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Background: We analyzed the impact of social distancing (SD) on vitamin D status and associated morbidity in neonates during the coronavirus disease (COVID-19) pandemic. Methods: Serum levels of 25-hydroxy vitamin D (25OHD) and clinical characteristics of newborn infants before (2019) and during SD (2021) were compared. Results: A total of 526 neonates (263 in 2019 and 263 in 2021) were included. The rate of vitamin D deficiency in neonates (47.1% vs. 35.4 %, p = 0.008) decreased and the rate of maternal vitamin D intake increased (6.8% vs. 37.6%, p < 0.001), respectively, during SD compared to those in 2019. The rates of hypocalcemia (12.5% vs. 3.8%, p < 0.001) and respiratory illness (57.0% vs. 43.0%, p = 0.002) decreased during SD. Neonatal vitamin D deficiency during SD was associated with maternal vitamin D supplementation (odds ratio [OR] = 0.463, p = 0.003) but was not associated with SD (OR = 0.772, p = 0.189). The mediation effect of SD on neonatal morbidity by neonatal vitamin D status was statistically insignificant. Conclusions: SD might affect the increased maternal vitamin D intake and decreased neonatal vitamin D deficiency. However, neonatal morbidity was not affected by SD, even with neonatal vitamin D status changes. [ABSTRACT FROM AUTHOR]

This document explores the potential of Cephalotaxus alkaloids (CAs) as anti-cancer agents. Through data analysis using various tools and software, the study identifies heat shock protein 90 alpha family class A member 1 (HSP90AA1) as a potential target for inhibiting cancer progression and the NOD-like receptor (NLR) signaling pathway as a promising pathway for cancer treatment. The compound Nordeoxyharringtonine is identified as a potential anti-cancer mediator, and its toxicity is found to be manageable. The study suggests that Nordeoxyharringtonine can be used to validate its anti-pan-cancer effects by targeting multiple pathways. The research was supported by multiple funding sources and has been approved by all authors. [Extracted from the article]

The relationship between ammonia and liver-related complications (LRCs) in acute-on-chronic liver failure (ACLF) patients is not clearly established. This study aimed to evaluate the association between ammonia levels and LRCs in patients with ACLF. The study also evaluated the ability of ammonia in predicting mortality and progression of LRCs. The study prospectively recruited ACLF patients based on the APASL definition from the ACLF Research Consortium (AARC) from 2009 to 2019. LRCs were a composite endpoint of bacterial infection, overt hepatic encephalopathy (HE), and ascites. A total of 3871 cases were screened. Of these, 701 ACLF patients were enrolled. Patients with LRCs had significantly higher ammonia levels than those without. Ammonia was significantly higher in patients with overt HE and ascites, but not in those with bacterial infection. Multivariate analysis found that ammonia was associated with LRCs. Additionally, baseline arterial ammonia was an independent predictor of 30-day mortality, but it was not associated with the development of new LRCs within 30 days. In summary, baseline arterial ammonia levels are associated with 30-day mortality and LRCs, mainly overt HE and ascites in ACLF patients. [ABSTRACT FROM AUTHOR]

Persea americana fruit (PAF) is a favorable nutraceutical resource that comprises diverse unsaturated fatty acids (UFAs). UFAs are significant dietary supplementation, as they relieve metabolic disorders, including obesity (OB). In another aspect, this study was focused on the anti‐OB efficacy of the non‐fatty acids (NFAs) in PAF through network pharmacology (NP). Natural product activity & species source (NPASS), SwissADME, similarity ensemble approach (SEA), Swiss target prediction (STP), DisGeNET, and online Mendelian inheritance in man (OMIM) were utilized to gather significant molecules and its targets. The crucial targets were adopted to construct certain networks: protein–protein interaction (PPI), PAF‐signaling pathways‐targets‐compounds (PSTC) networks, a bubble chart, molecular docking assay (MDA), and density function theory (DFT). Finally, the toxicities of the key compounds were validated by ADMETlab 2.0 platform. All 41 compounds in PAF conformed to Lipinski's rule, and the key 31 targets were identified between OB and PAF. On the bubble chart, PPAR signaling pathway had the highest rich factor, suggesting that the pathway might be an agonism for anti‐OB. Conversely, estrogen signaling pathway had the lowest rich factor, indicating that the mechanism might be antagonism against OB. Likewise, the PSTC network represented that AKT1 had the greatest degree value. The MDA results showed that AKT1‐gamma‐tocopherol, PPARA‐fucosterol, PPARD‐stigmasterol, (PPARG)‐fucosterol, (NR1H3)‐campesterol, and ILK‐alpha‐tocopherol formed the most stable conformers. The DFT represented that the five molecules might be promising agents via multicomponent targeting. Overall, this study suggests that the NFAs in PAF might play important roles against OB. [ABSTRACT FROM AUTHOR]

Multiple attempts of thrombectomy have been linked to a higher risk of intracerebral hemorrhage and worsened functional outcomes, potentially influenced by blood pressure (BP) management strategies. Nonetheless, the impact of intensive BP management following successful recanalization through multiple attempts remains uncertain.This study aimed to investigate whether conventional and intensive BP managements differentially affect outcomes according to multiple-attempt recanalization (MAR) and first-attempt recanalization (FAR) groups.In this secondary analysis of the OPTIMAL-BP trial, which was a comparison of intensive (systolic BP target: <140 mm Hg) and conventional (systolic BP target = 140–180 mm Hg) BP managements during the 24 h after successful recanalization, we included intention-to-treat population of the trial. Patients were divided into the MAR and the FAR groups. We examined a potential interaction between the number of thrombectomy attempts (MAR and FAR groups) and the effect of BP managements on clinical and safety outcomes. The primary outcome was functional independence at 3 months. Safety outcomes were symptomatic intracerebral hemorrhage within 36 h and mortality within 3 months.Of the 305 patients (median = 75 years), 102 (33.4%) were in the MAR group and 203 (66.6%) were in the FAR group. The intensive BP management was significantly associated with a lower rate of functional independence in the MAR group (intensive, 32.7% vs conventional, 54.9%, adjusted odds ratio (OR) = 0.33, 95% confidence interval (CI) = 0.12–0.90, p = 0.03). In the FAR group, the proportion of patients with functional independence was not significantly different between the BP managements (intensive, 42.5% vs conventional, 54.2%, adjusted OR = 0.73, 95% CI = 0.38–1.40). Incidences of symptomatic intracerebral hemorrhage and mortality rates were not significantly different according to the BP managements in both MAR and FAR groups.Among stroke patients who received multiple attempts of thrombectomy, intensive BP management for 24 h resulted in a reduced chance of functional independence at 3 months and did not reduce symptomatic intracerebral hemorrhage following successful reperfusion. [ABSTRACT FROM AUTHOR]

Background and Aim: The Model for End-Stage Liver Disease (MELD) is a reliable prognostic tool for short-term outcome prediction in patients with end-stage liver disease. MELD 3.0 was introduced to enhance the predictive accuracy. This study assessed the performance of MELD 3.0, in comparison to MELD and MELD-Na, in patients with alcoholic liver cirrhosis., Methods: This multicenter prospective cohort study comprised patients with alcoholic cirrhosis admitted for acute deterioration of liver function in the Republic of Korea between 2015 and 2019. This study compared the predictive abilities of MELD, MELD-Na, and MELD 3.0, for 30-day and 90-day outcomes, specifically death or liver transplantation, and explored the factors influencing these outcomes., Results: A total of 1096 patients were included in the study, with a mean age of 53.3 ± 10.4 years, and 82.0% were male. The mean scores for MELD, MELD-Na, and MELD 3.0 at the time of admission were 18.7 ± 7.2, 20.6 ± 7.7, and 21.0 ± 7.8, respectively. At 30 and 90 days, 7.2% and 14.1% of patients experienced mortality or liver transplantation. The areas under the receiver operating characteristic curves for MELD, MELD-Na, and MELD 3.0 at 30 days were 0.823, 0.820, and 0.828; and at 90 days were 0.765, 0.772, and 0.776, respectively. Factors associated with the 90-day outcome included concomitant chronic viral hepatitis, prolonged prothrombin time, elevated levels of aspartate transaminase, bilirubin, and creatinine, and low albumin levels., Conclusion: MELD 3.0 demonstrated improved performance compared to previous models, although the differences were not statistically significant., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

As chronic inflammation and oxidative stress cause various diseases in the human body, this study aimed to develop functional materials to prevent inflammation and oxidative stress. This study investigated the biological function and components of Terminalia catappa L. extract prepared using its leaves and branches (TCE). TCE was determined using ultraperformance liquid chromatographyquadrupole-time-of-flight mass spectrometry. Using RAW 264.7 mouse macrophages, inhibitory effects of the identified compounds on nitric oxide (NO) and reactive oxygen species (ROS) generation were analyzed. Therefore, α-punicalagin was selected as an active compound with the highest content (986.6 ± 68.4 μg/g) and physiological activity. TCE exhibited an inhibitory effect on lipopolysaccharide (LPS)-induced inflammatory markers, including NO, inducible nitric oxide synthase, and inflammatory cytokines without exerting cytotoxicity. Moreover, TCE prevented excessive ROS production mediated by LPS and upregulated hemeoxygenase-1 expression via the nuclear translocation of nuclear factor erythroid 2-related factor 2. Interestingly, TCE prevented LPS-induced mitochondrial membrane potential loss, mitochondrial ROS production, and dynaminrelated protein 1 phosphorylation (serine 616), a marker of abnormal mitochondrial fission. Furthermore, TCE considerably repressed the activation of LPS-induced mitogen-activated protein kinase pathway. Thus, TCE is a promising anti-inflammatory and antioxidant pharmaceutical or nutraceutical, as demonstrated via mitochondrial dysfunction and cellular signaling pathway regulation.

Tranexamic acid (TXA) is a synthetic antifibrinolytic agent that has been used for several decades to reduce blood loss during surgery and after trauma. TXA was traditionally used to reduce bleeding in various clinical settings such as menorrhagia, hemophilia, or other bleeding disorder. Numerous studies have demonstrated the efficacy of TXA in reducing blood loss and the need for transfusions. Interest in the potential applications of TXA beyond its traditional use has been growing recently, with studies investigating the use of TXA in postpartum hemorrhage, cardiac surgery, trauma, neurosurgery, and orthopedic surgery. Despite its widespread use and expanding indications, data regarding the safe and appropriate use of TXA is lacking. Recent clinical trials have found various potential risks and limitations in the long-term benefits of TXA. This narrative review summarizes the clinical applications and limitations of TXA.

Background/aims: Shifts in the gut microbiota and metabolites are interrelated with liver cirrhosis progression and complications. However, causal relationships have not been evaluated comprehensively. Here, we identified complication-dependent gut microbiota and metabolic signatures in patients with liver cirrhosis., Methods: Microbiome taxonomic profiling was performed on 194 stool samples (52 controls and 142 cirrhosis patients) via V3-V4 16S rRNA sequencing. Next, 51 samples (17 controls and 34 cirrhosis patients) were selected for fecal metabolite profiling via gas chromatography mass spectrometry and liquid chromatography coupled to time-of-flight-mass spectrometry. Correlation analyses were performed targeting the gut- microbiota, metabolites, clinical parameters, and presence of complications (varices, ascites, peritonitis, encephalopathy, hepatorenal syndrome, hepatocellular carcinoma, and deceased)., Results: Veillonella bacteria, Ruminococcus gnavus, and Streptococcus pneumoniae are cirrhosis-related microbiotas compared with control group. Bacteroides ovatus, Clostridium symbiosum, Emergencia timonensis, Fusobacterium varium, and Hungatella&#95;uc were associated with complications in the cirrhosis group. The areas under the receiver operating characteristic curve (AUROCs) for the diagnosis of cirrhosis, encephalopathy, hepatorenal syndrome, and deceased were 0.863, 0.733, 0.71, and 0.69, respectively. The AUROCs of mixed microbial species for the diagnosis of cirrhosis and complication were 0.808 and 0.847, respectively. According to the metabolic profile, 5 increased fecal metabolites in patients with cirrhosis were biomarkers (AUROC > 0.880) for the diagnosis of cirrhosis and complications. Clinical markers were significantly correlated with the gut microbiota and metabolites., Conclusion: Cirrhosis-dependent gut microbiota and metabolites present unique signatures that can be used as noninvasive biomarkers for the diagnosis of cirrhosis and its complications.

Background: Futile recanalization (FR) after endovascular therapy (EVT) is common in basilar artery occlusion (BAO). The purpose of this study was to investigate the predictors of FR in the posterior circulation with an emphasis on the role of perfusion imaging and its relation to the underlying etiology., Methods: We included BAO patients who had pretreatment perfusion imaging and successful recanalization after EVT. Patients were dichotomized into futile and non-futile groups according to the favorable functional outcome at 90 days (modified Rankin Scale (mRS) 0-3). Perfusion abnormalities were assessed using an automated software for Tmax volume measurement and identification of hypoperfusion area based on Tmax>6 s involvement of the pons-midbrain-thalamus (PMT), cerebellum, and temporo-occipital lobe., Results: Of the 134 enrolled patients, the incidence of FR was 47.8% (64/134). Multivariate logistic analysis showed that a higher National Institutes of Health Stroke Scale (NIHSS) score on admission (adjusted OR (aOR) 1.066; 95% CI 1.011 to 1.125), a longer onset-to-recanalization time (aOR 1.002; 95% CI 1.001 to 1.004), incomplete recanalization (aOR 3.909; 95% CI 1.498 to 10.200), and PMT hypoperfusion (aOR 4.444; 95% CI 1.203 to 16.415) were independent predictors of FR. In patients with embolic occlusion of etiology, PMT hypoperfusion was associated with FR (aOR 8.379; 95% CI 1.377 to 50.994), whereas intracranial atherosclerotic stenosis (ICAS)-related occlusion was not (p=0.587)., Conclusions: In patients with BAO, the likelihood of FR is associated with PMT hypoperfusion on pretreatment perfusion imaging. In particular, PMT hypoperfusion may be used as an imaging predictor of FR in patients with embolic cause of BAO., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Backgruound: It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia., Methods: This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment., Results: After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. -0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (-55.20% vs. -7.69%, P<0.001) without previously unknown adverse drug events., Conclusion: The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin's preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.

Background: To evaluate the association between retinal artery/arteriole occlusion (RAO) and unruptured intracranial aneurysm (UIA)., Methods: Incident UIA patients from a nationwide cohort (n=253 240) were categorised into three groups based on subsequent treatment: observation (n=208 993), microsurgical clipping (n=14 168) and endovascular treatment (EVT) groups (n=30 079). The incidence and the incident time of RAO were analysed. HRs of RAO and associated risk factors were evaluated. Additionally, a hospital cohort comprising 2569 consecutive UIA patients treated at a tertiary hospital was analysed with detailed clinical information of UIAs., Results: In the nationwide cohort analysis, the incidence of RAO was significantly higher in EVT group than in observation and clipping groups, especially within 60 days (early RAO (within 60 days): HR=4.00, 95% CI: 2.44 to 6.56); delayed RAO (after 60 days): HR=1.74, 95% CI: 1.13 to 2.68). Multivariable analysis showed that the presence of chronic kidney disease (p=0.009) and use of a balloon microcatheter during the procedure (p=0.013) were associated with a higher risk of RAO. In hospital cohort analysis, 11 (0.8%) cases of RAO occurred after EVT, whereas none occurred after microsurgical clipping (p<0.001). Patients with RAO were younger and received balloon microcatheters more frequently than their counterparts. Ten cases of RAO (90.9%) occurred in paraclinoid aneurysms, where EVT was preferred over microsurgical clipping., Conclusions: Performing EVT for UIA may increase the risk of subsequent RAO. Care should be taken when treating paraclinoid aneurysms with balloon microcatheters., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The administration of an appropriate empirical antibiotic treatment is essential in cirrhosis and severe bacterial infections. We aimed to investigate the predictors of clinical response of empirical antibiotic treatment in a prospective cohort of patients with cirrhosis and bacterial and fungal infections included in the International Club of Ascites "Global Study.", Methods: Patients hospitalized with cirrhosis and bacterial/fungal infection were prospectively enrolled at 46 centers. Clinical response to antibiotic treatment was defined according to changes in markers of infection/inflammation, vital signs, improvement of organ failure, and results of cultures., Results: From October 2015 to September 2016, 1302 patients were included at 46 centers. A clinical response was achieved in only 61% of cases. Independent predictors of lack of clinical response to empirical treatment were C-reactive protein (OR = 1.16; 95% CI = 1.02-1.31), blood leukocyte count (OR = 1.39;95% CI = 1.09-1.77), serum albumin (OR = 0.70; 95% CI = 0.55-0.88), nosocomial infections (OR = 1.96; 95% CI = 1.20-2.38), pneumonia (OR = 1.75; 95% CI = 1.22-2.53), and ineffective treatment according to antibiotic susceptibility test (OR = 5.32; 95% CI = 3.47-8.57). Patients with a lack of clinical response to first-line antibiotic treatment had a significantly lower resolution rate of infections (55% vs. 96%; p < 0.001), a higher incidence of second infections (29% vs. 15%; p < 0.001), shock (35% vs. 7%; p < 0.001) and new organ failures (52% vs. 19 %; p < 0.001) than responders. Clinical response to empirical treatment was an independent predictor of 28-day survival ( subdistribution = 0.20; 95% CI = 0.14-0.27)., Conclusions: Four out of 10 patients with cirrhosis do not respond to the first-line antibiotic therapy, leading to lower resolution of infections and higher mortality. Broader-spectrum antibiotics and strategies targeting systemic inflammation may improve prognosis in patients with a high degree of inflammation, low serum albumin levels, and severe liver impairment., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Persea americana fruit (PAF) is a favorable nutraceutical resource that comprises diverse unsaturated fatty acids (UFAs). UFAs are significant dietary supplementation, as they relieve metabolic disorders, including obesity (OB). In another aspect, this study was focused on the anti-OB efficacy of the non-fatty acids (NFAs) in PAF through network pharmacology (NP). Natural product activity & species source (NPASS), SwissADME, similarity ensemble approach (SEA), Swiss target prediction (STP), DisGeNET, and online Mendelian inheritance in man (OMIM) were utilized to gather significant molecules and its targets. The crucial targets were adopted to construct certain networks: protein-protein interaction (PPI), PAF-signaling pathways-targets-compounds (PSTC) networks, a bubble chart, molecular docking assay (MDA), and density function theory (DFT). Finally, the toxicities of the key compounds were validated by ADMETlab 2.0 platform. All 41 compounds in PAF conformed to Lipinski's rule, and the key 31 targets were identified between OB and PAF. On the bubble chart, PPAR signaling pathway had the highest rich factor, suggesting that the pathway might be an agonism for anti-OB. Conversely, estrogen signaling pathway had the lowest rich factor, indicating that the mechanism might be antagonism against OB. Likewise, the PSTC network represented that AKT1 had the greatest degree value. The MDA results showed that AKT1-gamma-tocopherol, PPARA-fucosterol, PPARD-stigmasterol, (PPARG)-fucosterol, (NR1H3)-campesterol, and ILK-alpha-tocopherol formed the most stable conformers. The DFT represented that the five molecules might be promising agents via multicomponent targeting. Overall, this study suggests that the NFAs in PAF might play important roles against OB., (© 2024 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)