BACKGROUND The use of induction immunosuppression agents has improved kidney transplant outcomes,but selecting the optimal agent remains a point of debate.AIM To compare the long-term outcomes of kidney transplant rec...BACKGROUND The use of induction immunosuppression agents has improved kidney transplant outcomes,but selecting the optimal agent remains a point of debate.AIM To compare the long-term outcomes of kidney transplant recipients receiving alemtuzumab vs basiliximab induction,focusing on graft function,acute rejection,infection,malignancy,post-transplant glomerulonephritis,and survival,using a propensity score matched cohort design.METHODS Kidney transplant recipients who received alemtuzumab or basiliximab induction from 2014 to 2019 across two nephrology centres in Northwest England were evaluated.Propensity score matching at a 1:1.5 ratio ensured comparability between cohorts.Baseline characteristics,immunosuppression regimens,and outcomes were analyzed.Linear,binary logistic and Cox proportional hazard regression models.RESULTS A total of 436 recipients were included,with a median follow-up of 5.2 years.The matched cohort(n=262)had a mean age of 51.1±13.5 years;39%were female and 92%were white.There was no significant difference in the cumulative incidence of acute rejection[odds ratio(OR)=2.10;95%CI:0.9-4.9;P=0.110].Compared with basiliximab,alemtuzumab was associated with lower estimated glomerular filtration rate at 12 months(-6.6 mL/minute/1.73 m2;95%CI:-10.5 to-2.7;P<0.001)and higher risks of cytomegalovirus viremia(OR=3.2;95%CI:1.6-6.5;P<0.001),BK viremia(OR=2.4;95%CI:1.1-5.5;P=0.02),post-transplant malignancy(OR=6.2;95%CI:1.6-29.9;P=0.013),and death-censored graft loss(hazard ratio=3.6;95%CI:1.2-11.4;P=0.03).No significant differences were observed in post-transplant glomerulonephritis or recipient mortality.CONCLUSION In this propensity score-matched analysis,alemtuzumab induction was associated with lower graft function at 12 months and higher risks of viral infection,post-transplant malignancy,and graft loss compared with basiliximab.These findings highlight the need for further studies to confirm the long-term safety and effectiveness of alemtuzumab in kidney transplantation.展开更多
Background:Information on the association between physical activity(PA)and the risk of chronic kidney disease(CKD)is limited.We aimed to explore the associations of total,domain-specific,and intensity-specific PA with...Background:Information on the association between physical activity(PA)and the risk of chronic kidney disease(CKD)is limited.We aimed to explore the associations of total,domain-specific,and intensity-specific PA with CKD and its subtypes in China.Methods:The study included 475,376 adults from the China Kadoorie Biobank aged 30-79 years during 2004-2008 at baseline.An interviewer-administered questionnaire was used to collect the information about PA,which was quantified as metabolic equivalent of task hours per day(MET-h/day)and categorized into 4 groups based on quartiles.Cox regression was used to analyze the association between PA and CKD risk.Results:During a median follow-up of 12.1 years,5415 incident CKD cases were documented,including 1159 incident diabetic kidney disease(DKD)cases and 362 incident hypertensive nephropathy(HTN)cases.Total PA was inversely associated with CKD risk,with an adjusted hazard ratio(HR,95%confidence interval(95%CI))of 0.83(0.75-0.92)for incident CKD in the highest quartile of total PA as compared with participants in the lowest quartile.Similar results were observed for risk of DKD and HTN,and the corresponding HRs(95%CIs)were 0.75(0.58-0.97)for DKD risk and 0.56(0.37-0.85)for HTN risk.Increased nonoccupational PA,low-intensity PA,and moderate-to-vigorous-intensity PA were significantly associated with a decreased risk of CKD,with HRs(95%CIs)of 0.80(0.73-0.88),0.85(0.77-0.94),and 0.85(0.76-0.95)in the highest quartile,respectively.Conclusion:PA,including nonoccupational PA,low-intensity PA,and moderate-to-vigorous-intensity PA,was inversely associated with the risk of CKD,including DKD,HTN,and other CKD,and such associations were dose dependent.展开更多
Objective:Accurate measurement of QT interval,the ventricular action potential from depolarization to repolarization,is important for the early detection of Long QT syndrome.The most effective QT correction(QTc)formul...Objective:Accurate measurement of QT interval,the ventricular action potential from depolarization to repolarization,is important for the early detection of Long QT syndrome.The most effective QT correction(QTc)formula has yet to be determined in the pediatric population,although it has intrinsically greater extremes in heart rate(HR)and is more susceptible to errors in measurement.The authors of this study compare six dif-ferent QTc methods(Bazett,Fridericia,Framingham,Hodges,Rautaharju,and a computer algorithm utilizing the Bazett formula)for consistency against variations in HR and RR interval.Methods:Descriptive Retrospective Study.We included participants from a pediatric cardiology practice of a community hospital who had an ECG performed in 2017.All participants were healthy patients with no past medical history and no regular med-ications.Results:ECGs from 95 participants from one month to 21 years of age(mean 9.7 years)were included with a mean HR of 91 beats per minute(bpm).The two-sample paired t-test or Wilcoxon signed-rank test assessed for any difference between QTc methods.A statistically significant difference was observed between every combination of two QTc formulae.The Spearman’s rank correlation analysis explored the QTc/HR and QTc/RR relationships for each formula.Fridericia method was most independent of HR and RR with the lowest absolute value of correlation coefficients.Bazett and Computer had moderate correlations,while Framingham and Rautaharju exhibited strong correlations.Correlations were positive for Bazett and Computer,reflecting results from prior studies demonstrating an over-correction of Bazett at higher HRs.In the linear QTc/HR regression analysis,Bazett had the slope closest to zero,although Computer,Hodges,and Fridericia had comparable values.Alternatively,Fridericia had the linear QTc/RR regression coefficient closest to zero.The Bland-Altman method assessed for bias and the limits of agreement between correction formulae.Bazett and Computer exhibited good agreement with minimal bias along with Framingham and Rautaharju.To account for a possible skewed distri-bution of QT,all the above analyses were also performed excluding the top and bottom 2%of data as sorted by heart rate ranges(N=90).Results from this data set were consistent with those derived from all participants(N=95).Conclusions:Overall,the Fridericia correction method provided the best rate correction in our pedia-tric study cohort.展开更多
BACKGROUND The neurological and psychiatric sequelae of coronavirus disease 2019(COVID-19)have been documented,yet further data are needed to thoroughly evaluate the impact of COVID-19 on brain health years after the ...BACKGROUND The neurological and psychiatric sequelae of coronavirus disease 2019(COVID-19)have been documented,yet further data are needed to thoroughly evaluate the impact of COVID-19 on brain health years after the infection.AIM To examine whether COVID-19 infection is associated with exacerbation,recurrence,or progression of pre-existing neurological or psychiatric disorders-a highrisk population that is underrepresented in COVID-19 outcome research in National Guard Health Affair patients in 4-years following a COVID-19 diagnosis.METHODS For this multicenter retrospective cohort study,we used data from the National Guard hospitals electronic health records network(BestCare)with over 10 million patients.Our cohort comprised patients who had a COVID-19 diagnosis;a matched control cohort included patient did not expose to COVID-19 in same period.Age and sex were matching factors.We estimated the incidence of 14 neurological and psychiatric outcomes in nearly 4 years after a confirmed diagnosis of COVID-19.Using a multiple logistic regression,we compared incidences with those in propensity score-matched cohorts of patients with no exposure to COVID-19.Ramadan M et al.Neurological and psychiatric risks post-COVID-19 RESULTS Our primary cohort comprised 4437 patients diagnosed with COVID-19,and our propensity-score 1:1 matched control cohort comprised 4437 individuals.Nearly two-third of the COVID-19 cohort(71%)were diagnosed in 2020,and 2021.The most prevalent diagnoses for both cohorts were epilepsy 30.68%,mood disorder 23.92%,and nerve plexus disorder 22.13%.Dementia was nearly 4 times higher among COVID-19 cohort(8.27%)compared to the control cohort(2.57%).Five neurological and psychiatric outcomes had odds ratios(OR)that were significantly higher than 1 for people who had COVID-19 compared to people who had never been infected.These outcomes were cognitive deficit OR=1.54,95%confidence interval(CI):1.23-1.91,P=0.0001;nerve plexus disorder OR=1.13,95%CI:1.01-1.25,P=0.02;substance use disorder OR=1.95,95%CI:1.12-3.38,P=0.01;mood disorder OR=1.16,95%CI:1.05-1.29,P=0.003;and anxiety disorder OR=1.39,95%CI:1.07-1.79,P=0.01.CONCLUSION The study highlights the persistent risk of neurological and psychiatric conditions in COVID-19 survivors up to four years post-infection.Although the incidence was lower than in previous large studies,long-term consequences remain significant,emphasizing the need for ongoing monitoring and support in mental health and neurological care.展开更多
Background L-Glutamate and L-aspartate are functional amino acids that play pivotal roles in the cellular metabolic pathways of swine enterocytes.Therefore,this study aimed to investigate the effects of dietary L-glut...Background L-Glutamate and L-aspartate are functional amino acids that play pivotal roles in the cellular metabolic pathways of swine enterocytes.Therefore,this study aimed to investigate the effects of dietary L-glutamate and L-aspartate on growth performance,diarrhea severity,intestinal barrier integrity,and fecal microbiota of weaned piglets challenged with F18 enterotoxigenic Escherichia coli(ETEC).Weaned piglets were randomly assigned to seven dietary treatments,including unchallenged and ETEC-challenged controls,amino acid-supplemented groups,and an antibiotic control,to assess their responses to ETEC challenge.Results Supplementation with 1%L-glutamate or 2%L-aspartate enhanced growth performance,with significantly greater(P<0.05)average daily weight gain and gain-to-feed ratio compared with the positive control group from d 0 to d 5 post-inoculation.Pigs fed with 1%or 2%L-aspartate had reduced(P<0.05)diarrhea severity in ETEC-challenged pigs compared with the positive control group.The 1%L-aspartate supplementation also supported intestinal structure by increasing(P<0.05)duodenal villi height and ileal villi width compared with carbadox supplementation.Additionally,1%L-glutamate supplementation significantly improved(P<0.05)resilience in ETEC-challenged pigs by reducing fecal shedding ofβ-hemolysin-producing bacteria compared with the positive control group on d 14 post-inoculation.Moreover,1%L-aspartate supplementation promoted intestinal barrier integrity by significantly up-regulated(P<0.05)the expression of ileal OCDN and ileal ZO-1 compared with the positive control group on d 14 post-inoculation.Interestingly,2%L-aspartate supplementation altered the intestinal mucosa by down-regulating(P<0.05)the expression of jejunal CLDN-1,while up-regulating(P<0.05)the expression of ileal CLDN-1 compared with the negative control group on d 14 post-inoculation.Furthermore,L-glutamate supplementation significantly changed proportions of Firmicutes and Bacteroidota and showed the trend for enrichment in beneficial bacterial genera such as Bifidobacterium and Megasphaera in ETEC-infected pigs by d 14 post-inoculation.Conclusion Supplementation with L-glutamate or L-aspartate promoted growth performance,supported gut health,and enhanced disease resistance in weaned pigs challenged with F18 ETEC.During the weaning period,L-glutamate or L-aspartate could potentially be considered conditionally essential amino acids,helping to alleviate weaning complications and reduce the need for antibiotic use in swine farming.展开更多
Purpose:The purpose of this narrative review is to:1)summarize findings from the three Studies of a Targeted Risk Reduction Intervention through Defined Exercise(STRRIDE)randomized trials regarding the differential ef...Purpose:The purpose of this narrative review is to:1)summarize findings from the three Studies of a Targeted Risk Reduction Intervention through Defined Exercise(STRRIDE)randomized trials regarding the differential effects of exercise amount,intensity,and mode on metabolic syndrome(MetS);and 2)compare the STRRIDE findings with other published randomized exercise trials related to changes in MetS.Methods:A literature review was performed to investigate the effects of exercise on composite measures of MetS.PubMed was searched between October 2023 and December 2023.To be included in this review,studies must have employed a randomized study design,whereby exercise amount,intensity,or mode was varied.Results:Findings from the STRRIDE trials and other randomized exercise trials suggest:1)there is a relationship between exercise energy expenditure(ExEE)and improvements in composite measures of MetS;2)there may be an asymptotic effect for ExEE beyond which further improvements in MetS are negligible or counterproductive;3)improvements in composite measures of MetS are closely linked to insulin sensitivity;and 4)without controlling for total ExEE,combined aerobic and resistance training interventions offer the most robust improvements for composite MetS outcomes compared to either mode alone.Conclusion:Additional,large-scale,randomized exercise trials should be designed to investigate the potential asymptotic effect and associated threshold for ExEE,the interaction between exercise intensity and baseline insulin sensitivity,and the independent effects of exercise mode on MetS.展开更多
The specific and cumulative effects of fine particulate matter(PM_(2.5))components on hypertension remain less defined,notably in susceptible older adults.This national study utilized a representative sample of 220,42...The specific and cumulative effects of fine particulate matter(PM_(2.5))components on hypertension remain less defined,notably in susceptible older adults.This national study utilized a representative sample of 220,425 older adults in China,to scrutinize their relationship.Residential PM_(2.5)and five chemical components(black carbon(BC),organic matter(OM),sulphate(SO_(4)^(2−)),nitrate(NO_(3)^(−)),and ammonium(NH_(4)^(+)))were estimated by the bilinear interpolation.Associations between PM_(2.5)and five chemical components with hypertension were examined through two-stage logistic regression models,with population attributable fractions(PAFs)determined via counterfactual analysis.Elevated exposure to PM_(2.5)and its components was generally linked to higher hypertension prevalence.With each interquartile range increase,the odds ratio(OR)of hypertension rose by 1.09(95%CI:1.08–1.11)for NO_(3)^(−),1.06(95%CI:1.05–1.08)for NH_(4)^(+),1.06(95%CI:1.05–1.07)for OM,1.05(95%CI:1.04–1.06)for BC,and 1.06(95%CI:1.04–1.07)for SO42-.Notably,the cumulative impact of five PM_(2.5)chemical components(OR:1.13,95%CI:1.12–1.13)was significantly greater than the effect of total PM_(2.5)mass alone(OR:1.04,95%CI:1.03–1.05).Regarding PAFs,NO_(3)^(−)represented the strongest contribution to hypertension,followed by OM,NH_(4)^(+),SO_(4)^(2−),and BC.Furthermore,the effects were accentuated in low socio-economic population.These findings underline that using total PM_(2.5)as a surrogate marker may underestimate the comprehensive impact of its chemical components,underscoring the necessity for targeted interventions to reduce emissions of specific PM_(2.5)chemical constituents.展开更多
Objective:The World Health Organization recommends annual preventive chemotherapy with a single dose of praziquantel at≥75%treatment coverage,but as of 2021,the national coverage rate in Nigeria among children falls ...Objective:The World Health Organization recommends annual preventive chemotherapy with a single dose of praziquantel at≥75%treatment coverage,but as of 2021,the national coverage rate in Nigeria among children falls below 10%.This qualitative study sought to explore the barriers and facilitators to implementing large-scale praziquantel mass drug administration(MDA)programs for school-aged children in Nigeria to delineate tools and strategies that could improve the scaling-up and effectiveness of school-based praziquantel MDA programs.Methods:An exploratory qualitative study was conducted with stakeholders with experience in MDAs involving praziquantel or related preventive chemotherapy drugs in Nigeria.Through snowball sampling,30 stakeholders with experience in praziquantel school-based MDA in Nigeria were interviewed.An inductive approach was used to generate broad themes based on the barriers and facilitators identified by the key informants.Results:A total of 45 barriers and 36 facilitators were identified and grouped inductively into eight themes:funding and resources,design and composition of praziquantel tablets,knowledge and awareness mobilization,government,nongovernmental organization,and school engagement,data management,logistics,training,and security.Conclusion:This qualitative study reveals a wide range of barriers and facilitators in the MDA of praziquantel in Nigeria and uncovered critical points along the implementation pathway based on the locus of the barriers and facilitators identified.Collaboration with national,international,and non-profit organizations,and drug education through promotional materials,were the most frequently mentioned facilitators of the MDA program.In addition,insufficient program funding,and the complexity of the supply chain were the most cited barriers.展开更多
Background Higher accelerometer-assessed volume and intensity of physical activity(PA)have been associated with a longer life expectancy but can be difficult to translate into recommended doses of PA.We aimed to:(a)im...Background Higher accelerometer-assessed volume and intensity of physical activity(PA)have been associated with a longer life expectancy but can be difficult to translate into recommended doses of PA.We aimed to:(a)improve interpretability by producing UK Biobank age-referenced centiles for PA volume and intensity;(b)inform public-health messaging by examining how adding recommended quantities of moderate and vigorous PA affect PA volume and intensity.Methods 92,480 UK Biobank participants aged 43-80 years with wrist-worn accelerometer data were included.Average acceleration and intensity gradient were derived as proxies for PA volume and intensity.We generated sex-specific centile curves using Generalized Additive Models for Location Scale and Shape(GAMLSS)and modeled the effect of adding moderate(walking)or vigorous(running)activity on the combined change in the volume and intensity centiles(change in PA profile).Results In men,volume was lower as age increased while intensity was lower after age 55;in women,both volume and intensity were lower as age increased.Adding 150 min of moderate PA weekly(5×30 min walking)increased the PA profile by 4 percentage points.Defining moderate PA as brisk walking approximately doubled the increase(9 percentage points)while 75 min of vigorous PA weekly(5×15 min running)trebled the increase(13 percentage points).Conclusion These UK Biobank reference centiles provide a benchmark for interpretation of accelerometer data.Application of our translational methods demonstrate that meeting PA guidelines through shorter duration vigorous activity is more beneficial to the PA profile(volume and intensity)than longer duration moderate activity.展开更多
Background:Muscular strength is a powerful marker of current health status and robust predictor of age-related disease and disability.Handgrip strength(HGS)using isometric dynamometry is a convenient,feasible,and wide...Background:Muscular strength is a powerful marker of current health status and robust predictor of age-related disease and disability.Handgrip strength(HGS)using isometric dynamometry is a convenient,feasible,and widely used method of assessing muscular strength among people of all ages.While adult HGS norms have been published for many countries,no study has yet synthesized available data to produce international norms.The objective of this study was to generate international sex-and age-specific norms for absolute and body size-normalized HGS across the adult lifespan.Methods:Systematic searches were conducted in 6 databases/web search engines(MEDLINE,SPORTDiscus,Embase,Web of Science,CINAHL,and Google Scholar)up to December 1,2023.We included full-text peer-reviewed observational studies that reported normative HGS data for adults aged ≥20 years by sex and age.Pseudo data were generated using Monte Carlo simulation following harmonization for methodo-logical variation.Population-weighted Generalized Additive Models for Location,Scale,and Shape were used to develop sex-and age-specific norms for absolute HGS(kg)and HGS normalized by height(Ht,m)squared(i.e.,HGS/Ht^(2)in kg/m^(2)).Norms were tabulated as percentile values(5th to 95th)and visualized as smoothed percentile curves.Results:We included data from 100 unique observational studies representing 2,405,863 adults(51.9%female)aged 20 to 100+years from 69 countries and regions tested from the year 2000 onward.On average,absolute and normalized HGS values negligibly improved throughout early adulthood,peaked from age 3039 years(at 49.7 kg(males)and 29.7 kg(females)for absolute HGS or 16.3 kg/m^(2)(males)and 11.3 kg/m^(2)(females)for HGS/Ht^(2)),and declined afterwards.The age-related decline in HGS accelerated from middle to late adulthood and was slightly larger for males than for females during middle adulthood.Conclusion:This study provides the world’s largest and most geographically comprehensive international norms for adult HGS by sex and age.These norms have utility for global peer-comparisons,health screening,and surveillance.展开更多
Selenium is an essential trace mineral important for the maintenance of homeostasis in animals and humans.It evinces a strong antioxidant,anti-inflammatory and potential antimicrobial capacity.Selenium biological func...Selenium is an essential trace mineral important for the maintenance of homeostasis in animals and humans.It evinces a strong antioxidant,anti-inflammatory and potential antimicrobial capacity.Selenium biological function is primarily achieved by its presence in selenoproteins as a form of selenocysteine.Selenium deficiency may result in an array of health disorders,affecting many organs and systems;to prevent this,dietary supplementation,mainly in the forms of organic(i.e.,selenomethionine and selenocysteine)inorganic(i.e.,selenate and selenite)sources is used.In pigs as well as other food animals,dietary selenium supplementation has been used for improving growth performance,immune function,and meat quality.A substantial body of knowledge demonstrates that dietary selenium supplementation is positively associated with overall animal health especially due to its immunomodulatory activity and protection from oxidative damage.Selenium also possesses potential antiviral activity and this is achieved by protecting immune cells against oxidative damage and decreasing viral replication.In this review we endeavor to combine established and novel knowledge on the beneficial effects of dietary selenium supplementation,its antioxidant and immunomodulatory actions,and the putative antimicrobial effect thereof.Furthermore,our review demonstrates the gaps in knowledge pertaining to the use of selenium as an antiviral,underscoring the need for further in vivo and in vitro studies,particularly in pigs.展开更多
The virus SARS-CoV2,which causes the Coronavirus disease COVID-19 has become a pandemic and has spread to every inhabited continent.Given the increasing caseload,there is an urgent need to augment clinical skills in o...The virus SARS-CoV2,which causes the Coronavirus disease COVID-19 has become a pandemic and has spread to every inhabited continent.Given the increasing caseload,there is an urgent need to augment clinical skills in order to identify from among the many mild cases the few that will progress to critical illness.We present a first step towards building an artificial intelligence(AI)framework,with predictive analytics(PA)capabilities applied to real patient data,to provide rapid clinical decision-making support.COVID-19 has presented a pressing need as a)clinicians are still developing clinical acumen given the disease’s novelty,and b)resource limitations in a rapidly expanding pandemic require difficult decisions relating to resource allocation.The objectives of this research are:(1)to algorithmically identify the combinations of clinical characteristics of COVID-19 that predict outcomes,and(2)to develop a tool with AI capabilities that will predict patients at risk for more severe illness on initial presentation.The predictive models learn from historical data to help predict specifically who will develop acute respiratory distress syndrome(ARDS),a severe outcome in COVID-19.Our experimental results based on two hospitals in Wenzhou,Zhejang,China identify features most predictive of ARDS in COVID-19 initial presentation which would not have stood out to clinicians.A mild increase in elevated alanine aminotransferase(ALT)(a liver enzyme)),a presence of myalgias(body aches),and an increase in hemoglobin,in this order,are the clinical features,on presentation,that are the most predictive.Those two centers’COVID-19 case series symptoms on initial presentation can help predict severe outcomes.Predictive models that learned from historical data of patients from two Chinese hospitals achieved 70%to 80%accuracy in predicting severe cases.展开更多
Social stability in group-living animals is an emergent property which arises from the interaction amongst multiple behavioral networks. However, pinpointing when a social group is at risk of collapse is difficult. We...Social stability in group-living animals is an emergent property which arises from the interaction amongst multiple behavioral networks. However, pinpointing when a social group is at risk of collapse is difficult. We used a joint network model- ing approach to examine the interdependencies between two behavioral networks, aggression and status signaling, from four sta- ble and three unstable groups of rhesus macaques in order to identify characteristic patterns of network interdependence in stable groups that are readily distinguishable from unstable groups. Our results showed that the most prominent source of aggres- sion-status network interdependence in stable social groups came from more frequent dyads than expected with opposite direc- tion status-aggression （i.e. A threatens B and B signals acceptance of subordinate status）. In contrast, unstable groups showed a decrease in opposite direction aggression-status dyads （but remained higher than expected） as well as more frequent than ex- pected dyads with bidirectional aggression. These results demonstrate that not only was the stable joint relationship between ag- gression and status networks readily distinguishable from unstable time points, social instability manifested in at least two differ- ent ways. In sum, our joint modeling approach may prove useful in quantifying and monitoring the complex social dynamics of any wild or captive social system, as all social systems are composed of multiple interconnected networks [Current Zoology 61 （1）： 70-84, 2015].展开更多
Background： Creep feeding is used to stimulate piglet post-weaning feed consumption.L-Glutamine（GLN） is an important source of fuel for intestinal epithelial cells.The objective of this study was to determine the i...Background： Creep feeding is used to stimulate piglet post-weaning feed consumption.L-Glutamine（GLN） is an important source of fuel for intestinal epithelial cells.The objective of this study was to determine the impact of creep feeding and adding GLN or AminoGut（AG;containing glutamine ＋ glutamate） to pre-and post-weaning diets on pig performance and intestinal health.Litters（N = 120） were allotted to four treatments during 14–21 d of lactation： 1） No creep feed（NC,n = 45）;2） creep fed control diet（CFCD,n = 45）;3） creep fed 1% GLN（CFGLN,n = 15）;4） creep fed.88% AG（CFAG,n = 15）.After weaning,the NC and CFCD groups were sub-divided into three groups（n = 15 each）,receiving either a control nursery diet（NC-CD,CFCD-CD） or a diet supplemented with either GLN（NC-GLN,CFCD-GLN） or with AG（NC-AG,CFCD-AG）.Litters that were creep fed with diets containing GLN or AG also were supplemented with those amino acids in the nursery diets（CFGLN-GLN,CFAG-AG）.Glutamine was added at 1% in all three post-weaning diet phases and AG was added at.88% in phase 1 and 2 and at.66% in phase 3.Results： Feed conversion（feed/gain） showed means among treatment means close to significance（P = 0.056） and Tukey＇s test for pairwise mean comparisons showed that Pigs in the CFGLN-GLN group had the best feed conversion（feed/gain） in the first three-week period post-weaning,exceeding（P = 0.044） controls（CFCD-CD） by 34%.The NC-AG group had（P = 0.02） the greatest feed intake in the last three week of the study,exceeding controls（CFCD-CD） by 12%.CFGLN-GLN,CFCD-GLN and sow reared（SR） pigs had the greatest（P = 0.049） villi height exceeding the CFCD-AG group by 18%,20% and 19% respectively.The CFAG-AG group had the deepest（P = 0.001） crypts among all treatments.CFGLN-GLN,CFCD-GLN and SR groups had the greatest（P = 0.001） number of cells proliferating（PCNA） exceeding those in the NC-CD group by 43%,54% and 63% respectively.Sow reared pigs showed the greatest（P = 0.001） intestinal absorption capacity for xylose and mannitol.Conclusion： Supplementation of creep feed and nursery diets with GLN and/or AminoGut in the first three week improved feed conversion possibly due to improved intestinal health.展开更多
AIM： To analyze the biological role of the surface antigen of Toxoplasma gondii（Tgondii） in development of vaccine. METHODS： The surface antigen of Tgondii （SAG1） was expressed in vitro. The immune response of t...AIM： To analyze the biological role of the surface antigen of Toxoplasma gondii（Tgondii） in development of vaccine. METHODS： The surface antigen of Tgondii （SAG1） was expressed in vitro. The immune response of the host to the antigen was investigated by detection of specific antibody reaction to SAG1 and production of cytokines. Mice were immunized with recombinant SAG1 and challenged with lethal strain of Tgondii RH. The monoclonal antibody to r-SAG1 was prepared and used to study the effects of SAG1 on Tgondii tachyzoites under electromicroscope. RESULTS： The mice immunized with recombinant SAG1 delayed death for 60 h compared to the control group. The recombinant SAG1 induced specific high titer of IgG and IgM antibodies as well as IFN-y, IL-2 and IL-4 cytokines in mice. In contrast, IL-12, IL-6 and TNF-α were undetectable. When T gondii tachyzoites were treated with the monoclonal antibody to r-SAG1, the parasites were gathered together, destroyed, deformed, swollen, and holes and gaps formed on the surface. CONCLUSION： SAG1 may be an excellent vaccine candidate against T gondii. The immune protection induced by SAG1 against Tgondii may be regulated by both hormone- and cell-mediated immune response.展开更多
BACKGROUND Liver cirrhosis is the late stage of hepatic fibrosis and is characterized by portal hypertension that can clinically lead to decompensation in the form of ascites,esophageal/gastric varices or encephalopat...BACKGROUND Liver cirrhosis is the late stage of hepatic fibrosis and is characterized by portal hypertension that can clinically lead to decompensation in the form of ascites,esophageal/gastric varices or encephalopathy.The most common sequelae associated with liver cirrhosis are neurologic and neuropsychiatric impairments labeled as hepatic encephalopathy(HE).Well established triggers for HE include infection,gastrointestinal bleeding,constipation,and medications.Alterations to the gut microbiome is one of the leading ammonia producers in the body,and therefore may make patients more susceptible to HE.AIM To investigate the relationship between the use of proton pump inhibitors(PPIs)and HE in patients with cirrhosis.METHODS This is a single center,retrospective analysis.Patients were included in the study with an admitting diagnosis of HE.The degree of HE was determined from subjective and objective portions of hospital admission notes using the West Haven Criteria.The primary outcome of the study was to evaluate the grade of HE in PPI users versus non-users at admission to the hospital and throughout their hospital course.Secondary outcomes included rate of infection,gastrointestinal bleeding within the last 12 mo,mean ammonia level,and model for end-stage liver disease scores at admission.RESULTS The HE grade at admission using the West Haven Criteria was 2.3 in the PPI group compared to 1.7 in the PPI nonuser group(P=0.001).The average length of hospital stay in PPI group was 8.3 d compared to 6.5 d in PPI nonusers(P=0.046).Twenty-seven(31.8%)patients in the PPI user group required an Intensive Care Unit admission during their hospital course compared to 6 in the PPI nonuser group(16.7%)(P=0.138).Finally,10(11.8%)patients in the PPI group expired during their hospital stay compared to 1 in the PPI nonuser group(2.8%)(P=0.220).CONCLUSION Chronic PPI use in cirrhotic patients is associated with significantly higher average West Haven Criteria for HE compared to patients that do not use PPIs.展开更多
Diabetes mellitus(DM)is a growing epidemic with global proportions.It is estimated that in 2019,463 million adults aged 20-79 years were living with DM.The latest evidence shows that DM continues to be a significant g...Diabetes mellitus(DM)is a growing epidemic with global proportions.It is estimated that in 2019,463 million adults aged 20-79 years were living with DM.The latest evidence shows that DM continues to be a significant global health challenge and is likely to continue to grow substantially in the next decades,which would have major implications for healthcare expenditures,particularly in developing countries.Hence,new conceptual and methodological approaches to tackle the epidemic are long overdue.Spatial epidemiology has been a successful approach to control infectious disease epidemics like malaria and human immunodeficiency virus.The implementation of this approach has been expanded to include the study of non-communicable diseases like cancer and cardiovascular diseases.In this review,we discussed the implementation and use of spatial epidemiology and Geographic Information Systems to the study of DM.We reviewed several spatial methods used to understand the spatial structure of the disease and identify the potential geographical drivers of the spatial distribution of DM.Finally,we discussed the use of spatial epidemiology on the design and implementation of geographically targeted prevention and treatment interventions against DM.展开更多
The discovery of artemisinin is significant because not only it is an innovative new drug,but also its treatment of malaria has saved millions of lives worldwide,especially in(tropical)developing countries.The 2015 No...The discovery of artemisinin is significant because not only it is an innovative new drug,but also its treatment of malaria has saved millions of lives worldwide,especially in(tropical)developing countries.The 2015 Nobel Prize in Physiology or Medicine was awarded to Professor Tu You-You,a scientist from China,who made this seminal discovery.Malaria is one of the most prevalent展开更多
In contrast to the cries of human infants, sounds made by non-human infants in different stressful behavioral contexts （hunger or physical discomfort, isolation, capture by humans or predators） are usually treated a...In contrast to the cries of human infants, sounds made by non-human infants in different stressful behavioral contexts （hunger or physical discomfort, isolation, capture by humans or predators） are usually treated as distinct types of vocalizations. However, if distress vocalizations produced by different species and in different contexts share a common motivational state and associated neurochemical pathways, we can expect them to share a common acoustic structure and adaptive function, showing only limited variation that corresponds to the infant＇s level of arousal. Based on this premise, we review the acoustic structure and adaptive function of two types of distress calls, those given when infants were isolated from their mothers （isolation caUs） or captured by humans （capture calls）. We conducted a within-context comparison examining the two call types across a diverse se- lection of mammalian species and other vertebrate groups, followed by a comparison of how acoustic structure and function dif- fers between these contexts. In addition, we assessed acoustic traits that are critical to the response of caregivers. Across verte- brate species, distress vocalizations produced in these two behavioral contexts tend to be tonal with a simple chevron, flat or de- scending pattern of frequency modulation. Reports that both isolation and capture calls of vertebrate infants serve to attract care- givers are universal, and the fundamental frequency of infant vocalizations is often critical to this response. The results of our re- view are consistent with the hypothesis that differences in the acoustic structure of isolation and capture distress vocalizations re- flect differences in arousal, and not discrete functions. The similarity in acoustic structure and caregiver response observed across vertebrates adds support to the hypothesis that the production and processing of distress vocalizations are part of a highly-conserved system of social vocal behaviour in vertebrates. Bioacoustic research may move forward by recognizing the commonality among different forms of infant solicitations that attract caregivers, and the commonality of these solicitations with vocalizations that attract conspecifics in still other behavioral contexts [Current Zoology 58 （5）： 698-726, 2012].展开更多
Background Though engaging patients with atrial fibrillation(AF) in understanding their stroke risk is encouraged by guidelines, little is known regarding AF patients' perceived stroke risk or its relationship wit...Background Though engaging patients with atrial fibrillation(AF) in understanding their stroke risk is encouraged by guidelines, little is known regarding AF patients' perceived stroke risk or its relationship with oral anticoagulation(OAC) use. We aim to identify factors associated with underestimation of stroke risk among older patients with AF and relate this to OAC use. Methods Data are from the ongoing SAGE(Systematic Assessment of Geriatric Elements)-AF study, which included older patients(> 65 years) with non-valvular AF and a CHA2 DS2-VASc score of ≥ 2. Participants reported their perceived risk of having a stroke without OAC. We compared the perceived risk to CHA2 DS2-VASc predicted stroke risk and classified participants as "over" or "under" estimators, and identified factors associated with underestimation of risk using multiple logistic regression. Results The average CHA2 DS2-VASc score of 915 participants(average age: 75 years, 47% female, 86% white) was 4.3 ± 1.6, 43% of participants had discordant predicted and self-reported stroke risks. Among the 376 participants at highest risk(CHA2 DS2-VASc score ≥ 5), 46% of participants underestimated their risk. Older participants(≥ 85 years) were more likely and OAC treated patients less likely to underestimate their risk of developing a future stroke than respective comparison groups. Conclusions A significant proportion of study participants misperceived their stroke risk, mostly by overestimating. Almost half of participants at high risk of stroke underestimated their risk, with older patients more likely to do so. Patients on OAC were less likely to underestimate their risk, suggesting that successful efforts to educate patients about their stroke risk may influence treatment choices.展开更多
文摘BACKGROUND The use of induction immunosuppression agents has improved kidney transplant outcomes,but selecting the optimal agent remains a point of debate.AIM To compare the long-term outcomes of kidney transplant recipients receiving alemtuzumab vs basiliximab induction,focusing on graft function,acute rejection,infection,malignancy,post-transplant glomerulonephritis,and survival,using a propensity score matched cohort design.METHODS Kidney transplant recipients who received alemtuzumab or basiliximab induction from 2014 to 2019 across two nephrology centres in Northwest England were evaluated.Propensity score matching at a 1:1.5 ratio ensured comparability between cohorts.Baseline characteristics,immunosuppression regimens,and outcomes were analyzed.Linear,binary logistic and Cox proportional hazard regression models.RESULTS A total of 436 recipients were included,with a median follow-up of 5.2 years.The matched cohort(n=262)had a mean age of 51.1±13.5 years;39%were female and 92%were white.There was no significant difference in the cumulative incidence of acute rejection[odds ratio(OR)=2.10;95%CI:0.9-4.9;P=0.110].Compared with basiliximab,alemtuzumab was associated with lower estimated glomerular filtration rate at 12 months(-6.6 mL/minute/1.73 m2;95%CI:-10.5 to-2.7;P<0.001)and higher risks of cytomegalovirus viremia(OR=3.2;95%CI:1.6-6.5;P<0.001),BK viremia(OR=2.4;95%CI:1.1-5.5;P=0.02),post-transplant malignancy(OR=6.2;95%CI:1.6-29.9;P=0.013),and death-censored graft loss(hazard ratio=3.6;95%CI:1.2-11.4;P=0.03).No significant differences were observed in post-transplant glomerulonephritis or recipient mortality.CONCLUSION In this propensity score-matched analysis,alemtuzumab induction was associated with lower graft function at 12 months and higher risks of viral infection,post-transplant malignancy,and graft loss compared with basiliximab.These findings highlight the need for further studies to confirm the long-term safety and effectiveness of alemtuzumab in kidney transplantation.
基金supported by National Natural Science Foundation of China(82192900,82192901,82192904,81941018,and 91846303)Peking University Medicine Seed Fund for Interdisciplinary Research(BMU2022MX025)+5 种基金the Fundamental Research Funds for the Central Universitiessupported by a grant from the Kadoorie Charitable Foundation in Hong Kongsupported by grants from the UK Wellcome Trust(212946/Z/18/Z,202922/Z/16/Z,104085/Z/14/Z,and 088158/Z/09/Z)the National Key R&D Program of China(2016YFC0900500)National Natural Science Foundation of China(81390540)Chinese Ministry of Science and Technology(2011BAI09B01)。
文摘Background:Information on the association between physical activity(PA)and the risk of chronic kidney disease(CKD)is limited.We aimed to explore the associations of total,domain-specific,and intensity-specific PA with CKD and its subtypes in China.Methods:The study included 475,376 adults from the China Kadoorie Biobank aged 30-79 years during 2004-2008 at baseline.An interviewer-administered questionnaire was used to collect the information about PA,which was quantified as metabolic equivalent of task hours per day(MET-h/day)and categorized into 4 groups based on quartiles.Cox regression was used to analyze the association between PA and CKD risk.Results:During a median follow-up of 12.1 years,5415 incident CKD cases were documented,including 1159 incident diabetic kidney disease(DKD)cases and 362 incident hypertensive nephropathy(HTN)cases.Total PA was inversely associated with CKD risk,with an adjusted hazard ratio(HR,95%confidence interval(95%CI))of 0.83(0.75-0.92)for incident CKD in the highest quartile of total PA as compared with participants in the lowest quartile.Similar results were observed for risk of DKD and HTN,and the corresponding HRs(95%CIs)were 0.75(0.58-0.97)for DKD risk and 0.56(0.37-0.85)for HTN risk.Increased nonoccupational PA,low-intensity PA,and moderate-to-vigorous-intensity PA were significantly associated with a decreased risk of CKD,with HRs(95%CIs)of 0.80(0.73-0.88),0.85(0.77-0.94),and 0.85(0.76-0.95)in the highest quartile,respectively.Conclusion:PA,including nonoccupational PA,low-intensity PA,and moderate-to-vigorous-intensity PA,was inversely associated with the risk of CKD,including DKD,HTN,and other CKD,and such associations were dose dependent.
基金This study was reviewed and approved by the New York-Presbyterian Brooklyn Methodist Hospital Institutional Review Committee.The study follows the guidelines outlined in the Declaration of Helsinki.
文摘Objective:Accurate measurement of QT interval,the ventricular action potential from depolarization to repolarization,is important for the early detection of Long QT syndrome.The most effective QT correction(QTc)formula has yet to be determined in the pediatric population,although it has intrinsically greater extremes in heart rate(HR)and is more susceptible to errors in measurement.The authors of this study compare six dif-ferent QTc methods(Bazett,Fridericia,Framingham,Hodges,Rautaharju,and a computer algorithm utilizing the Bazett formula)for consistency against variations in HR and RR interval.Methods:Descriptive Retrospective Study.We included participants from a pediatric cardiology practice of a community hospital who had an ECG performed in 2017.All participants were healthy patients with no past medical history and no regular med-ications.Results:ECGs from 95 participants from one month to 21 years of age(mean 9.7 years)were included with a mean HR of 91 beats per minute(bpm).The two-sample paired t-test or Wilcoxon signed-rank test assessed for any difference between QTc methods.A statistically significant difference was observed between every combination of two QTc formulae.The Spearman’s rank correlation analysis explored the QTc/HR and QTc/RR relationships for each formula.Fridericia method was most independent of HR and RR with the lowest absolute value of correlation coefficients.Bazett and Computer had moderate correlations,while Framingham and Rautaharju exhibited strong correlations.Correlations were positive for Bazett and Computer,reflecting results from prior studies demonstrating an over-correction of Bazett at higher HRs.In the linear QTc/HR regression analysis,Bazett had the slope closest to zero,although Computer,Hodges,and Fridericia had comparable values.Alternatively,Fridericia had the linear QTc/RR regression coefficient closest to zero.The Bland-Altman method assessed for bias and the limits of agreement between correction formulae.Bazett and Computer exhibited good agreement with minimal bias along with Framingham and Rautaharju.To account for a possible skewed distri-bution of QT,all the above analyses were also performed excluding the top and bottom 2%of data as sorted by heart rate ranges(N=90).Results from this data set were consistent with those derived from all participants(N=95).Conclusions:Overall,the Fridericia correction method provided the best rate correction in our pedia-tric study cohort.
文摘BACKGROUND The neurological and psychiatric sequelae of coronavirus disease 2019(COVID-19)have been documented,yet further data are needed to thoroughly evaluate the impact of COVID-19 on brain health years after the infection.AIM To examine whether COVID-19 infection is associated with exacerbation,recurrence,or progression of pre-existing neurological or psychiatric disorders-a highrisk population that is underrepresented in COVID-19 outcome research in National Guard Health Affair patients in 4-years following a COVID-19 diagnosis.METHODS For this multicenter retrospective cohort study,we used data from the National Guard hospitals electronic health records network(BestCare)with over 10 million patients.Our cohort comprised patients who had a COVID-19 diagnosis;a matched control cohort included patient did not expose to COVID-19 in same period.Age and sex were matching factors.We estimated the incidence of 14 neurological and psychiatric outcomes in nearly 4 years after a confirmed diagnosis of COVID-19.Using a multiple logistic regression,we compared incidences with those in propensity score-matched cohorts of patients with no exposure to COVID-19.Ramadan M et al.Neurological and psychiatric risks post-COVID-19 RESULTS Our primary cohort comprised 4437 patients diagnosed with COVID-19,and our propensity-score 1:1 matched control cohort comprised 4437 individuals.Nearly two-third of the COVID-19 cohort(71%)were diagnosed in 2020,and 2021.The most prevalent diagnoses for both cohorts were epilepsy 30.68%,mood disorder 23.92%,and nerve plexus disorder 22.13%.Dementia was nearly 4 times higher among COVID-19 cohort(8.27%)compared to the control cohort(2.57%).Five neurological and psychiatric outcomes had odds ratios(OR)that were significantly higher than 1 for people who had COVID-19 compared to people who had never been infected.These outcomes were cognitive deficit OR=1.54,95%confidence interval(CI):1.23-1.91,P=0.0001;nerve plexus disorder OR=1.13,95%CI:1.01-1.25,P=0.02;substance use disorder OR=1.95,95%CI:1.12-3.38,P=0.01;mood disorder OR=1.16,95%CI:1.05-1.29,P=0.003;and anxiety disorder OR=1.39,95%CI:1.07-1.79,P=0.01.CONCLUSION The study highlights the persistent risk of neurological and psychiatric conditions in COVID-19 survivors up to four years post-infection.Although the incidence was lower than in previous large studies,long-term consequences remain significant,emphasizing the need for ongoing monitoring and support in mental health and neurological care.
基金Funding support was from the Novo Nordisk Foundation with the project's grant number NNFSA210073688.
文摘Background L-Glutamate and L-aspartate are functional amino acids that play pivotal roles in the cellular metabolic pathways of swine enterocytes.Therefore,this study aimed to investigate the effects of dietary L-glutamate and L-aspartate on growth performance,diarrhea severity,intestinal barrier integrity,and fecal microbiota of weaned piglets challenged with F18 enterotoxigenic Escherichia coli(ETEC).Weaned piglets were randomly assigned to seven dietary treatments,including unchallenged and ETEC-challenged controls,amino acid-supplemented groups,and an antibiotic control,to assess their responses to ETEC challenge.Results Supplementation with 1%L-glutamate or 2%L-aspartate enhanced growth performance,with significantly greater(P<0.05)average daily weight gain and gain-to-feed ratio compared with the positive control group from d 0 to d 5 post-inoculation.Pigs fed with 1%or 2%L-aspartate had reduced(P<0.05)diarrhea severity in ETEC-challenged pigs compared with the positive control group.The 1%L-aspartate supplementation also supported intestinal structure by increasing(P<0.05)duodenal villi height and ileal villi width compared with carbadox supplementation.Additionally,1%L-glutamate supplementation significantly improved(P<0.05)resilience in ETEC-challenged pigs by reducing fecal shedding ofβ-hemolysin-producing bacteria compared with the positive control group on d 14 post-inoculation.Moreover,1%L-aspartate supplementation promoted intestinal barrier integrity by significantly up-regulated(P<0.05)the expression of ileal OCDN and ileal ZO-1 compared with the positive control group on d 14 post-inoculation.Interestingly,2%L-aspartate supplementation altered the intestinal mucosa by down-regulating(P<0.05)the expression of jejunal CLDN-1,while up-regulating(P<0.05)the expression of ileal CLDN-1 compared with the negative control group on d 14 post-inoculation.Furthermore,L-glutamate supplementation significantly changed proportions of Firmicutes and Bacteroidota and showed the trend for enrichment in beneficial bacterial genera such as Bifidobacterium and Megasphaera in ETEC-infected pigs by d 14 post-inoculation.Conclusion Supplementation with L-glutamate or L-aspartate promoted growth performance,supported gut health,and enhanced disease resistance in weaned pigs challenged with F18 ETEC.During the weaning period,L-glutamate or L-aspartate could potentially be considered conditionally essential amino acids,helping to alleviate weaning complications and reduce the need for antibiotic use in swine farming.
基金Leanna M.Ross is supported by the American Heart Association Career Development Award 23CDA1051777National Institute on Aging grant 5P30AG028716-18。
文摘Purpose:The purpose of this narrative review is to:1)summarize findings from the three Studies of a Targeted Risk Reduction Intervention through Defined Exercise(STRRIDE)randomized trials regarding the differential effects of exercise amount,intensity,and mode on metabolic syndrome(MetS);and 2)compare the STRRIDE findings with other published randomized exercise trials related to changes in MetS.Methods:A literature review was performed to investigate the effects of exercise on composite measures of MetS.PubMed was searched between October 2023 and December 2023.To be included in this review,studies must have employed a randomized study design,whereby exercise amount,intensity,or mode was varied.Results:Findings from the STRRIDE trials and other randomized exercise trials suggest:1)there is a relationship between exercise energy expenditure(ExEE)and improvements in composite measures of MetS;2)there may be an asymptotic effect for ExEE beyond which further improvements in MetS are negligible or counterproductive;3)improvements in composite measures of MetS are closely linked to insulin sensitivity;and 4)without controlling for total ExEE,combined aerobic and resistance training interventions offer the most robust improvements for composite MetS outcomes compared to either mode alone.Conclusion:Additional,large-scale,randomized exercise trials should be designed to investigate the potential asymptotic effect and associated threshold for ExEE,the interaction between exercise intensity and baseline insulin sensitivity,and the independent effects of exercise mode on MetS.
基金supported by the National Key Research and Development Program of China(No.2022YFC3600800)the non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(No.2023-RC330–01)+1 种基金the Special Research Fund for Central Universities,Peking Union Medical College(No.3332023087)the Population and Aging Health Science Program(No.WH10022023035).
文摘The specific and cumulative effects of fine particulate matter(PM_(2.5))components on hypertension remain less defined,notably in susceptible older adults.This national study utilized a representative sample of 220,425 older adults in China,to scrutinize their relationship.Residential PM_(2.5)and five chemical components(black carbon(BC),organic matter(OM),sulphate(SO_(4)^(2−)),nitrate(NO_(3)^(−)),and ammonium(NH_(4)^(+)))were estimated by the bilinear interpolation.Associations between PM_(2.5)and five chemical components with hypertension were examined through two-stage logistic regression models,with population attributable fractions(PAFs)determined via counterfactual analysis.Elevated exposure to PM_(2.5)and its components was generally linked to higher hypertension prevalence.With each interquartile range increase,the odds ratio(OR)of hypertension rose by 1.09(95%CI:1.08–1.11)for NO_(3)^(−),1.06(95%CI:1.05–1.08)for NH_(4)^(+),1.06(95%CI:1.05–1.07)for OM,1.05(95%CI:1.04–1.06)for BC,and 1.06(95%CI:1.04–1.07)for SO42-.Notably,the cumulative impact of five PM_(2.5)chemical components(OR:1.13,95%CI:1.12–1.13)was significantly greater than the effect of total PM_(2.5)mass alone(OR:1.04,95%CI:1.03–1.05).Regarding PAFs,NO_(3)^(−)represented the strongest contribution to hypertension,followed by OM,NH_(4)^(+),SO_(4)^(2−),and BC.Furthermore,the effects were accentuated in low socio-economic population.These findings underline that using total PM_(2.5)as a surrogate marker may underestimate the comprehensive impact of its chemical components,underscoring the necessity for targeted interventions to reduce emissions of specific PM_(2.5)chemical constituents.
基金the Flourish Collective,a Cluster of Scholarly Prominence at the University of Toronto,Scarborough。
文摘Objective:The World Health Organization recommends annual preventive chemotherapy with a single dose of praziquantel at≥75%treatment coverage,but as of 2021,the national coverage rate in Nigeria among children falls below 10%.This qualitative study sought to explore the barriers and facilitators to implementing large-scale praziquantel mass drug administration(MDA)programs for school-aged children in Nigeria to delineate tools and strategies that could improve the scaling-up and effectiveness of school-based praziquantel MDA programs.Methods:An exploratory qualitative study was conducted with stakeholders with experience in MDAs involving praziquantel or related preventive chemotherapy drugs in Nigeria.Through snowball sampling,30 stakeholders with experience in praziquantel school-based MDA in Nigeria were interviewed.An inductive approach was used to generate broad themes based on the barriers and facilitators identified by the key informants.Results:A total of 45 barriers and 36 facilitators were identified and grouped inductively into eight themes:funding and resources,design and composition of praziquantel tablets,knowledge and awareness mobilization,government,nongovernmental organization,and school engagement,data management,logistics,training,and security.Conclusion:This qualitative study reveals a wide range of barriers and facilitators in the MDA of praziquantel in Nigeria and uncovered critical points along the implementation pathway based on the locus of the barriers and facilitators identified.Collaboration with national,international,and non-profit organizations,and drug education through promotional materials,were the most frequently mentioned facilitators of the MDA program.In addition,insufficient program funding,and the complexity of the supply chain were the most cited barriers.
基金supported by the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre and NIHR Applied Research Collaboration East Midlands (ARC EM, (IS-BRC-1215-20010))funded by the National Institute for Health and Care Research Bristol Biomedical Research Centre (IS-BRC-1215-20011)supported by a UKRI research grant (EP/X042464/1)。
文摘Background Higher accelerometer-assessed volume and intensity of physical activity(PA)have been associated with a longer life expectancy but can be difficult to translate into recommended doses of PA.We aimed to:(a)improve interpretability by producing UK Biobank age-referenced centiles for PA volume and intensity;(b)inform public-health messaging by examining how adding recommended quantities of moderate and vigorous PA affect PA volume and intensity.Methods 92,480 UK Biobank participants aged 43-80 years with wrist-worn accelerometer data were included.Average acceleration and intensity gradient were derived as proxies for PA volume and intensity.We generated sex-specific centile curves using Generalized Additive Models for Location Scale and Shape(GAMLSS)and modeled the effect of adding moderate(walking)or vigorous(running)activity on the combined change in the volume and intensity centiles(change in PA profile).Results In men,volume was lower as age increased while intensity was lower after age 55;in women,both volume and intensity were lower as age increased.Adding 150 min of moderate PA weekly(5×30 min walking)increased the PA profile by 4 percentage points.Defining moderate PA as brisk walking approximately doubled the increase(9 percentage points)while 75 min of vigorous PA weekly(5×15 min running)trebled the increase(13 percentage points).Conclusion These UK Biobank reference centiles provide a benchmark for interpretation of accelerometer data.Application of our translational methods demonstrate that meeting PA guidelines through shorter duration vigorous activity is more beneficial to the PA profile(volume and intensity)than longer duration moderate activity.
基金supported by European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska Curie grant agreement(No.101028929)BJFis supported by National Heart Foundation of Australia Postdoc-toral Fellowship(No.106588)+1 种基金BG is supported by Australian Government Research Training Program ScholarshipDPLis supported by Clive Kearon Award,McMaster University.Additional funding information can be found in Supplemen-tary Funding.
文摘Background:Muscular strength is a powerful marker of current health status and robust predictor of age-related disease and disability.Handgrip strength(HGS)using isometric dynamometry is a convenient,feasible,and widely used method of assessing muscular strength among people of all ages.While adult HGS norms have been published for many countries,no study has yet synthesized available data to produce international norms.The objective of this study was to generate international sex-and age-specific norms for absolute and body size-normalized HGS across the adult lifespan.Methods:Systematic searches were conducted in 6 databases/web search engines(MEDLINE,SPORTDiscus,Embase,Web of Science,CINAHL,and Google Scholar)up to December 1,2023.We included full-text peer-reviewed observational studies that reported normative HGS data for adults aged ≥20 years by sex and age.Pseudo data were generated using Monte Carlo simulation following harmonization for methodo-logical variation.Population-weighted Generalized Additive Models for Location,Scale,and Shape were used to develop sex-and age-specific norms for absolute HGS(kg)and HGS normalized by height(Ht,m)squared(i.e.,HGS/Ht^(2)in kg/m^(2)).Norms were tabulated as percentile values(5th to 95th)and visualized as smoothed percentile curves.Results:We included data from 100 unique observational studies representing 2,405,863 adults(51.9%female)aged 20 to 100+years from 69 countries and regions tested from the year 2000 onward.On average,absolute and normalized HGS values negligibly improved throughout early adulthood,peaked from age 3039 years(at 49.7 kg(males)and 29.7 kg(females)for absolute HGS or 16.3 kg/m^(2)(males)and 11.3 kg/m^(2)(females)for HGS/Ht^(2)),and declined afterwards.The age-related decline in HGS accelerated from middle to late adulthood and was slightly larger for males than for females during middle adulthood.Conclusion:This study provides the world’s largest and most geographically comprehensive international norms for adult HGS by sex and age.These norms have utility for global peer-comparisons,health screening,and surveillance.
基金supported in part by the USDA National Institute of Food and Agriculture,Hatch project 1016618.
文摘Selenium is an essential trace mineral important for the maintenance of homeostasis in animals and humans.It evinces a strong antioxidant,anti-inflammatory and potential antimicrobial capacity.Selenium biological function is primarily achieved by its presence in selenoproteins as a form of selenocysteine.Selenium deficiency may result in an array of health disorders,affecting many organs and systems;to prevent this,dietary supplementation,mainly in the forms of organic(i.e.,selenomethionine and selenocysteine)inorganic(i.e.,selenate and selenite)sources is used.In pigs as well as other food animals,dietary selenium supplementation has been used for improving growth performance,immune function,and meat quality.A substantial body of knowledge demonstrates that dietary selenium supplementation is positively associated with overall animal health especially due to its immunomodulatory activity and protection from oxidative damage.Selenium also possesses potential antiviral activity and this is achieved by protecting immune cells against oxidative damage and decreasing viral replication.In this review we endeavor to combine established and novel knowledge on the beneficial effects of dietary selenium supplementation,its antioxidant and immunomodulatory actions,and the putative antimicrobial effect thereof.Furthermore,our review demonstrates the gaps in knowledge pertaining to the use of selenium as an antiviral,underscoring the need for further in vivo and in vitro studies,particularly in pigs.
文摘The virus SARS-CoV2,which causes the Coronavirus disease COVID-19 has become a pandemic and has spread to every inhabited continent.Given the increasing caseload,there is an urgent need to augment clinical skills in order to identify from among the many mild cases the few that will progress to critical illness.We present a first step towards building an artificial intelligence(AI)framework,with predictive analytics(PA)capabilities applied to real patient data,to provide rapid clinical decision-making support.COVID-19 has presented a pressing need as a)clinicians are still developing clinical acumen given the disease’s novelty,and b)resource limitations in a rapidly expanding pandemic require difficult decisions relating to resource allocation.The objectives of this research are:(1)to algorithmically identify the combinations of clinical characteristics of COVID-19 that predict outcomes,and(2)to develop a tool with AI capabilities that will predict patients at risk for more severe illness on initial presentation.The predictive models learn from historical data to help predict specifically who will develop acute respiratory distress syndrome(ARDS),a severe outcome in COVID-19.Our experimental results based on two hospitals in Wenzhou,Zhejang,China identify features most predictive of ARDS in COVID-19 initial presentation which would not have stood out to clinicians.A mild increase in elevated alanine aminotransferase(ALT)(a liver enzyme)),a presence of myalgias(body aches),and an increase in hemoglobin,in this order,are the clinical features,on presentation,that are the most predictive.Those two centers’COVID-19 case series symptoms on initial presentation can help predict severe outcomes.Predictive models that learned from historical data of patients from two Chinese hospitals achieved 70%to 80%accuracy in predicting severe cases.
文摘Social stability in group-living animals is an emergent property which arises from the interaction amongst multiple behavioral networks. However, pinpointing when a social group is at risk of collapse is difficult. We used a joint network model- ing approach to examine the interdependencies between two behavioral networks, aggression and status signaling, from four sta- ble and three unstable groups of rhesus macaques in order to identify characteristic patterns of network interdependence in stable groups that are readily distinguishable from unstable groups. Our results showed that the most prominent source of aggres- sion-status network interdependence in stable social groups came from more frequent dyads than expected with opposite direc- tion status-aggression （i.e. A threatens B and B signals acceptance of subordinate status）. In contrast, unstable groups showed a decrease in opposite direction aggression-status dyads （but remained higher than expected） as well as more frequent than ex- pected dyads with bidirectional aggression. These results demonstrate that not only was the stable joint relationship between ag- gression and status networks readily distinguishable from unstable time points, social instability manifested in at least two differ- ent ways. In sum, our joint modeling approach may prove useful in quantifying and monitoring the complex social dynamics of any wild or captive social system, as all social systems are composed of multiple interconnected networks [Current Zoology 61 （1）： 70-84, 2015].
文摘Background： Creep feeding is used to stimulate piglet post-weaning feed consumption.L-Glutamine（GLN） is an important source of fuel for intestinal epithelial cells.The objective of this study was to determine the impact of creep feeding and adding GLN or AminoGut（AG;containing glutamine ＋ glutamate） to pre-and post-weaning diets on pig performance and intestinal health.Litters（N = 120） were allotted to four treatments during 14–21 d of lactation： 1） No creep feed（NC,n = 45）;2） creep fed control diet（CFCD,n = 45）;3） creep fed 1% GLN（CFGLN,n = 15）;4） creep fed.88% AG（CFAG,n = 15）.After weaning,the NC and CFCD groups were sub-divided into three groups（n = 15 each）,receiving either a control nursery diet（NC-CD,CFCD-CD） or a diet supplemented with either GLN（NC-GLN,CFCD-GLN） or with AG（NC-AG,CFCD-AG）.Litters that were creep fed with diets containing GLN or AG also were supplemented with those amino acids in the nursery diets（CFGLN-GLN,CFAG-AG）.Glutamine was added at 1% in all three post-weaning diet phases and AG was added at.88% in phase 1 and 2 and at.66% in phase 3.Results： Feed conversion（feed/gain） showed means among treatment means close to significance（P = 0.056） and Tukey＇s test for pairwise mean comparisons showed that Pigs in the CFGLN-GLN group had the best feed conversion（feed/gain） in the first three-week period post-weaning,exceeding（P = 0.044） controls（CFCD-CD） by 34%.The NC-AG group had（P = 0.02） the greatest feed intake in the last three week of the study,exceeding controls（CFCD-CD） by 12%.CFGLN-GLN,CFCD-GLN and sow reared（SR） pigs had the greatest（P = 0.049） villi height exceeding the CFCD-AG group by 18%,20% and 19% respectively.The CFAG-AG group had the deepest（P = 0.001） crypts among all treatments.CFGLN-GLN,CFCD-GLN and SR groups had the greatest（P = 0.001） number of cells proliferating（PCNA） exceeding those in the NC-CD group by 43%,54% and 63% respectively.Sow reared pigs showed the greatest（P = 0.001） intestinal absorption capacity for xylose and mannitol.Conclusion： Supplementation of creep feed and nursery diets with GLN and/or AminoGut in the first three week improved feed conversion possibly due to improved intestinal health.
基金Supported by China Ministry of Human Affairs and Department of Science and Technology of Shandong Province, No. 031050115
文摘AIM： To analyze the biological role of the surface antigen of Toxoplasma gondii（Tgondii） in development of vaccine. METHODS： The surface antigen of Tgondii （SAG1） was expressed in vitro. The immune response of the host to the antigen was investigated by detection of specific antibody reaction to SAG1 and production of cytokines. Mice were immunized with recombinant SAG1 and challenged with lethal strain of Tgondii RH. The monoclonal antibody to r-SAG1 was prepared and used to study the effects of SAG1 on Tgondii tachyzoites under electromicroscope. RESULTS： The mice immunized with recombinant SAG1 delayed death for 60 h compared to the control group. The recombinant SAG1 induced specific high titer of IgG and IgM antibodies as well as IFN-y, IL-2 and IL-4 cytokines in mice. In contrast, IL-12, IL-6 and TNF-α were undetectable. When T gondii tachyzoites were treated with the monoclonal antibody to r-SAG1, the parasites were gathered together, destroyed, deformed, swollen, and holes and gaps formed on the surface. CONCLUSION： SAG1 may be an excellent vaccine candidate against T gondii. The immune protection induced by SAG1 against Tgondii may be regulated by both hormone- and cell-mediated immune response.
文摘BACKGROUND Liver cirrhosis is the late stage of hepatic fibrosis and is characterized by portal hypertension that can clinically lead to decompensation in the form of ascites,esophageal/gastric varices or encephalopathy.The most common sequelae associated with liver cirrhosis are neurologic and neuropsychiatric impairments labeled as hepatic encephalopathy(HE).Well established triggers for HE include infection,gastrointestinal bleeding,constipation,and medications.Alterations to the gut microbiome is one of the leading ammonia producers in the body,and therefore may make patients more susceptible to HE.AIM To investigate the relationship between the use of proton pump inhibitors(PPIs)and HE in patients with cirrhosis.METHODS This is a single center,retrospective analysis.Patients were included in the study with an admitting diagnosis of HE.The degree of HE was determined from subjective and objective portions of hospital admission notes using the West Haven Criteria.The primary outcome of the study was to evaluate the grade of HE in PPI users versus non-users at admission to the hospital and throughout their hospital course.Secondary outcomes included rate of infection,gastrointestinal bleeding within the last 12 mo,mean ammonia level,and model for end-stage liver disease scores at admission.RESULTS The HE grade at admission using the West Haven Criteria was 2.3 in the PPI group compared to 1.7 in the PPI nonuser group(P=0.001).The average length of hospital stay in PPI group was 8.3 d compared to 6.5 d in PPI nonusers(P=0.046).Twenty-seven(31.8%)patients in the PPI user group required an Intensive Care Unit admission during their hospital course compared to 6 in the PPI nonuser group(16.7%)(P=0.138).Finally,10(11.8%)patients in the PPI group expired during their hospital stay compared to 1 in the PPI nonuser group(2.8%)(P=0.220).CONCLUSION Chronic PPI use in cirrhotic patients is associated with significantly higher average West Haven Criteria for HE compared to patients that do not use PPIs.
文摘Diabetes mellitus(DM)is a growing epidemic with global proportions.It is estimated that in 2019,463 million adults aged 20-79 years were living with DM.The latest evidence shows that DM continues to be a significant global health challenge and is likely to continue to grow substantially in the next decades,which would have major implications for healthcare expenditures,particularly in developing countries.Hence,new conceptual and methodological approaches to tackle the epidemic are long overdue.Spatial epidemiology has been a successful approach to control infectious disease epidemics like malaria and human immunodeficiency virus.The implementation of this approach has been expanded to include the study of non-communicable diseases like cancer and cardiovascular diseases.In this review,we discussed the implementation and use of spatial epidemiology and Geographic Information Systems to the study of DM.We reviewed several spatial methods used to understand the spatial structure of the disease and identify the potential geographical drivers of the spatial distribution of DM.Finally,we discussed the use of spatial epidemiology on the design and implementation of geographically targeted prevention and treatment interventions against DM.
文摘The discovery of artemisinin is significant because not only it is an innovative new drug,but also its treatment of malaria has saved millions of lives worldwide,especially in(tropical)developing countries.The 2015 Nobel Prize in Physiology or Medicine was awarded to Professor Tu You-You,a scientist from China,who made this seminal discovery.Malaria is one of the most prevalent
文摘In contrast to the cries of human infants, sounds made by non-human infants in different stressful behavioral contexts （hunger or physical discomfort, isolation, capture by humans or predators） are usually treated as distinct types of vocalizations. However, if distress vocalizations produced by different species and in different contexts share a common motivational state and associated neurochemical pathways, we can expect them to share a common acoustic structure and adaptive function, showing only limited variation that corresponds to the infant＇s level of arousal. Based on this premise, we review the acoustic structure and adaptive function of two types of distress calls, those given when infants were isolated from their mothers （isolation caUs） or captured by humans （capture calls）. We conducted a within-context comparison examining the two call types across a diverse se- lection of mammalian species and other vertebrate groups, followed by a comparison of how acoustic structure and function dif- fers between these contexts. In addition, we assessed acoustic traits that are critical to the response of caregivers. Across verte- brate species, distress vocalizations produced in these two behavioral contexts tend to be tonal with a simple chevron, flat or de- scending pattern of frequency modulation. Reports that both isolation and capture calls of vertebrate infants serve to attract care- givers are universal, and the fundamental frequency of infant vocalizations is often critical to this response. The results of our re- view are consistent with the hypothesis that differences in the acoustic structure of isolation and capture distress vocalizations re- flect differences in arousal, and not discrete functions. The similarity in acoustic structure and caregiver response observed across vertebrates adds support to the hypothesis that the production and processing of distress vocalizations are part of a highly-conserved system of social vocal behaviour in vertebrates. Bioacoustic research may move forward by recognizing the commonality among different forms of infant solicitations that attract caregivers, and the commonality of these solicitations with vocalizations that attract conspecifics in still other behavioral contexts [Current Zoology 58 （5）： 698-726, 2012].
基金supported by the National Heart,Lung,and Blood Institute(R01HL126911)supported by the NIH Training Grant entitled Transdisciplinary Training in Cardiovascular Research 5T32HL120823-05supported by the National Heart,Lung,and Blood Institute(R01HL137734&R01HL 137794&R01HL13660&R01HL141434&U54HL143541)。
文摘Background Though engaging patients with atrial fibrillation(AF) in understanding their stroke risk is encouraged by guidelines, little is known regarding AF patients' perceived stroke risk or its relationship with oral anticoagulation(OAC) use. We aim to identify factors associated with underestimation of stroke risk among older patients with AF and relate this to OAC use. Methods Data are from the ongoing SAGE(Systematic Assessment of Geriatric Elements)-AF study, which included older patients(> 65 years) with non-valvular AF and a CHA2 DS2-VASc score of ≥ 2. Participants reported their perceived risk of having a stroke without OAC. We compared the perceived risk to CHA2 DS2-VASc predicted stroke risk and classified participants as "over" or "under" estimators, and identified factors associated with underestimation of risk using multiple logistic regression. Results The average CHA2 DS2-VASc score of 915 participants(average age: 75 years, 47% female, 86% white) was 4.3 ± 1.6, 43% of participants had discordant predicted and self-reported stroke risks. Among the 376 participants at highest risk(CHA2 DS2-VASc score ≥ 5), 46% of participants underestimated their risk. Older participants(≥ 85 years) were more likely and OAC treated patients less likely to underestimate their risk of developing a future stroke than respective comparison groups. Conclusions A significant proportion of study participants misperceived their stroke risk, mostly by overestimating. Almost half of participants at high risk of stroke underestimated their risk, with older patients more likely to do so. Patients on OAC were less likely to underestimate their risk, suggesting that successful efforts to educate patients about their stroke risk may influence treatment choices.
