Facile Synthesis of Some New Peptidomimetic ß3 -and ß2,3 -Amino Alcohols Possessing Pyridyl Moiety via Reductive Ring Opening of Pyridyl-isoxazolidines.

Regio- and stereoselective 1,3-dipolar cycloadditions of C-(3-pyridyl)-N-phenylnitrone (2) with variedly substituted dipolarophiles (3, 4) were carried out to obtain substituted pyridyl-isoxazolidines (5-8). Reductive cleavage of pyridyl-isoxazolidines (5-8) with ammonium formate, methanol-THF solvents, at ambient temperature, in the presence of Pd/C provided a facile route for the synthesis of ß3 -and ß2,3 -amino alcohols (9-12), with a substitution pattern having pronounced influence on torsional angles. The obtained compounds (9-12) are valuable scaffolds which can be utilized for peptidomimetics. Thus, the present methodology for reductive opening of isoxazolidine ring avoids the disadvantages of using expensive apparatus and hazards involved in the use of hydrogen gas. The preferential formation of amino-alcohols in case of bicyclic isoxazolidines (8a-c), which precludes any recyclization is rationalized by DFT calculations.

Direct costs of care for hepatocellular carcinoma in patients with hepatitis C cirrhosis.

BACKGROUND: Hepatitis C virus (HCV) is the commonest cause of hepatocellular carcinoma (HCC) in the United States. The benefits of HCV therapy may be measured in part by the prevention of HCC and other complications of cirrhosis. The true cost of care of the HCV patient with HCC is unknown. METHODS: One hundred patients were randomly selected from a cohort of all HCC patients with HCV at a US transplant center between 2003 and 2013. Patients were categorized by the primary treatment modality, Barcelona class, and ultimate transplant status. Costs included the unit costs of procedures, imaging, hospitalizations, medications, and all subsequent care of the HCC patient until either death or the end of follow-up. Associations with survival and cost were assessed in multivariate regression models. RESULTS: Overall costs included a median of $176,456 (interquartile range [IQR], $84,489-$292,192) per patient or $6279 (IQR, $4043-$9720) per patient-month of observation. The median costs per patient-month were $7492 (IQR, $5137-$11,057) for transplant patients and $4830 for nontransplant patients. The highest median monthly costs were for transplant patients with Barcelona A4 disease ($11,349) and patients who received chemoembolization whether they underwent transplantation ($10,244) or not ($8853). Transarterial chemoembolization and radiofrequency ablation were independently associated with a 28% increase and a 22% decrease in costs, respectively, with adjustments for the severity of liver disease and Barcelona class. CONCLUSIONS: These data represent real-world estimates of the cost of HCC care provided at a transplant center and should inform economic studies of HCV therapy.

Inpatient burden of constipation in the United States: an analysis of national trends in the United States from 1997 to 2010.

OBJECTIVES: Constipation is one of the most common outpatient diagnoses in primary care and gastroenterology clinics; however, there is limited data on the inpatient burden of constipation in the United States. The aim of this study was to evaluate inpatient admission rates, length of stay, and associated costs related to constipation from 1997 to 2010. METHODS: We analyzed the National Inpatient Sample Database for all patients in which constipation (ICD-9 codes: 564.0-564.09) was the principal discharge diagnosis from 1997 to 2010. The statistical significance of the difference in the number of hospital discharges, length of stay, and hospital costs over the study period was determined by utilizing the Spearman's coefficient to describe various trends. RESULTS: Between 1997 and 2010, the number of hospitalizations for patients with a primary discharge diagnosis of constipation increased from 21,190 patients to 48,450 (P<0.001, GoF test), whereas the mean length of hospital stay increased only slightly from 3.0 days to 3.1 days (b=0.008 (0.003-0.014); P=0.004). The mean charges per hospital discharge for constipation increased from $8869 in 1997 (adjusted for long-term inflation) to $17,518 in 2010 (b=745.4 (685.3-805.6); P<0.001)), whereas the total costs increased from $188,109,249 (adjusted for inflation) in 1997 to $851,713,263 in 2010. Although the elderly (65-84 years) accounted for the largest percentage of constipation discharges, patients in the 1-17 years age group had the highest frequency of constipation per 10,000 discharges. CONCLUSIONS: The number of inpatient discharges for constipation and associated costs has significantly increased between 1997 and 2010.

Propofol versus traditional sedative agents for advanced endoscopic procedures: a meta-analysis.

BACKGROUND AND AIM: The optimum method for sedation for advanced endoscopic procedures is not known. Propofol deep sedation has a faster recovery time than traditional sedative agents, but may be associated with increased complication rates. The aim of the present study was to pool data from all available studies to systematically compare the efficacy and safety of propofol with traditional sedative agents for advanced endoscopic procedures. METHODS: Databases including PubMed, Embase, Web of Science and the Cochrane Central Register of Controlled Trials updated as of January 2013 were searched. Main outcome measures were procedure duration, recovery time, incidence of complications (hypotension, hypoxia), sedation level, patient cooperation and amnesia during advanced endoscopic procedures such as endoscopic retrograde cholangiopancreatography, endoscopic ultrasonography, and deep small bowel enteroscopy. RESULTS: Nine prospective randomized trials with a total of 969 patients (485 propofol, 484 conscious sedation) were included in the meta-analysis. Pooled mean difference in procedure duration between propofol and traditional sedative agents was -2.3 min [95% CI: -6.36 to 1.76, P = 0.27], showing no significant difference in procedure duration between the two groups. Pooled mean difference in recovery time was -30.26 min [95% CI: -46.72 to -13.80, P < 0.01], showing significantly decreased recovery time with propofol. There was also no significant difference between the two groups with regard to hypoxia and hypotension. CONCLUSIONS: Propofol for advanced endoscopic procedures is associated with shorter recovery time, better sedation and amnesia level without an increased risk of cardiopulmonary complications. Overall patient cooperation was also improved with propofol sedation.

Hepatoprotective effects of fruits pulp, seed, and peel against chemical-induced toxicity: Insights from in vivo studies.

The liver is a vital organ in human physiology positioned in the upper right quadrant of the peritoneal cavity, which plats a critical role in metabolic processes, detoxification of various substances and overall homeostasis. Along with these critical functions, hepatic diseases impose as significant global health threat. Liver illness is the cause of two million fatalities every year, or 4% of all deaths. Traditionally, healthcare providers have prescribed antibacterial and antiviral medications to address liver illness. Nephrotoxicity is a frequently observed negative reaction to drugs, with the majority of such events happening in individuals who have advanced cirrhosis. Thus, recognizing this gap, there is a dire need of exploration of pharmaceutical alterative for hepatic diseases, with special focus on their efficacy and reduced toxicity. Fruits have long been known to therapeutic impact on human health, thus exploration of fruits components namely pulp, seeds and peels containing phytochemicals have emerged as a promising avenue for hepatoprotective interventions. Thus, review comprehends the information about worldwide burden of chemical induced toxicity and injuries as well as highlight the on-going challenges in hepatic disease management. It also shed light on the valuable contributions fruit parts and their phytocompounds obtained from different components of fruits. Fruit pulp, especially when rich in flavonoids, has demonstrated significant potential in animal model studies. It has been observed to enhance the activity of antioxidant enzymes and reduce the expression of pro-inflammatory markers. The methanolic and ethanolic extracts have demonstrated the most favorable outcomes. Further, this review also discusses about the safety assessments of fruits extracts for their utilization as hepatoprotective agents.

Valorization of non-edible fruit seeds into valuable products: A sustainable approach towards circular bioeconomy.

Global imperatives have recently shown a paradigm shift in the prevailing resource utilization model from a linear approach to a circular bioeconomy. The primary goal of the circular bioeconomy model is to minimize waste by effective re-usage of organic waste and efficient nutrient recycling. In essence, circular bioeconomy integrates the fundamental concept of circular economy, which strives to offer sustainable goods and services by leveraging biological resources and processes. Notably, the circular bioeconomy differs from conventional waste recycling by prioritizing the safeguarding and restoration of production ecosystems, focusing on harnessing renewable biological resources and their associated waste streams to produce value-added products like food, animal feed, and bioenergy. Amidst these sustainability efforts, fruit seeds are getting considerable attention, which were previously overlooked and commonly discarded but were known to comprise diverse chemicals with significant industrial applications, not limited to cosmetics and pharmaceutical industries. While, polyphenols in these seeds offer extensive health benefits, the inadequate conversion of fruit waste into valuable products poses substantial environmental challenges and resource wastage. This review aims to comprehend the known information about the application of non-edible fruit seeds for synthesising metallic nanoparticles, carbon dots, biochar, biosorbent, and biodiesel. Further, this review sheds light on the potential use of these seeds as functional foods and feed ingredients; it also comprehends the safety aspects associated with their utilization. Overall, this review aims to provide a roadmap for harnessing the potential of non-edible fruit seeds by adhering to the principles of a sustainable circular bioeconomy.

CoMFA and CoMSIA of diverse pyrrolidine analogues as dipeptidyl peptidase IV inhibitors: active site requirements.

The inhibition of dipeptidyl peptidase IV (DPP-IV) has emerged as an attractive target in the treatment of type 2 diabetes. In view of this development, a critical analysis of structural requirements of the DPP-IV inhibitors is envisioned to identify the significant features toward design of selective inhibitors. The comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) contour plots of pyrrolidine based analogues are used to analyze the structural requirements of a DPP-IV active site. The CoMFA model has shown a cross-validated q (2) of 0.651 with a non-cross-validated r (2) of 0.882 and explained 70.6% variance in the activity of external test compounds. In this, the steric and electrostatic fields have respectively contributed 59.8 and 40.2%, respectively, to the explained activity of the compounds. The CoMSIA model has shown optimum predictivity (cross-validated q (2) = 0.661; non-cross-validated r (2) = 0.803; external test set's predictive r (2) = 0.706) with four molecular fields namely, steric, electrostatic, hydrogen bond (HB)-donor, and HB-acceptor. The contour plots of molecular fields resulting from these studies have suggested: (i) steric restriction with small electron rich substituent at 2- and 3-position of pyrrolidine ring, (ii) presence of electropositive ring linker between the pyrrolidine head and aryl tail, (iii) presence of electron-rich groups around the aryl tail moiety, and (iv) presence of sulfonamide between the ring linker and aryl tail which would increase DPP-IV binding affinity of the compounds. These findings will help in the design of structurally related/new compounds as potential DPP-IV inhibitors.

A meta-analysis on efficacy and safety: single-balloon vs. double-balloon enteroscopy.

BACKGROUND AND AIM: Double-balloon enteroscopy (DBE) and single-balloon enteroscopy (SBE) are new techniques capable of providing deep enteroscopy. Results of individual studies comparing these techniques have not been able to identify a superior strategy. Our aim was to systematically pool all available studies to compare the efficacy and safety of DBE with SBE for evaluation of the small bowel. METHODS: Databases were searched, including PubMed, Embase, and the Cochrane Central Register of Controlled Trials. The main outcome measures were complete small-bowel visualization, diagnostic yield, therapeutic yield, and complication rate. Statistical analysis was performed using Review Manager (RevMan version 5.2). Meta-analysis was performed using fixed-effect or random-effect methods, depending on the absence or presence of significant heterogeneity. We used the χ(2) and I(2) test to assess heterogeneity between trials. Results were expressed as risk ratios (RR) or mean differences with 95% confidence intervals (CI). RESULTS: Four prospective, randomized, controlled trials with a total of 375 patients were identified. DBE was superior to SBE for visualization of the entire small bowel [pooled RR = 0.37 (95% CI: 0.19-0.73; P = 0.004)]. DBE and SBE were similar in ability to provide diagnosis [pooled RR = 0.95 (95% CI: 0.77-1.17; P = 0.62)]. There was no significant difference between DBE and SBE in therapeutic yield [pooled RR = 0.78 (95% CI: 0.59-1.04; P = 0.09)] and complication rate [pooled RR = 1.08 (95% CI: 0.28-4.22); P = 0.91]. CONCLUSIONS: DBE was superior to SBE with regard to complete small bowel visualization. DBE was similar to SBE with regard to diagnostic yield, ability to provide treatment and complication rate, but these results should be interpreted with caution as they is based on very few studies and the overall quality of the evidence was rated as low to moderate, due to the small sample size.

A meta-analysis on the role of rectal diclofenac and indomethacin in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis.

Clinical trials evaluating the protective effect of nonsteroidal anti-inflammatory drugs (NSAIDs) for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) have yielded inconclusive results. Our objective was to conduct a meta-analysis of the data to date to evaluate the efficacy and safety of rectal NSAIDs for PEP prophylaxis. We did a systematic search of PubMed/MEDLINE, Embase, and Web of Science databases and the Cochrane Central Register of Controlled Trials. The meta-analysis was performed using a fixed-effect method because of the absence of significant heterogeneity in the included trials. Seven randomized, controlled trials involving 2133 patients were included. The meta-analysis showed that rectal NSAIDs decreased the overall incidence of PEP (risk ratio, 0.44; 95% confidence interval, 0.34-0.57; P < 0.01). The number needed to treat was 11. The NSAID prophylaxis also decreased the incidence of moderate to severe PEP (risk ratio, 0.37; 95% confidence interval, 0.27-0.63; P < 0.01). The number needed to treat was 34. No differences of the adverse events attributable to NSAIDs were observed. In conclusion, prophylactic use of rectal NSAIDs reduces the incidence and severity of PEP. There is neither a difference in efficacy between rectal indomethacin and diclofenac nor a difference in efficacy between the timing of administration of rectal NSAIDs, that is, immediate pre-ERCP and post-ERCP.