the expression of adhesion and angiogenic molecules and properties in ECs and may be involved in enhancing inflammation and disease severity in NASH.

Objective:To determine the costs associated with delirium in critically ill children.Design:Prospective observational study.Setting:An urban, academic, tertiary-care PICU in New York city.Patients:Four-hundred and sixty-four consecutive PICU admissions between September 2, 2014, and December 12, 201