Alcoholic Hepatitis and TNF-α Antagonists: The Rise and Fall

Alcoholic liver disease (ALD) is the most prevalent cause of advanced liver disease. The disease spectrum ranges from mild steatohepatitis to progressive fibrosis and finally hepatocellular carcinoma. In 2015 in the United States liver cirrhosis was the 12th leading cause of death. The crude death rate from alcohol-related cirrhosis was 6.6 deaths per 100,000 population. Keywords: Alcoholic Hepatitis (AH); TNF-α Antagonists Inflammatory cytokines have an important role in the pathogenesis of ALD and drugs targeting inflammatory cytokines like tumor necrosis factor alpha (TNF-α) have been used. Corticosteroid treatment in Alcoholic Hepatitis have been argued for and against many times over the last few decades. Corticosteroids treatment for severe AH as a reference treatment has been established in the last two decades after multiple metanalyses of randomized controlled trials concluded that corticosteroids improved the short-term survival of patients with severe Alcoholic Hepatitis (AH). Experimental and clinical evidence indicates that TNF-α and its downstream inflammatory cytokines correlate with disease severity and may contribute to the pathogenesis and clinical sequelae of alcoholic hepatitis thereby implicating a possible role for inhibition of TNF-α in the treatment of alcoholic hepatitis. In the early 21st century, an initial pilot study demonstrated the ability of TNF-α Antagonists to augment the treatment of steroid. However further studies have shown TNF-α to not be helpful in Moderate or Severe AH. Newer therapeutic strategies including Pentoxifylline to improve outcomes are being developed and trialed in the population

Mesoporous materials for dental and biotechnological applications, curcumin polymers and enzymatic saccharification of biomass

The nonsurfactant templated sol–gel route has been demonstrated to be a cost effective, green and biofriendly pathway to obtain mesoporous materials with an interconnected network ofwormhole–like pores. It involves the formation of a metal–oxide network around an inert organic molecule (e.g., sugar molecules) which functions as a template and can be later removed bysimple extraction with water or other solvents.This research describes the preparation of mesoporous zirconia and organo–functionalized silica by the acid–catalyzed nonsurfactant templated sol–gel route and also describes the use of sublimation as a method for the template removal. Mesoporous silica nanospheres with tunable particle size were also prepared by modifying the base–catalyzed Stober process with the addition of various sugar molecules as templates. The materials were characterized using TGA, nitrogen adsorption–desorption, SEM, TEM, XRD and FTIR.The application of nonsurfactant templated mesoporous materials in the area of enzyme encapsulation and stabilization is explored in this research. A novel ‘double encapsulation’approach that enables a sol–gel encapsulated protease to retain 60 % of its original activity after 4 weeks in harsh environments, such as high pH buffer and laundry detergent, is demonstrated.The need for aesthetic, as well as durable, dental restorations has led to extensive research in the area of dental composites. This study examines the use of nonsurfactant templated mesoporous materials as fillers in dental composites. Mesoporous materials of irregular morphology prepared by acid–catalyzed sol–gel routes as well as mesoporous silica spheres prepared via base–catalyzed sol–gel reactions were both employed as fillers in experimental dental composites. This research led to the development of novel ‘dental monomertemplated mesoporous materials’, which were also evaluated as fillers in dental composites. Various approaches, such as dense packing, addition of nanosilica and spherical fillers, etc., were employed to fabricate nanocomposites with improved mechanical properties. The composites were evaluated using flexural and compression testing.Curcumin, the ground rhizome of Curcuma longa, a common South Asian herb has attracted much attention due to its chemopreventive and anti–inflammatory properties. This research describes the synthesis of a series of poly [(arylenedioxy)(diorganylsilylene)]s via polycondensation between curcumin and various diorganodichlorosilanes. These novel polymersincorporate the β–diketone unit of curcumin as well as the Si–O bond in the backbone. The polymer structure was characterized by means of 1HNMR, FTIR and elemental analysis, whileGPC results showed high molecular weights. Preliminary cell culture results suggested lack of cytotoxicity, which is important for potential applications, such as implants and tissueengineering scaffold materials. The unique and interesting thermal behavior of these polymers was studied by DSC.The technology of enzymatically degrading biomass into simple sugars, such as glucose, is a critical step towards viable production of bio–based ethanol from non–food related sources.This research demonstrates the use of a biosensor–based diabetic blood glucose monitor as a rapid glucose detector and compares it to time consuming UV assays that are currently employed in research laboratories. Pretreatment of wood shavings with ferric chloride, followed by treatment in cold NaOH/urea solution was found to significantly enhance glucose production upon enzymatic hydrolysis.Finally, accounts of exploratory experiments in the areas of thermally crosslinkable high temperature elastomers and inorganic–organic hybrid materials are provided in the appendixsections of this thesis.Ph.D., Polymer Chemistry -- Drexel University, 200

Rare sugars: metabolic impacts and mechanisms of action: a scoping review

Food manufacturers are under increasing pressure to limit the amount of free sugars in their products. Many have reformulated products to replace sucrose, glucose and fructose with alternative sweeteners, but some of these have been associated with additional health concerns. Rare sugars are "monosaccharides and their derivatives that hardly exist in nature", and there is increasing evidence that they could have health benefits. This review aimed to scope the existing literature in order to identify the most commonly researched rare sugars, to ascertain their proposed health benefits, mechanisms of action and potential uses, and to highlight knowledge gaps. A process of iterative database searching identified 55 relevant articles. The reported effects of rare sugars were noted, along with details of the research methodologies conducted. Our results indicated that the most common rare sugars investigated are D-psicose and D-tagatose, with the potential health benefits divided into three topics: glycaemic control, body composition and cardiovascular disease. All the rare sugars investigated have the potential to suppress postprandial elevation of blood glucose and improve glycaemic control in both human and animal models. Some animal studies have suggested that certain rare sugars may also improve lipid profiles, alter the gut microbiome and reduce pro-inflammatory cytokine expression. The present review demonstrates that rare sugars could play a role in reducing the development of obesity, type 2 diabetes, and/or cardiovascular disease. However, understanding of the mechanisms by which rare sugars may exert their effects is limited, and their effectiveness when used in reformulated products is unknown

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity > 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI