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Background and Aim Materials and Methods Results Conclusion Vitamin K deficiency is common in persons with kidney disease, which is a known complication of diabetes. We aimed to assess the association of vitamin K status as reflected by plasma dephosphorylated‐uncarboxylated matrix Gla protein (dp‐ucMGP) with mortality, cardiovascular disease (CVD) and progression to end‐stage kidney disease (ESKD) in persons with type 1 diabetes.We analysed plasma dp‐ucMGP in stored baseline samples from a cohort of 667 persons with type 1 diabetes (baseline visit: 2009–2011). Information on mortality and CVD was obtained through linkage to registers. Cox‐proportional hazards models were applied to estimate hazard ratios (HRs) of mortality, CVD and ESKD per one doubling of dp‐ucMGP.A total of 53 deaths were recorded during follow‐up. Persons with higher dp‐ucMGP (reflecting lower vitamin K status) had higher mortality in the unadjusted model (HR: 2.06 [95% confidence interval—CI: 1.22–3.45]), but not in the fully adjusted model (HR: 0.88 [95% CI: 0.44–1.73]). Particularly, adjustment for glomerular filtration rate and urinary albumin excretion rate attenuated the HR. A similar pattern was observed in unadjusted models for incidence of CVD (HR: 1.58 [95% CI: 1.03–2.42]) and risk of ESKD (HR: 7.62 [95% CI: 4.25–13.68]). In the fully adjusted models, the HRs became statistically insignificant.In persons with type 1 diabetes, lower vitamin K status was associated with higher mortality, CVD and progression to ESKD, however, not after adjustment for other risk factors. Interventional studies are needed to elucidate the role of vitamin K in persons with type 1 diabetes. [ABSTRACT FROM AUTHOR]

Background: The suicide risk in patients with atrial fibrillation receiving novel oral anticoagulants or warfarin has not been evaluated in real-world practice. Moreover, reducing vitamin K levels may increase the suicide risk, underscoring the importance of selecting appropriate oral anticoagulants to prevent unintended outcomes. Therefore, we aimed to evaluate the association between different types of oral anticoagulants and the risk of attempted and completed suicide among patients with atrial fibrillation. Methods: This nationwide study retrieved data from Taiwan's National Health Insurance Research Database from 2012 to 2020. This study included patients with atrial fibrillation aged 20 years and older who newly received oral anticoagulant treatment, and who had no contraindications for NOACs and no history of suicide-related events. The main outcomes were suicide-related outcomes, including attempted suicide and completed suicide. This study employed the target trial emulation framework to improve the causal inference for the observed association. Results: A total of 103,768 (71.74%) patients taking NOACs and 40,877 (28.26%) patients taking warfarin were included in this study. Compared to those receiving warfarin, patients receiving NOACs were associated with a lower risk of suicide-related outcomes (HR, 0.82; 95% CIs, 0.69–0.96). Conclusions: The findings of this cohort study suggested that patients receiving NOACs were associated with a lower risk of suicidal attempts but similar risk of complete suicide, compared to those receiving warfarin. Considering the risk of suicide, NOACs could be the preferred anticoagulants for patients with atrial fibrillation. [ABSTRACT FROM AUTHOR]

Simple Summary: Vitamin D3 and vitamin K3 each play a crucial role in the growth, skeletal development, and regulation of bone biomarkers and calcium homeostasis in larval and juvenile gilthead seabream. Although their interaction has been shown to influence these parameters in animals and humans, there is limited research on this interaction in fish. In this study, juvenile gilthead seabream was fed diets with varying combinations of vitamin D3 and K3. The results showed no significant effects on growth, serum calcitriol levels, or morphometric parameters. However, a significant impact was observed on bone biomarkers and calcium-regulating genes across different tissues. Additionally, there was an increasing tendency of skeletal anomalies with higher vitamin levels. These findings suggest that, while dietary vitamin D3 and K3 can modulate bone biomarkers and calcium-regulating genes in fish, they do not significantly influence growth or serum calcitriol, likely due to the size and developmental stage of the fish. Based on this, we recommend considering vitamin D3 and K3 in diets to support skeletal health but note that they may not yield substantial changes in growth outcomes for juvenile gilthead seabream. The interaction between vitamin D and vitamin K is crucial for regulating bone metabolism and maintaining calcium homeostasis across diverse animal species due to their complementary roles in calcium metabolism and bone health. However, research on this interaction of vitamin D and K in fish, particularly Mediterranean species like gilthead seabream, is limited or not studied. This study aimed to understand the effects of different dietary combinations of vitamin D3 and K3 on juvenile gilthead seabream. Accordingly, seabream juveniles were fed with varying combinations of vitamin D3/vitamin K3 (mg/kg diet) for 3 months: (0.07/0.01), (0.20/0.58), (0.19/1.65), (0.51/0.74), (0.56/1.00). At the end of the trial, survival, growth, body morphology, serum calcitriol, and vertebral mineral composition remained unaffected by varying vitamin levels, while gene expression patterns related to bone formation, resorption, and calcium regulation in various tissues were significantly influenced by both vitamins and their interaction. Gilthead seabream juveniles fed the 0.07/0.01 mg/kg diet upregulated calcium-regulating genes in the gills, indicating an effort to enhance calcium absorption to compensate for dietary deficiencies. Conversely, an increase in vitamin D3 and K3 up to 0.19 and 1.65 mg/kg, respectively, upregulated bone formation, bone remodeling, and calcium homeostasis-related gene expression in vertebra and other tissues. On the contrary, a dietary increase in these vitamins up to 0.56 mg/kg vitamin D3 and 1.00 mg/kg vitamin K3 downregulated calcium metabolism-related genes in tissues, suggesting an adverse interaction resulting from elevated levels of these vitamins in the diet. Hence, sustaining an equilibrium in the dietary intake of vitamin D3 and vitamin K3, in an appropriately combined form, may potentially induce interactions between the vitamins, contributing to favorable effects on bone development and calcium regulation in gilthead seabream juveniles. [ABSTRACT FROM AUTHOR]

Background/Objectives: Chronic kidney disease and mineral bone disorders (CKD-MBD) are frequently associated with an increased risk of both vascular calcifications (VCs) and bone fractures (BFs). The complex pathogenesis of VCs and BFs involves various factors such as calcium overload, phosphate imbalance, and secondary hyperparathyroidism. Key players, such as the vitamin K-dependent proteins (VKDPs) matrix Gla protein (MGP) and bone Gla protein (BGP), have pivotal roles both for VCs and BFs. The VIKI study highlighted that hemodialysis patients treated with calcimimetics had higher levels of total BGP and MGP compared to those untreated, suggesting a potential protective effect of these drugs on BFs and VCs beyond the beneficial effect of reducing PTH levels. Methods: ETERNITY-ITA is a multi-center, comparative effectiveness, observational, longitudinal study that will enroll 160 hemodialysis patients (80 patients treated with Etelcalcetide and 80 age- and sex-matched patients treated with calcitriol or vitamin D analogs). Nephrologists will tailor the target dose of Etelcalcetide on an individual level to achieve the KDIGO PTH target. In the Etelcalcetide-treated group, the addition of calcitriol will be allowed when required by clinical practice (for correction of hypocalcemia). Conclusions: This study will evaluate the real-world effect of Etelcalcetide on VKDP levels, such as BGP and MGP, at 3, 9, and 18 months from baseline. The resulting preservation of vascular and bone health will be assessed for the first time by examining aortic and iliac artery calcifications and vertebral fractures, respectively. [ABSTRACT FROM AUTHOR]

Background: The optimal approach for anticoagulation in patients with bioprosthetic valves and atrial fibrillation (AF) remains a subject of debate. A meta-analysis using updated evidence to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) compared to vitamin K antagonists (VKAs) in patients with AF and bioprosthetic valves to address this controversy. Methods: A comprehensive search was conducted in multiple databases, including PubMed, Scopus, Web of Science, ProQuest, and the Cochrane Central Register of Controlled Trials, up until March 2023. The search aimed to identify relevant randomized controlled trials (RCTs) that examined the efficacy and safety outcomes of both direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in patients with bioprosthetic valves and atrial fibrillation. The primary outcomes of interest were major bleeding and all-cause mortality. Results: Our study demonstrated that despite the difference was not significant, the hazard of all-cause mortality was 2.5% higher in the DOAC group (HR = 1.03, 95% CI = [0.88, 1.19], p-value =.75). Similarly, the hazard of stroke (HR = 1.03, 95% CI = [0.87, 1.32], p-value =.71) and major bleeding (HR = 1.11, 95% CI = [0.89, 1.38], p-value =.36) were found to be respectively 3.2 and 10.7% higher in the DOAC group, although the difference was not significant. However, the hazard of intracranial hemorrhage was found to be 28.8 lower in the DOAC treatment group (HR = 0.71, 95% CI = [0.39, 1.31], p-value =.27), which again was not statistically significant. Conclusions: Our meta-analysis demonstrates that in patients undergoing bioprosthetic valve surgery and presenting with AF afterward, DOAC and VKA are similar regarding life-threatening and all-cause mortality outcomes, including major bleeding, stroke, and intracranial hemorrhage. [ABSTRACT FROM AUTHOR]

Background: Four-factor prothrombin complex concentrate (4F-PCC) is indicated for vitamin K antagonist (VKA) reversal but is associated with thrombotic events (TE). In 2018, the institution revised 4F-PCC dosing for VKA reversal from INR and weight-based dosing to a fixed-dose of 1500 units. Objective: The purpose of this study was to compare hemostatic efficacy and TE rate of fixed-dose 4PCC to weight-based dosing. Methods: This was a retrospective, single-center, quasi-experimental study of adult patients who received 4F-PCC for VKA reversal from January 2014 through May 2016 (INR and weight-based dosing) or April through October 2018 (fixed-dosing). The primary endpoint was hemostatic efficacy, defined by achieving an INR of ≤1.4, or an INR of ≤1.7 with evidence of hemostasis. The key secondary endpoint was TE within 14 days of 4F-PCC administration. Data were analyzed using descriptive statistics, chi-squared for nominal data and Mann-Whitney U for ordinal and continuous data. Results: The study included 163 patients who received weight-based dosing and 45 who received fixed-dose 4F-PCC. Hemostatic efficacy was 76.9% of patients in the weight-based group and 77.4% of patients in the fixed-dose group (P =.229). TE occurred in 13.5% of the weight-based vs 6.7% of the fixed-dose group (P =.181). Conclusion: This study found no difference in hemostatic efficacy with fixed-dose 4F-PCC for VKA reversal compared to INR and weight-based dosing. The occurrence of TE was reduced by 50% with the 4F-PCC fixed-dose strategy; however, this difference was not statistically significant. Further randomized studies are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Aim: Evaluating the impact of vitamin K prophylaxis on cefoperazone-sulbactam-induced coagulopathy in critically ill patients. Methods: We conducted a randomized controlled trial on critically ill adult patients treated with cefoperazone-sulbactam. Patients received systemic cefoperazone-sulbactam antibiotics of 1.5 to 2 g every 12 hours. Patients were randomized into 2 groups: the intervention group (Gp-I), who received a 10 mg intravenous dose of vitamin K every week until cefoperazone-sulbactam therapy ended, and the control group (Gp-C), who received only cefoperazone-sulbactam. Results: Our main finding was the significantly higher survival probability from coagulopathy in Gp-I than in Gp-C using the Kaplan-Myers curve (χ2 = 25.5, P <.001). The adjusted hazard ratios for coagulopathy obtained from the Cox regression analysis revealed that the intervention was significantly associated with a 99% reduction in the hazard of coagulopathy relative to Gp-C (HR = 0.01, P =.001). The Kaplan-Myers curve indicated a significantly higher survival probability from bleeding in Gp-I than in Gp-C (χ2 = 9, degree of freedom = 1, P =.005). Conclusion: In critically ill patients, intravenous prophylactic doses of vitamin K of 10 mg per week prevent cefoperazone-sulbactam-induced coagulopathy. Therefore, we recommend adding vitamin K supplementation to ICU protocols in Egypt for cefoperazone-sulbactam safety. [ABSTRACT FROM AUTHOR]

Introduction: Direct oral anticoagulants (DOACs) become the recommended treatment over vitamin K antagonists (VKA) in patients with non‐valvular atrial fibrillation (AF). However, their effectiveness in reducing cognitive impairment and dementia compared to VKA remains unclear. Methods: A systematic literature search was conducted on Ovid MEDLINE, EMBASE, and Cochrane Database. Randomized controlled trials, cohort, or case–control study that assessed incident dementia between AF patients who received DOAC compared to VKA were selected. Relevant study characteristics and the number of incident dementia diagnosis or hazard ratios (HRs) for incident dementia and each dementia subtypes were extracted. Random‐effects model was used to perform meta‐analysis. Standardized mean differences (SMDs) were used to estimate effect sizes for continuous data. Results: Twelve cohort studies comprising 1 451 069 individuals were included. The incidence of dementia was lower in AF patients prescribed DOACs compared to VKA (HR 0.88, 95% CI 0.83–0.93, I2 = 61.2%). A lower incident dementia in DOACs group relative to VKA was significantly observed in those less than 75 years of age (< 65 years, HR 0.83 (95% CI 0.72–0.97, I2 = 0%); 65–74 years, HR 0.86 (95% CI 0.81–0.92, I2 = 55.4%); and ≥ 75 years, HR 1.07 (95% CI 0.74–1.55, I2 = 92.5%)) and for the subgroup of patients with vascular dementia (HR 0.91, 95% CI 0.824–0.997, I2 = 0%). Conclusions: This meta‐analysis reveals a reduction in incidence of dementia in AF patients prescribed DOACs compared to VKA, particularly in those less than 75 years old and in the vascular dementia subtype. [ABSTRACT FROM AUTHOR]

Aim: The present study aimed to investigate the histomorphometric and immunohistochemical impacts of vitamin K2 on guided bone regeneration (GBR) in calvarial critical‐size defects (CSDs) in diabetic rats. Methods: A total of 30 rats were used in this study, comprising 12 non‐diabetic (control) rats and 18 with streptozotocin‐nicotinamide‐induced experimental Diabetes mellitus (DM). In all rats, two calvarial CSDs were created: one defect was left empty (E), the other was treated with bovine‐derived bone graft and collagen‐based resorbable membrane (GM). Study groups were as follows: control rats administered saline (n = 6, C‐E and C‐GM groups) or vitamin K2 (n = 6, CK‐E and CK‐GM groups) and diabetic rats administered saline (n = 6, DM‐E and DM‐GM groups) or vitamin K2 (n = 6, DMK‐E and DMK‐GM groups). After 4 weeks of saline or vitamin K2 administration, the rats were euthanized. Bone defect healing and new bone formation were assessed histomorphometrically, and osteocalcin and osteopontin levels were examined immunohistochemically. Results: Percentage of new bone formation was greater in CK‐GM vs. CK‐E and in DMK‐GM vs. DMK‐E [d = 3.86 (95% CI = 16.38–28.61), d = 1.86, (95% CI = 10.74–38.58), respectively, p <.05]. Bone defect healing scores were higher in CK‐GM vs. CK‐E and in DMK‐GM vs. DMK‐E [d = 2.69 (95% CI = ‐2.12 to −0.87), d = 3.28 (95% CI = 0.98–1.91), respectively, p <.05]. Osteocalcin expression levels were elevated in CK‐GM vs. CK‐E, in DMK‐GM vs. DMK‐E [d = 1.19 (95% CI = 0.08–1.41), d = 1.10 (95% CI = 0.02–1.22), respectively p <.05]. Vitamin K2 enhanced osteocalcin expression levels in DMK‐E vs. DM‐E [d = 2.78, (95% CI = 0.56–1.53), p <.05] and in DMK‐GM vs. DM‐GM [d = 2.43, (95% CI = 0.65–2.10), p <.05]. Osteopontin expression was enhanced in defects treated with GM vs. E defects [C‐GM vs. C‐E, d = 1.56 (95% CI = 0.38–2.01); CK‐GM vs. CK‐E, d = 1.91 (95% CI = 0.49–1.72); DM‐GM vs. DM‐E, d = 2.34 (95% CI = ‐1.12 to −0.50); DMK‐GM vs. DMK‐E, d = 2.00 (95% CI = 0.58–1.91), p <.05]. Conclusion: The research findings suggest that administering vitamin K2 in GBR for rats with DM favorably impacts bone healing in CSDs, presenting an adjunctive strategy for bone regeneration. [ABSTRACT FROM AUTHOR]

Objectives: This study sought to understand the levels of vitamin K in the mature milk of Chinese lactating mothers, thereby providing a foundation for the development of appropriate intake (AI) of vitamin K for infants aged 0–5 months. Methods: Five hundred healthy lactating mothers were selected from the mature milk bank established by the Chinese Maternal and Infant Nutrition and Health Cohort by using a simple random sample procedure. Relevant information about lactating mothers and their infants was obtained by a questionnaire survey. Vitamin K1 and vitamin K2 (MK-4 and MK-7) in mature milk were determined by liquid chromatography–tandem mass spectrometry. Results: The total concentration of vitamin K in mature milk was 4.50 (2.85–6.33) ng/mL. The concentrations of vitamin K1, vitamin K2, MK-4, and MK-7 were 2.81 (1.66–4.39) ng/mL, 1.37 (0.75–2.11) ng/mL, 1.20 (0.58–1.97) ng/mL, and 0.13 (0.08–0.19) ng/mL, respectively. The concentration of vitamin K1 was highest and the concentration of MK-7 was lowest. The concentrations of vitamin K2 and MK-4 in mature milk from the south were significantly higher than those in mature milk from the north. The total vitamin K, vitamin K2, and MK-4 concentrations in mature milk of lactating mothers residing in urban areas were higher than those in rural areas. There was a tendency for the concentration of total vitamin K and vitamin K1 to increase with the mother's age. Moreover, the concentration of MK-4 in mature milk was highest in summer, followed by spring and winter. The levels of vitamin K1 and MK-4 in mature milk were found to be affected by lactation stage; they were highest at 91–120 days and lowest at 31–60 days. Conclusions: Based on the concentration of vitamin K in mature milk found in this study, it is recommended that the appropriate intake of VK for Chinese infants aged 0–5 months is 3.49 μg/d (2.18 μg/d for VK1 and 1.06 μg/d for VK2). [ABSTRACT FROM AUTHOR]

Background We assessed the influence of prior nonvitamin K antagonist (NOAC) use on stroke outcomes after endovascular treatment (EVT) in patients at a high risk of stroke based on their pre-stroke CHA2DS2-VASc score, and compared them with those who did not use any antithrombotic (NAU) or antiplatelet (APT) agents. Methods Data were collected from a multicenter database comprising consecutive acute ischemic stroke patients who underwent EVT during a span of 103 months. We evaluated pre-stroke CHA2DS2-VASc scores in enrolled patients and measured instances of successful reperfusion and symptomatic hemorrhagic transformation (SHT) following EVT as the main outcome measures. Results Among 12 807 patients with acute ischemic stroke, 3765 (29.4%) had a history of atrial fibrillation. Of these, 418 patients with CHA2DS2-VASc scores ≥2 received EVT alone. The prior NOAC group showed higher successful reperfusion rates compared with the prior NAU and APT groups (p=0.04). Multivariate analysis revealed that prior NOAC use increased the likelihood of successful reperfusion after EVT (OR [95% CI] 2.54 [1.34 to 4.83], p=0.004) and improved stroke outcomes, while the prior APT group did not. Furthermore, the prior NOAC use group was not associated with SHT after EVT. Propensity score matching confirmed these findings. Conclusion Prior use of NOAC is associated with improved outcomes in high-risk stroke patients (pre-stroke CHA2DS2-VASc score ≥2) undergoing EVT. [ABSTRACT FROM AUTHOR]

The Pharmacogene Variation Consortium (PharmVar) serves as a global repository providing star (*) allele nomenclature for the polymorphic human CYP4F2 gene. CYP4F2 genetic variation impacts the metabolism of vitamin K, which is associated with warfarin dose requirements, and the metabolism of drugs, such as imatinib or fingolimod, and certain endogenous compounds including vitamin E and eicosanoids. This GeneFocus provides a comprehensive overview and summary of CYP4F2 genetic variation including the characterization of 14 novel star alleles, CYP4F2*4 through *17. A description of how haplotype information cataloged by PharmVar is utilized by the Pharmacogenomics Knowledgebase (PharmGKB) and the Clinical Pharmacogenetics Implementation Consortium (CPIC) is also provided. [ABSTRACT FROM AUTHOR]

Phylloquinon (PK) and menaquinones (MK) are both naturally occurring compounds belonging to vitamin K group. Present study aimed to comprehensively analyze the influence of PK in several models of vascular dysfunction to determine whether PK has vasoprotective properties, similar to those previously described for MK. Effects of PK and MK on endothelial dysfunction were studied in ApoE/LDLR−/− mice in vivo, in the isolated aorta incubated with TNF, and in vascular cells as regard inflammation and cell senescence (including replicative and stress-induced models of senescence). Moreover, the vascular conversion of exogenous vitamins to endogenous MK-4 was analyzed. PK, as well as MK, given for 8 weeks in diet (10 mg/kg) resulted in comparable improvement in endothelial function in the ApoE/LDLR−/− mice. Similarly, PK and MK prevented TNF-induced impairment of endothelium-dependent vasorelaxation in the isolated aorta. In in vitro studies in endothelial and vascular smooth muscle cells, we identified that both PK and MK displayed anti-senescence effects via decreasing DNA damage while in endothelial cells anti-inflammatory activity was ascribed to the modulation of NFκB activation. The activity of PK and MK was comparable in terms of their effect on senescence and inflammation. Presence of endogenous synthesis of MK-4 from PK in aorta and endothelial and smooth muscle cells suggests a possible involvement of MK in vascular effects of PK. In conclusion, PK and MK display comparable vasoprotective effects, which may be ascribed, at least in part, to the inhibition of cell senescence and inflammation. The vasoprotective effect of PK in the vessel wall can be related to the direct effects of PK, as well as to the action of MK formed from PK in the vascular wall. [ABSTRACT FROM AUTHOR]

The health-promoting properties of vitamin K stimulate the growing interest in this compound, which translates into the development of new analytical methodologies for its determination. New, more efficient methods of its isolation are sought, paying increasingly more attention to the methods within currently available extraction techniques that, owing to the optimization of the process, not only increase the extraction efficiency but are also economical and environmentally friendly. This article proposes a procedure for the extraction and analysis of one of the vitamin K vitamers, i.e., vitamin K1, using PLE and LC-MS/MS. It has been shown that the PLE technique can be optimized with a mathematical model—accelerating and reducing the costs of the extraction process—which, together with process automation, bodes well for industrial applications. The optimized process was used to extract vitamin K1 from various vegetables, showing very different contents of the test compound ranging from 1.22 to 114.30 µg/g dry weight for avocado and spinach, respectively. In addition, by showing the effect of water within the material subjected to extraction on the variable yield of vitamin K1, attention was drawn to the need to standardize the analytical methods used in assessing the quality of food products. [ABSTRACT FROM AUTHOR]

Microgreens have recently gained popularity owing to their reliable economic and nutritional value. This study aimed to increase the quality of microgreen broccoli via treatment with different concentrations (1%, IPB-1; 3%, IPB-3; 5%, IPB-5; or 7%, IPB-7 w/v) of illite—a natural mineral powder. The results showed that the illite treatments considerably increased the content of mineral elements, such as Ca, P, and K; of vitamin C; and of free amino acids; and also increased the total weight of the broccoli sprouts. The content of sulforaphane, a bioactive compound, also increased by up to 47% with illite treatment, with the highest increase being in the IPB-5 group. However, several of the parameters were lower in the IPB-7 group. Aromatic compounds were categorized by functional groups such as hydrocarbons which numbered 36, 30, 34, 28, and 30 in the control, IPB-1, IPB-3, IPB-5, and IPB-7 groups, respectively. We found 16, 15, 15, 13, and 14 sulfides, including dimethyl sulfide, in the control, IPB-1, IPB-3, IPB-5, and IPB-7 groups, respectively. Additionally, aldehydes, comprising seven compounds, were detected in the IPB-1, IPB-3, IPB-5, and IPB-7 groups. Illite treatment significantly increased the activities of antioxidants such as DPPH and the polyphenol content of the microgreens. These results indicate a potential role for appropriate illite doses in microgreen treatment to address multinutrient deficiencies and to increase the quality of microgreen vegetables. [ABSTRACT FROM AUTHOR]

Background: Bromadiolone is a wide-use long-acting anticoagulant rodenticide known to cause severe coagulation dysfunction. At present, there have been no detailed reports of acute kidney injury (AKI) resulting from bromadiolone poisoning. Case presentation: A 27-year-old woman was admitted to the hospital due to severe coagulopathy and severe AKI. Coagulation test revealed a prothrombin time exceeding 120 s and an international normalized ratio (INR) greater than 10. Further examination for coagulation factors showed significantly reduced level of factors II, VII, IX and X, indicating a vitamin K deficiency. The AKI was non-oliguric and characterized by gross dysmorphic hematuria. Following the onset of the disease, the patient's serum creatinine rose from 0.86 to 6.96 mg/dL. Suspecting anticoagulant rodenticide poisoning, plasma bromadiolone was identified at a concentration of 117 ng/mL via gas chromatography/mass spectrometry. All other potential causes of AKI were excluded, except for the presence of a horseshoe kidney. The patient's kidney function fully recovered after the coagulopathy was corrected with high doses of vitamin K and plasma transfusion. At a follow-up 160 days post-discharge, the coagulation function had normalized, and the serum creatinine had returned to 0.51 mg/dL. Conclusion: Bromadiolone can induce AKI through a severe and prolonged coagulation disorder. Kidney function can be restored within days following treatment with high-dose vitamin K1. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is the second critical cause of cancer‐related deaths, with African Americans dying at higher rates in the U.S. The main reasons for the higher mortality rate are ethnic differences and lack of understanding of prostate cancer biology and affordable treatments, as well as the financial burden of African American men to obtain the most effective and safe treatments. The effect of micronutrients, including Vitamin K, on various cancer cell lines has been widely studied, but the potential anticancer effect of VK3‐OCH3, an analog of vitamin K3 (Menadione), on African American prostate cancer has not been evaluated. In this study, we compared the anticancer effect of VK3‐OCH3 on targeting African American derived PCa cell lines namely RC77‐T and MDA‐PCa‐2b. Our results show that VK3‐OCH3 significantly inhibits the proliferation of both RC77‐T and MDA‐PCa‐2b African American PCa cells and promotes apoptosis, and the underlying mechanism of cell death appears to be similar in both the cell lines. Notably, VK3‐OCH3 inhibits colony‐forming ability and induces apoptosis by blocking the cell cycle at G0 in African American PCa cells. VK3‐OCH3 also acts as an anti‐metastatic agent by inhibiting the migration ability of the metastatic properties of African American PCa cells. The cell death of African American PCa cells mediated by VK3‐OCH3 is associated with the production of free radicals, such as intracellular and mitochondrial reactive oxygen species (ROS). Interestingly, antioxidants such as N‐Acetylcysteine (NAC) and Glutathione (GSH) effectively negated the oxidative stress induced by VK3‐OCH3 on PCa cell lines derived from African American patients. Of note, VK3‐OCH3 reduces androgen receptor and prostate‐specific antigen expression in these PCa cells. Furthermore, molecular dynamic studies reiterated that VK3‐OCH3 strongly binds to the androgen receptor, suggesting that the androgen receptor is the potential molecular target of VK3‐OCH3. In addition, Western blot analysis showed that VK3‐OCH3 reduces the expression of androgen receptor, TRX2, and anti‐apoptotic signaling molecules such as Bcl‐2 and TCTP in the MDA‐PCa‐2b metastatic PCa cellular model. In conclusion, our results suggested that VK3‐OCH3 is a promising anticancer agent that could potentially reduce the mortality rates of African American PCa patients, warranting further preclinical and translational studies. [ABSTRACT FROM AUTHOR]

The experiment was conducted in Al-Diwaniyah Governorate, Iraq, during the 2022-2023 agricultural season (three months) on lettuce (Lactuca sativa var. capitata). The study aimed to investigate the effect of spraying lettuce plants with an algal extract from Cladophora glomerata, isolated from a stream at the University of Al-Qadisiyah, at concentrations of 2 and 4g/ L. Results indicated an increase in vegetative growth characteristics, including plant height, number of leaves, fresh weight, and total leaf area, with the highest averages being 20.66cm, 24 leaves, 135g, and 5260.26cm², respectively. Additionally, chemical content characteristics such as carbohydrates, vitamin C, total nitrogen, phosphorus, sulfur, and iron showed mean values of 1.6%, 4.12mg/ 100g fresh weight, 3.72%, 0.25%, 72.45mg/ g dry weight, and 1.32%, respectively, when treated with 4g/ L of algal extract. In comparison, control plants showed the lowest values. Treatment with 2g/L of algal extract resulted in higher mean values for dry weight, total chlorophyll, carotenoids, protein, vitamins A and K, potassium, zinc, calcium, and fiber, with values of 11.64g, 1.89mg/ g, 0.21%, 1.39%, 200.72mg/ 100g fresh weight, 108.47mg/ 100g fresh weight, 1.2%, 2.94mg/ 100g fresh weight, 60.9mg/ 100g, and 1.6%, respectively, compared to the control plants. Statistical analysis revealed significant differences (P≤ 0.05) between all parameters, except for plant height and iron, where the differences were not significant among the experimental treatments. [ABSTRACT FROM AUTHOR]

Le bilan d'hémostase standard (taux de prothrombine [TP] et temps de céphaline avec activateur [TCA]) est très couramment prescrit mais son interprétation peut poser problème pour les cliniciens. Nous rappelons ici les bases de la démarche diagnostique devant ces tests. Seule une connaissance très basique de la cascade de la coagulation est nécessaire pour identifier les dosages de facteurs de la coagulation à prescrire et interpréter les résultats. En cas de déficit en plusieurs facteurs, on s'orientera vers une insuffisance hépatocellulaire, une coagulation intravasculaire disséminée ou une carence en vitamine K. Devant la baisse d'un seul facteur de la coagulation, nous rappelons les différentes causes de déficits acquis et évoquons brièvement les caractéristiques des différents déficits congénitaux qui relèvent généralement d'une prise en charge spécialisée. L'anticoagulant circulant de type lupique est une cause fréquente et généralement bénigne d'allongement du TCA à connaître, ne devant pas faire craindre un risque hémorragique. Une bonne connaissance de la démarche diagnostique devant une anomalie du TP ou du TCA permet généralement de débrouiller les situations les plus courantes. The standard hemostasis workup [quick time (QT), and activated partial thrombin time (APTT)] is very commonly prescribed but its interpretation is often difficult for practitioners who are not specialized in hemostasis. Here, we review the principles of the diagnostic approach to these tests. Only a very basic knowledge of the coagulation cascade is necessary to identify which clotting factor tests to prescribe and to interpret the results. Deficiency in several clotting factors suggests liver dysfunction, disseminated intravascular coagulation (DIC) or vitamin K deficiency. If a single factor is deficient, we review the different causes of acquired deficiencies and briefly discuss the characteristics of the different congenital defects, which generally require specialized management. Lupus anticoagulant is a common and generally benign cause of prolonged APTT to be aware of, which is not related to a hemorrhagic risk. A good knowledge of the diagnostic approach to abnormal QT or APTT generally allows the resolution of the most common situations. [ABSTRACT FROM AUTHOR]

Vitamin K is one of the many health-promoting substances whose impact on the human body has been underestimated until recently. However, recently published research results have changed this situation, prompting some researchers to consider it a new panacea for diseases of old age. The result is a significant increase in interest in the accurate analysis of vitamin K in various types of samples, ranging from food, through dietary supplements, to biological matrices and clinical trials, both observational and interventional. This review summarizes the current state of knowledge about the proven and speculated biological activity of vitamin K and its importance for the world's aging societies, including the methods used for its isolation and analysis in various matrices types. Of all the analytical methods, the currently preferred methods of choice for the direct analysis of vitamin K are chromatographic methods, in particular liquid chromatography-tandem mass spectrometry. This technique, despite its sensitivity and selectivity, requires an appropriate stage of sample preparation. As there is still room for improvement in the efficiency of these methods, especially at the sample preparation stage, this review shows the directions that need to be taken to make these methods faster, more efficient and more environmentally friendly. [ABSTRACT FROM AUTHOR]

Contrecoup brain injury refers to the classical opposite of the primary impact. Tamil Nadu has the highest rate of road traffic accident in India. Madurai has peak mortality due to accidents in India. Previous studies done on contrecoup head injury had shown patterns of injuries and mechanism of injury. Outcome and management of only occipitofrontal contrecoup head injury has been taken in this study. Mortality in this specific group is very high. Seventy-six patients of this specific head injury were admitted at Government Rajaji Hospital, Madurai. Patients were assessed for Glasgow coma scale (GCS), age, sex, progression of volume, mortality, traumatic brain injury-induced coagulopathy, and pillion rider outcome. Fourteen patients were surgically treated by decompressive craniectomy. Conservative management was done by antiepileptic and antiedema measures. Mostly affected were males (n = 54) followed by females (n = 22). GCS on admission mean value 9. In our study, mortality was 32% with sudden death of three patients due to hypothalamic compression. Hospital stay of the patient was significantly increased with progression of lesion with mean 9 days and p -value less than 0.01. Pillion riders (n = 18) were also affected in our study. Traumatic brain injury-induced coagulopathy (n = 12) was also detected, which was treated by injection tranexamic acid and injection vitamin K, thereby not leading to any death due to coagulopathy with significant p -value less than 0.01. We recommend helmet for both main and pillion rider with strict speeding regulations. [ABSTRACT FROM AUTHOR]

The performance of MALDI-TOF MS combined with analysis platform for identification of toxin-producing Clostridiodes difficile is yet to be known. Between August 2018 and September 2020, 61 isolates from stool specimens of patients with C. difficile -associated diarrhea were analyzed using the MALDI Biotyper system. A C. difficile toxin-producer detection model was developed using ClinProTools. The model was validated using 28 known strains that differed from the isolates used to develop the model. The sensitivity and specificity of the Genetic Algorithm (GA) model using isolates grown on Brucella with hemin and vitamin K (BHK) agar plates were 91.7% and 44.4%, respectively. When isolates grown on cycloserine-cefoxitin mannitol agar were analyzed by the model, sensitivity and specificity were 6.3% and 100%, respectively. The GA model using BHK medium showed the highest discriminatory performance in detection of toxin-producing C. difficile. However, a discrepancy in detection of toxin-producing C. difficile was observed in the results generated when the model was being developed and when the model was validated which suggests that incubation conditions may have affected the results. MALDI-TOF analysis using ClinProTools has a potential to be a cost-effective tool for rapid diagnosis and contribute to antimicrobial stewardship by differentiating toxin-producing C. difficile from non-producers. [ABSTRACT FROM AUTHOR]

To investigate whether patients with severe motor and intellectual disability (SMID) have nutritional vitamin D and K insufficiencies and clarify the required vitamin supplementation. This prospective observational study enrolled Japanese adults with SMID receiving institutionalized care who underwent blood sampling between February 2020 and February 2022 during annual medical checkups. Serum vitamin K 1 and 25-hydroxy vitamin D (25(OH)D) levels were measured to determine their relationship with serum uncarboxylated osteocalcin (ucOC) levels. Vitamin D and K intake was compared among tube-fed and oral-intake patients with SMID and control participants using corresponding serum levels. The study included 124 patients with SMID (56 men and 68 women; mean age: 53.0 years) and 20 control participants. Serum 25(OH)D levels were significantly higher in the SMID group than in the control group and the oral intake SMID group than in the tube-fed SMID group. In the tube-fed SMID group, vitamin D intake was lower than the daily recommended intake and correlated with serum 25(OH)D levels. Daily vitamin K intake in the tube-fed group was lower than recommended but not correlated with serum vitamin K levels. Serum ucOC levels were significantly higher in the SMID group than in the control group. Tube feeding was significantly and positively correlated with serum 25(OH)D levels. Serum 25(OH)D levels were not correlated with serum vitamin K 1 levels. The SMID group had higher ucOC levels than the control group, possibly owing to daily vitamin K and D deficiencies. Vitamin D supplementation is recommended to decrease ucOC levels. [ABSTRACT FROM AUTHOR]

Proximal femur fractures (PFF) pose a major challenge in elderly patients with severe comorbidities and receiving antithrombotic therapy since according to the latest guidelines the surgery should be performed as soon as possible, preferably within 24 hours, to reduce mortality and morbidity. This review outlines the practical approach to surgical management of PFF that relies on increasing evidence of safety of early surgery in patients with PFF receiving antiplatelet and anticoagulant therapy. We have also used information from the existing evidence-based guidelines for elective/planned surgery in patients with antithrombotic therapy. The practical approach can be summarised as follows: • Antiplatelet therapy – discontinuation of acetylsalicylic acid (ASA) and clopidogrel in monotherapy or in combination is not necessary prior to surgery. In case of bleeding, antifibrinolytic therapy is recommended as well as administration of platelet concentrate which is rarely needed. • In patients taking warfarin, reversal of its effects is recommended by early administration of vitamin K to allow surgery to be performed within 24 hours. Prothrombin complex concentrate (PCC) as a second-line drug is reserved for extreme cases only. Warfarin therapy is resumed 24 hours after surgery. • Direct oral anticoagulants must be discontinued 24–48 hours prior to surgery, possibly longer depending on the type of drug, time of administration of the last dose, and renal function. In extreme cases, an antidote (idarucizumab, off-label andexanet) can be administered prior to surgery, or PCC in case they are unavailable. Anticoagulation therapy is resumed in 24–48 hours. • Neuraxial anaesthesia is possible when ASA is taken by the patient and in case of effective warfarin reversal. • In early surgery and rapid restart of anticoagulant therapy, bridging therapy with LMWH is not indicated except for in cases with extreme risk of thrombosis. [ABSTRACT FROM AUTHOR]

Tomatoes are one of the most important vegetables in every home, especially in South Asian countries, used as a vegetable, ketchup, and condiment in many kitchen recipes. It is a good source of calcium, potassium, folate, vitamin A, vitamin K, and lycopene, which are beneficial for the human body and protect it against different diseases. Nutrient management is a key factor for the best quality production of tomato fruit. The present study was conducted to compare the efficiency of different calcium salts (calcium sulphate, calcium carbonate, calcium nitrate, and calcium chloride) in improving the growth, yield, and other quality-related parameters of tomatoes. A single field experiment was conducted and laid out according to the Randomized Complete Block Design (RCBD) with a single factor in the field and a Complete Randomized Design (CRD)) for postharvest fruit storage. The results obtained from this experiment suggest that plants treated with 2% calcium chloride solution exhibited the greatest plant height (85.27 cm), number of leaves (221), yield per plant (2.3 kg), ascorbate peroxidase (290.75 m mol s−1 kg−1), superoxide dismutase (7.13 m mol s−1 kg−1), catalase (18.74 m mol s−1 kg−1), total phenolics (2.44 mg g−1), and β carotene (0.48 µg g−1). During postharvest storage, the maximum shelf life (18 days), minimum disease incidence (4.78%), weight loss (6.61%), and ethylene production (119.6 µL C2H4 kg−1h−1) rate were also observed in calcium-treated fruits. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) poses a significant stroke risk in heart disease patients. This systematic review aims to evaluate the efficacy and safety of non-vitamin K oral antagonists (NOACs) versus vitamin K antagonists (VKAs) in AF patients with and without any valvular heart disease (VHD/N-VHD). Methods: A systematic search was conducted on PubMed, Scopus, and Google Scholar up to March 3, 2022. Efficacy and safety parameters were analyzed. Results: A total of 85,423 subjects from 10 studies were included in this meta-analysis. NOACs and VKAs showed similar effects on ischemic stroke in AF patients with VHD/N-VHD (RR 0.97; 95% CI 0.72–1.30; p = 0.83) and also on systemic embolic events (RR 1.02; 95% CI 0.83–1.25; p = 0.86). Similar effects were seen in VHD and N-VHD subgroups. Both treatments had similar effects on myocardial infarction in AF patients with VHD/N-VHD (RR 0.79; 95% CI 0.49–1.26; p = 0.32), VHD (RR 0.78; 95% CI 0.59–1.02; p = 0.07), and N-VHD subgroups (RR 0.82; 95% CI 0.30–2.21; p = 0.69). NOACs reduced the risk of intracranial bleeding in AF VHD/N-VHD (RR 0.64; 95% CI 0.54–0.77; p < 0.0001), VHD (RR 0.59; 95% CI 0.42–0.82; p = 0.002), and N-VHD subgroups (RR 0.70; 95% CI 0.57–0.85; p = 0.0003). Additionally, NOACs reduced the risk of gastrointestinal bleeding in AF VHD/N-VHD (RR 0.80; 95% CI 0.66–0.96; p = 0.02), specifically in the VHD subgroup (RR 0.69; 95% CI 0.54–0.89; p = 0.004). Moreover, NOACs were associated with a decreased risk for minor and non-fatal bleeding in AF patients with VHD/N-VHD (RR 0.86; 95% CI 0.75–0.99; p = 0.04). Conclusion: NOACs are effective and safe for ischemic stroke, systemic embolic events, myocardial infarction, intracranial bleeding, and gastrointestinal bleeding in AF patients with VHD/N-VHD. [ABSTRACT FROM AUTHOR]

Tempeh is one of the popular fermented soybeas products in Indonesia and in involves yeast in its manufacture. In addition to its delicious taste and relatively affordable price, tempeh has many nutritional values including vitamin B6 (pyridoxine), vitamin K, protein and high essential amino acids. The good tempeh quality can be affected by materials preference and accuracy throughout making process. Besides soybeans, the tempeh quality is affected by type of yeast and packaging materials. Currently, tempeh making process commonly use instant yeast and plastic as wrapping material than either usar or other wrapping material in the market. The research objective was to elaborate the yeast types impact and wrapping materials on the quality and shelf life of soybean tempeh. The organoleptic assessment was carried out by the hedonic test analyzed by the Kruskal Wallis test and proceeded by the Mann Whitney test if there was a significant difference. Meanwhile, the observation of shelf life was carried out by means of a sensory test until the tempeh rotted. The results showed the type of yeast and packaging materials influencing on the quality of tempeh. Tempeh treatment P5 (using usar and banana leaves) had the highest score in color criteria (3.76±0.0737), smell (2.73±0.1447ceg), texture (2.93±0.1047ceg), taste (3.74±0.1407fj), shelf life (4 days) and faster mold growth than other treatment. According to the results, the panelists preferred tempeh fermented using usar and wrapped in banana leaves, because it was more natural and had the longest durability. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a major public health problem worldwide that still lacks effective treatments. Recent studies have suggested that ferroptosis is a key mediator of AKI due to its activation of lipid peroxidation. Therefore, we hypothesized that antiferroptosis agents might be a novel potential therapeutic strategy for AKI. Herein, we demonstrated that liquiritigenin (LG), an active ingredient of liquorice, improves renal function by inhibiting vitamin K epoxide reductase complex subunit 1 (VKORC1)-mediated ferroptosis, both in vivo and in vitro. In a folic acid-induced murine AKI model, after a single pre-treatment intravenous injection, LG markedly alleviated the loss of renal function through suppressing ferroptosis induced by iron accumulation. LG prevented mitochondrial morphological changes and upregulated glutathione and glutathione peroxidase 4 levels, while downregulating malonaldehyde and divalent iron levels. An in vitro RNA-sequence analysis suggested that the protective role of LG may involve upregulation of VKORC1. Moreover, knockdown of VKORC1 diminished the renal protective and antiferroptosis roles of LG. Collectively, our findings demonstrated that LG protected against AKI by inhibiting VKORC1-mediated ferroptosis. This suggests that inhibiting ferroptosis might be a novel therapeutic approach in the future. [ABSTRACT FROM AUTHOR]

Multiple Coagulation Factor Deficiency (MCFD) is an uncommon haematological disorder characterised by simultaneous deficiency of multiple clotting factors, which leads to an increased risk of bleeding and compromised haemostasis. The present series aimed to provide a comprehensive analysis of MCFD, shedding light on its aetiology, clinical manifestations, and potential therapeutic interventions in a case-by-case manner, highlighting the individualised treatment options that are needed for many of these cases. A prospective combined clinical and laboratory study was performed on all patients who presented with bleeding tendencies and were subsequently diagnosed with MCFD. Clinical records and laboratory data of all these patients were reviewed to identify commonalities and variations among affected individuals. Haematological assays were performed to quantify the extent of coagulation factor deficiencies. The present series identified a diverse cohort of eight individuals (2 females and 6 males) with MCFD, showcasing variability in age of onset, severity of symptoms, and potential underlying genetic mutations. Clotting factor assays revealed deficiencies of Factor V and Factor VIII (F5F8D), Vitamin K-dependent clotting factor deficiency, and failure of synthesis of clotting factors of hepatic origin. Clinically, patients presented with a spectrum of bleeding phenotypes, ranging from mild to severe, requiring tailored therapeutic strategies. The present series provides an overview of some of the presentations of MCFD, emphasising the need for a multidisciplinary approach in its diagnosis and management. Clinicians should be vigilant in recognising the varied clinical presentations of MCFD and consider genetic testing for precise diagnosis and management. [ABSTRACT FROM AUTHOR]

Background: Due to their efficient insulation, lack of sweat glands, relatively quick metabolic rate, and heightened sensitivity to heat, the poultry industry faces a serious problem with heat stress. Combining vitamins has been demonstrated to be more effective than implementing a single vitamin in reducing the effects of heat stress. Aim: This study aimed to investigate the efficacy of the multivitamin combination in feed on the growth performance, egg quality, and antioxidant enzymes in laying hens exposed to heat stress. Methods: A total of 28 Isa Brown strains aged 18 weeks were randomly designated into seven groups with four replications, i.e., (C-) normal temperature group, (C+) heat stress group, and the others with the administration of vitamin A and E (AE), vitamin K and C (KC), vitamin C and E (CE), vitamin E and selenium (ESE), and vitamin C and folic acid (CAF). Feed intake, feed efficiency, eggshell thickness, shape index, haugh unit (HU), yolk, and albumen index were evaluated at 22, 23, 24, and 25 weeks. Meanwhile, antioxidant enzymes were quantified at 22 and 25 weeks. Results: As a result, feed intake was reported a significant improvement in the AE and CE groups compared to the C+ group. Meanwhile, the feed efficiency was reported to be efficient in the CE and ESE groups. Based on egg quality evaluation, we reported significant shell thickness in the CE, ESE, and CAF groups compared to the C+; yolk index was reported slightly significant results in the AE and CAF groups; albumen index and HU were reported to increase significantly in the CAF group. Meanwhile, superoxide dismutase (SOD), malondialdehyde (MDA), and GPx activity were ameliorated significantly in the ESE and CAF groups. Conclusion: Combinations of multivitamins can thereby enhance feed intake, feed efficiency, egg quality, and antioxidant activity. The CE, ESE, and CAF groups were found to have made equivalent improvements in the eggshell thickness, shape index, HU, yolk, and albumen index. [ABSTRACT FROM AUTHOR]