Effects of maternal methyl donor intake during pregnancy on ileum methylation and function in an intrauterine growth restriction pig model

Background Intrauterine growth retardation(IUGR)affects intestinal growth,morphology,and function,which leads to poor growth performance and high mortality.The present study explored whether maternal dietary methyl donor(MET)supplementation alleviates IUGR and enhances offspring’s growth performance by improving intestinal growth,function,and DNA methylation of the ileum in a porcine IUGR model.Methods Forty multiparous sows were allocated to the control or MET diet groups from mating until delivery.After farrowing,8 pairs of IUGR and normal birth weight piglets from 8 litters were selected for sampling before suckling colostrum.Results The results showed that maternal MET supplementation tended to decrease the IUGR incidence and increased the average weaning weight of piglets.Moreover,maternal MET supplementation significantly reduced the plasma concentrations of isoleucine,cysteine,urea,and total amino acids in sows and newborn pig-lets.It also increased lactase and sucrase activity in the jejunum of newborn piglets.MET addition resulted in lower ileal methionine synthase activity and increased betaine homocysteine S-methyltransferase activity in the ileum of newborn piglets.DNA methylation analysis of the ileum showed that MET supplementation increased the methyla-tion level of DNA CpG sites in the ileum of newborn piglets.Down-regulated differentially methylated genes were enriched in folic acid binding,insulin receptor signaling pathway,and endothelial cell proliferation.In contrast,up-regulated methylated genes were enriched in growth hormone receptor signaling pathway and nitric oxide biosyn-thetic process.Conclusions Maternal MET supplementation can reduce the incidence of IUGR and increase the weaning litter weight of piglets,which may be associated with better intestinal function and methylation status.

Concerns about the application of resistance exercise with blood-flow restriction and thrombosis risk in hemodialysis patients

Background:Hemodialysis(HD) per se is a risk factor for thrombosis.Considering the growing body of evidence on blood-flow restriction(BFR) exercise in HD patients,identification of possible risk factors related to the prothrombotic agent D-dimer is required for the safety and feasibility of this training model.The aim of the present study was to identify risk factors associated with higher D-dimer levels and to determine the acute effect of resistance exercise(RE) with BFR on this molecule.Methods:Two hundred and six HD patients volunteered for this study(all with a glomerular filtration rate of <15 mL/min/1.73 m2).The RE+BFR session consisted of 50% arterial occlusion pressure during 50 min sessions of HD(intradialytic exercise).RE repetitions included concentric and eccentric lifting phases(each lasting 2 s) and were supervised by a strength and conditioning specialist.Results:Several variables were associated with elevated levels of D-dimer,including higher blood glucose,citrate use,recent cardiovascular events,recent intercurrents,higher inflammatory status,catheter as vascular access,older patients(>70 years old),and HD vintage.Furthermore,RE+BFR significantly increases D-dimer after 4 h.Patients with borderline baseline D-dimer levels(400-490 ng/mL) displayed increased risk of elevating D-dimer over the normal range(≥500 ng/mL).Conclusion:These results identified factors associated with a heightened prothrombotic state and may assist in the screening process for HD patients who wish to undergo RE+BFR.D-dimer and/or other fibrinolysis factors should be assessed at baseline and throughout the protocol as a precautionary measure to maximize safety during RE+BFR.

Acute suppurative terminal cholangitis:Clinical characteristics of a new subtype of acute cholangitis

Background:Acute suppurative terminal cholangitis(ASTC)is rarer than acute obstructive cholangitis and is not well studied.To explore this subtype of acute cholangitis,we described our clinical experience with ASTC.Methods:We performed a retrospective review of patients with ASTC admitted to our center from September 2014 to August 2020.We analyzed their clinical characteristics,including etiology,clinical manifestations,imaging features,treatment and prognosis.Results:A total of 32 ASTC patients were included in the analysis.The majority of the patients had a history of biliary operations,and clinical manifestations were occult and atypical.The positive rate of bacterial culture was 46.9%.All the patients had typical imaging features on computed tomography and magnetic resonance imaging.Treatment with effective antibiotics was provided as soon as diagnosis was established.After treatment,most patients had a good outcome.Elevated levels of total bilirubin,aspartate aminotransferase,procalcitonin and gamma-glutamyltransferase were the characteristics of critically ill patients and were associated with relatively poor prognosis.Conclusions:Our results demonstrated that ASTC should be recognized as a new subtype of acute cholangitis,and that earlier diagnosis and more personalized treatments are needed.

Mechanisms underlying the role of endoplasmic reticulum stress in the placental injury and fetal growth restriction in an ovine gestation model

Background Exposure to bisphenol A(BPA),an environmental pollutant known for its endocrine-disrupting properties,during gestation has been reported to increase the risk of fetal growth restriction(FGR)in an ovine model of pregnancy.We hypothesized that the FGR results from the BPA-induced insufficiency and barrier dysfunction of the placenta,oxidative stress,inflammatory responses,autophagy and endoplasmic reticulum stress(ERS).However,precise mechanisms underlying the BPA-induced placental dysfunction,and subsequently,FGR,as well as the potential involvement of placental ERS in these complications,remain to be investigated.Methods In vivo experiment,16 twin-pregnant(from d 40 to 130 of gestation)Hu ewes were randomly distributed into two groups(8 ewes each).One group served as a control and received corn oil once a day,whereas the other group received BPA(5 mg/kg/d as a subcutaneous injection).In vitro study,ovine trophoblast cells(OTCs)were exposed to 4 treatments,6 replicates each.The OTCs were treated with 400μmol/L BPA,400μmol/L BPA+0.5μg/m L tunicamycin(Tm;ERS activator),400μmol/L BPA+1μmol/L 4-phenyl butyric acid(4-PBA;ERS antagonist)and DMEM/F12 complete medium(control),for 24 h.Results In vivo experiments,pregnant Hu ewes receiving the BPA from 40 to 130 days of pregnancy experienced a decrease in placental efficiency,progesterone(P4)level and fetal weight,and an increase in placental estrogen(E2)level,together with barrier dysfunctions,OS,inflammatory responses,autophagy and ERS in type A cotyledons.In vitro experiment,the OTCs exposed to BPA for 24 h showed an increase in the E2 level and related protein and gene expressions of autophagy,ERS,pro-apoptosis and inflammatory response,and a decrease in the P4 level and the related protein and gene expressions of antioxidant,anti-apoptosis and barrier function.Moreover,treating the OTCs with Tm aggravated BPA-induced dysfunction of barrier and endocrine(the increased E2 level and decreased P4 level),OS,inflammatory responses,autophagy,and ERS.However,treating the OTCs with 4-PBA reversed the counteracted effects of Tm mentioned above.Conclusions In general,the results reveal that BPA exposure can cause ERS in the ovine placenta and OTCs,and ERS induction might aggravate BPA-induced dysfunction of the placental barrier and endocrine,OS,inflammatory responses,and autophagy.These data offer novel mechanistic insights into whether ERS is involved in BPA-mediated placental dysfunction and fetal development.

Mixed Integer Robust Programming Model for Multimodal Fresh Agricultural Products Terminal Distribution Network Design

The low efficiency and high cost of fresh agricultural product terminal distribution directly restrict the operation of the entire supply network.To reduce costs and optimize the distribution network,we construct a mixed integer programmingmodel that comprehensively considers tominimize fixed,transportation,fresh-keeping,time,carbon emissions,and performance incentive costs.We analyzed the performance of traditional rider distribution and robot distribution modes in detail.In addition,the uncertainty of the actual market demand poses a huge threat to the stability of the terminal distribution network.In order to resist uncertain interference,we further extend the model to a robust counterpart form.The results of the simulation show that the instability of random parameters will lead to an increase in the cost.Compared with the traditional rider distribution mode,the robot distribution mode can save 12.7%on logistics costs,and the distribution efficiency is higher.Our research can provide support for the design of planning schemes for transportation enterprise managers.

Machine learning for predicting the outcome of terminal ballistics events

Machine learning(ML) is well suited for the prediction of high-complexity,high-dimensional problems such as those encountered in terminal ballistics.We evaluate the performance of four popular ML-based regression models,extreme gradient boosting(XGBoost),artificial neural network(ANN),support vector regression(SVR),and Gaussian process regression(GP),on two common terminal ballistics’ problems:(a)predicting the V50ballistic limit of monolithic metallic armour impacted by small and medium calibre projectiles and fragments,and(b) predicting the depth to which a projectile will penetrate a target of semi-infinite thickness.To achieve this we utilise two datasets,each consisting of approximately 1000samples,collated from public release sources.We demonstrate that all four model types provide similarly excellent agreement when interpolating within the training data and diverge when extrapolating outside this range.Although extrapolation is not advisable for ML-based regression models,for applications such as lethality/survivability analysis,such capability is required.To circumvent this,we implement expert knowledge and physics-based models via enforced monotonicity,as a Gaussian prior mean,and through a modified loss function.The physics-informed models demonstrate improved performance over both classical physics-based models and the basic ML regression models,providing an ability to accurately fit experimental data when it is available and then revert to the physics-based model when not.The resulting models demonstrate high levels of predictive accuracy over a very wide range of projectile types,target materials and thicknesses,and impact conditions significantly more diverse than that achievable from any existing analytical approach.Compared with numerical analysis tools such as finite element solvers the ML models run orders of magnitude faster.We provide some general guidelines throughout for the development,application,and reporting of ML models in terminal ballistics problems.

Improved STNModels and Heuristic Rules for Cooperative Scheduling in Automated Container Terminals

Improving the cooperative scheduling efficiency of equipment is the key for automated container terminals to copewith the development trend of large-scale ships. In order to improve the solution efficiency of the existing spacetimenetwork (STN) model for the cooperative scheduling problem of yard cranes (YCs) and automated guidedvehicles (AGVs) and extend its application scenarios, two improved STN models are proposed. The flow balanceconstraints in the original model are decomposed, and the trajectory constraints of YCs and AGVs are added toacquire the model STN_A. The coupling constraint in STN_A is updated, and buffer constraints are added toSTN_A so that themodel STN_B is built.As the size of the problem increases, the solution speed of CPLEX becomesthe bottleneck. So a heuristic method containing three groups of heuristic rules is designed to obtain a near-optimalsolution quickly. Experimental results showthat the computation time of STN_A is shortened by 49.47% on averageand the gap is reduced by 1.69% on average compared with the original model. The gap between the solution ofthe heuristic rules and the solution of CPLEX is less than 3.50%, and the solution time of the heuristic rules is onaverage 99.85% less than the solution time of CPLEX. Compared with STN_A, the computation time for solvingSTN_B increases by 58.93% on average.

Clinical Epidemiology and Surgical Treatment of Spontaneous Perforations of the Terminal Ileum: A Multicentre Study in Cameroon

Background: Perforations of the terminal ileum are a frequent clinical situation and a therapeutic challenge. Surgical treatment is controversial. Several surgical modalities have been proposed and postoperative morbidity and mortality remain high. The aim of this study was to review our experience in the surgical management of perforations of the terminal ileum. Patients and methods: This is a descriptive cross-sectional study with retrospective data collection from January 1, 2017 to December 31, 2021, in five hospitals in Cameroon. Patients’ demographic, clinical presentation, surgical findings and 30-days postoperative outcomes data were collected. Results: We collected 34 files. The sex ratio was 1.4 and the average age was 20.28 years. The average consultation time was 9.1 days. Abdominal pain was present in all our patients. Peritoneal irritation was present in 46 cases (88.5%). The mean time to treatment after admission was 17.5 hours. The perforation was unique in 40 cases (76.9%) and located between 6 and 10 cm from the ileocecal valve in 29 cases (55.8%). Typhoid was the most suspected etiology intraoperatively in 38 cases (73.1%). A simple suture was performed in 18 patients (34.6%), resection with anastomosis in 11 patients (21.2%) and an ileostomy in 5 patients (9.6%). The average length of hospitalization was 21.74 days. Postoperative morbidity and mortality were 32.7% and 17.3% respectively. Conclusion: Perforations of the terminal ileum are common and affect young people. Surgical procedures are varied. Reducing consultation and care times and respecting treatment principles could improve postoperative morbidity and mortality, which remain high.

Associations of serum D-dimer and glycosylated hemoglobin levels with third-trimester fetal growth restriction in gestational diabetes mellitus

BACKGROUND Gestational diabetes mellitus(GDM)is a special type of diabetes that commonly occurs in women during pregnancy and involves impaired glucose tolerance and abnormal glucose metabolism;GDM is diagnosed for the first time during pregnancy and can affect fetal growth and development.AIM To investigate the associations of serum D-dimer(D-D)and glycosylated hemoglobin(HbA1c)levels with third-trimester fetal growth restriction(FGR)in GDM patients.METHODS The clinical data of 164 pregnant women who were diagnosed with GDM and delivered at the Obstetrics and Gynecology Hospital of Fudan University from January 2021 to January 2023 were analyzed retrospectively.Among these women,63 whose fetuses had FGR were included in the FGR group,and 101 women whose fetuses had normal body weights were included in the normal body weight group(normal group).Fasting venous blood samples were collected from the elbow at 28-30 wk gestation and 1-3 d before delivery to measure serum D-D and HbA1c levels for comparative analysis.The diagnostic value of serum D-D and HbA1c levels for FGR was evaluated by receiver operating characteristic analysis,and the influencing factors of third-trimester FGR in GDM patients were analyzed by logistic regression.RESULTS Serum fasting blood glucose,fasting insulin,D-D and HbA1c levels were significantly greater in the FGR group than in the normal group,while the homeostasis model assessment of insulin resistance values were lower(P<0.05).Regarding the diagnosis of FGR based on serum D-D and HbA1c levels,the areas under the curves(AUCs)were 0.826 and 0.848,the cutoff values were 3.04 mg/L and 5.80%,the sensitivities were 81.0%and 79.4%,and the specificities were 88.1%and 87.1%,respectively.The AUC of serum D-D plus HbA1c levels for diagnosing FGR was 0.928,and the sensitivity and specificity were 84.1%and 91.1%,respectively.High D-D and HbA1c levels were risk factors for third-trimester FGR in GDM patients(P<0.05).CONCLUSION D-D and HbA1c levels can indicate the occurrence of FGR in GDM patients in the third trimester of pregnancy to some extent,and their combination can be used as an important index for the early prediction of FGR.

The Effect of Macronutrient Restrictions on Gut Microbiome and Biochemical Parameters of Wistar Albino Rats

Macronutrients serve as a source of energy for both gut microbiota and its host. An increase or decrease in macronutrients can either increase or decrease the composition of gut microbiota, leading to gut dysbiosis which has been implicated in many diseases state including non-communicable diseases. To achieve this, seven diets were formulated by restricting 60% of each macronutrient. These diets were fed on 42 albino rats (Wistar), divided into 7 groups of 6 rats each. Group 1 was fed on a normal laboratory chow diet (ND), group 2 received a fat-restricted diet (FRD), group 3 received a protein-restricted diet, (PFD), group 4 received a carbohydrate-restricted diet (CRD), group 5 received a protein and fat-restricted diet (PFRD), group 6 re-ceived a carbohydrate and fat-restricted diet (CFRD) and group 7 received a carbohydrate and protein-restricted diet (CPRD). Feed and water intake were given ad libitum and daily weight and food intake were recorded. The experiment went on for 4 weeks after which animals were sacrificed and intestinal content and blood were collected for analysis (gut microbial composition, glucose, insulin levels, serum lipid, and enzyme). Compared to the control group results showed a decrease in Bacteroides (40.50 - 14.00 CFU), HDL (68.20 - 40.40 mg/dl), and AST (66.62 - 64.74 U/L) in FRD. An increase in AST (66.6 - 69.43 U/L), Bifidobacterial (59.50 - 92.00 CFU) and decreased Bacteroides (40.5 - 19.5 CFU) for PRD was also recorded. CRD reduced Lactobacillus (73 - 33.5 CFU), total bacterial count (129 - 48 CFU), HDL (68.2 - 30.8 mg/dl), and cholesterol (121.44 - 88.65 mg/dl) whereas intestinal composition of E. coli (30.5 - 51.5 CFU) increased. PFRD increased Lactobacillus (73.00 - 102.5 CFU), Bifidobacterial (59.5 - 100 CFU), HDL (68.2 - 74.7 mg/dl), and Triglyceride (111.67 - 146.67 mg/dl) concentration. Meanwhile, a reduction in Bifidobacterial (59.5 - 41.5 CFU), and an increasing of AST (66.62 - 70.30 U/l) were recorded for CFRD. However, Bacteroides (40.5 69.5 CFU), LDL (30.95 - 41.98 mg/dl) increased and Bifidobacterial (59.5 - 38.00 CFU) and HDL (68.2 - 53.5 mg/dl) decreased for CPRD. This work, therefore, concludes that macronutrient restriction causes significant changes in serum marker and enzyme profile, and gut microbial composition which can cause gut dysbiosis and later on could expose the host to inflammatory diseases in the long run.

An Improved Bounded Conflict-Based Search for Multi-AGV Pathfinding in Automated Container Terminals

As the number of automated guided vehicles(AGVs)within automated container terminals(ACT)continues to rise,conflicts have becomemore frequent.Addressing point and edge conflicts ofAGVs,amulti-AGVconflict-free path planning model has been formulated to minimize the total path length of AGVs between shore bridges and yards.For larger terminalmaps and complex environments,the grid method is employed to model AGVs’road networks.An improved bounded conflict-based search(IBCBS)algorithmtailored to ACT is proposed,leveraging the binary tree principle to resolve conflicts and employing focal search to expand the search range.Comparative experiments involving 60 AGVs indicate a reduction in computing time by 37.397%to 64.06%while maintaining the over cost within 1.019%.Numerical experiments validate the proposed algorithm’s efficacy in enhancing efficiency and ensuring solution quality.

Transformation of marginal zone lymphoma into high-grade B-cell lymphoma expressing terminal deoxynucleotidyl transferase:A case report

BACKGROUND High-grade B-cell lymphoma(HGBL)is an unusual malignancy that includes myelocytomatosis viral oncogene(MYC),B-cell lymphoma-2(BCL-2),and/or BCL-6 rearrangements,termed double-hit or triple-hit lymphomas,and HGBL-not otherwise specific(HGBL-NOS),which are morphologically characteristic of HGBL but lack MYC,BCL-2,or BCL-6 rearrangements.HGBL is partially transformed by follicular lymphoma and other indolent lymphoma,with few cases of marginal zone lymphoma(MZL)transformation.HGBL often has a poor prognosis and intensive therapy is currently mainly advocated,but there is no good treatment for these patients who cannot tolerate chemotherapy.CASE SUMMARY We reported a case of MZL transformed into HGBL-NOS with TP53 mutation and terminal deoxynucleotidyl transferase expression.Gene analysis revealed the gene expression profile was identical in the pre-and post-transformed tissues,suggesting that the two diseases are homologous,not secondary tumors.The chemotherapy was ineffective and the side effect was severe,so we tried combination therapy including venetoclax and obinutuzumab.The patient tolerated treatment well,and reached partial response.The patient had recurrence of hepatocellular carcinoma and died of multifunctional organ failure.He survived for 12 months after diagnosis.CONCLUSION Venetoclax combined with obinutuzumab might improve the survival in some HGBL patients,who are unsuitable for chemotherapy.

Investigation on Breakdown Characteristics of Various Surface Terminal Structures for GaN-Based Vertical P-i-N Diodes

GaN-based vertical P-i-N diode with mesa edge terminal structure due to electric field crowding effect, the breakdown voltage of the device is significantly reduced. This work investigates three terminal structures, including deeply etched, bevel, and stepped-mesas terminal structures, to suppress electric field crowding effects at the device and junction edges. Deeply-etched mesa terminal yields a breakdown voltage of 1205 V, i.e., 89% of the ideal voltage. The bevel-mesa terminal achieves about 89% of the ideal breakdown voltage, while the step-mesa terminal is less effective in mitigating electric field crowding, at about 32% of the ideal voltage. This work can provide an important reference for the design of high-power, high-voltage GaN-based P-i-N power devices, finding a terminal protection structure suitable for GaNPiN diodes to further enhance the breakdown performance of the device and to unleash the full potential of GaN semiconductor materials.

Diversity of Microflora in Colonic Mucus from Severe Ulcerative Colitis Patients Analyzed by Terminal Restriction Fragment Length Polymorphism and Clone Libraries of Bacterial 16S rRNA Gene Sequences

Although the gut microflora is thought to be an essential factor in the development of ulcerative colitis (UC), the entire gut microflora occurring in UC remains unknown. Most studies use feces to represent the microflora distribution;however, here we analyzed the bacterial diversity in colonic mucus from UC patients receiving colectomy surgery and control patients. The diversity of microflora was investigated using a combination of terminal restriction fragment length polymorphism (T-RFLP) and clone library analyses of the 16S rRNA gene sequences. In the T-RFLP analysis, the number of terminal restriction fragments (T-RFs) decreased significantly in UC patients when compared to control samples. Also in the clone library analysis, the number of operational taxonomic units (OTU) and the Shannon diversity index were reduced significantly in UC patients. These molecular analyses reveal an overall dysbiosis in UC patients. No specific pathogen was found, and a strong negative correlation in relative abundance of bacterial populations was observed between the phyla Bacteroidetes and Firmicutes in the UC patients. This is the first report showing a significant correlation between these two phyla, which may be important characteristics in the pathogenesis of UC.

Necessary Conditions for Optimal Control of Diffusions with Hard Terminal State Restrictions

Necessary conditions are proved for certain problems of optimal control of diffusions where hard end constraints occur. The main results apply to several dimensional problems, where some of the state equations involve Brownian motions, but not the equations corresponding to states being hard restricted at the terminal time. The necessary conditions are stated in terms of weak variations. Two versions of necessary conditions are given, one version involving solutions of variational equations, the other one involving first order adjoint equations.

Terminal Blend橡胶泡沫沥青制备及性能评价

为弥补传统泡沫沥青高温稳定性和黏附性的不足,解决传统橡胶沥青发泡效果不理想的缺陷,对terminal blend(TB)橡胶泡沫沥青进行了研究,探究了TB橡胶泡沫沥青发泡效果的影响规律,对其微观形貌与特征进行了表征,同时评估了TB橡胶泡沫沥青的高温性能、温度敏感性和黏度.结果表明:采用TB橡胶沥青制备泡沫沥青具备可行性;相比传统泡沫沥青,TB橡胶泡沫沥青在温度敏感性降低的同时,还显著提升了高温性能和黏度;微观结果显示TB橡胶泡沫沥青的发泡过程仅为物理过程,而且受发泡温度和发泡用水量的影响,其中后者对整体发泡效果的影响更加明显;TB橡胶泡沫沥青的最佳发泡温度为160°C、发泡用水量为2.7%.

Long-term implications of fetal growth restriction

Fetal growth restriction(FGR),or intrauterine growth restriction(IUGR),is a complication of pregnancy where the fetus does not achieve its genetic growth potential.FGR is characterized by a pathological retardation of intrauterine growth velocity in the curve of intrauterine growth.However,the FGR definition is still debated,and there is a lack of a uniform definition in the literature.True IUGR,compared to constitutional smallness,is a pathological condition in which the placenta fails to deliver an adequate supply of oxygen and nutrients to the developing fetus.Infants with IUGR,compared to appropriately grown gestational age infants,have a significantly higher risk of mortality and neonatal complications with long-term consequences.Several studies have demonstrated how suboptimal fetal growth leads to long-lasting physiological alterations for the developing fetus as well as for the newborn and adult in the future.The long-term effects of fetal growth retardation may be adaptations to poor oxygen and nutrient supply that are effective in the fetal period but deleterious in the long term through structural or functional alterations.Epidemiologic studies showed that FGR could be a contributing factor for adult chronic diseases including cardiovascular disease,metabolic syndrome,diabetes,respiratory diseases and impaired lung function,and chronic kidney disease.In this review we discussed pathophysiologic mechanisms of FGR-related complications and potential preventive measures for FGR.

Caloric restriction-mimetics for the reduction of heart failure risk in aging heart: with consideration of gender-related differences

The literature is full of claims regarding the consumption of polyphenol or polyamine-rich foods that offer some protection from developing cardiovascular disease(CVD). This is achieved by preventing cardiac hypertrophy and protecting blood vessels through improving the function of endothelium. However, do these interventions work in the aged human hearts? Cardiac aging is accompanied by an increase in left ventricular hypertrophy, along with diastolic and systolic dysfunction. It also confers significant cardiovascular risks for both sexes. The incidence and prevalence of CVD increase sharply at an earlier age in men than women. Furthermore, the patterns of heart failure differ between sexes, as do the lifetime risk factors. Do caloric restriction(CR)-mimetics, rich in polyphenol or polyamine, delay or reverse cardiac aging equally in both men and women? This review will discuss three areas:(1) mechanisms underlying age-related cardiac remodeling;(2) gender-related differences and potential mechanisms underlying diminished cardiac response in older men and women;(3) we select a few polyphenol or polyamine rich compounds as the CRmimetics, such as resveratrol, quercetin, curcumin, epigallocatechin gallate and spermidine, due to their capability to extend health-span and induce autophagy. We outline their abilities and issues on retarding aging in animal hearts and preventing CVD in humans. We discuss the confounding factors that should be considered for developing therapeutic strategies against cardiac aging in humans.

The effect of caloric restriction on genetical pathways

Energy restriction is defined as reducing nutrient intake without dragging the organism into malnutrition. Energy restriction is preferred because it is a non-genetic intervention that increases life expectancy. Nicotinamide adenine dinucleotide(NAD~+)and adenosine monophosphate(AMP)levels, which are the indicators of intracellular energy deficiency, increase with energy restriction. The increase in NAD~+ level stimulates sirtuin(SIRT)enzymes, and the increase in AMP level stimulates AMP-activated protein kinase(AMPK). Various mechanisms are regulated by stimulating these enzymes. By Forkhead box O(FoxO)transcription factors, the ability of resistance to oxidative stress increases, and antioxidant genes, DNA repair, and autophagy genes are stimulated. Apoptosis is induced by stimulation of the p53 protein, and tumor growth is suppressed by the disruption of aging cells. The suppression of phosphoinositide 3-kinase(PI3K)-/-Akt, and therefore mTOR signal stimulates autophagy and mitophagia, and cleanses damaged cells and organelles. Mitochondrial biogenesis is stimulated, antioxidant capacity increases, and inflammatory response decreases. Adipose tissue and lipid metabolism are regulated by the regulation of fatty acid synthesis and oxidation. As a consequence, the effects of caloric restriction on cellular metabolism are regulated through the genetic pathways.

Dietary Vitamin K Restriction and Effectiveness of Vitamin K Antagonists Prescribed at the CNHU-HKM University Cardiology Clinic/BENIN

Introduction: Their efficacy in preventing thrombotic and embolic events has been proven in numerous studies, but their narrow therapeutic index requires particular vigilance, especially in terms of biology. In addition, treatment-related hemorrhagic complications are not uncommon. This study explores the influence of dietary vitamin K restriction on the efficacy of antivitamin K treatment at the University Cardiology Clinic of CNHU-HKM. Methods: Cross-sectional and descriptive study that took place from 25 April to 29 August 2019. Patients’ dietary behaviors and successive INR values were collected. Information on dietary intake was obtained by 2 non-consecutive 24-hour recalls. The effectiveness of VKA treatment was assessed by the “Time in Therapeutic Range” (TTR) of the INR. VKA treatment was considered effective for a TTR greater than 65%. Results: At the end of this study, 40 patients were surveyed. The mean age of the participants was 58.05 years ± 13.32 years, with a sex ratio of 1.35. Complete arrhythmia due to atrial fibrillation was the main indication for VKA treatment (37.50%) and fluindione was the most commonly prescribed drug (77.50%). The duration of treatment was less than or equal to 2 years in 47.5% of the subjects surveyed. Before starting treatment, 85% of patients received advice on restricting vitamin K-rich foods, and 45% of patients reported “food burnout” after a period of compliance with the restriction. The majority of respondents (97.50%) complied with the restriction on vitamin K-rich foods. All respondents had high energy intakes and a poor distribution of macronutrients, with a predominance of carbohydrates and proteins. 2.5% of respondents were on effective anti-vitamin K therapy with a TTR of over 65%. Conclusion: Restriction of vitamin K-rich foods is not conducive to effective treatment with vitamin K antagonists.