BACKGROUND The spread of the severe acute respiratory syndrome coronavirus 2 outbreak worldwide has caused concern regarding the mortality rate caused by the infection.The determinants of mortality on a global scale c...BACKGROUND The spread of the severe acute respiratory syndrome coronavirus 2 outbreak worldwide has caused concern regarding the mortality rate caused by the infection.The determinants of mortality on a global scale cannot be fully understood due to lack of information.AIM To identify key factors that may explain the variability in case lethality across countries.METHODS We identified 21 Potential risk factors for coronavirus disease 2019(COVID-19)case fatality rate for all the countries with available data.We examined univariate relationships of each variable with case fatality rate(CFR),and all independent variables to identify candidate variables for our final multiple model.Multiple regression analysis technique was used to assess the strength of relationship.RESULTS The mean of COVID-19 mortality was 1.52±1.72%.There was a statistically significant inverse correlation between health expenditure,and number of computed tomography scanners per 1 million with CFR,and significant direct correlation was found between literacy,and air pollution with CFR.This final model can predict approximately 97%of the changes in CFR.CONCLUSION The current study recommends some new predictors explaining affect mortality rate.Thus,it could help decision-makers develop health policies to fight COVID-19.展开更多
AIM To evaluate alterations of memory B cell subpopulations during a 48-wk period in human immunodeficiency virus type 1(HIV-1) patients. METHODS Forty-one antiretroviral na?ve and 41 treated HIV-1 patients matched fo...AIM To evaluate alterations of memory B cell subpopulations during a 48-wk period in human immunodeficiency virus type 1(HIV-1) patients. METHODS Forty-one antiretroviral na?ve and 41 treated HIV-1 patients matched for age and duration of HIV infection were recruited. All clinical, epidemiological and laboratory data were recorded or measured. The different B cell subsets were characterized according to their surface markers: Total B cells(CD19^+), memory B cells(CD19^+CD27^+, BMCs), resting BMCs(CD19^+CD27^+CD21^(high), RM), exhausted BMCs(CD19^+CD21^(low)CD27-, EM), IgM memory B(CD19^+CD27^+IgM^(high)), isotype-switched BMCs(CD19^+CD27^+IgM-, ITS) and activated BMCs(CD19^+CD21^(low+)CD27^+, AM) at baseline on week 4 and week 48.RESULTS Mean counts of BMCs were higher in treated patients. There was a marginal upward trend of IgM memory B cell proportions which differed significantly in the treated group(overall trend, P = 0.004). ITS BMC increased over time significantly in all patients. Naive patients had of ^(low)er levels of EM B cells compared to treated, with a downward trend, irrespectively of ^(high)ly active antiretroviral therapy(HAART) intake. Severe impairment of EM B cells was recorded to both treated(P = 0.024) and naive(P = 0.023) and patients. Higher proportions of RM cells were noted in HAART group, which differed significantly on week 4^(th)(P = 0.017) and 48th(P = 0.03). Higher levels of AM were preserved in HAART naive group during the whole study period(week 4: P = 0.018 and 48: P = 0.035). HIV-RNA viremia strongly correlated with AM B cells(r = 0.54, P = 0.01) and moderately with RM cells(r =-0.45, P = 0.026) at baseline.CONCLUSION HIV disrupts memory B cell subpopulations leading to impaired immunologic memory over time. BMC, RM, EM and ITS BMC were higher in patients under HAART. Activated BMCs(AM) were higher in patients without HAART. Viremia correlated with AM and RM. Significant depletion was recorded in EM B cells irrespectively of HAART intake. Perturbations in BMC-populations are not fully restored by antiretrovirals.展开更多
The availability of highly potent antiretroviral treatmentduring the last decades has transformed human immunodeficiency virus(HIV) infection into a chronic disease. Children that were diagnosed during the first month...The availability of highly potent antiretroviral treatmentduring the last decades has transformed human immunodeficiency virus(HIV) infection into a chronic disease. Children that were diagnosed during the first months or years of life and received treatment, are living longer and better and are presently reaching adolescence and adulthood. Perinatally HIV-infected adolescents(PHIV) and young adults may present specific clinical, behavior and social characteristics and demands. We have performed a literature review about different aspects that have to be considered in the care and follow-up of PHIV. The search included papers in the MEDLINE database via PubM ed, located using the keywords "perinatally HIV-infected" AND "adolescents". Only articles published in English or Portuguese from 2003 to 2014 were selected. The types of articles included original research, systematic reviews, and quantitative or qualitative studies; case reports and case series were excluded. Results are presented in the following topics: "Puberal development and sexual maturation", "Growth in weight and height", "Bone metabolism during adolescence", "Metabolic complications", "Brain development, cognition and mental health", "Reproductive health", "Viral drug resistance" and "Transition to adult outpatient care". We hope that this review will support the work of pediatricians, clinicians and infectious diseases specialists that are receiving these subjects to continue treatment.展开更多
For human immunodeficiency virus(HIV)-infected patients, the 1990s were marked by the introduction of highly active antiretroviral therapy(HAART) representing a new perspective of life for these patients. The use of H...For human immunodeficiency virus(HIV)-infected patients, the 1990s were marked by the introduction of highly active antiretroviral therapy(HAART) representing a new perspective of life for these patients. The use of HAART was shown to effectively suppress the replication of HIV-1 and dramatically reduce mortality and morbidity, which led to a better and longer quality of life for HIV-1-infected patients. Apart from the substantial benefits that result from the use of various HAART regimens, laboratory and clinical experience has shown that HAART can induce severe and considerable adverse effects related to metabolic complications of lipid metabolism, characterized by signs of lipodystrophy, insulin resistance, central adiposity, dyslipidemia, increased risk of cardiovascular disease and even an increased risk of atherosclerosis. New drugs are being studied, new therapeutic strategies are being implemented, and the use of statins, fibrates, and inhibitors of intestinal cholesterol absorption have been effective alternatives. Changes in diet and lifestyle have also shown satisfactory results.展开更多
Dengue is one of the most common arthropod-borne viral diseases in humans and it is a leading cause of illness and death in the tropical and subtropical regions of the world. It is thought to account for 400 million c...Dengue is one of the most common arthropod-borne viral diseases in humans and it is a leading cause of illness and death in the tropical and subtropical regions of the world. It is thought to account for 400 million cases annually among approximately 3.97 billion people at risk of infection in 128 endemic countries. Despite the global prevalence of the disease, the availability of a vaccine is limited in most countries in the endemic areas. Most endemic countries in South America, South East Asia and Africa serve as attractive touristic sites for people from non-endemic countries who become infected and export the virus to dengue-free regions. Dengue fever typically resembles malaria and in endemic countries most cases of dengue are treated as presumptive malaria. Consequently, routine dengue diagnosis among persons with fever will offer early treatment and reduce the burden of the disease. Also, routine testing among travellers from endemic countries will reduce importation and prevent the geographical expansion of dengue. In this essay, we seek to highlight the usefulness of routine dengue testing in endemic countries.展开更多
Mother-to-child-transmission of human immunodeficiency virus(HIV) is a primary cause of pediatric infections with HIV. Many of these infections involve women who were not tested early enough in pregnancy, or who didno...Mother-to-child-transmission of human immunodeficiency virus(HIV) is a primary cause of pediatric infections with HIV. Many of these infections involve women who were not tested early enough in pregnancy, or who didnot receive prevention services. HIV testing of pregnant women is considered to be one of the key strategies for preventing mother-to-child-transmission of HIV, but HIV testing rates among pregnant women in various countries remain suboptimal. Understanding the factors relating to women's willingness to be tested for HIV during pregnancy is critical for developing strategies to increase HIV testing rates among pregnant women. Extensive research points to various factors relating to women's willingness to be tested for HIV during pregnancy, and various recommendations aimed at improving testing rates among pregnant women have been suggested based on the research. In light of the goals set by the United Nations to reduce the rate of infants infected with HIV, it is necessary to summarize what is currently known regarding factors related to women's willingness to be tested for HIV during pregnancy. The purpose of this review is therefore to examine factors related to women's willingness to be tested for HIV during pregnancy, and to summarize recommendations for practice and further research.展开更多
Coronavirus disease 2019(COVID-19)has caused a global pandemic unprecedented in over a century.Although severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is a predominantly respiratory infection,various degre...Coronavirus disease 2019(COVID-19)has caused a global pandemic unprecedented in over a century.Although severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is a predominantly respiratory infection,various degrees of liver function abnormalities have been reported.Pre-existing liver disease in patients with SARS-CoV-2 infection has not been comprehensively evaluated in most studies,but it can critically compromise survival and trigger hepatic decompensation.The collapse of the healthcare services has negatively impacted the diagnosis,monitoring,and treatment of liver diseases in non-COVID-19 patients.In this review,we aim to discuss the impact of COVID-19 on liver disease from the experimental to the clinic perspective.展开更多
In December 2019,cases of unknown origin pneumonia appeared in Wuhan,China;the causal agent of this pneumonia was a new virus of the coronaviridae family called severe acute respiratory syndrome coronavirus-2(SARS-CoV...In December 2019,cases of unknown origin pneumonia appeared in Wuhan,China;the causal agent of this pneumonia was a new virus of the coronaviridae family called severe acute respiratory syndrome coronavirus-2(SARS-CoV-2).According to the clinical severity,symptoms and response to the different treatments,the evolution of the disease is divided in three phases.We analysed the most used treatments for coronavirus disease 2019 and the phase in which they are supposed to be effective.In the viral phase,remdesivir has demonstrated reduction in recovery time but no mortality reduction.Other drugs proposed for viral phase such as convalescent plasma and lopinavir/ritonavir did not demonstrate to be effective.In the inflammatory phase,corticosteroids demonstrated reduction of 28-d mortality in patients who needed oxygen,establishing that a corticosteroid regimen should be part of the standard treatment of critically ill patients.There are other immunosuppressive and immunomodulatory treatments such as anakinra,sarilumab,tocilizumab,colchicine or baricitinib that are being studied.Other treatments that were proposed at the beginning,like hydroxichloroquine or azithromycin,demonstrated no efficacy and increased mortality when combined.展开更多
Coronavirus disease 2019(COVID-19)is associated with poor cardiovascular outcomes in patients with heart failure(HF)of all categories of ejection fraction(EF),but mainly in patients with HF with reduced EF.Moreover,ca...Coronavirus disease 2019(COVID-19)is associated with poor cardiovascular outcomes in patients with heart failure(HF)of all categories of ejection fraction(EF),but mainly in patients with HF with reduced EF.Moreover,cardiac transplant patients exhibit worse cardiovascular prognosis,high mortality,and more admissions to the intensive care unit.In general,COVID-19 seems to deteriorate the clinical status of HF and favors the development of acute respiratory distress syndrome and multiorgan failure,especially in the presence of cardiovascular comorbidities such as diabetes mellitus,kidney dysfunction,and older age.COVID-19 may induce new-onset HF with complex mechanisms that involve myocardial injury.Indeed,myocardial injury comprises a large category of detrimental effects for the myocardium,such as myocardial infarction type 1 or type 2,Takotsubo cardiomyopathy,microvascular dysfunction and myocarditis,which are not easily distinguished by HF.The pathophysiologic mechanisms mainly involve direct myocardial damage by severe acute respiratory syndrome coronavirus 2,cytokine storm,hypercoagulation,inflammation,and endothelial dysfunction.The proper management of patients with COVID-19 involves careful patient evaluation and ongoing monitoring for complications such as HF.展开更多
BACKGROUND Diabetes mellitus(DM)is associated with adverse clinical outcomes and high mortality in patients with coronavirus disease 2019(COVID-19).The relationship between diabetes and COVID-19 is known to be bidirec...BACKGROUND Diabetes mellitus(DM)is associated with adverse clinical outcomes and high mortality in patients with coronavirus disease 2019(COVID-19).The relationship between diabetes and COVID-19 is known to be bidirectional.AIM To analyze the rate of new-onset diabetes in COVID-19 patients and compare the clinical outcomes of new-onset diabetes,pre-existing diabetes,hyperglycemic,and non-diabetes among COVID-19 patients.METHODS We used the Meta-analysis of Observational Studies in Epidemiology statement for the present meta-analysis.Online databases were searched for all peerreviewed articles published until November 6,2020.Articles were screened using Covidence and data extracted.Further analysis was done using comprehensive meta-analysis.Among the 128 studies detected after thorough database searching,seven were included in the quantitative analysis.The proportion was reported with 95%confidence interval(CI)and heterogeneity was assessed using I2.RESULTS Analysis showed that 19.70%(CI:10.93-32.91)of COVID-19 patients had associated DM,and 25.23%(CI:19.07-32.58)had associated hyperglycemia.The overall mortality rate was 15.36%(CI:12.57-18.68)of all COVID-19 cases,irrespective of their DM status.The mortality rate was 9.26%among non-diabetic patients,10.59%among patients with COVID-19 associated hyperglycemia,16.03%among known DM patients,and 24.96%among COVID-19 associated DM patients.The overall occurrence of adverse events was 20.52%(CI:14.21-28.70)among COVID-19 patients in the included studies,15.29%among non-diabetic patients,20.41%among patients with COVID-19 associated hyperglycemia,20.69%among known DM patients,and 45.85%among new-onset DM.Metaregression showed an increasing rate of mortality among new hyperglycemic patients,known diabetics,and new-onset DM patients in comparison to those without diabetes.CONCLUSION A significantly higher rate of new onset DM and hyperglycemia was observed.Higher mortality rates and adverse events were seen in patients with new-onset DM and hyperglycemia than in the non-diabetic population.展开更多
Critically ill patients are a vulnerable group at high risk of developing secondary infections.High disease severity,prolonged intensive care unit(ICU)stay,sepsis,and multiple drugs with immunosuppressive activity mak...Critically ill patients are a vulnerable group at high risk of developing secondary infections.High disease severity,prolonged intensive care unit(ICU)stay,sepsis,and multiple drugs with immunosuppressive activity make these patients prone to immuneparesis and increase the risk of various opportunistic infections,including cytomegalovirus(CMV).CMV seroconversion has been reported in up to 33%of ICU patients,but its impact on patient outcomes remains a matter of debate.Even though there are guidelines regarding the management of CMV infection in immunosuppressive patients with human immunodeficiency virus/acquired immuno deficiency syndrome,the need for treatment and therapeutic approaches in immunocompetent critically ill patients is still ambiguous.Even the diagnosis of CMV infection may be challenging in such patients due to non-specific symptoms and multiorgan involvement.Hence,a better understanding of the symptomatology,diagnostics,and treatment options may aid intensive care physicians in ensuring accurate diagnoses and instituting therapeutic interventions.展开更多
Coronavirus disease 2019(COVID-19)is associated with a high risk of mortality and complications in patients with diabetes mellitus.Achieving good glycemic control is very important in diabetic patients to reduce compl...Coronavirus disease 2019(COVID-19)is associated with a high risk of mortality and complications in patients with diabetes mellitus.Achieving good glycemic control is very important in diabetic patients to reduce complications and mortality due to COVID-19.Recent studies have shown the mortality benefit and anti-inflammatory effects of Dipeptidyl-peptidase-4 inhibitors(DPP-4i)in diabetic patients with COVID-19.DPP-4i may have a beneficial role in halting the severity of infection primarily by three routes,namely viral entry inhibition,anti-inflammatory and anti-fibrotic effects and glycemic control.This has raised the promising hypothesis that DPP-4i might be an optimal strategy for treating COVID-19 in patients with diabetes.This review aims to summarise the possible therapeutic non-glycemic effects of DPP-4i in diabetic patients diagnosed with COVID-19 in the light of available evidence.展开更多
BACKGROUND Hepatitis B virus(HBV)and hepatitis C virus(HCV)viral load(VL)estimation is essential for the management of both HBV and HCV infections.Due to a longer turnaround time for VL estimation,many patients drop o...BACKGROUND Hepatitis B virus(HBV)and hepatitis C virus(HCV)viral load(VL)estimation is essential for the management of both HBV and HCV infections.Due to a longer turnaround time for VL estimation,many patients drop out from the cascade of care.To achieve the global goals of reducing morbidity and mortality due to HBV/HCV and moving towards their elimination by 2030,molecular diagnostic platforms with faster and random(i.e.single sample)access are needed.AIM To evaluate the performance of the recently launched NeuMoDx 96 random access system with the conventional COBAS^(■)AmpliPrep/COBAS TaqMan system for HBV and HCV VL estimation.METHODS Archived once-thawed plasma samples were retrieved and tested on both platforms.Correlation between the assays was determined by linear regression and Bland-Altman analysis.The study included samples from 186 patients,99 for HBV of which 49 were true infected HBV cases(hepatitis B surface antigen,antihepatitis B core antibody,and HBV DNA-positive)and 87 for HCV assay in which 39 were true positives for HCV infection(anti-HCV and HCV RNA-positive).RESULTS The median VL detected by NeuMoDx for HBV was 2.9(interquartile range[IQR]:2.0-4.3)log_(10)IU/mL and by COBAS it was 3.70(IQR:2.28-4.56)log_(10)IU/mL,with excellent correlation(R2=0.98).In HCV,the median VL detected by NeuMoDx was 4.9(IQR:4.2-5.4)log_(10)IU/mL and by COBAS it was 5.10(IQR:4.07-5.80)log_(10)IU/mL with good correlation(R2=0.96).CONCLUSION The overall concordance between both the systems was 100%for both HBV and HCV VL estimation.Moreover,no genotype-specific bias for HBV/HCV VL quantification was seen in both the systems.Our findings reveal that NeuMoDx HBV and HCV quantitative assays have shown overall good clinical performance and provide faster results with 100%sensitivity and specificity compared to the COBAS AmpliPrep/COBAS TaqMan system.展开更多
The coronavirus disease 2019(COVID-19)pandemic has been challenging for healthcare professionals worldwide.One of the populations affected by the pandemic are patients on renal replacement therapy,as kidney disease is...The coronavirus disease 2019(COVID-19)pandemic has been challenging for healthcare professionals worldwide.One of the populations affected by the pandemic are patients on renal replacement therapy,as kidney disease is an independent risk factor for severe COVID-19 and maintenance dialysis(a lifesustaining therapy)cannot be interrupted in the vast majority of cases.Over the past months,several authors and medical societies have published recommendations and guidelines on the management of this population.This article is a comprehensive review regarding the measures to prevent,contain and deal with a COVID-19 pandemic in the dialysis setting.We recapitulate the epidemiology and pathophysiology of COVID-19 in kidney dysfunction and present the main recommendations concerning the screening of healthcare personnel,dialysis patients and visitors as well as measures to improve the safety of the dialysis facilities’environments.In addition to preventive measures,this article briefly describes actions directed towards management of an outbreak of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)within a dialysis facility,the management of complications in dialysis patients with COVID-19 and overall data regarding the management of children with kidney disease.展开更多
AIM: To characterize the circulating infectious bronchitis virus(IBV) strains in Egypt depending on the sequence of the spike-1(S1) gene [hypervariable region-3(HVR-3)] and to study the pathotypic features of these st...AIM: To characterize the circulating infectious bronchitis virus(IBV) strains in Egypt depending on the sequence of the spike-1(S1) gene [hypervariable region-3(HVR-3)] and to study the pathotypic features of these strains.METHODS: In this work, twenty flocks were sampled for IBV detection using RRT-PCR and isolation of IBV in specific pathogen free(SPF) chicks during the period from 2010 to 2015. Partial sequencing and phylogenetic analysis of 400 bp representing the HVR-3 of the S1 gene was conducted. Pathotypic characterization of one selected virus from each group(Egy/Var-Ⅰ, Egy/Var-Ⅱ and classic) was evaluated in one day old SPF chicks. The chicks were divided into 4 groups 10 birds each including the negative control group. Birds were inoculated at one day by intranasal instillation of 105EID50/100 μL of IBV viruses [IBV-EG/1212B-2012(Egy/Var-Ⅱ), IBV/EG/IBV1-2011(Egy/Var-Ⅰ) and IBV-EG/11539F-2011(classic)], while the remaining negative control group was kept uninfected. The birds were observed for clinical signs, gross lesions and virus pathogenicity. The real-time rR TPCR test was performed for virus detection in the tissues. Histopathological examinations were evaluated in both trachea and kidneys.RESULTS: The results revealed that these viruses were separated into two distinct groups; variant(GI-23) and classic(GI-1), where 16 viruses belonged to a variant group, including 2 subdivisions [Egy/Var-Ⅰ(6 isolates) and Egy/Var-Ⅱ(10 isolates)] and 4 viruses clustered to the classic group(Mass-like). IBV isolates in the variant group were grouped with other IBV strains from the Middle East. The variant subgroup(Egy/Var-Ⅰ) was likely resembling the original Egyptian variant strain(Egypt/Beni-Suif/01) and the Israeli strain(IS/1494/2006). The second subgroup(Egy/Var-Ⅱ) included the viruses circulating in the Middle East(Ck/EG/BSU-2 and Ck/EG/BSU-3/2011) and the Israeli strain(IS/885/00). The two variant subgroups(Egy/Var-Ⅰ and Egy/Var-Ⅱ) found to be highly pathogenic to SPF chicks with mortalities up to 50% than those of the classic group which was of low virulence(10% mortality). Pathogenicity indices were 25(Egy/Var-Ⅱ), 24(Egy/Var-Ⅰ) and 8(classic); with clinical scores 3, 2 and 1 respectively.CONCLUSION: These findings indicated that the recent circulating Egyptian IBVs have multiple heterogeneous origins in marked diversifying nature of their spread, with high pathotype in specific pathogen free chicks.展开更多
The coronavirus disease 2019 pandemic had deleterious effects on the healthcare systems around the world.To increase intensive care units(ICUs)bed capacities,multiple adaptations had to be made to increase surge capac...The coronavirus disease 2019 pandemic had deleterious effects on the healthcare systems around the world.To increase intensive care units(ICUs)bed capacities,multiple adaptations had to be made to increase surge capacity.In this editorial,we demonstrate the changes made by an ICU of a midwest community hospital in the United States.These changes included moving patients that used to be managed in the ICU to progressive care units,such as patients requiring noninvasive ventilation and high flow nasal cannula,ST-elevation myocardial infarction patients,and post-neurosurgery patients.Additionally,newer tactics were applied to the processes of assessing oxygen supply and demand,patient care rounds,and post-ICU monitoring.展开更多
There is a critical need to develop animal models to alleviate vaccine and drug development difficulties against zoonotic viral infections.The coronavirus family,which includes severe acute respiratory syndrome corona...There is a critical need to develop animal models to alleviate vaccine and drug development difficulties against zoonotic viral infections.The coronavirus family,which includes severe acute respiratory syndrome coronavirus 1 and severe acute respiratory syndrome coronavirus 2,crossed the species barrier and infected humans,causing a global outbreak in the 21st century.Because humans do not have pre-existing immunity against these viral infections and with ethics governing clinical trials,animal models are therefore being used in clinical studies to facilitate drug discovery and testing efficacy of vaccines.The ideal animal models should reflect the viral replication,clinical signs,and pathological responses observed in humans.Different animal species should be tested to establish an appropriate animal model to study the disease pathology,transmission and evaluation of novel vaccine and drug candidates to treat coronavirus disease 2019.In this context,the present review summarizes the recent progress in developing animal models for these two pathogenic viruses and highlights the utility of these models in studying SARS-associated coronavirus diseases.展开更多
Human noroviruses(No V) are associated with large proportion of non-bacterial diarrhea outbreaks together with > 50% of food-associated diarrheas. The function of histo-blood group antigens(HBGAs) in pathogenesis o...Human noroviruses(No V) are associated with large proportion of non-bacterial diarrhea outbreaks together with > 50% of food-associated diarrheas. The function of histo-blood group antigens(HBGAs) in pathogenesis of virus infection was implicated. Until recently however, due to lack of a robust animal and in vitro models of human NoV infection, only the partial knowledge concerning the virus pathogenesis(receptor, coreceptor and target cell) and absence of viable vaccine candidates were the frequently referenced attributes of this acute diarrheal illness. Recently, a novel group of enteric caliciviruses(CV) of rhesus macaque host origin was discovered and described. The new genus within the family Caliciviridae was identified: Rhesus Enteric CV, i.e., "Recovirus"(Re CV). Re CVs are genetically and biologically close relatives of human NoV s, exhibit similar genetic and biological features and are capable of being propagated in cell culture. ReC Vs cause symptomatic disease(diarrhea and fever) in experimentally inoculated macaques. Formulation and evaluation of efficient NoV vaccine might take several years. As suggested by recent studies, inhibition of HBGAs or HBGAbased antivirals could meanwhile be exploited as vaccine alternatives. The purpose of this minireview is to provide the guidance in respect to newly available primate model of enteric CV infection and its similarities with human NoV in utilizing the HBGAs as potential virus co-receptors to indirectly address the unresolved questions of NoV pathogenesis and immunity.展开更多
AIM To investigate the relationships among diverse metalloproteases(MMPs) and their tissue inhibitors(TIMPs) and non-alcoholic liver fibrosis in human immunodeficiency virus(HIV)-infected patients.METHODS Single nucle...AIM To investigate the relationships among diverse metalloproteases(MMPs) and their tissue inhibitors(TIMPs) and non-alcoholic liver fibrosis in human immunodeficiency virus(HIV)-infected patients.METHODS Single nucleotide polymorphisms(SNPs) in MMPs, TNF-α and CCR5 genes, and serum levels of MMPs and TIMPs were determined in HIV-infected individuals with/out hepatitis C virus(HCV) coinfection. A total of 158 patients were included, 57 of whom were HCVcoinfected. All patients drank < 50 g ethanol/day. Diverse SNPs(MMP-1-1607 1G/2G, MMP-8-799C/T, MMP-9-1562 C/T, MMP-13-77A/G, TNF-α-308 G/A,CCR5-?32), and serum levels of MMPs(2, 3, 8, 9 and 10) and TIMPs(1, 2 and 4) were assessed. Liver fibrosis was determined by transient elastometry, although other non-invasive markers of fibrosis were also considered. Significant liver fibrosis(F ≥ 2) was defined by a transient elastometry value ≥ 7.1 kP a.RESULTS A total of 34 patients(21.5%) had liver fibrosis ≥ F2. MMP-2 and TIMP-2 serum levels were higher in patients with liver fibrosis ≥ F2(P = 0.02 and P = 0.03, respectively) and correlated positively with transient elastometry values(P = 0.02 and P = 0.0009, respectively), whereas MMP-9 values were negatively correlated with transient elastometry measurements(P = 0.01). Multivariate analyses showed that high levels of MMP-2(OR = 2.397; 95%CI: 1.191-4.827, P = 0.014) were independently associated with liver fibrosis ≥ F2 in the patients as a whole. MMP-2(OR = 7.179; 95%CI: 1.210-42.581, P = 0.03) and male gender(OR = 10.040; 95%CI: 1.621-62.11, P = 0.013) were also independent predictors of fibrosis ≥ F2 in the HCV-infected subgroup. Likewise, MMP-2, TIMP-2 and MMP-9 were independently associated with transient elastometry values and other non-invasive markers of liver fibrosis. None of the six SNPs evaluated had any significant association with liver fibrosis ≥ F2.CONCLUSION Certain MMPs and TIMPs, particularly MMP-2, seems to be associated with non-alcoholic liver fibrosis in HIVinfected patients with/without HCV coinfection.展开更多
The Wnt/β-catenin signaling pathway is instrumental in successful differentiation and proliferation of mammalian cells. It is therefore not surprising that the herpesvirus family has developed mechanisms to interact ...The Wnt/β-catenin signaling pathway is instrumental in successful differentiation and proliferation of mammalian cells. It is therefore not surprising that the herpesvirus family has developed mechanisms to interact with and manipulate this pathway. Successful coexistence with the host requires that herpesviruses establish a lifelong infection that includes periods of latency and reactivation or persistence. Many herpesviruses establish latency in progenitor cells and viral reactivation is linked to host-cell proliferation and differentiation status. Importantly, Wnt/β-catenin is tightly connected to stem/progenitor cell maintenance and differentiation. Numerous studies have linked Wnt/β-catenin signaling to a variety of cancers, emphasizing the importance of Wnt/β-catenin pathways in development, tissue homeostasis and disease. This review details how the alpha-, beta-, and gammaherpesviruses interact and manipulate the Wnt/β-catenin pathway to promote a virus-centric agenda.展开更多
文摘BACKGROUND The spread of the severe acute respiratory syndrome coronavirus 2 outbreak worldwide has caused concern regarding the mortality rate caused by the infection.The determinants of mortality on a global scale cannot be fully understood due to lack of information.AIM To identify key factors that may explain the variability in case lethality across countries.METHODS We identified 21 Potential risk factors for coronavirus disease 2019(COVID-19)case fatality rate for all the countries with available data.We examined univariate relationships of each variable with case fatality rate(CFR),and all independent variables to identify candidate variables for our final multiple model.Multiple regression analysis technique was used to assess the strength of relationship.RESULTS The mean of COVID-19 mortality was 1.52±1.72%.There was a statistically significant inverse correlation between health expenditure,and number of computed tomography scanners per 1 million with CFR,and significant direct correlation was found between literacy,and air pollution with CFR.This final model can predict approximately 97%of the changes in CFR.CONCLUSION The current study recommends some new predictors explaining affect mortality rate.Thus,it could help decision-makers develop health policies to fight COVID-19.
文摘AIM To evaluate alterations of memory B cell subpopulations during a 48-wk period in human immunodeficiency virus type 1(HIV-1) patients. METHODS Forty-one antiretroviral na?ve and 41 treated HIV-1 patients matched for age and duration of HIV infection were recruited. All clinical, epidemiological and laboratory data were recorded or measured. The different B cell subsets were characterized according to their surface markers: Total B cells(CD19^+), memory B cells(CD19^+CD27^+, BMCs), resting BMCs(CD19^+CD27^+CD21^(high), RM), exhausted BMCs(CD19^+CD21^(low)CD27-, EM), IgM memory B(CD19^+CD27^+IgM^(high)), isotype-switched BMCs(CD19^+CD27^+IgM-, ITS) and activated BMCs(CD19^+CD21^(low+)CD27^+, AM) at baseline on week 4 and week 48.RESULTS Mean counts of BMCs were higher in treated patients. There was a marginal upward trend of IgM memory B cell proportions which differed significantly in the treated group(overall trend, P = 0.004). ITS BMC increased over time significantly in all patients. Naive patients had of ^(low)er levels of EM B cells compared to treated, with a downward trend, irrespectively of ^(high)ly active antiretroviral therapy(HAART) intake. Severe impairment of EM B cells was recorded to both treated(P = 0.024) and naive(P = 0.023) and patients. Higher proportions of RM cells were noted in HAART group, which differed significantly on week 4^(th)(P = 0.017) and 48th(P = 0.03). Higher levels of AM were preserved in HAART naive group during the whole study period(week 4: P = 0.018 and 48: P = 0.035). HIV-RNA viremia strongly correlated with AM B cells(r = 0.54, P = 0.01) and moderately with RM cells(r =-0.45, P = 0.026) at baseline.CONCLUSION HIV disrupts memory B cell subpopulations leading to impaired immunologic memory over time. BMC, RM, EM and ITS BMC were higher in patients under HAART. Activated BMCs(AM) were higher in patients without HAART. Viremia correlated with AM and RM. Significant depletion was recorded in EM B cells irrespectively of HAART intake. Perturbations in BMC-populations are not fully restored by antiretrovirals.
文摘The availability of highly potent antiretroviral treatmentduring the last decades has transformed human immunodeficiency virus(HIV) infection into a chronic disease. Children that were diagnosed during the first months or years of life and received treatment, are living longer and better and are presently reaching adolescence and adulthood. Perinatally HIV-infected adolescents(PHIV) and young adults may present specific clinical, behavior and social characteristics and demands. We have performed a literature review about different aspects that have to be considered in the care and follow-up of PHIV. The search included papers in the MEDLINE database via PubM ed, located using the keywords "perinatally HIV-infected" AND "adolescents". Only articles published in English or Portuguese from 2003 to 2014 were selected. The types of articles included original research, systematic reviews, and quantitative or qualitative studies; case reports and case series were excluded. Results are presented in the following topics: "Puberal development and sexual maturation", "Growth in weight and height", "Bone metabolism during adolescence", "Metabolic complications", "Brain development, cognition and mental health", "Reproductive health", "Viral drug resistance" and "Transition to adult outpatient care". We hope that this review will support the work of pediatricians, clinicians and infectious diseases specialists that are receiving these subjects to continue treatment.
基金financially supported in the our laboratory with resources from The National Council of Technological and Scientific Developmentthe State of Sao Paulo Research Foundationthe National Institute of Science and Technology of Complex Fluids.
文摘For human immunodeficiency virus(HIV)-infected patients, the 1990s were marked by the introduction of highly active antiretroviral therapy(HAART) representing a new perspective of life for these patients. The use of HAART was shown to effectively suppress the replication of HIV-1 and dramatically reduce mortality and morbidity, which led to a better and longer quality of life for HIV-1-infected patients. Apart from the substantial benefits that result from the use of various HAART regimens, laboratory and clinical experience has shown that HAART can induce severe and considerable adverse effects related to metabolic complications of lipid metabolism, characterized by signs of lipodystrophy, insulin resistance, central adiposity, dyslipidemia, increased risk of cardiovascular disease and even an increased risk of atherosclerosis. New drugs are being studied, new therapeutic strategies are being implemented, and the use of statins, fibrates, and inhibitors of intestinal cholesterol absorption have been effective alternatives. Changes in diet and lifestyle have also shown satisfactory results.
文摘Dengue is one of the most common arthropod-borne viral diseases in humans and it is a leading cause of illness and death in the tropical and subtropical regions of the world. It is thought to account for 400 million cases annually among approximately 3.97 billion people at risk of infection in 128 endemic countries. Despite the global prevalence of the disease, the availability of a vaccine is limited in most countries in the endemic areas. Most endemic countries in South America, South East Asia and Africa serve as attractive touristic sites for people from non-endemic countries who become infected and export the virus to dengue-free regions. Dengue fever typically resembles malaria and in endemic countries most cases of dengue are treated as presumptive malaria. Consequently, routine dengue diagnosis among persons with fever will offer early treatment and reduce the burden of the disease. Also, routine testing among travellers from endemic countries will reduce importation and prevent the geographical expansion of dengue. In this essay, we seek to highlight the usefulness of routine dengue testing in endemic countries.
文摘Mother-to-child-transmission of human immunodeficiency virus(HIV) is a primary cause of pediatric infections with HIV. Many of these infections involve women who were not tested early enough in pregnancy, or who didnot receive prevention services. HIV testing of pregnant women is considered to be one of the key strategies for preventing mother-to-child-transmission of HIV, but HIV testing rates among pregnant women in various countries remain suboptimal. Understanding the factors relating to women's willingness to be tested for HIV during pregnancy is critical for developing strategies to increase HIV testing rates among pregnant women. Extensive research points to various factors relating to women's willingness to be tested for HIV during pregnancy, and various recommendations aimed at improving testing rates among pregnant women have been suggested based on the research. In light of the goals set by the United Nations to reduce the rate of infants infected with HIV, it is necessary to summarize what is currently known regarding factors related to women's willingness to be tested for HIV during pregnancy. The purpose of this review is therefore to examine factors related to women's willingness to be tested for HIV during pregnancy, and to summarize recommendations for practice and further research.
文摘Coronavirus disease 2019(COVID-19)has caused a global pandemic unprecedented in over a century.Although severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is a predominantly respiratory infection,various degrees of liver function abnormalities have been reported.Pre-existing liver disease in patients with SARS-CoV-2 infection has not been comprehensively evaluated in most studies,but it can critically compromise survival and trigger hepatic decompensation.The collapse of the healthcare services has negatively impacted the diagnosis,monitoring,and treatment of liver diseases in non-COVID-19 patients.In this review,we aim to discuss the impact of COVID-19 on liver disease from the experimental to the clinic perspective.
文摘In December 2019,cases of unknown origin pneumonia appeared in Wuhan,China;the causal agent of this pneumonia was a new virus of the coronaviridae family called severe acute respiratory syndrome coronavirus-2(SARS-CoV-2).According to the clinical severity,symptoms and response to the different treatments,the evolution of the disease is divided in three phases.We analysed the most used treatments for coronavirus disease 2019 and the phase in which they are supposed to be effective.In the viral phase,remdesivir has demonstrated reduction in recovery time but no mortality reduction.Other drugs proposed for viral phase such as convalescent plasma and lopinavir/ritonavir did not demonstrate to be effective.In the inflammatory phase,corticosteroids demonstrated reduction of 28-d mortality in patients who needed oxygen,establishing that a corticosteroid regimen should be part of the standard treatment of critically ill patients.There are other immunosuppressive and immunomodulatory treatments such as anakinra,sarilumab,tocilizumab,colchicine or baricitinib that are being studied.Other treatments that were proposed at the beginning,like hydroxichloroquine or azithromycin,demonstrated no efficacy and increased mortality when combined.
文摘Coronavirus disease 2019(COVID-19)is associated with poor cardiovascular outcomes in patients with heart failure(HF)of all categories of ejection fraction(EF),but mainly in patients with HF with reduced EF.Moreover,cardiac transplant patients exhibit worse cardiovascular prognosis,high mortality,and more admissions to the intensive care unit.In general,COVID-19 seems to deteriorate the clinical status of HF and favors the development of acute respiratory distress syndrome and multiorgan failure,especially in the presence of cardiovascular comorbidities such as diabetes mellitus,kidney dysfunction,and older age.COVID-19 may induce new-onset HF with complex mechanisms that involve myocardial injury.Indeed,myocardial injury comprises a large category of detrimental effects for the myocardium,such as myocardial infarction type 1 or type 2,Takotsubo cardiomyopathy,microvascular dysfunction and myocarditis,which are not easily distinguished by HF.The pathophysiologic mechanisms mainly involve direct myocardial damage by severe acute respiratory syndrome coronavirus 2,cytokine storm,hypercoagulation,inflammation,and endothelial dysfunction.The proper management of patients with COVID-19 involves careful patient evaluation and ongoing monitoring for complications such as HF.
文摘BACKGROUND Diabetes mellitus(DM)is associated with adverse clinical outcomes and high mortality in patients with coronavirus disease 2019(COVID-19).The relationship between diabetes and COVID-19 is known to be bidirectional.AIM To analyze the rate of new-onset diabetes in COVID-19 patients and compare the clinical outcomes of new-onset diabetes,pre-existing diabetes,hyperglycemic,and non-diabetes among COVID-19 patients.METHODS We used the Meta-analysis of Observational Studies in Epidemiology statement for the present meta-analysis.Online databases were searched for all peerreviewed articles published until November 6,2020.Articles were screened using Covidence and data extracted.Further analysis was done using comprehensive meta-analysis.Among the 128 studies detected after thorough database searching,seven were included in the quantitative analysis.The proportion was reported with 95%confidence interval(CI)and heterogeneity was assessed using I2.RESULTS Analysis showed that 19.70%(CI:10.93-32.91)of COVID-19 patients had associated DM,and 25.23%(CI:19.07-32.58)had associated hyperglycemia.The overall mortality rate was 15.36%(CI:12.57-18.68)of all COVID-19 cases,irrespective of their DM status.The mortality rate was 9.26%among non-diabetic patients,10.59%among patients with COVID-19 associated hyperglycemia,16.03%among known DM patients,and 24.96%among COVID-19 associated DM patients.The overall occurrence of adverse events was 20.52%(CI:14.21-28.70)among COVID-19 patients in the included studies,15.29%among non-diabetic patients,20.41%among patients with COVID-19 associated hyperglycemia,20.69%among known DM patients,and 45.85%among new-onset DM.Metaregression showed an increasing rate of mortality among new hyperglycemic patients,known diabetics,and new-onset DM patients in comparison to those without diabetes.CONCLUSION A significantly higher rate of new onset DM and hyperglycemia was observed.Higher mortality rates and adverse events were seen in patients with new-onset DM and hyperglycemia than in the non-diabetic population.
文摘Critically ill patients are a vulnerable group at high risk of developing secondary infections.High disease severity,prolonged intensive care unit(ICU)stay,sepsis,and multiple drugs with immunosuppressive activity make these patients prone to immuneparesis and increase the risk of various opportunistic infections,including cytomegalovirus(CMV).CMV seroconversion has been reported in up to 33%of ICU patients,but its impact on patient outcomes remains a matter of debate.Even though there are guidelines regarding the management of CMV infection in immunosuppressive patients with human immunodeficiency virus/acquired immuno deficiency syndrome,the need for treatment and therapeutic approaches in immunocompetent critically ill patients is still ambiguous.Even the diagnosis of CMV infection may be challenging in such patients due to non-specific symptoms and multiorgan involvement.Hence,a better understanding of the symptomatology,diagnostics,and treatment options may aid intensive care physicians in ensuring accurate diagnoses and instituting therapeutic interventions.
文摘Coronavirus disease 2019(COVID-19)is associated with a high risk of mortality and complications in patients with diabetes mellitus.Achieving good glycemic control is very important in diabetic patients to reduce complications and mortality due to COVID-19.Recent studies have shown the mortality benefit and anti-inflammatory effects of Dipeptidyl-peptidase-4 inhibitors(DPP-4i)in diabetic patients with COVID-19.DPP-4i may have a beneficial role in halting the severity of infection primarily by three routes,namely viral entry inhibition,anti-inflammatory and anti-fibrotic effects and glycemic control.This has raised the promising hypothesis that DPP-4i might be an optimal strategy for treating COVID-19 in patients with diabetes.This review aims to summarise the possible therapeutic non-glycemic effects of DPP-4i in diabetic patients diagnosed with COVID-19 in the light of available evidence.
文摘BACKGROUND Hepatitis B virus(HBV)and hepatitis C virus(HCV)viral load(VL)estimation is essential for the management of both HBV and HCV infections.Due to a longer turnaround time for VL estimation,many patients drop out from the cascade of care.To achieve the global goals of reducing morbidity and mortality due to HBV/HCV and moving towards their elimination by 2030,molecular diagnostic platforms with faster and random(i.e.single sample)access are needed.AIM To evaluate the performance of the recently launched NeuMoDx 96 random access system with the conventional COBAS^(■)AmpliPrep/COBAS TaqMan system for HBV and HCV VL estimation.METHODS Archived once-thawed plasma samples were retrieved and tested on both platforms.Correlation between the assays was determined by linear regression and Bland-Altman analysis.The study included samples from 186 patients,99 for HBV of which 49 were true infected HBV cases(hepatitis B surface antigen,antihepatitis B core antibody,and HBV DNA-positive)and 87 for HCV assay in which 39 were true positives for HCV infection(anti-HCV and HCV RNA-positive).RESULTS The median VL detected by NeuMoDx for HBV was 2.9(interquartile range[IQR]:2.0-4.3)log_(10)IU/mL and by COBAS it was 3.70(IQR:2.28-4.56)log_(10)IU/mL,with excellent correlation(R2=0.98).In HCV,the median VL detected by NeuMoDx was 4.9(IQR:4.2-5.4)log_(10)IU/mL and by COBAS it was 5.10(IQR:4.07-5.80)log_(10)IU/mL with good correlation(R2=0.96).CONCLUSION The overall concordance between both the systems was 100%for both HBV and HCV VL estimation.Moreover,no genotype-specific bias for HBV/HCV VL quantification was seen in both the systems.Our findings reveal that NeuMoDx HBV and HCV quantitative assays have shown overall good clinical performance and provide faster results with 100%sensitivity and specificity compared to the COBAS AmpliPrep/COBAS TaqMan system.
文摘The coronavirus disease 2019(COVID-19)pandemic has been challenging for healthcare professionals worldwide.One of the populations affected by the pandemic are patients on renal replacement therapy,as kidney disease is an independent risk factor for severe COVID-19 and maintenance dialysis(a lifesustaining therapy)cannot be interrupted in the vast majority of cases.Over the past months,several authors and medical societies have published recommendations and guidelines on the management of this population.This article is a comprehensive review regarding the measures to prevent,contain and deal with a COVID-19 pandemic in the dialysis setting.We recapitulate the epidemiology and pathophysiology of COVID-19 in kidney dysfunction and present the main recommendations concerning the screening of healthcare personnel,dialysis patients and visitors as well as measures to improve the safety of the dialysis facilities’environments.In addition to preventive measures,this article briefly describes actions directed towards management of an outbreak of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)within a dialysis facility,the management of complications in dialysis patients with COVID-19 and overall data regarding the management of children with kidney disease.
文摘AIM: To characterize the circulating infectious bronchitis virus(IBV) strains in Egypt depending on the sequence of the spike-1(S1) gene [hypervariable region-3(HVR-3)] and to study the pathotypic features of these strains.METHODS: In this work, twenty flocks were sampled for IBV detection using RRT-PCR and isolation of IBV in specific pathogen free(SPF) chicks during the period from 2010 to 2015. Partial sequencing and phylogenetic analysis of 400 bp representing the HVR-3 of the S1 gene was conducted. Pathotypic characterization of one selected virus from each group(Egy/Var-Ⅰ, Egy/Var-Ⅱ and classic) was evaluated in one day old SPF chicks. The chicks were divided into 4 groups 10 birds each including the negative control group. Birds were inoculated at one day by intranasal instillation of 105EID50/100 μL of IBV viruses [IBV-EG/1212B-2012(Egy/Var-Ⅱ), IBV/EG/IBV1-2011(Egy/Var-Ⅰ) and IBV-EG/11539F-2011(classic)], while the remaining negative control group was kept uninfected. The birds were observed for clinical signs, gross lesions and virus pathogenicity. The real-time rR TPCR test was performed for virus detection in the tissues. Histopathological examinations were evaluated in both trachea and kidneys.RESULTS: The results revealed that these viruses were separated into two distinct groups; variant(GI-23) and classic(GI-1), where 16 viruses belonged to a variant group, including 2 subdivisions [Egy/Var-Ⅰ(6 isolates) and Egy/Var-Ⅱ(10 isolates)] and 4 viruses clustered to the classic group(Mass-like). IBV isolates in the variant group were grouped with other IBV strains from the Middle East. The variant subgroup(Egy/Var-Ⅰ) was likely resembling the original Egyptian variant strain(Egypt/Beni-Suif/01) and the Israeli strain(IS/1494/2006). The second subgroup(Egy/Var-Ⅱ) included the viruses circulating in the Middle East(Ck/EG/BSU-2 and Ck/EG/BSU-3/2011) and the Israeli strain(IS/885/00). The two variant subgroups(Egy/Var-Ⅰ and Egy/Var-Ⅱ) found to be highly pathogenic to SPF chicks with mortalities up to 50% than those of the classic group which was of low virulence(10% mortality). Pathogenicity indices were 25(Egy/Var-Ⅱ), 24(Egy/Var-Ⅰ) and 8(classic); with clinical scores 3, 2 and 1 respectively.CONCLUSION: These findings indicated that the recent circulating Egyptian IBVs have multiple heterogeneous origins in marked diversifying nature of their spread, with high pathotype in specific pathogen free chicks.
文摘The coronavirus disease 2019 pandemic had deleterious effects on the healthcare systems around the world.To increase intensive care units(ICUs)bed capacities,multiple adaptations had to be made to increase surge capacity.In this editorial,we demonstrate the changes made by an ICU of a midwest community hospital in the United States.These changes included moving patients that used to be managed in the ICU to progressive care units,such as patients requiring noninvasive ventilation and high flow nasal cannula,ST-elevation myocardial infarction patients,and post-neurosurgery patients.Additionally,newer tactics were applied to the processes of assessing oxygen supply and demand,patient care rounds,and post-ICU monitoring.
基金COVID Therapeutics,Department of Biotechnology,Government of India,Ref.No.BT/PR4094/COT/142/20/2021.
文摘There is a critical need to develop animal models to alleviate vaccine and drug development difficulties against zoonotic viral infections.The coronavirus family,which includes severe acute respiratory syndrome coronavirus 1 and severe acute respiratory syndrome coronavirus 2,crossed the species barrier and infected humans,causing a global outbreak in the 21st century.Because humans do not have pre-existing immunity against these viral infections and with ethics governing clinical trials,animal models are therefore being used in clinical studies to facilitate drug discovery and testing efficacy of vaccines.The ideal animal models should reflect the viral replication,clinical signs,and pathological responses observed in humans.Different animal species should be tested to establish an appropriate animal model to study the disease pathology,transmission and evaluation of novel vaccine and drug candidates to treat coronavirus disease 2019.In this context,the present review summarizes the recent progress in developing animal models for these two pathogenic viruses and highlights the utility of these models in studying SARS-associated coronavirus diseases.
文摘Human noroviruses(No V) are associated with large proportion of non-bacterial diarrhea outbreaks together with > 50% of food-associated diarrheas. The function of histo-blood group antigens(HBGAs) in pathogenesis of virus infection was implicated. Until recently however, due to lack of a robust animal and in vitro models of human NoV infection, only the partial knowledge concerning the virus pathogenesis(receptor, coreceptor and target cell) and absence of viable vaccine candidates were the frequently referenced attributes of this acute diarrheal illness. Recently, a novel group of enteric caliciviruses(CV) of rhesus macaque host origin was discovered and described. The new genus within the family Caliciviridae was identified: Rhesus Enteric CV, i.e., "Recovirus"(Re CV). Re CVs are genetically and biologically close relatives of human NoV s, exhibit similar genetic and biological features and are capable of being propagated in cell culture. ReC Vs cause symptomatic disease(diarrhea and fever) in experimentally inoculated macaques. Formulation and evaluation of efficient NoV vaccine might take several years. As suggested by recent studies, inhibition of HBGAs or HBGAbased antivirals could meanwhile be exploited as vaccine alternatives. The purpose of this minireview is to provide the guidance in respect to newly available primate model of enteric CV infection and its similarities with human NoV in utilizing the HBGAs as potential virus co-receptors to indirectly address the unresolved questions of NoV pathogenesis and immunity.
基金Supported by the Oviedo University research grants,Nos.UNIOV-12-MA-03 and SV-PA-13-ECOEMP-57
文摘AIM To investigate the relationships among diverse metalloproteases(MMPs) and their tissue inhibitors(TIMPs) and non-alcoholic liver fibrosis in human immunodeficiency virus(HIV)-infected patients.METHODS Single nucleotide polymorphisms(SNPs) in MMPs, TNF-α and CCR5 genes, and serum levels of MMPs and TIMPs were determined in HIV-infected individuals with/out hepatitis C virus(HCV) coinfection. A total of 158 patients were included, 57 of whom were HCVcoinfected. All patients drank < 50 g ethanol/day. Diverse SNPs(MMP-1-1607 1G/2G, MMP-8-799C/T, MMP-9-1562 C/T, MMP-13-77A/G, TNF-α-308 G/A,CCR5-?32), and serum levels of MMPs(2, 3, 8, 9 and 10) and TIMPs(1, 2 and 4) were assessed. Liver fibrosis was determined by transient elastometry, although other non-invasive markers of fibrosis were also considered. Significant liver fibrosis(F ≥ 2) was defined by a transient elastometry value ≥ 7.1 kP a.RESULTS A total of 34 patients(21.5%) had liver fibrosis ≥ F2. MMP-2 and TIMP-2 serum levels were higher in patients with liver fibrosis ≥ F2(P = 0.02 and P = 0.03, respectively) and correlated positively with transient elastometry values(P = 0.02 and P = 0.0009, respectively), whereas MMP-9 values were negatively correlated with transient elastometry measurements(P = 0.01). Multivariate analyses showed that high levels of MMP-2(OR = 2.397; 95%CI: 1.191-4.827, P = 0.014) were independently associated with liver fibrosis ≥ F2 in the patients as a whole. MMP-2(OR = 7.179; 95%CI: 1.210-42.581, P = 0.03) and male gender(OR = 10.040; 95%CI: 1.621-62.11, P = 0.013) were also independent predictors of fibrosis ≥ F2 in the HCV-infected subgroup. Likewise, MMP-2, TIMP-2 and MMP-9 were independently associated with transient elastometry values and other non-invasive markers of liver fibrosis. None of the six SNPs evaluated had any significant association with liver fibrosis ≥ F2.CONCLUSION Certain MMPs and TIMPs, particularly MMP-2, seems to be associated with non-alcoholic liver fibrosis in HIVinfected patients with/without HCV coinfection.
文摘The Wnt/β-catenin signaling pathway is instrumental in successful differentiation and proliferation of mammalian cells. It is therefore not surprising that the herpesvirus family has developed mechanisms to interact with and manipulate this pathway. Successful coexistence with the host requires that herpesviruses establish a lifelong infection that includes periods of latency and reactivation or persistence. Many herpesviruses establish latency in progenitor cells and viral reactivation is linked to host-cell proliferation and differentiation status. Importantly, Wnt/β-catenin is tightly connected to stem/progenitor cell maintenance and differentiation. Numerous studies have linked Wnt/β-catenin signaling to a variety of cancers, emphasizing the importance of Wnt/β-catenin pathways in development, tissue homeostasis and disease. This review details how the alpha-, beta-, and gammaherpesviruses interact and manipulate the Wnt/β-catenin pathway to promote a virus-centric agenda.
