A library of novel regioselective 1,4-di and 1,4,5-trisubstituted-1,2,3-triazole based benzothiazole-piperazine conjugates were designed and synthesized using the click synthesis approach in the ...presence and absence of the Cu(I) catalyst. Some of these 1,2,3-triazole hybrids possess in their structures different heterocyclic scaffold including 1,2,4-triazole, benzothiazole, isatin and/or benzimidazole. The newly designed 1,2,3-triazole hybrids were assessed for their antiproliferative inhibition potency against four selected human cancer cell lines (MCF7, T47D, HCT116 and Caco2). The majority of the synthesized compounds demonstrated moderate to potent activity against all the cancer cell lines examined. Further, we have established a structure activity relationship with respect to the in silico analysis of ADME (adsorption, distribution, metabolism and excretion) analysis and found good agreement with in vitro activity.
•Molecular thermodynamic association parameters for the bulk and nano-vanadyl sulfate were determined by the conductometry in aqueous solution at various temperatures for understanding the mechanism ...of oxidation and reduction of various vanadyl species in solutions.•From the interaction of the bulk & nano VOSO4 with Orange G, in the instance of the 1:1 complex as opposed to the 1:2 (VOSO4/Orange G) complex in water as the solvent, the estimated Kf and ΔGf were higher.•Molecular docking of VOSO4 versus 7 jwy of amino acid of covid-19 allows us to better understand the probable modes of engagement that provide more clarity on how well the molecules exert bioactivity towards the target.•VOSO4 show greater antioxidant behavior than the stander ascorbic acid with the same concentration.
Molecular thermodynamic association parameters for the bulk and nano-vanadyl sulfate were determined by the conductometry in aqueous solution at various temperatures. The thermodynamic parameters for complex formation 1:1, 1:2 (M/L) between bulk & nano vanadyl with Orange G were also determined by the conductivity measurements. From the interaction of the bulk & nano vanadyl sulfate (VOSO4) with Orange G, in the instance of the 1:1 complex as opposed to the 1:2 (VOSO4/Orange G) complex in water as the solvent, the estimated Kf and ΔGf were higher. When the temperature rises, the complex formation constants decrease. The molecular complexation's negative ΔGf values show that the production of molecular complexes is spontaneous and that it gets higher as the temperature rises. The molecular complexation is an endothermic and entropy-controlled reaction, which is supported by the negative values of ΔHf. Molecular docking of vanadyl sulfate versus 7 jwy of amino acid of covid-19 allows us to better understand the probable modes of engagement and binding affinities of the targeted molecule (vanadyl sulfate), that provide more clarity on how well the molecules exert bioactivity towards the target. The vanadyl sulfate show greater antioxidant behavior than the stander ascorbic acid with the same concentration. Also, the oxygen radicals ranging from 1.1 to 1.4 V which are reduced giving reduction peaks (broad) facilitating the use of vanadyl sulfate as a strong antioxidant solution.
This study reports an efficient eco-friendly microwave assisted synthesis of 1-(4-(benzothiazol-2-yl)piperazin-1-yl)-2-(4-phenyl-1H-1,2,3-triazol-1-yl)ethanone (4) through the click cyclocondensation ...of 2-azido-1-(4-(benzodthiazol-2-yl)piperazin-1-yl)ethanone (3) with phenyl acetylene. The synthesis was carried out under optimized copper catalyst copper(II) sulfate pentahydrate/sodium ascorbate, t-BuOH/water (1:1, v/v) to afford the regioselective 1,4-disubstituted 1,2,3-triazole isomer. The reactions were greatly accelerated using microwave irradiation. The new designed 1,2,3-triazole was fully characterizid by IR, NMR, MS spectral data and X-ray diffraction. The crystal structure of 4 demonstrated a conventional chair conformation for the piperazine ring. Interesting Hirshfeld Surface Analysis (HAS) was conducted showing clear agreement with the XRD analysis.
The present work aims to design and synthesize novel series of spiro pyrazole-3,3'-oxindoles analogues and investigate their bioactivity as antioxidant and antimicrobial agents, as well as ...antiproliferative potency against selected human cancerous cell lines (i.e., breast, MCF-7; colon, HCT-116 and liver, HepG-2) relative to healthy noncancerous control skin fibroblast cells (BJ-1). The mechanism of their cytotoxic activity has been also examined by immunoassaying the levels of key anti- and proapoptotic protein markers. The analytical and spectral data of the all synthesized target congeners were compatible with their structures. Synthesized compounds showed diverse moderate to powerful antimicrobial and antioxidant activities. Results of MTT assay revealed that seven synthesized compounds (i.e., 11a, 11b, 12a, 12b, 13b, 13c and 13h) particularly exhibited significant cytotoxicity against the three cancerous cell lines under investigation. Ranges of IC
values obtained were 5.7-21.3 and 5.8-37.4 µg/mL against HCT-116 and MCF-7, respectively; which is 3.8 and 6.5-fold (based on the least IC
values) more significant relative to the reference chemotherapeutic drug doxorubicin. In HepG-2 cells, the analogue 13h the highest cytotoxicity with IC
value of 19.2µg/mL relative to doxorubicin (IC
= 21.6µg/mL). The observed cytotoxicity was specific to cancerous cells, as evidenced by the minimal toxicity in the noncancerous control skin-fibroblast cells. ELISA results indicated that the observed antiproliferative effect against examined cancer cell lines is mediated
engaging the activation of apoptosis as illustrated by the significant increase in proapoptotic protein markers (p53, bax and caspase-3) and reduction in the antiapoptotic marker bcl-2. Taken together, results of the present study emphasize the potential of spiro pyrazole-oxindole analogues as valuable candidate anticancer agents against human cancer cells.
Background and Aim
The relationship between Helicobacter pylori (H. pylori) and nonalcoholic fatty liver disease (NAFLD) is a matter of debate. We achieved this prospective work to study whether ...H. pylori infection is a risk factor for NAFLD.
Methods
A cohort multicenter pilot study of 369 adults without NAFLD at baseline was followed up for 2 years. Serum leptin, insulin, tumor necrosis factor‐α, adiponectin, and interleukin‐6 were measured using an enzyme‐linked immunosorbent assay (ELISA). Homeostasis model assessment of insulin resistance (HOMA‐IR) and leptin/adiponectin ratio (LAR) were calculated. Fecal H. pylori antigen was measured by ELISA. A total of 127 participants with H. pylori positive were treated and then followed up for 3 months.
Results
Helicobacter pylori‐positive patients (46.3%) were associated with an increase in IR, proinflammatory cytokines, C‐reactive protein (CRP), LAR, NAFLD‐liver fat score (NAFLD‐LFS), and hepatic steatosis index (HSI) (all P < 0.01). Multivariate analysis of NAFLD according to HSI and NAFLD‐LFS reported that presence of H. pylori, LAR, CRP, IL‐6, smoking, and age (all P < 0.01) were independent risk factors for the presence of NAFLD. Multiple models adjusted for potential mediators or confounders such as metabolic, inflammatory, and biochemical factors were constructed. After therapy of H. pylori infection, there was a significant reduction in lipogenic profile, IR, leptin, LAR, CRP, proinflammatory cytokines, HSI, and NAFLD‐LFS, as well as, increasing HDL.
Conclusion
Helicobacter pylori infection was related to an increased risk of NAFLD development, through increased markers of IR, inflammatory mediators, and lipid metabolism. Moreover, its eradication can recover these NAFLD risk factors.
Abstract
Background
To evaluate the effect of screening for sepsis using an electronic sepsis alert vs. no alert in hospitalized ward patients on 90-day in-hospital mortality.
Methods
The SCREEN ...trial is designed as a stepped-wedge cluster randomized controlled trial. Hospital wards (total of 45 wards, constituting clusters in this design) are randomized to have active alert vs. masked alert, 5 wards at a time, with each 5 wards constituting a sequence. The study consists of ten 2-month periods with a phased introduction of the intervention. In the first period, all wards have a masked alert for 2 months. Afterwards the intervention (alert system) is implemented in a new sequence every 2-month period until the intervention is implemented in all sequences. The intervention includes the implementation of an electronic alert system developed in the hospital electronic medical records based on the quick sequential organ failure assessment (qSOFA). The alert system sends notifications of “possible sepsis alert” to the bedside nurse, charge nurse, and primary medical team and requires an acknowledgment in the health information system from the bedside nurse and physician. The calculated sample size is 65,250. The primary endpoint is in-hospital mortality by 90 days.
Discussion
The trial started on October 1, 2019, and is expected to complete patient follow-up by the end of October 2021.
Trial registration
ClinicalTrials.gov
NCT04078594
. Registered on September 6, 2019
Transradial (TR) percutaneous coronary intervention (PCI) is a preferable PCI route. The complication difference between TR and TF approaches is controversial.
PubMed, Embase, and the Cochrane ...databases were queried for PCI outcomes of TR TF in STEMI for major cardiac and cerebrovascular events (MACCE), major bleeding, and mortality. The odds ratio (OR) was calculated using the random-effect model.
We included 56 studies comprising of 68,733 patients (TR, n = 26,179; TF, n = 42,537). TR-PCI was associated with statistically significant lower odds of MACCE (OR = 0.66, 95% CI: 0.49-0.88, p-value = 0.005), major bleeding (OR = 0.47, 95% CI 0.32-0.68, p-value<0.001), mortality (OR = 0.59, 95% CI 0.43-0.80, p-value<0.001) at in hospital follow-up. TR-PCI was associated with statistically significant lower MACCE (OR = 0.59, 95% CI 0.43-0.80, p-value<0.001), major bleeding (OR = 0.58, 95% CI 0.49-0.68, p-value<0.001), and mortality (OR = 0.61, 95% CI 0.44-0.86, p-value = 0.005) at 30-day follow-up. The same difference was seen at 1-year.
TR-PCI was associated with lower odds of MACCE, major bleeding, and mortality during short- and long-term follow-up.
Background It is unclear whether screening for sepsis using an electronic alert in hospitalized ward patients improves outcomes. The objective of the Stepped-wedge Cluster Randomized Trial of ...Electronic Early Notification of Sepsis in Hospitalized Ward Patients (SCREEN) trial is to evaluate whether an electronic screening for sepsis compared to no screening among hospitalized ward patients reduces all-cause 90-day in-hospital mortality. Methods and design This study is designed as a stepped-wedge cluster randomized trial in which the unit of randomization or cluster is the hospital ward. An electronic alert for sepsis was developed in the electronic medical record (EMR), with the feature of being active (visible to treating team) or masked (inactive in EMR frontend for the treating team but active in the backend of the EMR). Forty-five clusters in 5 hospitals are randomized into 9 sequences of 5 clusters each to receive the intervention (active alert) over 10 periods, 2 months each, the first being the baseline period. Data are extracted from EMR and are compared between the intervention (active alert) and control group (masked alert). During the study period, some of the hospital wards were allocated to manage patients with COVID-19. The primary outcome of all-cause hospital mortality by day 90 will be compared using a generalized linear mixed model with a binary distribution and a log-link function to estimate the relative risk as a measure of effect. We will include two levels of random effects to account for nested clustering within wards and periods and two levels of fixed effects: hospitals and COVID-19 ward status in addition to the intervention. Results will be expressed as relative risk with a 95% confidence interval. Conclusion The SCREEN trial provides an opportunity for a novel trial design and analysis of routinely collected and entered data to evaluate the effectiveness of an intervention (alert) for a common medical problem (sepsis in ward patients). In this statistical analysis plan, we outline details of the planned analyses in advance of trial completion. Prior specification of the statistical methods and outcome analysis will facilitate unbiased analyses of these important clinical data. Trial registration ClinicalTrials.gov NCT04078594. Registered on September 6, 2019 Keywords: Sepsis, Alert, Screening, qSOFA, Mortality, Electronic medical records
Abstract
Background
It is unclear whether screening for sepsis using an electronic alert in hospitalized ward patients improves outcomes. The objective of the Stepped-wedge Cluster Randomized Trial ...of Electronic Early Notification of Sepsis in Hospitalized Ward Patients (SCREEN) trial is to evaluate whether an electronic screening for sepsis compared to no screening among hospitalized ward patients reduces all-cause 90-day in-hospital mortality.
Methods and design
This study is designed as a stepped-wedge cluster randomized trial in which the unit of randomization or cluster is the hospital ward. An electronic alert for sepsis was developed in the electronic medical record (EMR), with the feature of being active (visible to treating team) or masked (inactive in EMR frontend for the treating team but active in the backend of the EMR). Forty-five clusters in 5 hospitals are randomized into 9 sequences of 5 clusters each to receive the intervention (active alert) over 10 periods, 2 months each, the first being the baseline period. Data are extracted from EMR and are compared between the intervention (active alert) and control group (masked alert). During the study period, some of the hospital wards were allocated to manage patients with COVID-19. The primary outcome of all-cause hospital mortality by day 90 will be compared using a generalized linear mixed model with a binary distribution and a log-link function to estimate the relative risk as a measure of effect. We will include two levels of random effects to account for nested clustering within wards and periods and two levels of fixed effects: hospitals and COVID-19 ward status in addition to the intervention. Results will be expressed as relative risk with a 95% confidence interval.
Conclusion
The SCREEN trial provides an opportunity for a novel trial design and analysis of routinely collected and entered data to evaluate the effectiveness of an intervention (alert) for a common medical problem (sepsis in ward patients). In this statistical analysis plan, we outline details of the planned analyses in advance of trial completion. Prior specification of the statistical methods and outcome analysis will facilitate unbiased analyses of these important clinical data.
Trial registration
ClinicalTrials.gov
NCT04078594
. Registered on September 6, 2019
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