Background:Individuals with diabetes have greater central arterial stiffness,wave reflections,and hemodynamics,all of which promote the accelerated cardiovascular pathology seen in this population.Acute aerobic exerci...Background:Individuals with diabetes have greater central arterial stiffness,wave reflections,and hemodynamics,all of which promote the accelerated cardiovascular pathology seen in this population.Acute aerobic exercise has been shown to be an effective strategy for reducing central arterial stiffness,wave reflections,and hemodynamics in healthy individuals;however,the effects of acute aerobic exercise in reducing these outcomes is not well established in people with diabetes.Recently,implementation of high-intensity interval exercise(HIIE)has shown superior improvements in cardiovascular health outcomes when compared to traditional aerobic exercise.Yet,the effect of HIIE on the aforementioned outcomes in people with diabetes is not known.The purpose of this study was to(i)describe the central arterial stiffness,wave reflections,and hemodynamic responses to a bout of HIIE and moderate-intensity continuous exercise(MICE)in adults with diabetes;and(ii)compare the effects of HIIE and MICE on the aforementioned outcomes.Methods:A total of 24 adult men and women(aged 29-59 years old)with type 1(n=12)and type 2(n=12)diabetes participated in a randomized cross-over study.All participants completed the following protocols:(i)HIIE:cycling for 4×4 min at 85%-95%of heart rate peak(HR_(peak)),interspersed with 3 min of active recovery at 60%-70%HR_(peak);(ii)MICE:33 min of continuous cycling at 60%-70%HR_(peak);and(iii)control(CON):lying quietly in a supine position for 30 min.Results:A significant group￡time effect was found for changes in central systolic blood pressure(F=3.20,p=0.01)with a transient reduction for the HIIE group but not for the MICE or CON groups.There was a significant group￡time effect for changes in augmentation index at a heart rate of 75 beats/min(F=2.32,p=0.04)with a decrease following for HIIE and MICE but not for CON.For all other measures of central arterial stiffness and hemodynamics,no significant changes were observed(p>0.05).Conclusion:A bout of HIIE appears to lead to a greater transient reduction in central systolic blood pressure than the reduction observed following MICE;however,both HIIE and MICE improved augmentation index at a heart rate of 75 beats/min in people with diabetes.There was no significant difference in response to HIIE and MICE in all outcomes.This provides preliminary evidence on the role of HIIE on such outcomes in people with diabetes.展开更多
BACKGROUND Management of single small hepatocellular carcinoma(HCC)is straightforward with curative outcomes achieved by locoregional therapy or resection.Liver transplantation is often considered for multiple small o...BACKGROUND Management of single small hepatocellular carcinoma(HCC)is straightforward with curative outcomes achieved by locoregional therapy or resection.Liver transplantation is often considered for multiple small or single large HCC.Management of two small HCC whether presenting synchronously or sequentially is less clear.AIM To define the outcomes of patients presenting with two small HCC.METHODS Retrospective review of HCC databases from multiple institutions of patients with either two synchronous or sequential HCC≤3 cm between January 2000 and March 2018.Primary outcomes were overall survival(OS)and transplant-free survival(TFS).RESULTS 104 patients were identified(male n=89).Median age was 63 years(interquartile range 58-67.75)and the most common aetiology of liver disease was hepatitis C(40.4%).59(56.7%)had synchronous HCC and 45(43.3%)had sequential.36 patients died(34.6%)and 25 were transplanted(24.0%).1,3 and 5-year OS was 93.0%,66.1% and 62.3% and 5-year post-transplant survival was 95.8%.1,3 and 5-year TFS was 82.1%,45.85% and 37.8%.When synchronous and sequential groups were compared,OS(1,3 and 5 year synchronous 91.3%,63.8%,61.1%,sequential 95.3%,69.5%,64.6%,P=0.41)was similar but TFS was higher in the sequential group(1,3 and 5 year synchronous 68.5%,37.3% and 29.7%,sequential 93.2%,56.6%,48.5%,P=0.02)though this difference did not remain during multivariate analysis.CONCLUSION TFS in patients presenting with two HCC≤3 cm is poor regardless of the timing of the second tumor.All patients presenting with two small HCC should be considered for transplantation.展开更多
To the Editor:Immunoglobulin G4(IgG4)-associated autoimmune hepatitis(IgG4-AIH)is a novel and rare disease entity,characterized by sig-nificant infiltration of IgG4-expressing plasma cells in the liver.The classificat...To the Editor:Immunoglobulin G4(IgG4)-associated autoimmune hepatitis(IgG4-AIH)is a novel and rare disease entity,characterized by sig-nificant infiltration of IgG4-expressing plasma cells in the liver.The classification of of IgG4-AIH as a subtype of AIH or an early manifestation of IgG4-related disease(IgG4-RD)remains controversial.Herein,we discuss an interesting clinical vignette of IgG4-AIH in a gentleman with no significant past medical history,who presented with undifferentiated symptoms and elevated aminotransferases.展开更多
BACKGROUND Cold ischemia-reperfusion of the liver is an inevitable occurrence in liver trans-plantation that may also cause damage to the heart.Perioperative myocardial injury during liver transplantation can increase...BACKGROUND Cold ischemia-reperfusion of the liver is an inevitable occurrence in liver trans-plantation that may also cause damage to the heart.Perioperative myocardial injury during liver transplantation can increase the incidence of post-operative mortality,but there is little research on the incidence of myocardial injury in children who undergo living donor liver transplantation(LDLT).Therefore,this study mainly explores the independent risk factors for myocardial injury in children who undergo LDLT.factors for intraoperative myocardial injury.METHODS We retrospectively analyzed the inpatient records of pediatric patients who underwent LDLT in Tianjin First Central Hospital from January 1,2020,to January 31,2022.Recipient-related data and donor-related data were collected.The patients were divided into a myocardial injury group and a nonmyocardial injury group according to the value of the serum cardiac troponin I at the end of surgery for analysis.Univariate analysis and multivariate logistic regression were used to evaluate the risk factors for myocardial injury during LDLT in pediatric patients.RESULTS A total of 302 patients met the inclusion criteria.The myocardial injury group had 142 individuals(47%),and the nonmyocardial injury group included 160 patients(53%).Age,height,and weight were significantly lower in the myocardial injury group(P<0.001).The pediatric end-stage liver disease(PELD)score,total bilirubin,and interna-tional standardized ratio were significantly higher in the myocardial injury group(P<0.001).The mean arterial pressure,lactate,hemoglobin before reperfusion,duration of the anhepatic phase,cold ischemic time,incidence of postreperfusion syndrome(PRS),and fresh frozen plasma transfusion were significantly different between the two groups(P<0.05).The postoperative intensive care unit stay and peak total bilirubin values in the first 5 d after LDLT were significantly higher in the myocardial injury group(P<0.05).The pediatric patients with biliary atresia in the nonmyocardial injury group who underwent LDLT had a considerably higher one-year survival rate than those in the myocardial injury group(P=0.015).Multivariate logistic regression revealed the following independent risk factors for myocardial injury:a high PELD score[odds ratio(OR)=1.065,95%confidence interval(CI):1.013-1.121;P=0.014],a long duration of the anhepatic phase(OR=1.021,95%CI:1.003-1.040;P=0.025),and the occurrence of intraoperative PRS(OR=1.966,95%CI:1.111-3.480;P=0.020).CONCLUSION A high PELD score,a long anhepatic phase duration,and the occurrence of intraoperative PRS were independent risk factors for myocardial injury during LDLT in pediatric patients with biliary atresia.展开更多
Background:Physical inactivity and insomnia symptoms are independently associated with increased risk of depression and anxiety;however,few studies jointly examine these risk factors.This study aimed to prospectively ...Background:Physical inactivity and insomnia symptoms are independently associated with increased risk of depression and anxiety;however,few studies jointly examine these risk factors.This study aimed to prospectively examine the joint association of physical activity(PA)and insomnia symptoms with onset of poor mental health in adults.Methods:Participants from the 2013 to 2018 annnual waves of the Household Income and Labour Dynamics in Australia panel study who had good mental health(Mental Health Inventory-5>54)in 2013,and who completed at least 1 follow-up survey(2014-2018),were included(n=10,977).Poor mental health(Mental Health Inventory-5≤54)was assessed annually.Baseline(2013)PA was classified as high/moderate/low,and insomnia symptoms(i.e.,trouble sleeping)were classified as no insomnia symptoms/insomnia symptoms,with 6 mutually exclusive PAinsomnia symptom groups derived.Associations of PA-insomnia symptom groups with onset of poor mental health were examined using discrete-time proportional-hazards logit-hazard models.Results:There were 2322 new cases of poor mental health(21.2%).Relative to the high PA/no insomnia symptoms group,there were higher odds(odds ratio and 95%confidence interval(95%CI))of poor mental health among the high PA/insomnia symptoms(OR=1.87,95%CI:1.57-2.23),moderate PA/insomnia symptoms(OR=1.93,95%CI:1.61-2.31),low PA/insomnia symptoms(OR=2.33,95%CI:1.96-2.78),and low PA/no insomnia symptoms(OR=1.14,95%CI:1.01-1.29)groups.Any level of PA combined with insomnia symptoms was associated with increased odds of poor mental health,with the odds increasing as PA decreased.Conclusion:The se findings highlight the potential benefit of interventions targeting both PA and insomnia symptoms for promoting mental health.展开更多
BACKGROUND Capecitabine(CAP)is a classic antimetabolic drug and has shown potential antirejection effects after liver transplantation(LT)in clinical studies.Our previous study showed that metronomic CAP can cause the ...BACKGROUND Capecitabine(CAP)is a classic antimetabolic drug and has shown potential antirejection effects after liver transplantation(LT)in clinical studies.Our previous study showed that metronomic CAP can cause the programmed death of T cells by inducing oxidative stress in healthy mice.Ferroptosis,a newly defined non-apoptotic cell death that occurs in response to iron overload and lethal levels of lipid peroxidation,is an important mechanism by which CAP induces cell death.Therefore,ferroptosis may also play an important role in CAP-induced T cell death and play an immunosuppressive role in acute rejection after transplantation.AIM To investigate the functions and underlying mechanisms of antirejection effects of metronomic CAP.METHODS A rat LT model of acute rejection was established,and the effect of metronomic CAP on splenic hematopoietic function and acute graft rejection was evaluated 7 d after LT.In vitro,primary CD3+T cells were sorted from rat spleens and human peripheral blood,and co-cultured with or without 5-fluorouracil(5-FU)(active agent of CAP).The levels of ferroptosis-related proteins,ferrous ion concentration,and oxidative stress-related indicators were observed.The changes in mitochondrial structure were observed using electron microscopy.RESULTS With no significant myelotoxicity,metronomic CAP alleviated graft injury(Banff score 9 vs 7.333,P<0.001),prolonged the survival time of the recipient rats(11.5 d vs 16 d,P<0.01),and reduced the infiltration rate of CD3+T cells in peripheral blood(6.859 vs 3.735,P<0.001),liver graft(7.459 vs 3.432,P<0.001),and spleen(26.92 vs 12.9,P<0.001),thereby inhibiting acute rejection after LT.In vitro,5-FU,an end product of CAP metabolism,induced the degradation of the ferritin heavy chain by upregulating nuclear receptor coactivator 4,which caused the accumulation of ferrous ions.It also inhibited nuclear erythroid 2 p45-related factor 2,heme oxygenase-1,and glutathione peroxidase 4,eventually leading to oxidative damage and ferroptosis of T cells.CONCLUSION Metronomic CAP can suppress acute allograft rejection in rats by triggering CD3+T cell ferroptosis,which makes it an effective immunosuppressive agent after LT.展开更多
AIM:To analyze the expression of kallikrein gene 10(KLK10)in gastric cancer and to determine whether KLK10 has independent prognostic value in gastric cancer.METHODS:We studied KLK10 expression in 80 histologically co...AIM:To analyze the expression of kallikrein gene 10(KLK10)in gastric cancer and to determine whether KLK10 has independent prognostic value in gastric cancer.METHODS:We studied KLK10 expression in 80 histologically confirmed gastric cancer samples using realtime quantitative reverse transcription-PCR and hK10expression using immunohistochemistry.Correlations with clinicopathological variables(lymph node metastasis,depth of invasion and histology)and with outcomes(disease-free survival and overall survival)during a median follow-up period of 31 mo were assessed.Gastric cancer tissues were then classified as KLK10 positive or negative.RESULTS:KLK10 was found to be highly expressed in 57/80(70%)of gastric cancer samples,while its expression was very low in normal gastric tissues.Positive relationships between KLK10 expression and lymph node metastasis(P=0.048),depth of invasion(P=0.034)and histology(P=0.015)were observed.Univariate survival analysis revealed that gastric cancer patients with positive KLK10 expression had an increased risk for relapse/metastasis and death(P=0.005 and0.002,respectively).Cox multivariate analysis indicated that KLK10 was an independent prognostic indicator of disease-free survival and overall survival in patients with gastric cancer.CONCLUSION:KLK10 expression is an independent biomarker of unfavorable prognosis in patients with gastric cancer.展开更多
Heart failure represents the end point of a variety of cardiovascular diseases.It is a growing health burden and a leading cause of death worldwide.To date,limited treatment options exist for the treatment of heart fa...Heart failure represents the end point of a variety of cardiovascular diseases.It is a growing health burden and a leading cause of death worldwide.To date,limited treatment options exist for the treatment of heart failure,but exercise has been well-established as one of the few safe and effective interventions,leading to improved outcomes in patients.However,a lack of patient adherence remains a significant barrier in the implementation of exercise-based therapy for the treatment of heart failure.The insulin-like growth factor 1(IGF1)phosphoinositide 3-kinase(PI3K)pathway has been recognized as perhaps the most critical pathway for mediating exercisedinduced heart growth and protection.Here,we discuss how modulating activity of the IGF1PI3K pathway may be a valuable approach for the development of therapies that mimic the protective effects of exercise on the heart.We outline some of the promising approaches being investigated that utilize PI3K-based therapy for the treatment of heart failure.We discuss the implications for cardiac pathology and cardiotoxicity that arise in a setting of reduced PI3K activity.Finally,we discuss the use of animal models of cardiac health and disease,and genetic mice with increased or decreased cardiac PI3K activity for the discovery of novel drug targets and biomarkers of cardiovascular disease.展开更多
Myelin-associated inhibitory factors within the central nervous system(CNS) are considered to be one of the main obstacles for axonal regeneration following disease or injury. The nogo receptor 1(NgR1) has been well d...Myelin-associated inhibitory factors within the central nervous system(CNS) are considered to be one of the main obstacles for axonal regeneration following disease or injury. The nogo receptor 1(NgR1) has been well documented to play a key role in limiting axonal regrowth in the injured and diseased mammalian CNS. However, the role of nogo receptor in immune cell activation during CNS inflammation is yet to be mechanistically elucidated. Microglia/macrophages are immune cells that are regarded as pathogenic contributors to inflammatory demyelinating lesions in multiple sclerosis(MS). In this study, the animal model of MS, experimental autoimmune encephalomyelitis(EAE) was induced in ngr1^(+/+) and ngr1^(–/–) female mice following injection with the myelin oligodendrocyte glycoprotein(MOG_(35–55)) peptide. A fatemap analysis of microglia/macrophages was performed throughout spinal cord sections of EAE-induced mice at clinical scores of 0, 1, 2 and 3, respectively(increasing locomotor disability) from both genotypes, using the CD11 b and Iba1 cell markers. Western immunoblotting using lysates from isolated spinal cord microglia/macrophages, along with immunohistochemistry and flow cytometric analysis, was performed to demonstrate the expression of nogo receptor and its two homologs during EAE progression. Myelin protein engulfment during EAE progression in ngr1^(+/+) and ngr1^(–/–) mice was demonstrated by western immunblotting of lysates from isolated spinal cord microglia/macrophages, detecting levels of Nogo-A and MOG. The numbers of M1 and M2 microglia/macrophage phenotypes present in the spinal cords of EAE-induced ngr1^(+/+) and ngr1^(–/–) mice, were assessed by flow cytometric analysis using CD38 and Erg-2 markers. A significant difference in microglia/macrophage numbers between ngr1^(+/+) and ngr1^(–/–) mice was identified during the progression of the clinical symptoms of EAE, in the white versus gray matter regions of the spinal cord. This difference was unrelated to the expression of Ng R on these macrophage/microglial cells. We have identified that as EAE progresses, the phagocytic activity of microglia/macrophages with myelin debris, in ngr1^(–/–) mice, was enhanced. Moreover, we show a modulation from a predominant M1-pathogenic to the M2-neurotrophic cell phenotype in the ngr1^(–/–) mice during EAE progression. These findings suggest that CNS-specific macrophages and microglia of ngr1^(–/–) mice may exhibit an enhanced capacity to clear inhibitory molecules that are sequestered in inflammatory lesions.展开更多
AIM: To investigate over-expression of Osteopontin(OPN) pathway expression and mechanisms of action in human alcoholic liver disease(ALD), in vivo and in vitro acute alcohol models. METHODS: OPN pathway was evaluated ...AIM: To investigate over-expression of Osteopontin(OPN) pathway expression and mechanisms of action in human alcoholic liver disease(ALD), in vivo and in vitro acute alcohol models. METHODS: OPN pathway was evaluated in livers from patients with progressive stages of human ALD and serum from drinkers with and without liver cirrhosis. In vitro stellate LX2 cells exposed to acute alcohol and in vivo in acute alcoholic steatosis mouse models were also investigated for OPN pathway expression and function. WT and OPN-/- mice were administered an acute dose of alcohol and extent of liver injury was examined by histopathology and liver biochemistry after 16-24 h. The causative role of OPN was studied in OPN knockout animals and in vitro in stellate LX2 cells, utilizing siRNA, aptamer and neutralizing antibodies to block OPN and OPN pathway. OPN pathway expression and downstream functional consequences were measured for signaling by Western blotting, plasmin activation by spectrophotometric assays and cell migration by confocal imaging and quantitation. RESULTS: OPN expression positively correlated with disease severity in patients with progressive stages of ALD. In vivo, associated with alcoholic steatosis, a single dose of acute alcohol significantly increased hepatic OPN mRNA and protein, and a cleaved OPN form in a dose dependent manner. OPN mRNA and secreted OPN also increased in parallel with activation of LX2 stellate cells within 4 h of a single dose of alcohol. Expression of OPN receptors, αvβ3-integrin and CD44, increased in human ALD, and in vivo and in vitro with alcohol administration. This was accompanied by downstream phosphorylation of Akt and Erk, increased mRNA expression of several fibrogenesis, fibrinolysis and extracellular matrix pathway genes, plasmin activation and hepatic stellate cell(HSC) migration. Inhibition of OPN and OPN-receptor mediated signaling partially inhibited alcohol-induced HSC activation, plasmin activity and cell migration. CONCLUSION: OPN is a key mediator of the alcoholinduced effects on hepatic stellate cell functions and liver fibrogenesis.展开更多
Metabolic associated fatty liver disease(MAFLD),previously termed nonalcoholic fatty liver disease,is the leading global cause of liver disease and is fast becoming the most common indication for liver transplantation...Metabolic associated fatty liver disease(MAFLD),previously termed nonalcoholic fatty liver disease,is the leading global cause of liver disease and is fast becoming the most common indication for liver transplantation.The recent change in nomenclature to MAFLD refocuses the conceptualisation of this disease entity to its metabolic underpinnings and may help to spur a paradigm shift in the approach to its management,including in the setting of liver transplantation.Patients with MAFLD present significant challenges in the pre-,peri-and posttransplant settings,largely due to the presence of medical comorbidities that include obesity,metabolic syndrome and cardiovascular risk factors.As the community prevalence of MAFLD increases concurrently with the obesity epidemic,donor liver steatosis is also a current and future concern.This review outlines current epidemiology,nomenclature,management issues and outcomes of liver transplantation in patients with MAFLD.展开更多
AIM: To optimize the experimental protocols for a simple, sensitive and accurate bleeding assay.METHODS: Bleeding assay was performed in mice by tail tip amputation, immersing the tail in saline at 37 ℃, continuously...AIM: To optimize the experimental protocols for a simple, sensitive and accurate bleeding assay.METHODS: Bleeding assay was performed in mice by tail tip amputation, immersing the tail in saline at 37 ℃, continuously monitoring bleeding patterns and measuring bleeding volume from changes in the body weight. Sensitivity and extent of variation of bleeding time and bleeding volume were compared in mice treated with the P2 Y receptor inhibitor prasugrel at various doses or in mice deficient of Fc Rγ, a signaling protein of the glycoprotein VI receptor.RESULTS: We described details of the bleeding assay with the aim of standardizing this commonly used assay. The bleeding assay detailed here was simple to operate and permitted continuous monitoring of bleedingpattern and detection of re-bleeding. We also reported a simple and accurate way of quantifying bleeding volume from changes in the body weight, which correlated well with chemical assay of hemoglobin levels(r2 = 0.990, P < 0.0001). We determined by tail bleeding assay the dose-effect relation of the anti-platelet drug prasugrel from 0.015 to 5 mg/kg. Our results showed that the correlation of bleeding time and volume was unsatisfactory and that compared with the bleeding time, bleeding volume was more sensitive in detecting a partial inhibition of platelet's haemostatic activity(P < 0.01). Similarly, in mice with genetic disruption of Fc Rγ as a signaling molecule of P-selectin glycoprotein ligand-1 leading to platelet dysfunction, both increased bleeding volume and repeated bleeding pattern defined the phenotype of the knockout mice better than that of a prolonged bleeding time.CONCLUSION: Determination of bleeding pattern and bleeding volume, in addition to bleeding time, improved the sensitivity and accuracy of this assay, particularly when platelet function is partially inhibited.展开更多
AIM: Early calcification of atherosclerotic plaques are colocalized with macrophage and high mobility group box 1( HMGB1),a cytokine associated with biomineralizing process under physiological and pathological conditi...AIM: Early calcification of atherosclerotic plaques are colocalized with macrophage and high mobility group box 1( HMGB1),a cytokine associated with biomineralizing process under physiological and pathological conditions. Our study aims to evaluate whether HMGB1 induces ectopic mineralization via promoting the secretion of matrix vesicles( MVs) from macrophages. METHODS: HMGB1 was added to the medium of macrophages,the secretion of MVs in the supernatant was tested by flow cytometry analysis. The mineral deposition in calcifying medium was detected by Alizarin Red staining and von Kossa staining. Transmission electron microscopy showed the formation of hydroxyapatite crystals in MVs. Then we subcutaneous injection into mice with MVs to induce regional mineralization. RESULTS: HMGB1 significantly promoted secretion of MVs from macrophages as raveled by flow cytometry analysis. TNAP activity,considered as a marker of MVs maturation,was higher in HMGB1-induced MVs compared to the control-MVs. HMGB1-MVs also led to mineral deposition in an in vitro MVs-collagen mineralization model. Subcutaneous injection into mice with MVs derived from HMGB1-treated cells showed a greater potential to initiate regional mineralization. Mechanistic experiments revealed that HMGB1 activated neutral sphingomyelinase 2( n SMase2) that involved the receptor for advanced glycation end products( RAGE) and p38MAPK( upstream of n SMase2). Inhibition of n SMase2 with GW4869 or p38 MAPK with SB-239063 prevented MVs secretion and mineral deposition. CONCLUSIONS: HMGB1 induces MVs secretion from macrophages at least in part,via the RAGE / p38 MAPK /n SMase2 signaling pathway. Our findings thus reveal a novel mechanism by which HMGB1 may participated in the early calcification of atherosclerotic plaques.展开更多
Neurological heterotopic ossification(NHO)is a debilitating condition where bone forms in soft tissue,such as muscle surrounding the hip and knee,following an injury to the brain or spinal cord.This abnormal formation...Neurological heterotopic ossification(NHO)is a debilitating condition where bone forms in soft tissue,such as muscle surrounding the hip and knee,following an injury to the brain or spinal cord.This abnormal formation of bone can result in nerve impingement,pain,contractures and impaired movement.Patients are often diagnosed with NHO after the bone tissue has completely mineralised,leaving invasive surgical resection the only remaining treatment option.Surgical resection of NHO creates potential for added complications,particularly in patients with concomitant injury to the central nervous system(CNS).Although recent work has begun to shed light on the physiological mechanisms involved in NHO,there remains a significant knowledge gap related to the prognostic biomarkers and prophylactic treatments which are necessary to prevent NHO and optimise patient outcomes.This article reviews the current understanding pertaining to NHO epidemiology,pathobiology,biomarkers and treatment options.In particular,we focus on how concomitant CNS injury may drive ectopic bone formation and discuss considerations for treating polytrauma patients with NHO.We conclude that understanding of the pathogenesis of NHO is rapidly advancing,and as such,there is the strong potential for future research to unearth methods capable of identifying patients likely to develop NHO,and targeted treatments to prevent its manifestation.展开更多
Dear Editor,Severe Acute Respiratory Syndrome(SARS)has beendescribed as the first pandemic of the 21st century andbetween November 2002 and July 2003,over 8000 peo-ple were infected with the SARS-associated coronaviru...Dear Editor,Severe Acute Respiratory Syndrome(SARS)has beendescribed as the first pandemic of the 21st century andbetween November 2002 and July 2003,over 8000 peo-ple were infected with the SARS-associated coronavirus(SARS-CoV).Polymorphisms in the human leukocyteantigen(HLA)system have been shown to influencesusceptibility to SARS-CoV but here we were unable展开更多
Research indicates that high levels of sedentary behavior(sitting or lying with low energy expenditure) are adversely associated with health. A key factor in improving our understanding of the impact of sedentary beha...Research indicates that high levels of sedentary behavior(sitting or lying with low energy expenditure) are adversely associated with health. A key factor in improving our understanding of the impact of sedentary behavior(and patterns of sedentary time accumulation) on health is the use of objective measurement tools that collect date and time-stamped activity information. One such tool is the activP AL monitor. This thigh-worn device uses accelerometer-derived information about thigh position to determine the start and end of each period spent sitting/lying, standing, and stepping, as well as stepping speed, step counts, and postural transitions. The activP AL is increasingly being used within field-based research for its ability to measure sitting/lying via posture. We summarise key issues to consider when using the activP AL in physical activity and sedentary behavior field-based research with adult populations. It is intended that the findings and discussion points be informative for researchers who are currently using activP AL monitors or are intending to use them. Pre-data collection decisions, monitor preparation and distribution, data collection considerations, and manual and automated data processing possibilities are presented using examples from current literature and experiences from 2 research groups from the UK and Australia.展开更多
文摘Background:Individuals with diabetes have greater central arterial stiffness,wave reflections,and hemodynamics,all of which promote the accelerated cardiovascular pathology seen in this population.Acute aerobic exercise has been shown to be an effective strategy for reducing central arterial stiffness,wave reflections,and hemodynamics in healthy individuals;however,the effects of acute aerobic exercise in reducing these outcomes is not well established in people with diabetes.Recently,implementation of high-intensity interval exercise(HIIE)has shown superior improvements in cardiovascular health outcomes when compared to traditional aerobic exercise.Yet,the effect of HIIE on the aforementioned outcomes in people with diabetes is not known.The purpose of this study was to(i)describe the central arterial stiffness,wave reflections,and hemodynamic responses to a bout of HIIE and moderate-intensity continuous exercise(MICE)in adults with diabetes;and(ii)compare the effects of HIIE and MICE on the aforementioned outcomes.Methods:A total of 24 adult men and women(aged 29-59 years old)with type 1(n=12)and type 2(n=12)diabetes participated in a randomized cross-over study.All participants completed the following protocols:(i)HIIE:cycling for 4×4 min at 85%-95%of heart rate peak(HR_(peak)),interspersed with 3 min of active recovery at 60%-70%HR_(peak);(ii)MICE:33 min of continuous cycling at 60%-70%HR_(peak);and(iii)control(CON):lying quietly in a supine position for 30 min.Results:A significant group￡time effect was found for changes in central systolic blood pressure(F=3.20,p=0.01)with a transient reduction for the HIIE group but not for the MICE or CON groups.There was a significant group￡time effect for changes in augmentation index at a heart rate of 75 beats/min(F=2.32,p=0.04)with a decrease following for HIIE and MICE but not for CON.For all other measures of central arterial stiffness and hemodynamics,no significant changes were observed(p>0.05).Conclusion:A bout of HIIE appears to lead to a greater transient reduction in central systolic blood pressure than the reduction observed following MICE;however,both HIIE and MICE improved augmentation index at a heart rate of 75 beats/min in people with diabetes.There was no significant difference in response to HIIE and MICE in all outcomes.This provides preliminary evidence on the role of HIIE on such outcomes in people with diabetes.
文摘BACKGROUND Management of single small hepatocellular carcinoma(HCC)is straightforward with curative outcomes achieved by locoregional therapy or resection.Liver transplantation is often considered for multiple small or single large HCC.Management of two small HCC whether presenting synchronously or sequentially is less clear.AIM To define the outcomes of patients presenting with two small HCC.METHODS Retrospective review of HCC databases from multiple institutions of patients with either two synchronous or sequential HCC≤3 cm between January 2000 and March 2018.Primary outcomes were overall survival(OS)and transplant-free survival(TFS).RESULTS 104 patients were identified(male n=89).Median age was 63 years(interquartile range 58-67.75)and the most common aetiology of liver disease was hepatitis C(40.4%).59(56.7%)had synchronous HCC and 45(43.3%)had sequential.36 patients died(34.6%)and 25 were transplanted(24.0%).1,3 and 5-year OS was 93.0%,66.1% and 62.3% and 5-year post-transplant survival was 95.8%.1,3 and 5-year TFS was 82.1%,45.85% and 37.8%.When synchronous and sequential groups were compared,OS(1,3 and 5 year synchronous 91.3%,63.8%,61.1%,sequential 95.3%,69.5%,64.6%,P=0.41)was similar but TFS was higher in the sequential group(1,3 and 5 year synchronous 68.5%,37.3% and 29.7%,sequential 93.2%,56.6%,48.5%,P=0.02)though this difference did not remain during multivariate analysis.CONCLUSION TFS in patients presenting with two HCC≤3 cm is poor regardless of the timing of the second tumor.All patients presenting with two small HCC should be considered for transplantation.
文摘To the Editor:Immunoglobulin G4(IgG4)-associated autoimmune hepatitis(IgG4-AIH)is a novel and rare disease entity,characterized by sig-nificant infiltration of IgG4-expressing plasma cells in the liver.The classification of of IgG4-AIH as a subtype of AIH or an early manifestation of IgG4-related disease(IgG4-RD)remains controversial.Herein,we discuss an interesting clinical vignette of IgG4-AIH in a gentleman with no significant past medical history,who presented with undifferentiated symptoms and elevated aminotransferases.
基金Supported by Science and Technology Foundation of Tianjin Health Bureau,No.ZC20052Tianjin Key Medical Discipline(Specialty)Construction Project,No.TJYXZDXK-045A+2 种基金Tianjin Anesthesia Research Development Program of Bethune Charitable Foundation,No.TJMZ2022-005Natural Science Foundation of Tianjin,No.21JCQNJC01730Young Talent Program of Tianjin First Central Hospital.
文摘BACKGROUND Cold ischemia-reperfusion of the liver is an inevitable occurrence in liver trans-plantation that may also cause damage to the heart.Perioperative myocardial injury during liver transplantation can increase the incidence of post-operative mortality,but there is little research on the incidence of myocardial injury in children who undergo living donor liver transplantation(LDLT).Therefore,this study mainly explores the independent risk factors for myocardial injury in children who undergo LDLT.factors for intraoperative myocardial injury.METHODS We retrospectively analyzed the inpatient records of pediatric patients who underwent LDLT in Tianjin First Central Hospital from January 1,2020,to January 31,2022.Recipient-related data and donor-related data were collected.The patients were divided into a myocardial injury group and a nonmyocardial injury group according to the value of the serum cardiac troponin I at the end of surgery for analysis.Univariate analysis and multivariate logistic regression were used to evaluate the risk factors for myocardial injury during LDLT in pediatric patients.RESULTS A total of 302 patients met the inclusion criteria.The myocardial injury group had 142 individuals(47%),and the nonmyocardial injury group included 160 patients(53%).Age,height,and weight were significantly lower in the myocardial injury group(P<0.001).The pediatric end-stage liver disease(PELD)score,total bilirubin,and interna-tional standardized ratio were significantly higher in the myocardial injury group(P<0.001).The mean arterial pressure,lactate,hemoglobin before reperfusion,duration of the anhepatic phase,cold ischemic time,incidence of postreperfusion syndrome(PRS),and fresh frozen plasma transfusion were significantly different between the two groups(P<0.05).The postoperative intensive care unit stay and peak total bilirubin values in the first 5 d after LDLT were significantly higher in the myocardial injury group(P<0.05).The pediatric patients with biliary atresia in the nonmyocardial injury group who underwent LDLT had a considerably higher one-year survival rate than those in the myocardial injury group(P=0.015).Multivariate logistic regression revealed the following independent risk factors for myocardial injury:a high PELD score[odds ratio(OR)=1.065,95%confidence interval(CI):1.013-1.121;P=0.014],a long duration of the anhepatic phase(OR=1.021,95%CI:1.003-1.040;P=0.025),and the occurrence of intraoperative PRS(OR=1.966,95%CI:1.111-3.480;P=0.020).CONCLUSION A high PELD score,a long anhepatic phase duration,and the occurrence of intraoperative PRS were independent risk factors for myocardial injury during LDLT in pediatric patients with biliary atresia.
基金supported by a Career Development Fellowship(APP1141606)from the National Health and Medical Research Council,Australia。
文摘Background:Physical inactivity and insomnia symptoms are independently associated with increased risk of depression and anxiety;however,few studies jointly examine these risk factors.This study aimed to prospectively examine the joint association of physical activity(PA)and insomnia symptoms with onset of poor mental health in adults.Methods:Participants from the 2013 to 2018 annnual waves of the Household Income and Labour Dynamics in Australia panel study who had good mental health(Mental Health Inventory-5>54)in 2013,and who completed at least 1 follow-up survey(2014-2018),were included(n=10,977).Poor mental health(Mental Health Inventory-5≤54)was assessed annually.Baseline(2013)PA was classified as high/moderate/low,and insomnia symptoms(i.e.,trouble sleeping)were classified as no insomnia symptoms/insomnia symptoms,with 6 mutually exclusive PAinsomnia symptom groups derived.Associations of PA-insomnia symptom groups with onset of poor mental health were examined using discrete-time proportional-hazards logit-hazard models.Results:There were 2322 new cases of poor mental health(21.2%).Relative to the high PA/no insomnia symptoms group,there were higher odds(odds ratio and 95%confidence interval(95%CI))of poor mental health among the high PA/insomnia symptoms(OR=1.87,95%CI:1.57-2.23),moderate PA/insomnia symptoms(OR=1.93,95%CI:1.61-2.31),low PA/insomnia symptoms(OR=2.33,95%CI:1.96-2.78),and low PA/no insomnia symptoms(OR=1.14,95%CI:1.01-1.29)groups.Any level of PA combined with insomnia symptoms was associated with increased odds of poor mental health,with the odds increasing as PA decreased.Conclusion:The se findings highlight the potential benefit of interventions targeting both PA and insomnia symptoms for promoting mental health.
基金Supported by National Key Research and Development Program of China,No.2020YFA0710802The Youth Science Fund of the Nature Science Foundation of Tianjin,No.20JCQNJC01370+1 种基金The Key Projects of Tianjin Science and Technology Project,No.21JCZDJC00160The Science Foundation of Tianjin Health Commission,No.ZC20065 and No.ZC20089.
文摘BACKGROUND Capecitabine(CAP)is a classic antimetabolic drug and has shown potential antirejection effects after liver transplantation(LT)in clinical studies.Our previous study showed that metronomic CAP can cause the programmed death of T cells by inducing oxidative stress in healthy mice.Ferroptosis,a newly defined non-apoptotic cell death that occurs in response to iron overload and lethal levels of lipid peroxidation,is an important mechanism by which CAP induces cell death.Therefore,ferroptosis may also play an important role in CAP-induced T cell death and play an immunosuppressive role in acute rejection after transplantation.AIM To investigate the functions and underlying mechanisms of antirejection effects of metronomic CAP.METHODS A rat LT model of acute rejection was established,and the effect of metronomic CAP on splenic hematopoietic function and acute graft rejection was evaluated 7 d after LT.In vitro,primary CD3+T cells were sorted from rat spleens and human peripheral blood,and co-cultured with or without 5-fluorouracil(5-FU)(active agent of CAP).The levels of ferroptosis-related proteins,ferrous ion concentration,and oxidative stress-related indicators were observed.The changes in mitochondrial structure were observed using electron microscopy.RESULTS With no significant myelotoxicity,metronomic CAP alleviated graft injury(Banff score 9 vs 7.333,P<0.001),prolonged the survival time of the recipient rats(11.5 d vs 16 d,P<0.01),and reduced the infiltration rate of CD3+T cells in peripheral blood(6.859 vs 3.735,P<0.001),liver graft(7.459 vs 3.432,P<0.001),and spleen(26.92 vs 12.9,P<0.001),thereby inhibiting acute rejection after LT.In vitro,5-FU,an end product of CAP metabolism,induced the degradation of the ferritin heavy chain by upregulating nuclear receptor coactivator 4,which caused the accumulation of ferrous ions.It also inhibited nuclear erythroid 2 p45-related factor 2,heme oxygenase-1,and glutathione peroxidase 4,eventually leading to oxidative damage and ferroptosis of T cells.CONCLUSION Metronomic CAP can suppress acute allograft rejection in rats by triggering CD3+T cell ferroptosis,which makes it an effective immunosuppressive agent after LT.
文摘AIM:To analyze the expression of kallikrein gene 10(KLK10)in gastric cancer and to determine whether KLK10 has independent prognostic value in gastric cancer.METHODS:We studied KLK10 expression in 80 histologically confirmed gastric cancer samples using realtime quantitative reverse transcription-PCR and hK10expression using immunohistochemistry.Correlations with clinicopathological variables(lymph node metastasis,depth of invasion and histology)and with outcomes(disease-free survival and overall survival)during a median follow-up period of 31 mo were assessed.Gastric cancer tissues were then classified as KLK10 positive or negative.RESULTS:KLK10 was found to be highly expressed in 57/80(70%)of gastric cancer samples,while its expression was very low in normal gastric tissues.Positive relationships between KLK10 expression and lymph node metastasis(P=0.048),depth of invasion(P=0.034)and histology(P=0.015)were observed.Univariate survival analysis revealed that gastric cancer patients with positive KLK10 expression had an increased risk for relapse/metastasis and death(P=0.005 and0.002,respectively).Cox multivariate analysis indicated that KLK10 was an independent prognostic indicator of disease-free survival and overall survival in patients with gastric cancer.CONCLUSION:KLK10 expression is an independent biomarker of unfavorable prognosis in patients with gastric cancer.
基金All authors are supported by the Victorian Government’s Operational Infrastructure Support ProgramSBS is supported by a joint Baker Heart and Diabetes Institute-La Trobe University doctoral scholarshipRM is supported by a National Health and Medical Research Council Senior Research Fellowship(Grant No.1078985).
文摘Heart failure represents the end point of a variety of cardiovascular diseases.It is a growing health burden and a leading cause of death worldwide.To date,limited treatment options exist for the treatment of heart failure,but exercise has been well-established as one of the few safe and effective interventions,leading to improved outcomes in patients.However,a lack of patient adherence remains a significant barrier in the implementation of exercise-based therapy for the treatment of heart failure.The insulin-like growth factor 1(IGF1)phosphoinositide 3-kinase(PI3K)pathway has been recognized as perhaps the most critical pathway for mediating exercisedinduced heart growth and protection.Here,we discuss how modulating activity of the IGF1PI3K pathway may be a valuable approach for the development of therapies that mimic the protective effects of exercise on the heart.We outline some of the promising approaches being investigated that utilize PI3K-based therapy for the treatment of heart failure.We discuss the implications for cardiac pathology and cardiotoxicity that arise in a setting of reduced PI3K activity.Finally,we discuss the use of animal models of cardiac health and disease,and genetic mice with increased or decreased cardiac PI3K activity for the discovery of novel drug targets and biomarkers of cardiovascular disease.
基金supported by Multiple Sclerosis Research Australia and Trish Multiple Sclerosis Research Foundation Postgraduate Scholarship(to JYL)the National Multiple Sclerosis Society Project Grant#RG4398A1/1+2 种基金International Progressive Multiple Sclerosis Alliance Challenge Award#PA0065Multiple Sclerosis Research Australia and Trish Multiple Sclerosis Research Foundation#15-022Bethlehem Griffiths Research Foundation#BGRF1706(to SP)
文摘Myelin-associated inhibitory factors within the central nervous system(CNS) are considered to be one of the main obstacles for axonal regeneration following disease or injury. The nogo receptor 1(NgR1) has been well documented to play a key role in limiting axonal regrowth in the injured and diseased mammalian CNS. However, the role of nogo receptor in immune cell activation during CNS inflammation is yet to be mechanistically elucidated. Microglia/macrophages are immune cells that are regarded as pathogenic contributors to inflammatory demyelinating lesions in multiple sclerosis(MS). In this study, the animal model of MS, experimental autoimmune encephalomyelitis(EAE) was induced in ngr1^(+/+) and ngr1^(–/–) female mice following injection with the myelin oligodendrocyte glycoprotein(MOG_(35–55)) peptide. A fatemap analysis of microglia/macrophages was performed throughout spinal cord sections of EAE-induced mice at clinical scores of 0, 1, 2 and 3, respectively(increasing locomotor disability) from both genotypes, using the CD11 b and Iba1 cell markers. Western immunoblotting using lysates from isolated spinal cord microglia/macrophages, along with immunohistochemistry and flow cytometric analysis, was performed to demonstrate the expression of nogo receptor and its two homologs during EAE progression. Myelin protein engulfment during EAE progression in ngr1^(+/+) and ngr1^(–/–) mice was demonstrated by western immunblotting of lysates from isolated spinal cord microglia/macrophages, detecting levels of Nogo-A and MOG. The numbers of M1 and M2 microglia/macrophage phenotypes present in the spinal cords of EAE-induced ngr1^(+/+) and ngr1^(–/–) mice, were assessed by flow cytometric analysis using CD38 and Erg-2 markers. A significant difference in microglia/macrophage numbers between ngr1^(+/+) and ngr1^(–/–) mice was identified during the progression of the clinical symptoms of EAE, in the white versus gray matter regions of the spinal cord. This difference was unrelated to the expression of Ng R on these macrophage/microglial cells. We have identified that as EAE progresses, the phagocytic activity of microglia/macrophages with myelin debris, in ngr1^(–/–) mice, was enhanced. Moreover, we show a modulation from a predominant M1-pathogenic to the M2-neurotrophic cell phenotype in the ngr1^(–/–) mice during EAE progression. These findings suggest that CNS-specific macrophages and microglia of ngr1^(–/–) mice may exhibit an enhanced capacity to clear inhibitory molecules that are sequestered in inflammatory lesions.
基金Supported by Philanthropic Anonymous Sourcethe University of Sydney Bridging Support Grant,in part for Honours ProjectSupported by the National Health and Medical Research Council,No.NHMRC Practitioner Research Fellowship for PH support
文摘AIM: To investigate over-expression of Osteopontin(OPN) pathway expression and mechanisms of action in human alcoholic liver disease(ALD), in vivo and in vitro acute alcohol models. METHODS: OPN pathway was evaluated in livers from patients with progressive stages of human ALD and serum from drinkers with and without liver cirrhosis. In vitro stellate LX2 cells exposed to acute alcohol and in vivo in acute alcoholic steatosis mouse models were also investigated for OPN pathway expression and function. WT and OPN-/- mice were administered an acute dose of alcohol and extent of liver injury was examined by histopathology and liver biochemistry after 16-24 h. The causative role of OPN was studied in OPN knockout animals and in vitro in stellate LX2 cells, utilizing siRNA, aptamer and neutralizing antibodies to block OPN and OPN pathway. OPN pathway expression and downstream functional consequences were measured for signaling by Western blotting, plasmin activation by spectrophotometric assays and cell migration by confocal imaging and quantitation. RESULTS: OPN expression positively correlated with disease severity in patients with progressive stages of ALD. In vivo, associated with alcoholic steatosis, a single dose of acute alcohol significantly increased hepatic OPN mRNA and protein, and a cleaved OPN form in a dose dependent manner. OPN mRNA and secreted OPN also increased in parallel with activation of LX2 stellate cells within 4 h of a single dose of alcohol. Expression of OPN receptors, αvβ3-integrin and CD44, increased in human ALD, and in vivo and in vitro with alcohol administration. This was accompanied by downstream phosphorylation of Akt and Erk, increased mRNA expression of several fibrogenesis, fibrinolysis and extracellular matrix pathway genes, plasmin activation and hepatic stellate cell(HSC) migration. Inhibition of OPN and OPN-receptor mediated signaling partially inhibited alcohol-induced HSC activation, plasmin activity and cell migration. CONCLUSION: OPN is a key mediator of the alcoholinduced effects on hepatic stellate cell functions and liver fibrogenesis.
文摘Metabolic associated fatty liver disease(MAFLD),previously termed nonalcoholic fatty liver disease,is the leading global cause of liver disease and is fast becoming the most common indication for liver transplantation.The recent change in nomenclature to MAFLD refocuses the conceptualisation of this disease entity to its metabolic underpinnings and may help to spur a paradigm shift in the approach to its management,including in the setting of liver transplantation.Patients with MAFLD present significant challenges in the pre-,peri-and posttransplant settings,largely due to the presence of medical comorbidities that include obesity,metabolic syndrome and cardiovascular risk factors.As the community prevalence of MAFLD increases concurrently with the obesity epidemic,donor liver steatosis is also a current and future concern.This review outlines current epidemiology,nomenclature,management issues and outcomes of liver transplantation in patients with MAFLD.
基金Supported by Project and Fellowship Grants from the National Health and Medical Research Council of Australia
文摘AIM: To optimize the experimental protocols for a simple, sensitive and accurate bleeding assay.METHODS: Bleeding assay was performed in mice by tail tip amputation, immersing the tail in saline at 37 ℃, continuously monitoring bleeding patterns and measuring bleeding volume from changes in the body weight. Sensitivity and extent of variation of bleeding time and bleeding volume were compared in mice treated with the P2 Y receptor inhibitor prasugrel at various doses or in mice deficient of Fc Rγ, a signaling protein of the glycoprotein VI receptor.RESULTS: We described details of the bleeding assay with the aim of standardizing this commonly used assay. The bleeding assay detailed here was simple to operate and permitted continuous monitoring of bleedingpattern and detection of re-bleeding. We also reported a simple and accurate way of quantifying bleeding volume from changes in the body weight, which correlated well with chemical assay of hemoglobin levels(r2 = 0.990, P < 0.0001). We determined by tail bleeding assay the dose-effect relation of the anti-platelet drug prasugrel from 0.015 to 5 mg/kg. Our results showed that the correlation of bleeding time and volume was unsatisfactory and that compared with the bleeding time, bleeding volume was more sensitive in detecting a partial inhibition of platelet's haemostatic activity(P < 0.01). Similarly, in mice with genetic disruption of Fc Rγ as a signaling molecule of P-selectin glycoprotein ligand-1 leading to platelet dysfunction, both increased bleeding volume and repeated bleeding pattern defined the phenotype of the knockout mice better than that of a prolonged bleeding time.CONCLUSION: Determination of bleeding pattern and bleeding volume, in addition to bleeding time, improved the sensitivity and accuracy of this assay, particularly when platelet function is partially inhibited.
基金Supported by the grants from the National Natural Science Foundation of China(No.81270362No.81470561)State Project For Essential Drug Research and Development(No.2013ZX09103003-001)
文摘AIM: Early calcification of atherosclerotic plaques are colocalized with macrophage and high mobility group box 1( HMGB1),a cytokine associated with biomineralizing process under physiological and pathological conditions. Our study aims to evaluate whether HMGB1 induces ectopic mineralization via promoting the secretion of matrix vesicles( MVs) from macrophages. METHODS: HMGB1 was added to the medium of macrophages,the secretion of MVs in the supernatant was tested by flow cytometry analysis. The mineral deposition in calcifying medium was detected by Alizarin Red staining and von Kossa staining. Transmission electron microscopy showed the formation of hydroxyapatite crystals in MVs. Then we subcutaneous injection into mice with MVs to induce regional mineralization. RESULTS: HMGB1 significantly promoted secretion of MVs from macrophages as raveled by flow cytometry analysis. TNAP activity,considered as a marker of MVs maturation,was higher in HMGB1-induced MVs compared to the control-MVs. HMGB1-MVs also led to mineral deposition in an in vitro MVs-collagen mineralization model. Subcutaneous injection into mice with MVs derived from HMGB1-treated cells showed a greater potential to initiate regional mineralization. Mechanistic experiments revealed that HMGB1 activated neutral sphingomyelinase 2( n SMase2) that involved the receptor for advanced glycation end products( RAGE) and p38MAPK( upstream of n SMase2). Inhibition of n SMase2 with GW4869 or p38 MAPK with SB-239063 prevented MVs secretion and mineral deposition. CONCLUSIONS: HMGB1 induces MVs secretion from macrophages at least in part,via the RAGE / p38 MAPK /n SMase2 signaling pathway. Our findings thus reveal a novel mechanism by which HMGB1 may participated in the early calcification of atherosclerotic plaques.
基金R.B.is supported by a grant from NINDS(NINDS RFA-NS-16-012)to T.O.B.and S.S.S.S.is supported by a fellowship from NHMRC.
文摘Neurological heterotopic ossification(NHO)is a debilitating condition where bone forms in soft tissue,such as muscle surrounding the hip and knee,following an injury to the brain or spinal cord.This abnormal formation of bone can result in nerve impingement,pain,contractures and impaired movement.Patients are often diagnosed with NHO after the bone tissue has completely mineralised,leaving invasive surgical resection the only remaining treatment option.Surgical resection of NHO creates potential for added complications,particularly in patients with concomitant injury to the central nervous system(CNS).Although recent work has begun to shed light on the physiological mechanisms involved in NHO,there remains a significant knowledge gap related to the prognostic biomarkers and prophylactic treatments which are necessary to prevent NHO and optimise patient outcomes.This article reviews the current understanding pertaining to NHO epidemiology,pathobiology,biomarkers and treatment options.In particular,we focus on how concomitant CNS injury may drive ectopic bone formation and discuss considerations for treating polytrauma patients with NHO.We conclude that understanding of the pathogenesis of NHO is rapidly advancing,and as such,there is the strong potential for future research to unearth methods capable of identifying patients likely to develop NHO,and targeted treatments to prevent its manifestation.
文摘Dear Editor,Severe Acute Respiratory Syndrome(SARS)has beendescribed as the first pandemic of the 21st century andbetween November 2002 and July 2003,over 8000 peo-ple were infected with the SARS-associated coronavirus(SARS-CoV).Polymorphisms in the human leukocyteantigen(HLA)system have been shown to influencesusceptibility to SARS-CoV but here we were unable
基金supported by the National Institute for Health Researsch (NIHR) DietLifestyle & Physical Activity Biomedical Research Unit based at University Hospitals of Leicester and Loughborough University+5 种基金the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care-East Midlands (NIHR CLAHRC- EM)the Leicester Clinical Trials Unitsupported by a National Health and Medical Research Council (NHMRC) Centre for Research Excellence Grant on Sitting Time and Chronic Disease Prevention-Measurement, Mechanisms and Interventions (APP1057608)supported by a Heart Foundation Postdoctoral (PH 12B 7054)NHMRC Career Development (#1086029) Fellowshipsupported by an Australian Research Council Future Fellowship (FTE 100100918)
文摘Research indicates that high levels of sedentary behavior(sitting or lying with low energy expenditure) are adversely associated with health. A key factor in improving our understanding of the impact of sedentary behavior(and patterns of sedentary time accumulation) on health is the use of objective measurement tools that collect date and time-stamped activity information. One such tool is the activP AL monitor. This thigh-worn device uses accelerometer-derived information about thigh position to determine the start and end of each period spent sitting/lying, standing, and stepping, as well as stepping speed, step counts, and postural transitions. The activP AL is increasingly being used within field-based research for its ability to measure sitting/lying via posture. We summarise key issues to consider when using the activP AL in physical activity and sedentary behavior field-based research with adult populations. It is intended that the findings and discussion points be informative for researchers who are currently using activP AL monitors or are intending to use them. Pre-data collection decisions, monitor preparation and distribution, data collection considerations, and manual and automated data processing possibilities are presented using examples from current literature and experiences from 2 research groups from the UK and Australia.
