Therapeutic efficacy of Strobilanthes urticifolia-infused pectin/polyacrylic acid hydrogel for targeted hepatorenal fibrosis mitigation: A multifaceted biomaterial approach.

Pectin/polyacrylic acid (PPAA) hydrogel is a unique and versatile biomaterial with applications in drug delivery, wound healing, tissue engineering, and agriculture, owing to its tailored properties and multifunctional attributes. This study aims to harness the therapeutic potential of Strobilanthes urticifolia extract within a PPAA hydrogel matrix to attenuate liver and kidney fibrosis through targeted and sustained delivery of biologically active substances. PPAA hydrogel was prepared by free radical polymerization, followed by its porosity and swelling determination. The results depicted the porous nature of PPAA hydrogel and improved swelling properties at pH 7.4, confirming its drug delivery promise. The polyphenolic-enriched S. urticifolia extracts of leaf and flower were loaded onto PPAA hydrogel, and the loading efficiency was 87% (leaf) and 62.5% (flower). Moreover, slow-release studies showed controlled and prolonged release of polyphenols for 7 days. The polyphenolic-enriched hydrogel's microstructure was characterized using SEM, FTIR, and thermogravimetric analysis (TGA). SEM results revealed a highly porous structure of polyphenol enriched PPAA hydrogel, while FTIR analysis confirmed the presence of functional groups such as OH group of carboxylic acid, aliphatic CH2 stretching due to acrylic acid grafting with pectin, CO stretching due to acid linkage with pectin, CH of aromatic ring, and CH of carboxylate salt in PPAA hydrogel. TGA of PPAA hydrogel showed its stability up to 488°C. Additionally, the S. urticifolia extract loaded PPAA hydrogel displayed significant antibacterial properties and minimum inhibitory concentrations against both Gram-positive and Gram-negative bacteria. In vivo studies carried out on rats demonstrated that polyphenolic enriched PPAA hydrogel significantly attenuates liver and kidney fibrosis. Therefore, it is concluded from the present study that loading of polyphenolic enriched extract from leaves and flower of S. urticifolia enhanced the biomedical applications of PPAA hydrogel. RESEARCH HIGHLIGHTS: The PPAA hydrogel developed in this study exhibits a highly porous structure and improved swelling properties at physiological pH (7.4), making it an excellent candidate for drug delivery systems. S. urticifolia extracts, rich in polyphenols, were successfully incorporated into the PPAA hydrogel with high loading efficiencies of 87% for leaf and 62.5% for flower extracts. Loading of polyphenolic enriched extracts of S. urticifolia onto PPAA enhanced its biological activities such as antibacterial, hepatoprotective, and reno-protective activities as depicted by in vitro and in vivo studies.

The Global, Regional, and National Burden of Adult Lip, Oral, and Pharyngeal Cancer in 204 Countries and Territories: A Systematic Analysis for the Global Burden of Disease Study 2019.

Importance: Lip, oral, and pharyngeal cancers are important contributors to cancer burden worldwide, and a comprehensive evaluation of their burden globally, regionally, and nationally is crucial for effective policy planning. Objective: To analyze the total and risk-attributable burden of lip and oral cavity cancer (LOC) and other pharyngeal cancer (OPC) for 204 countries and territories and by Socio-demographic Index (SDI) using 2019 Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study estimates. Evidence Review: The incidence, mortality, and disability-adjusted life years (DALYs) due to LOC and OPC from 1990 to 2019 were estimated using GBD 2019 methods. The GBD 2019 comparative risk assessment framework was used to estimate the proportion of deaths and DALYs for LOC and OPC attributable to smoking, tobacco, and alcohol consumption in 2019. Findings: In 2019, 370 000 (95% uncertainty interval [UI], 338 000-401 000) cases and 199 000 (95% UI, 181 000-217 000) deaths for LOC and 167 000 (95% UI, 153 000-180 000) cases and 114 000 (95% UI, 103 000-126 000) deaths for OPC were estimated to occur globally, contributing 5.5 million (95% UI, 5.0-6.0 million) and 3.2 million (95% UI, 2.9-3.6 million) DALYs, respectively. From 1990 to 2019, low-middle and low SDI regions consistently showed the highest age-standardized mortality rates due to LOC and OPC, while the high SDI strata exhibited age-standardized incidence rates decreasing for LOC and increasing for OPC. Globally in 2019, smoking had the greatest contribution to risk-attributable OPC deaths for both sexes (55.8% [95% UI, 49.2%-62.0%] of all OPC deaths in male individuals and 17.4% [95% UI, 13.8%-21.2%] of all OPC deaths in female individuals). Smoking and alcohol both contributed to substantial LOC deaths globally among male individuals (42.3% [95% UI, 35.2%-48.6%] and 40.2% [95% UI, 33.3%-46.8%] of all risk-attributable cancer deaths, respectively), while chewing tobacco contributed to the greatest attributable LOC deaths among female individuals (27.6% [95% UI, 21.5%-33.8%]), driven by high risk-attributable burden in South and Southeast Asia. Conclusions and Relevance: In this systematic analysis, disparities in LOC and OPC burden existed across the SDI spectrum, and a considerable percentage of burden was attributable to tobacco and alcohol use. These estimates can contribute to an understanding of the distribution and disparities in LOC and OPC burden globally and support cancer control planning efforts.

The Role of p90 Ribosomal S6 Kinase (RSK) in Tyrosine Kinase Inhibitor (TKI)-Induced Cardiotoxicity.

Targeted therapy, such as tyrosine kinase inhibitors (TKIs), has been approved to manage various cancer types. However, TKI-induced cardiotoxicity is a limiting factor for their use. This issue has raised the need for investigating potential cardioprotective techniques to be combined with TKIs. Ribosomal S6-kinases (RSKs) are a downstream effector of the mitogen-activated-protein-kinase (MAPK) pathway; specific RSK isoforms, such as RSK1 and RSK2, have been expressed in cancer cells, in which they increase tumour proliferation. Selective targeting of those isoforms would result in tumour suppression. Moreover, activation of RSKs expressed in the heart has resulted in cardiac hypertrophy and arrhythmia; thus, inhibiting RSKs would result in cardio-protection. This review article presents an overview of the usefulness of RSK inhibitors that can be novel agents to be assessed in future research for their effect in reducing cancer proliferation, as well as protecting the heart from cardiotoxicity induced by TKIs.

Outcomes of Patients with Gastrointestinal Stromal Tumors in the Past Decade.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms of the gastrointestinal tract (GIT) that represent approximately 1 to 2 percent of primary gastrointestinal (GI) cancers. Owing to their rarity, very little is known about their overall epidemiology, and the prognostic factors of their pathology. The current study aimed to evaluate the independent determinants of mortality in patients diagnosed with GISTs over the past decade. METHODS: Our study comprised 2374 patients diagnosed with GISTs from 2000 to 2017 from the Surveillance, Epidemiology, and End Results (SEER) database. We analyzed the baseline characteristics, and overall mortality (OM), as well as the cancer-specific mortality (CSM) of GISTs. Variables with a p value < 0.01 in the univariate Cox regression were incorporated into the multivariate Cox model, to determine the independent prognostic factors. RESULTS: Multivariate Cox proportional hazard regression analyses of factors affecting the all-cause mortality and GIST-related mortality among US patients between 2010 and 2017 revealed a higher overall mortality in non-Hispanic Black patients (HR = 1.516, 95% CI 1.172-1.961, p = 0.002), patients aged 80+ (HR = 9.783, 95% CI 4.185-22.868, p = 0), followed by those aged 60-79 (HR = 3.408, 95% CI 1.488-7.807, p = 0.004); male patients (HR = 1.795, 95% CI 1.461-2.206, p < 0.001); patients with advanced disease with distant metastasis (HR = 3.865, 95% CI 2.977-5.019, p < 0.001), followed by cases with regional involvement via both direct extension and lymph node involvement (HR = 3.853, 95% CI 1.551-9.57, p = 0.004); and widowed patients (HR = 1.975, 95% CI 1.494-2.61, p < 0.001), followed by single patients (HR = 1.53, 95% CI 1.154-2.028, p = 0.003). The highest CSM was observed in the same groups, except widowed patients and patients aged 60-79. The highest CSM was also observed among patients that underwent chemotherapy (HR = 1.687, 95% CI 1.19-2.392, p = 0.003). CONCLUSION: In this updated study on the outcomes of patients with GISTs, we found that non-Hispanic Black patients, male patients, and patients older than 60 years have a higher mortality with GISTs. Furthermore, patients who have received chemotherapy have a higher GIST-specific mortality, and married patients have a lower mortality. However, we do not know to what extent these independent prognostic factors interact with each other to influence mortality. This study paves the way for future studies addressing these interactions. The results of this study may help treating clinicians to identify patient populations associated with a dismal prognosis, as those may require closer follow-up and more intensive therapy; furthermore, with married patients having a better survival rate, we hope to encourage clinicians to involve family members of the affected patients early in the disease course, as the social support might impact the prognosis.

Bisphenol A is a carcinogen that induces lipid accumulation, peroxisome proliferator­activated receptor­Î³ expression and liver disease.

Bisphenol (BP) A is an exogenous endocrine disruptor that mimics hormones closely associated with health complications, e.g., obesity and cancers. The present study aimed to evaluate the effects of BPA on human liver cells and tissue. The peroxisome proliferator-activated receptor (PPAR)-γ expression profile across tumour samples and paired normal tissue was first analysed using GEPIA. Subsequently, BPA-treated liver THLE-2 cell viability was evaluated using an MTT assay. Clusterin, PPARα and PPARγ gene expression in BPA-treated THLE-2 cells was assessed using GEPIA before validating the gene expression using real-time PCR and analysing overall survival using TCGA data in GEPIA. Cytoplasmic lipid accumulation was examined in BPA-treated THLE-2 cells using Oil Red O staining, and liver tissue was examined using haematoxylin and eosin staining. Finally, cytochrome P450 (CYP) gene expression was assessed in BPA-treated THLE-2 cells using real-time PCR. PPARγ is likely the primary nuclear receptor protein involved in lipid accumulation in THLE-2 cells following BPA treatment and is associated with liver disease. THLE-2 cells exposed to BPA showed a decrease in viability and lipid accumulation after 48 h treatment. Higher PPARγ gene expression was significantly associated with survival of patients with liver cancer, with an average survival time of <80 months. Haematoxylin and eosin-stained sections showed notable disruption of the liver architecture in tissue exposed to BPA. Downregulated CYP1A1 and CYP1B1 gene expression implied that BPA-treated THLE-2 cells decreased capacity for carcinogen metabolism, while upregulated CYP2S1 gene expression exerted minimal cytotoxicity. The present study revealed that BPA served as a carcinogen, enhanced tumorigenesis susceptibility and may induce other types of liver disease.

Adverse Effects of Bisphenol A on the Liver and Its Underlying Mechanisms: Evidence from In Vivo and In Vitro Studies.

BPA is a known endocrine-disrupting agent that is capable of binding to the estrogen receptor and has exhibited adverse effects in many laboratory animal and in vitro studies. Moreover, it also been shown to have estrogenic, antiandrogenic, inflammatory, and oxidative properties. The widespread presence of BPA in the environment presents a considerable threat to humans. BPA has been shown to be leached into the human ecosystem, where it is commonly found in food products consumed by humans. Although the concentration is relatively low, its prolonged consumption may cause a variety of deleterious health effects. The liver is an important organ for metabolizing and detoxifying toxic metabolites to protect organisms from potentially toxic chemical insults. BPA that is ingested will be eliminated by the liver. However, it has also induced hepatoxicity and injury via various mechanisms. To find research demonstrating the effects of BPA on kidney, a number of databases, including Google Scholar, MEDLINE, PubMed, and the Directory of Open Access Journals, were searched. Thus, this review summarizes the research on the relationship between BPA and its effects on the liver-derived from animals and cellular studies. The underlying mechanism of liver injury caused by BPA is also elucidated.

Single-Cell RNA Sequencing with Spatial Transcriptomics of Cancer Tissues.

Single-cell RNA sequencing (RNA-seq) techniques can perform analysis of transcriptome at the single-cell level and possess an unprecedented potential for exploring signatures involved in tumor development and progression. These techniques can perform sequence analysis of transcripts with a better resolution that could increase understanding of the cellular diversity found in the tumor microenvironment and how the cells interact with each other in complex heterogeneous cancerous tissues. Identifying the changes occurring in the genome and transcriptome in the spatial context is considered to increase knowledge of molecular factors fueling cancers. It may help develop better monitoring strategies and innovative approaches for cancer treatment. Recently, there has been a growing trend in the integration of RNA-seq techniques with contemporary omics technologies to study the tumor microenvironment. There has been a realization that this area of research has a huge scope of application in translational research. This review article presents an overview of various types of single-cell RNA-seq techniques used currently for analysis of cancer tissues, their pros and cons in bulk profiling of transcriptome, and recent advances in the techniques in exploring heterogeneity of various types of cancer tissues. Furthermore, we have highlighted the integration of single-cell RNA-seq techniques with other omics technologies for analysis of transcriptome in their spatial context, which is considered to revolutionize the understanding of tumor microenvironment.

Selective Extraction of Trace Arsenite Ions Using a Highly Porous Aluminum Oxide Membrane with Ordered Nanopores.

Metal ion extraction and determination at trace level concentration are challenging due to sample complexity or spectral interferences. Herein, we prepared a through-hole aluminum oxide membrane (AOM) by electrochemical anodization of aluminum substrates. The prepared AOM was characterized by scanning electron microscopy, surface area analysis, porosity measurements, and X-ray photoelectron spectroscopy. The AOM with ordered nanopores was highly porous and possess inherent binding sites for selective arsenite sorption. The AOM was used as a novel sorbent for solid-phase microextraction and preconcentration of arsenite ions in water samples. The AOM's sub-micrometer thickness allows water molecules to flow freely across the pores. Before instrumental determination, the suggested microextraction approach removes spectral interferents and improves the analyte ion concentration, with a detection limit of 0.02 µg L-1. Analyzing a standard reference material was used to validate the procedure. Student's t-test value was less than critical Student's t-value of 4.303 at a 95% confidence level. With coefficients of variation of 3.25%, good precision was achieved.

Spatial mapping of cancer tissues by OMICS technologies.

Spatial mapping of heterogeneity in gene expression in cancer tissues can improve our understanding of cancers and help in the rapid detection of cancers with high accuracy and reliability. Significant advancements have been made in recent years in OMICS technologies, which possess the strong potential to be applied in the spatial mapping of biopsy tissue samples and their molecular profiling to a single-cell level. The clinical application of OMICS technologies in spatial profiling of cancer tissues is also advancing. The current review presents recent advancements and prospects of applying OMICS technologies to the spatial mapping of various analytes in cancer tissues. We benchmark the current state of the art in the field to advance existing OMICS technologies for high throughput spatial profiling. The factors taken into consideration include spatial resolution, types of biomolecules, number of different biomolecules that can be detected from the same assay, labeled versus label-free approaches, and approximate time required for each assay. Further advancements are still needed for the widespread application of OMICs technologies in performing fast and high throughput spatial mapping of cancer tissues as well as their effective use in research and clinical applications.

Bariatric surgery during COVID-19 in the UK: a British Obesity and Metabolic Surgery Society (BOMSS) survey.

BACKGROUND: After the declaration of COVID-19 as a pandemic last March 2020, several adjustments in surgical services were implemented. Plans are now being formulated for restarting bariatric surgery. The aim of this survey is to capture the practice during the pandemic and the readiness to restart to provide a framework to deal with the backlog of bariatric cases. METHOD: A survey was delivered to consultant surgeon members of the British Obesity and Metabolic Surgery Society and non-bariatric surgery consultant members of the Association of Upper GI Surgeons. RESULTS: The survey elicited a response rate of 40% (n = 66) among bariatric surgeons and 15.5% (n = 34) between non-bariatric surgeons. The average question response rate was 93% (88-100%). Most of the elective bariatric surgeries and clinics were cancelled early after declaration of the pandemic. Remote technologies for patient education evolved and were used heavily during the pandemic. The average cancelled elective bariatric surgery operations per week was 9. Nearly a quarter of responders reported performing emergency bariatric surgery during the pandemic. Most of the bariatric surgeons reported being ready to restart the service within 1-2 months. Responders recommended using private sector beds to increase NHS capacity and using the link between obesity and poor COVID-19 outcomes to push for prioritisation of bariatric patients. CONCLUSION: This survey is an attempt to understand the impact of COVID-19 on UK bariatric service and the preparedness to restart. It expressed the bariatric surgery consultants' view of prioritisation of bariatric patients on clinical basis rather than the first-come-first-served basis.

Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life Years for 29 Cancer Groups From 2010 to 2019: A Systematic Analysis for the Global Burden of Disease Study 2019.

IMPORTANCE: The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden. OBJECTIVE: To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019. EVIDENCE REVIEW: The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs). FINDINGS: In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3% (95% UI, 20.3%-32.3%) increase in new cases, a 20.9% (95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4% (1.1%-1.8%) in the low SDI quintile to 5.7% (4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and DALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles. CONCLUSIONS AND RELEVANCE: The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world.

Cancer Mortality and Research Outcomes in a Rural State.

BACKGROUND: North Dakota is a rural state with high rates of cancer. Determining how various demographic, geographic, and funding factors contributed to cancer incidence on a state and county level helps improve cancer prevention and control. OBJECTIVES: We examined cancer incidence rate trends by demographic (sex and ethnicity) and geographic (county, population, rural/frontier status) factors. We also examined cancer funding and research output by year. METHODS: Cancer incidence rates were obtained from the North Dakota Cancer Registry and stratified by sex, ethnicity, and county. US cancer rates also were obtained for comparison. Generalized linear models were used to compare overall incidence rates and yearly trends. RESULTS: Male melanoma incidence rates increased faster than the US average across year P = 0.020). Incidence rates for prostate, lung, and colorectal cancer among American Indians/Alaska Natives (AI/AN) decreased faster than Whites across year (P < 0.001, P= 0.001, P < 0.001, respectively). Four counties-2 for breast cancer and 2 for prostate cancer-had differential trends compared to the North Dakota average across year (P = 0.011, P = 0.029; P= 0.046, P = 0.042). County-level lung cancer incidence rates were positively correlated with county population size, while rates for cervix/uteri were negatively correlated (P = 0.001, P = 0.023). Funding from the National Institutes of Health for North Dakota increased across year along with cancer papers published increased (P < 0.001, P < 0.001). CONCLUSIONS: Examining state and county data revealed several surprising trends and the need for a more fine-scale approach to cancer cause, control, and prevention.

Imaging cancer cells with nanostructures: Prospects of nanotechnology driven non-invasive cancer diagnosis.

The application of nanostructured materials in medicine is a rapidly evolving area of research that includes both the diagnosis and treatment of various diseases. Metals, metal oxides and carbon-based nanomaterials have shown much promise in medical technological advancements due to their tunable physical, chemical and biological properties. The nanoscale properties, especially the size, shape, surface chemistry and stability makes them highly desirable for diagnosing and treating various diseases, including cancers. Major applications of nanomaterials in cancer diagnosis include in vivo bioimaging and molecular marker detection, mainly as image contrast agents using modalities such as radio, magnetic resonance, and ultrasound imaging. When a suitable targeting ligand is attached on the nanomaterial surface, it can help pinpoint the disease site during imaging. The application of nanostructured materials in cancer diagnosis can help in the early detection, treatment and patient follow-up . This review aims to gather and present the information regarding the application of nanotechnology in cancer diagnosis. We also discuss the challenges and prospects regarding the application of nanomaterials as cancer diagnostic tools.

Development of nitric oxide releasing visible light crosslinked gelatin methacrylate hydrogel for rapid closure of diabetic wounds.

Management of non-healing and slow to heal diabetic wounds is a major concern in healthcare across the world. Numerous techniques have been investigated to solve the issue of delayed wound healing, though, mostly unable to promote complete healing of diabetic wounds due to the lack of proper cell proliferation, poor cell-cell communication, and higher chances of wound infections. These challenges can be minimized by using hydrogel based wound healing patches loaded with bioactive agents. Gelatin methacrylate (GelMA) has been proven to be a highly cell friendly, cell adhesive, and inexpensive biopolymer for various tissue engineering and wound healing applications. In this study, S-Nitroso-N-acetylpenicillamine (SNAP), a nitric oxide (NO) donor, was incorporated in a highly porous GelMA hydrogel patch to improve cell proliferation, facilitate rapid cell migration, and enhance diabetic wound healing. We adopted a visible light crosslinking method to fabricate this highly porous biodegradable but relatively stable patch. Developed patches were characterized for morphology, NO release, cell proliferation and migration, and diabetic wound healing in a rat model. The obtained results indicate that SNAP loaded visible light crosslinked GelMA hydrogel patches can be highly effective in promoting diabetic wound healing.

Stem cells based in vitro models: trends and prospects in biomaterials cytotoxicity studies.

Advanced biomaterials are increasingly used for numerous medical applications from the delivery of cancer-targeted therapeutics to the treatment of cardiovascular diseases. The issues of foreign body reactions induced by biomaterials must be controlled for preventing treatment failure. Therefore, it is important to assess the biocompatibility and cytotoxicity of biomaterials on cell culture systems before proceeding to in vivo studies in animal models and subsequent clinical trials. Direct use of biomaterials on animals create technical challenges and ethical issues and therefore, the use of non-animal models such as stem cell cultures could be useful for determination of their safety. However, failure to recapitulate the complex in vivo microenvironment have largely restricted stem cell cultures for testing the cytotoxicity of biomaterials. Nevertheless, properties of stem cells such as their self-renewal and ability to differentiate into various cell lineages make them an ideal candidate for in vitro screening studies. Furthermore, the application of stem cells in biomaterials screening studies may overcome the challenges associated with the inability to develop a complex heterogeneous tissue using primary cells. Currently, embryonic stem cells, adult stem cells, and induced pluripotent stem cells are being used as in vitro preliminary biomaterials testing models with demonstrated advantages over mature primary cell or cell line based in vitro models. This review discusses the status and future directions of in vitro stem cell-based cultures and their derivatives such as spheroids and organoids for the screening of their safety before their application to animal models and human in translational research.

Ultrasound-Guided Out-of-Plane Versus In-Plane Radial Artery Cannulation in Adult Cardiac Surgical Patients.

OBJECTIVES: The primary objective was to compare the rate of first-pass radial arterial cannulation using out-of-plane ultrasound guidance with in-plane imaging. The secondary endpoints were a comparison of the number of times the cannula was redirected, the number of attempts, the number of skin punctures, the incidence of hematoma, the time to completion of the cannulation procedure, and the number of failed attempts between the 2 ultrasound imaging techniques. DESIGN: A prospective, randomized, observational study. SETTING: A tertiary cardiac care center. PARTICIPANTS: Adult patients undergoing elective cardiac surgery. INTERVENTIONS: Radial artery cannulation with ultrasound guidance. MEASUREMENTS AND MAIN RESULTS: Eighty-four adult patients scheduled for elective cardiac surgery were randomly assigned to the out-of-plane ultrasound group (group I, n = 42) or the in-plane ultrasound group (group II, n = 42) for left radial artery cannulation. A linear ultrasound probe was used to identify the radial artery. In each approach, the number of times first-pass success was achieved, the number of times the cannula was redirected, the number of skin punctures, the incidence of hematomas, and the number of failed attempts were recorded. The first-pass success rate was greater in the in-plane ultrasound group and was statistically significant (p = 0.007). In the out-of-plane ultrasound group, a larger number of patients needed redirection of the cannula (p = 0.002). The number of patients in whom the skin needed to be punctured more than once was greater in the out-of-plane ultrasound group compared with the in-plane ultrasound group (p = 0.002). The incidence of hematoma formation and time to completion of the technique were similar in both groups (p = 0.241 and p = 0.792, respectively). CONCLUSIONS: In-plane ultrasound guidance appeared to be superior for achieving a higher first-pass success rate more often with minimal redirections and skin punctures compared with out-of-plane ultrasound guidance.

Bone marrow mesenchymal stem cells preconditioned with nitric-oxide-releasing chitosan/PVA hydrogel accelerate diabetic wound healing in rabbits.

Impaired diabetic wounds are one of the major pathophysiological complications caused by persistent microbial infections, prolonged inflammation, and insufficient angiogenic responses. Here, we report the development of nitric-oxide (NO) -releasing S-nitroso-N-acetyl-penicillamine (SNAP) -loaded chitosan/polyvinyl-alcohol hydrogel and its efficacy in enhancing the wound-healing potential of bone marrow mesenchymal stem cells in diabetic wounds. NO-releasing hydrogels significantly increased the cell viability and cell proliferation of hydrogen-peroxide (H2O2) -pretreated bone marrow stem cells (BMSCs), demonstrating their cytoprotective activity, which was further confirmed by gene expression of many times as much B-cell lymphoma 2 (Bcl-2), stromal cell-derived factor-1alpha (SDF-1α), proliferating cell nuclear antigen (PCNA) and vascular endothelial growth factor (VEGF). Furthermore, the SNAP-loaded hydrogel showed continuous cell-proliferating activity for six days, due to the slow release of NO from the hydrogel. Wound-healing studies of rabbits with induced diabetes showed that the application of SNAP-preconditioned BMSCs and NO-releasing hydrogels significantly sped up the healing process, compared to the control group. The wound-healing potential of BMSCs plus NO-releasing hydrogel was further validated by improved collagen deposition and epithelial layer formation, as confirmed by histopathological examination, as well as upregulation of VEGF and SDF-1α biomarkers, as evidenced by gene-expression analysis. These results demonstrated that the application of BMSCs with NO-releasing hydrogel can promote faster regeneration of damaged tissues. Therefore, BMSCs plus NO-releasing hydrogels can be very useful for the treatment of diabetic wounds.

The Effect of Standard Versus Longer Intestinal Bypass on GLP-1 Regulation and Glucose Metabolism in Patients With Type 2 Diabetes Undergoing Roux-en-Y Gastric Bypass: The Long-Limb Study.

OBJECTIVE: Roux-en-Y gastric bypass (RYGB) characteristically enhances postprandial levels of glucagon-like peptide 1 (GLP-1), a mechanism that contributes to its profound glucose-lowering effects. This enhancement is thought to be triggered by bypass of food to the distal small intestine with higher densities of neuroendocrine L-cells. We hypothesized that if this is the predominant mechanism behind the enhanced secretion of GLP-1, a longer intestinal bypass would potentiate the postprandial peak in GLP-1, translating into higher insulin secretion and, thus, additional improvements in glucose tolerance. To investigate this, we conducted a mechanistic study comparing two variants of RYGB that differ in the length of intestinal bypass. RESEARCH DESIGN AND METHODS: A total of 53 patients with type 2 diabetes (T2D) and obesity were randomized to either standard limb RYGB (50-cm biliopancreatic limb) or long limb RYGB (150-cm biliopancreatic limb). They underwent measurements of GLP-1 and insulin secretion following a mixed meal and insulin sensitivity using euglycemic hyperinsulinemic clamps at baseline and 2 weeks and at 20% weight loss after surgery. RESULTS: Both groups exhibited enhancement in postprandial GLP-1 secretion and improvements in glycemia compared with baseline. There were no significant differences in postprandial peak concentrations of GLP-1, time to peak, insulin secretion, and insulin sensitivity. CONCLUSIONS: The findings of this study demonstrate that lengthening of the intestinal bypass in RYGB does not affect GLP-1 secretion. Thus, the characteristic enhancement of GLP-1 response after RYGB might not depend on delivery of nutrients to more distal intestinal segments.

A High-Performing Plasma Metabolite Panel for Early-Stage Lung Cancer Detection.

The objective of this research is to use metabolomic techniques to discover and validate plasma metabolite biomarkers for the diagnosis of early-stage non-small cell lung cancer (NSCLC). The study included plasma samples from 156 patients with biopsy-confirmed NSCLC along with age and gender-matched plasma samples from 60 healthy controls. A fully quantitative targeted mass spectrometry (MS) analysis (targeting 138 metabolites) was performed on all samples. The sample set was split into a discovery set and validation set. Metabolite concentration data, clinical data, and smoking history were used to determine optimal sets of biomarkers and optimal regression models for identifying different stages of NSCLC using the discovery sets. The same biomarkers and regression models were used and assessed on the validation models. Univariate and multivariate statistical analysis identified ß-hydroxybutyric acid, LysoPC 20:3, PC ae C40:6, citric acid, and fumaric acid as being significantly different between healthy controls and stage I/II NSCLC. Robust predictive models with areas under the curve (AUC) > 0.9 were developed and validated using these metabolites and other, easily measured clinical data for detecting different stages of NSCLC. This study successfully identified and validated a simple, high-performing, metabolite-based test for detecting early stage (I/II) NSCLC patients in plasma. While promising, further validation on larger and more diverse cohorts is still required.