METHODS: ENACT-HF was an international, multicenter, open-label, pragmatic, 2-phase study, comparing the current standard of care of each center with a standardized diuretic protocol, including urinary sodium to guide therapy. The primary end point was natriuresis after 1 day. Secondary end points included cumulative natriuresis and diuresis after 2 days of treatment, length of stay, and in-hospital mortality. All end points were adjusted for baseline differences between both treatment arms.
RESULTS: Four hundred one patients from 29 centers in 18 countries worldwide were included in the study. The natriuresis after 1 day was significantly higher in the protocol arm compared with the standard of care arm (282 versus 174 mmol; adjusted mean ratio, 1.64; P<0.001). After 2 days, the natriuresis remained higher in the protocol arm (538 versus 365 mmol; adjusted mean ratio, 1.52; P<0.001), with a significantly higher diuresis (5776 versus 4381 mL; adjusted mean ratio, 1.33; P<0.001). The protocol arm had a shorter length of stay (5.8 versus 7.0 days; adjusted mean ratio, 0.87; P=0.036). In-hospital mortality was low and did not significantly differ between the 2 arms (1.4% versus 2.0%; P=0.852).
CONCLUSIONS: A standardized natriuresis-guided diuretic protocol to guide decongestion in acute heart failure was feasible, safe, and resulted in higher natriuresis and diuresis, as well as a shorter length of stay.
METHODS: Formalin-induced paw licking model was used to assess the anti-nociceptive activity of CMEO and its major constituent, terpinolene (TP). The anti-nociceptive activity of these compounds was determined by investigating the roles of various non-opioid and NO-cGMP-K+ channels. Additionally, the anti-neuropathic potential of CMEO and TP was determined using cervical spinal cord contusion/CCS technique.
RESULTS: The CMEO exerted significant anti-nociceptive activity with a remarkable activity seen in the second phase of formalin-induced paw licking model and this activity were remarkably reversed by pre-treatment of naloxone (an opioid antagonist). Pretreatment with several types of NO-cGMP-potassium channel pathway meaningfully reversed the anti-nociceptive potential of CMEO in phase II of formalin model. Moreover, pre-treatment with several antagonists of non-opioid receptors revealed that only the antagonist of TRPV-1, serotonin type 3, 5-HT2, α2 adrenergic, and CB1 receptors (capsaicin, ondansetron, ketanserin, yohimbine, and SR141716A, respectively) reversed CMEO anti-nociception. CMEO and TP also remarkably reversed hyperalgesia and mechanical allodynia in the CCS technique.
CONCLUSION: The CMEO exerts anti-nociceptive and anti-neuropathic activities via the modulation of NO-cGMP potassium channel pathway, opioid as well as several non-opioid receptor activity. TP might partly contribute to the observed activities of CMEO.
MATERIALS AND METHODS: Four online databases (PubMed, ScienceDirect, Scopus, and Web of Science) were searched using different MeSH terms and Boolean Operators to retrieve the articles (until June 2021), followed by a hand-search of the reference list of the included articles. All full-text, original studies in English that evaluated SDF staining and at least one SDF modification/alternative were included.
RESULTS: Among the assessed studies, nine studies explored the stain-minimization effect of potassium iodide (KI) post-application following SDF treatment. Among these, eight concluded that KI application after SDF treatment significantly reduced tooth staining, while one showed marginal staining following glass ionomer restoration of the SDF-treated dentine. Additionally, one study applied potassium fluoride (KF) and silver nitrate (AgNO3 ) concurrently to mitigate SDF-mediated staining. One study compared SDF staining with polyethylene glycol (PEG)-coated nanoparticles containing sodium fluoride (NaF), and another used nanosilver fluoride (NSF) for staining comparison with SDF.
CONCLUSIONS: Within the limitations of this study, the addition of different materials to SDF has proven to be a beneficial strategy for overcoming tooth staining associated with SDF. Future studies are warranted, particularly clinical trials, to validate these findings.
CLINICAL SIGNIFICANCE: SDF-mediated tooth staining is a serious concern that limits its clinical use. A review of various strategies to overcome this problem will help clinicians enhance its clinical use and patient acceptance.
METHODS: As a preliminary step, a molecular docking study was performed to investigate the potency of seventy-one compounds from four classes of inhibitors. The molecular characteristics of the best-performing five compounds were predicted by estimating the drug-likeness and drug score. Molecular dynamics simulations (MD) over 100 ns were performed to inspect the relative stability of the best compound within the Omicron receptor-binding site.
RESULTS: The current findings point out the crucial roles of Q493R, G496S, Q498R, N501Y, and Y505H in the RBD region of SARS-CoV-2 Omicron. Raltegravir, hesperidin, pyronaridine, and difloxacin achieved the highest drug scores compared with the other compounds in the four classes, with values of 81%, 57%, 18%, and 71%, respectively. The calculated results showed that raltegravir and hesperidin had high binding affinities and stabilities to Omicron with ΔGbinding of - 75.7304 ± 0.98324 and - 42.693536 ± 0.979056 kJ/mol, respectively. Further clinical studies should be performed for the two best compounds from this study.
METHODS: Young shoots of E. crassipes, L. flava, and N. oleracea were collected from shallow channels of Puchong (3°00'11.89″N, 101°42'43.12″E), Ladang 10, Universiti Putra Malaysia (2°58'44.41″N, 101°42'44.45″E), and Kampung Alur Selibong, Langgar (06°5'50.9″N, 100°26'49.8″E), Kedah, Peninsular Malaysia. The nutritional values of these macrophytes were analysed by using a standard protocol from the Association of Official Analytical Chemists. Eight replicates of E. crassipes and L. flava and four replicates of N. oleracea were used for the subsequent analyses.
RESULTS: In the proximate analysis, N. oleracea possessed the highest percentage of crude protein (29.61%) and energy content (4,269.65 cal g-1), whereas L. flava had the highest percentage of crude fat (5.75%) and ash (18.31%). The proximate composition trend for each species was different; specifically, all of the species possessed more carbohydrates and fewer crude lipids. All of the species demonstrated a similar mineral trend, with high nitrogen and potassium and lower copper contents. Nitrogen and potassium levels ranged from 12,380-40,380 mg kg-1 and from 11,212-33,276 mg kg-1, respectively, and copper levels ranged from 16-27 mg kg-1. The results showed that all three plant species, i.e., E. crassipes, N. oleracea, and L. flava are plant-based sources of macro- and micronutrient beneficial supplements for human consumption.
METHODS: We searched up to June 5, 2022, for randomized controlled trials of gastric acid-related diseases that included erosive esophagitis, symptomatic gastroesophageal reflux disease (GERD), peptic ulcers, and Helicobacter pylori infection. The pooled risk ratio (RR) was evaluated for the efficacy outcome and treatment-emergent adverse events (TEAEs) as the safety outcome. Sensitivity analyses were performed to test the robustness of the study findings.
RESULTS: Of the 710 screened studies, 19 studies including 7023 participants were analyzed. The RRs for the healing of erosive esophagitis with Vonoprazan versus PPI were 1.09 (95% confidence interval [CI] 1.03-1.14), 1.03 (95% CI 1.00-1.07), and 1.02 (95% CI 1.00-1.05) in Weeks 2, 4, and 8, respectively. There were no differences in the improvement of GERD symptoms and healing of gastric and duodenal ulcers between PCAB and PPI. The pooled eradication rates of H. pylori were significantly higher in Vonoprazan versus PPI first-line treatment (RR 1.13; 95% CI 1.04-1.22). The overall RR of TEAEs with Vonoprazan versus PPI was 1.08 (95% CI 0.89-1.31). Overall, the risk of bias was low to some concerns. Furthermore, sensitivity analyses confirmed the robustness of the study's conclusion.
CONCLUSION: Vonoprazan is superior to PPI in first-line H. pylori eradication and erosive esophagitis but non-inferior in other gastric acid-related diseases. Likewise, short-term safety is comparable in both treatment groups.