Background:The prevalence of pediatric mental illnesses has been increasing in recent years,with a great potential to impact on individual's functionality and adaptation in adulthood.Objective:This study aims to a...Background:The prevalence of pediatric mental illnesses has been increasing in recent years,with a great potential to impact on individual's functionality and adaptation in adulthood.Objective:This study aims to assess emotional and behavioral problems among schoolchildren in Herat City of Afghanistan.Methods:This cross-sectional study was conducted on schoolchildren(grade 5-10),between September and November 2021.Sociodemographic data was collected using a paper-based 14-item structured questionnaire.Data on emotional and behavioral problems was collected using the Strengths and Difficulties Questionnaire(SDQ)based on teachers'and children's report.Statistical analyses were performed in IBM SPSS Statistics(version 27).Results:A total of 418 students,including 190(45.5%)males and 228(54.5%)females with a mean age of 14.1±1.7(11-<18)years were included in the study.The prevalence of students*self-reported total difficulties and prosocial problem were 5.7%and 1.2%,respectively.An insignificant difference was observed between mean total difficulties scores between students'self-reported and teachers'reported SDQ.Gender,grade,concern about shortage of food,and concern about losing house were significantly predicting students'self-reported total difficulties scores.Conclusion:This is the first study to report the prevalence of emotional and behavioral problems among schoolchildren in Herat City,Afghanistan.This,together with relevant global literature,highlight the need to address pediatric mental health,and provide services aimed at preventing,and treating children with these problems around the world.展开更多
Neoplasms can be considered as a group of aberrant cells that need more vascular supply to fulfill all their functions.Therefore,they promote angiogenesis through the same neovascularization pathway used physiological...Neoplasms can be considered as a group of aberrant cells that need more vascular supply to fulfill all their functions.Therefore,they promote angiogenesis through the same neovascularization pathway used physiologically.Angiogenesis is a process characterized by a heterogeneous distribution of oxygen caused by the tumor and oxidative stress;the latter being one of the most powerful stimuli of angiogenesis.As a result of altered tumor metabolism due to hypoxia,acidosis occurs.The angiogenic process and oxidative stress can be detected by measuring serum and tissue biomarkers.The study of the mechanisms underlying angiogenesis and oxidative stress could lead to the identification of new biomarkers,ameliorating the selection of patients with neoplasms and the prediction of their response to possible anti-tumor therapies.In particular,in the treatment of patients with similar clinical tumor phenotypes but different prognoses,the new biomarkers could be useful.Moreover,they may lead to a better understanding of the mechanisms underlying drug resistance.Experimental studies show that blocking the vascular supply results in antiproliferative activity in vivo in neuroendocrine tumor cells,which require a high vascular supply.展开更多
Objective:Afghanistan has witnessed a long-lasting 4-decade armed conflict,which together with high levels of poverty and interpersonal violence,resulted in high incidence and prevalence of mental disorders in general...Objective:Afghanistan has witnessed a long-lasting 4-decade armed conflict,which together with high levels of poverty and interpersonal violence,resulted in high incidence and prevalence of mental disorders in general population,including children and adolescents.Until mid-2018,there was neither mental health care facility nor a child psychiatrist in Afghanistan.Here,we report the establishment of the first children and adolescents'mental health center(CAMHC)in Herat province of Afghanistan.Methods:In July 2018,CAMHC was initiated at Mental Health Training Center-Herat.CAMHC was initially planned by the International Assistance Mission(IAM)and Herat Public Health Directorate;and financially supported by the Tearfund UK,the United Methodist Committee on Relief and Tearfund Australia.The target population of CAMHC was children and adolescents in Herat and neighboring provinces,healthcare professionals,staff of government and non-governmental organizations,school teachers and community leaders.Results:A group of eight mental health professionals were trained and made the interdisciplinary board for diagnosis and management of mental disorders in children and adolescents.During the initial three-year period,2448 patients,including 1264(51.6%)boys and 1184(48.4%)girls,presented with mental disorders to CAMHC.Diagnosis and management of mental disorders were performed according to standard international protocols.Eighteen awareness-raising seminars were held;2000 leaflets,10000 posters,and 30000 brochures were prepared and distributed;and two short video clips were produced and broadcast via IAM website,social media and local TV channels.A database was developed to house for project data,assessment of outcomes and reporting to stakeholders.Conclusion:Establishment of CAMHC resulted in significant achievements in diagnosis and management of mental disorders among children and adolescents,healthcare staff capacity building,and awareness-raising about mental disorders.Data obtained in CAMHC offers government,mental health professionals and the community the opportunity of improving mental health in the region.展开更多
Background:Porto-sinusoidal vascular disease(PSVD)and portal vein thrombosis(PVT)are causes of portal hypertension characterized respectively by an intrahepatic and a pre-hepatic obstacle to the flow in the portal sys...Background:Porto-sinusoidal vascular disease(PSVD)and portal vein thrombosis(PVT)are causes of portal hypertension characterized respectively by an intrahepatic and a pre-hepatic obstacle to the flow in the portal system.As PVT may be a consequence of PSVD,in PVT patients at presentation,a pre-existing PSVD should be suspected.In these patients the identification of an underlying PSVD would have relevant implication regarding follow-up and therapeutic management,but it could be challenging.In this setting ultrasonography may be valuable in differential diagnosis.The aim of the study was to use ultrasonography to identify parameters to discriminate between PSVD and“pure”PVT and then to suspect PVT secondary to a pre-existing PSVD.Methods:Fifty-three patients with histologically proven PSVD and forty-eight patients affected by chronic PVT were enrolled and submitted to abdominal ultrasonography with elastography by acoustic radiation force impulse(ARFI).Results:ARFI was higher and superior mesenteric vein(SMV)diameter was wider in PSVD patients than in PVT patients.Thus,a prognostic score was obtained as linear combinations of the two parameters with a good discrimination capacity between PSVD and PVT(the area under the curve=0.780;95%confidence interval:0.690-0.869).Conclusions:A score based on ARFI and SMV diameter may be useful to suspect an underlying PSVD in patients with PVT and to identify a subgroup of patients to be submitted to liver biopsy.展开更多
Non-alcoholic fatty liver disease(NAFLD) represents the most common and emerging chronic liver disease worldwide. It includes a wide spectrum of liver diseasesranging from simple fatty liver to non-alcoholic steatohep...Non-alcoholic fatty liver disease(NAFLD) represents the most common and emerging chronic liver disease worldwide. It includes a wide spectrum of liver diseasesranging from simple fatty liver to non-alcoholic steatohepatitis(NASH),which may progress to fibrosis and more severe liver complications such as cirrhosis,hepatocellular carcinoma and liver mortality. NAFLD is strongly associated with obesity,insulin resistance,hypertension,and dyslipidaemia,and is now regarded as the liver manifestation of the metabolic syndrome. The increased mortality of patients with NAFLD is primarily a result of cardiovascular disease and,to a lesser extent,to liver related diseases. Increased oxidative stress has been reported in both patients with NAFLD and patient with cardiovascular risk factors. Thus,oxidative stress represents a shared pathophysiological disorder between the two conditions. Several therapeutic strategies targeting oxidative stress reduction in patients with NAFLD have been proposed,with conflicting results. In particular,vitamin E supplementation has been suggested for the treatment of non-diabetic,non-cirrhotic adults with active NASH,although this recommendation is based only on the results of a single randomized controlled trial. Other antioxidant treatments suggested are resveratrol,silybin,L-carnitine and pentoxiphylline. No trial so far,has evaluated the cardiovascular effects of antioxidant treatment in patients with NAFLD. New,large-scale studies including as end-point also the assessment of the atherosclerosis markers are needed.展开更多
Atherosclerotic cardiovascular diseases, chronic inflam-matory diseases of multifactorial etiology, are the lead-ing cause of death worldwide. In the last decade, more infectious agents, labeled as "infectious bu...Atherosclerotic cardiovascular diseases, chronic inflam-matory diseases of multifactorial etiology, are the lead-ing cause of death worldwide. In the last decade, more infectious agents, labeled as "infectious burden", rather than any single pathogen, have been showed to con-tribute to the development of atherosclerosis through different mechanisms. Some microorganisms, such as Chlamydia pneumoniae(C. pneumoniae), human cytomegalovirus, etc. may act directly on the arterial wall contributing to endothelial dysfunction, foam cell formation, smooth muscle cell proliferation, platelet ag-gregation as well as cytokine, reactive oxygen specie, growth factor, and cellular adhesion molecule produc-tion. Others, such as Helicobacter pylori(H. pylori), in-fluenza virus, etc. may induce a systemic inflammation which in turn may damage the vascular wall(e.g., by cytokines and proteases). Moreover, another indirect mechanism by which some infectious agents(such as H. pylori, C. pneumoniae, periodontal pathogens, etc.) may play a role in the pathogenesis of atherosclero-sis is molecular mimicry. Given the complexity of the mechanisms by which each microorganism may con-tribute to atherosclerosis, defining the interplay of moreinfectious agents is far more difficult because the pro-atherogenic effect of each pathogen might be ampli-fied. Clearly, continued research and a greater aware-ness will be helpful to improve our knowledge on the complex interaction between the infectious burden and atherosclerosis.展开更多
Objective:To study the genetic diversity of Murray Valley encephalitis virus(MVEV) in Australia and Papua New Guinea.Methods:MVEV envelope gene sequences were aligned using Clustal X and manual editing was performed w...Objective:To study the genetic diversity of Murray Valley encephalitis virus(MVEV) in Australia and Papua New Guinea.Methods:MVEV envelope gene sequences were aligned using Clustal X and manual editing was performed with Bioedit.ModelTest v.3.7 was used to select the simplest evolutionary model that adequately fitted the sequence data.Maximum likelihood analysis was performed using PhyML.The phylogenetic signal of the dataset wa.s investigated by the likelihood mapping analysis.The Bayesian phylogenetic tree was built using BEAST.Results:The phylogenetic trees showed two main clades.The clade Ⅰincluding eight strains isolated from West Australia.The clade Ⅱ was characterized by at least four epidemic entries,three of which localized in Northern West Australia and one in Papua New Guinea.The estimated mean evolutionary rate value of the MVEV envelope gene wa.s0.407 × 10^(-3) substitution/site/year(95%HPD:0.623 × 10~4-0.780× 10^(-3)).Population dynamics defines a relative constant population until the year 2000.when a reduction occurred,probably due to a bottleneck.Conclusions:This study has been useful in supporting the probable connection between climate changes and viral evolution also by the vector point of view:multidisciplinary monitoring studies are important to prevent new viral epidemics inside and outside new endemic areas.展开更多
The aim of this paper is to highlight the current development in the research field for helping people just exposed to Ebola virus survive(treatment) and to prevent the disease when given at various times after exposu...The aim of this paper is to highlight the current development in the research field for helping people just exposed to Ebola virus survive(treatment) and to prevent the disease when given at various times after exposure(vaccine).Concerning the treatment,recombinant anti-Ebola monoclonal antibodies and small interfering RNAs that block the expression of essential viral proteins,are the most promising way in stopping the disease when it has already reached the humans.As far as concerns the prevention field,two candidate vaccines have clinical-grade vials available for phase 1 pre-licensure clinical trials,and demonstrated to have a 100%efficacy in studies on non human primates.Well-informed communities can reduce the main ways of spread the infection,by avoiding unprotected home-based care of people who are infected and also by completely modifying traditional burial practices that are way of diffusion of the contagion.展开更多
AIM To determine factors independently influencing response to ingenol mebutate therapy and assess efficacy on clinical setting of non-hypertrophic non-hyperkeratotic actinic keratosis (AK).METHODS Consecutive patient...AIM To determine factors independently influencing response to ingenol mebutate therapy and assess efficacy on clinical setting of non-hypertrophic non-hyperkeratotic actinic keratosis (AK).METHODS Consecutive patients affected by non-hypertrophic non-hyperkeratotic AKs of the face or scalp were enrolled to receive ingenol mebutate 0.015% gel on a selected skin area of 25 cm^2 for 3 consecutive days.Local skin reactions were calculated at each follow up visit using a validated composite score.Efficacy was evaluated by the comparison of clinical and dermoscopic pictures before the treatment and at day 57,and classified as complete,partial and poor response.RESULTS A number of 130 patients were enrolled,of which 101(77.7%) were treated on the face,while 29 (22.3%) on the scalp.The great majority of our study population (n = 119,91.5%) reached at least a 75% clearance of AKs and,in particular,58 patients (44.6%) achieved a complete response while 61(46.9%) a partial one.Logistic backward multivariate analysis showed that facial localization,level of local skin reaction (LSR) at day 2,the highest LSR values and level of crusts at day 8 were factors independently associated with the achievement of a complete response.CONCLUSION Ingenol mebutate 0.015% gel,when properly applied,is more effective on the face than on the scalp and efficacy is directly associated to LSR score.展开更多
Objective:To explore the genetic diversity and the modification of antibody response in the recent outbreak of Ebola Virus.Methods:Sequences retrieved from public databases,the selective pressure analysis and the homo...Objective:To explore the genetic diversity and the modification of antibody response in the recent outbreak of Ebola Virus.Methods:Sequences retrieved from public databases,the selective pressure analysis and the homology modelling based on the all protein(nucleoprotein.VP35,VP40.soluble glycoprotein,small soluble glycoprotein.VP30,VP24 and polymerase) were used.Results:Structural proteins VP24.VP30.VP35 and VP40 showed relative conserved sequences making them suitable target candidates for antiviral treatment.On the contrary,nucleoprotein.polymerase and soluble glycoprotein have high mutation frequency.Conclusions:Data from this study point out important aspects of Ebola virus sequence variability that for epitope and vaccine design should be considered for appropriate targeting of conserved protein regions.展开更多
Objectives:Coronavirus disease 2019(COVID-19)pandemic has been associated with a great level of psychological distresses in people around the world.This study aims to assess the prevalence of depression,anxiety and st...Objectives:Coronavirus disease 2019(COVID-19)pandemic has been associated with a great level of psychological distresses in people around the world.This study aims to assess the prevalence of depression,anxiety and stress among COVID-19 patients and identify the associated factors,in Herat Province of Afghanistan.Methods:This cross-sectional study was conducted on 459 hospitalized patients between May and September 2021.Data was collected with a structured questionnaire on depression,anxiety and stress scale,which was the validated Dari-version.Chi-square test was adopted to analyze the associations of the prevalence of the mental disorders and the factors.Results:The mean age of participants was 38.05;51.9%(238/459)were male and 84.1%(386/459)were married.Median scores for depression,anxiety and stress were 5.0,8.0,and 10.0,respectively.Gender,general health condition,nutritional status,COVID-19 clinical manifestation and concurrent comorbidities(except diabetes and hypertension)were significantly associated with mental disorders;while association between marital status and these psychological disorders was not significant.Moreover,a significant difference was observed in the level of anxiety between healthcare workers and other respondents.Conclusion:This is the first study to report the high prevalence of depression,anxiety and stress among COVID-19 patients in Herat,which indicates the negative effect of mental health for COVID-19 patients globally and highlights the need for urgent and appropriate interventions to improve mental health of people during the pandemic.展开更多
The pathophysiological mechanisms that underlie the progression of human immunodeficiency virus-1(HIV-1) disease to full-blown AIDS are not well understood. Findings suggest that, during HIV-1 infection, plasma lipopo...The pathophysiological mechanisms that underlie the progression of human immunodeficiency virus-1(HIV-1) disease to full-blown AIDS are not well understood. Findings suggest that, during HIV-1 infection, plasma lipopolysaccharide(LPS) levels, which are used as an indicator of microbial translocation(MT), are elevated throughout the acute and chronic phases of HIV-1 disease. The translocation of bacterial products through the damaged gastrointestinal barrier into the systemic circulation has been described as a driver of immune activation. In contrast, comorbidities that are associated with HIV-1 infection have been attributed to chronic inflammation and immune system dysfunction secondary to MT or low-level HIV-1 replication in plasma and cell reservoirs. Moreover, accelerated aging is significantly associated with chronic inflammation, immune activation, and immune senescence. In this review, we aimed to investigate the role of inflammation as a pivotal marker in the pathogenesis of HIV-1 disease. We will discuss the key features of chronic inflammation and immune activation that are observed during the natural course of the disease and those features that are detected in c ART-modified infection. The review will focus on the following aspects of HIV-1 infection:(1) MT;(2) the role of residual viremia; and(3) "immune senescence" or "inflammaging." Many questions remain unanswered about the potential mechanisms that are involved in HIV-1 pathogenesis. Further studies are needed to better investigate the mechanisms that underlie immune activation and their correlation with HIV-1 disease progression.展开更多
Dear Editor,Urinary incontinence(UI)is defined as involuntary leakage of urine.[1]Higa and Lopes.[2]found that nursing activities that require greater physical effort increase urinary loss among female nurses with UI,...Dear Editor,Urinary incontinence(UI)is defined as involuntary leakage of urine.[1]Higa and Lopes.[2]found that nursing activities that require greater physical effort increase urinary loss among female nurses with UI,resulting in stress,humiliation,and lack of focus at work.Pelvic floor muscle exercises(PFME)should be used as a health promotion strategy for the prevention and management of UI among female nurses,especially in the time of COVID‑19 pandemic as nurses are faced with numerous tasks and stress.The use of sanitary pad is the most frequent strategy used by female nurses to manage UI during working hours,and this approach is not usually convenient for them.[2]UI affects the quality of life and sexual health of female nurses.[3]The risk factors for UI among females are aging,childbearing,increase in body mass index,anxiety,depression,and musculoskeletal disorders.展开更多
Liver disease is associated with qualitative and quantitative changes in the intestinal microbiota.In cirrhotic patients the alteration in gut microbiota is characterized by an overgrowth of potentially pathogenic bac...Liver disease is associated with qualitative and quantitative changes in the intestinal microbiota.In cirrhotic patients the alteration in gut microbiota is characterized by an overgrowth of potentially pathogenic bacteria(i.e.,gram negative species)and a decrease in autochthonous familiae.Here we summarize the available literature on the risk of gut dysbiosis in liver cirrhosis and its clinical consequences.We therefore described the features of the complex interaction between gut microbiota and cirrhotic host,the so called"gut-liver axis",with a particular attention to the acquired risk of bacterial translocation,systemic inflammation and the relationship with systemic infections in the cirrhotic patient.Such knowledge might help to develop novel and innovative strategies for the prevention and therapy of gut dysbiosis and its complication in liver cirrhosis.展开更多
Hepatitis B virus (HBV) reactivation represents an emerging cause of liver disease in patients undergoing treatment with biologic agents. In particular, the risk ofHBV reactivation is heightened by the use monoclonala...Hepatitis B virus (HBV) reactivation represents an emerging cause of liver disease in patients undergoing treatment with biologic agents. In particular, the risk ofHBV reactivation is heightened by the use monoclonalantibodies, such as rituximab (anti-CD20) and alemtuzumab (anti-CD52) that cause profound and longlasting immunosuppression. Emerging data indicatethat HBV reactivation could also develop following theuse of other biologic agents, such as tumor necrosis factor (TNF)-α inhibitors. When HBV reactivation is di-agnosed, it is mandatory to suspend biologic treatmentand start antiviral agents immediately. However, preemptive antiviral therapy prior to monoclonal antibodyadministration is crucial in preventing HBV reactivationand its clinical consequences. Several lines of evidencehave shown that risk of HBV reactivation is greatlyreduced by the identifi cation of high-risk patients andthe use of prophylactic antiviral therapy. In this article, we discuss current trends in the management of HBV reactivation in immunosuppressed patients receiving biologic therapy, such as rituximab, alemtuzumab and TNF-α antagonists.展开更多
Non-alcoholic fatty liver disease(NAFLD)is the most common and emerging form of chronic liver disease worldwide.It includes a wide spectrum of liver diseases ranging from simple fatty liver to steatohepatitis,which ma...Non-alcoholic fatty liver disease(NAFLD)is the most common and emerging form of chronic liver disease worldwide.It includes a wide spectrum of liver diseases ranging from simple fatty liver to steatohepatitis,which may progress to cirrhosis,liver cancer,and liver mortality.Common metabolic diseases,which are well established cardiovascular risk factors,have been associated to NAFLD and cardiovascular disease is the single most important cause of morbidity and mortality in this patient population.The pathogenesis of NAFLD appears multifactorial and many mechanisms have been proposed as possible causes of fatty liver infiltration.Management of fatty liver has become a major challenge to healthcare systems as the consequence of the increasing rates of obesity worldwide.First-line management focuses on lifestyle modifications.Moderate weight reduction either by dietary restriction or by increased habitual physical activity is safe and highly recommended.Several therapeutic interventions have been proposed.These include insulin sensitizer agents,lipid lowering drugs,antioxidants such as vitamin E and supplementation of vitamin D3.However,therapeutic strategies have been largely empirical so far,and experimental trials have mostly been carried out in uncontrolled settings with small sample sizes.Metabolic conditions such as diabetes mellitus,obesity,hypertension and hyperlipidemia,should be strongly considered and a multidisciplinary approach should be personalized for individual patients.Treatment of co-morbidities should be regarded as of paramount importance in the management of these patients.The purpose of this review is to examine different approaches for the clinical management of non-alcoholic fatty liver disease.展开更多
BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is an emerging liver disease and currently the most common cause of incidental abnormal liver tests.The pathogenesis of NAFLD is multifactorial and many mechanisms th...BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is an emerging liver disease and currently the most common cause of incidental abnormal liver tests.The pathogenesis of NAFLD is multifactorial and many mechanisms that cause fatty liver infiltration,inflammation,oxidative stress and progressive fibrosis have been proposed.Obstructive sleep apnea(OSA)may be linked with the pathogenesis and the severity of NAFLD.AIM To study the association between NAFLD and OSA considering also the efficacy of continuous positive airway pressure(CPAP)treatment.METHODS A Pub Med search was conducted using the terms"non-alcoholic fatty liver disease AND(obstructive sleep apnea OR obstructive sleep disorders OR sleep apnea)".Research was limited to title/abstract of articles published in English in the last 5 years;animal and child studies,case reports,commentaries,letters,editorials and meeting abstracts were not considered.Data were extracted on a standardized data collection table which included:First author,publication year,country,study design,number of patients involved,diagnosis and severity of OSA,diagnosis of NAFLD,patient characteristics,results of the study.RESULTSIn total,132 articles were initially retrieved on Pub Med search and 77 in the last five years.After removal of irrelevant studies,13 articles were included in the qualitative analysis.There was a total of 2753 participants across all the studies with a mean age between 42 and 58 years.The proportion of males ranged from21%to 87.9%and the mean body mass index ranged from 24.0 to 49.9 kg/m2.The results of this review showed an increased prevalence of NAFLD in patients with diagnosis of OSA,even in the absence of coexisting comorbidities such as obesity or metabolic syndrome.Furthermore,the severity of NAFLD is associated with the increase in OSA severity.Effective CPAP treatment,although not always decisive,may stabilize or slow NAFLD progression with benefits on metabolic and cardiovascular functions.CONCLUSION In NAFLD patients,although asymptomatic,it is recommended to systematically perform polysomnography in order to early and better treat them before the development of potentially life threatening systemic dysfunctions.展开更多
Over the last two decades, the rise in the prevalence rates of overweight and obesity explains the emergence of nonalcoholic fatty liver disease(NAFLD) as the leading cause of chronic liver disease worldwide. As descr...Over the last two decades, the rise in the prevalence rates of overweight and obesity explains the emergence of nonalcoholic fatty liver disease(NAFLD) as the leading cause of chronic liver disease worldwide. As described in adults, children and adolescents with fatty liver display insulin resistance, glucose intolerance, and dyslipidemia. Thus NAFLD has emerged as the hepatic component of the metabolic syndrome(MetS) and a strong cardiovascular risk factor even at a very early age. Several studies, including pediatric populations, have reported independent associations between NAFLD and markers of subclinical atherosclerosis including impaired flow-mediated vasodilation, increased carotid artery intima-media thickness, and arterial stiffness, after adjusting for cardiovascular risk factors and MetS. Also, it has been shown that NAFLD is associated with cardiac alterations, including abnormal left ventricular structure and impaired diastolic function. The duration of these subclinical abnormalities may be important, because treatment to reverse the process is most likely to be effective earlier in the disease. In the present review, we examine the current evidence on the association between NAFLD and atherosclerosis as well as between NAFLD and cardiac dysfunction in the pediatric population, and discuss briefly the possible biological mechanisms linking NAFLD and cardiovascular changes. We also address the approach to treatment for this increasingly prevalent disease, which is likely to have an important future global impact on the burden of ill health, to prevent not only end-stage liver disease but also cardiovascular disease.展开更多
Lysosomal acid lipase(LAL)plays a key role in intracellular lipid metabolism.Reduced LAL activity promotes increased multi-organ lysosomal cholesterol ester storage,as observed in two recessive autosomal genetic disea...Lysosomal acid lipase(LAL)plays a key role in intracellular lipid metabolism.Reduced LAL activity promotes increased multi-organ lysosomal cholesterol ester storage,as observed in two recessive autosomal genetic diseases,Wolman disease and Cholesterol ester storage disease.Severe liver steatosis and accelerated liver fibrosis are common features in patients with genetic LAL deficiency.By contrast,few reliable data are available on the modulation of LAL activity in vivo and on the epigenetic and metabolic factors capable of regulating its activity in subjects without homozygous mutations of the Lipase A gene.In the last few years,a less severe and non-genetic reduction of LAL activity was reported in children and adults with non-alcoholic fatty liver disease(NAFLD),suggesting a possible role of LAL reduction in the pathogenesis and progression of the disease.Patients with NAFLD show a significant,progressive reduction of LAL activity from simple steatosis to non-alcoholic steatohepatitis and cryptogenic cirrhosis.Among cirrhosis of different etiologies,those with cryptogenic cirrhosis show the most significant reductions of LAL activity.These findings suggest that the modulation of LAL activity may become a possible new therapeutic target for patients with more advanced forms of NAFLD.Moreover,the measurement of LAL activity may represent a possible new marker of disease severity in this clinical setting.展开更多
Objective: To investigate the genetic diversity of Zika virus(ZIKV) and the relationships existing among these circulating viruses worldwide. To evaluate the genetic polymorphisms harboured from ZIKV that can have an ...Objective: To investigate the genetic diversity of Zika virus(ZIKV) and the relationships existing among these circulating viruses worldwide. To evaluate the genetic polymorphisms harboured from ZIKV that can have an influence on the virus circulation. Methods: Three different ZIKV dataset were built. The first dataset included 63 E gene sequences, the second one 22 NS3 sequences and the third dataset was composed of 108 NS5 gene sequences. Phylogenetic and selective pressure analysis was performed. The edited nucleic acid alignment from the Envelope dataset was used to generate a conceptual translation to the corresponding peptide sequences through UGene software. Results: The phylogeographic reconstruction was able to discriminate unambiguously that the Brazilian strains are belonged to the Asian lineage. The structural analysis reveals instead the presence of the Ser residue in the Brazilian sequences(however already observed in other previously reported ZIKV infections) that could suggest the presence of a neutralization-resistant population of viruses. Conclusions: Phylogenetic, evolutionary and selective pressure analysis contributed to improve the knowledge on the circulation of ZIKV.展开更多
基金supported by the International Assistance Mission,Herat Office(Grant number#IDR0220526IAM).
文摘Background:The prevalence of pediatric mental illnesses has been increasing in recent years,with a great potential to impact on individual's functionality and adaptation in adulthood.Objective:This study aims to assess emotional and behavioral problems among schoolchildren in Herat City of Afghanistan.Methods:This cross-sectional study was conducted on schoolchildren(grade 5-10),between September and November 2021.Sociodemographic data was collected using a paper-based 14-item structured questionnaire.Data on emotional and behavioral problems was collected using the Strengths and Difficulties Questionnaire(SDQ)based on teachers'and children's report.Statistical analyses were performed in IBM SPSS Statistics(version 27).Results:A total of 418 students,including 190(45.5%)males and 228(54.5%)females with a mean age of 14.1±1.7(11-<18)years were included in the study.The prevalence of students*self-reported total difficulties and prosocial problem were 5.7%and 1.2%,respectively.An insignificant difference was observed between mean total difficulties scores between students'self-reported and teachers'reported SDQ.Gender,grade,concern about shortage of food,and concern about losing house were significantly predicting students'self-reported total difficulties scores.Conclusion:This is the first study to report the prevalence of emotional and behavioral problems among schoolchildren in Herat City,Afghanistan.This,together with relevant global literature,highlight the need to address pediatric mental health,and provide services aimed at preventing,and treating children with these problems around the world.
文摘Neoplasms can be considered as a group of aberrant cells that need more vascular supply to fulfill all their functions.Therefore,they promote angiogenesis through the same neovascularization pathway used physiologically.Angiogenesis is a process characterized by a heterogeneous distribution of oxygen caused by the tumor and oxidative stress;the latter being one of the most powerful stimuli of angiogenesis.As a result of altered tumor metabolism due to hypoxia,acidosis occurs.The angiogenic process and oxidative stress can be detected by measuring serum and tissue biomarkers.The study of the mechanisms underlying angiogenesis and oxidative stress could lead to the identification of new biomarkers,ameliorating the selection of patients with neoplasms and the prediction of their response to possible anti-tumor therapies.In particular,in the treatment of patients with similar clinical tumor phenotypes but different prognoses,the new biomarkers could be useful.Moreover,they may lead to a better understanding of the mechanisms underlying drug resistance.Experimental studies show that blocking the vascular supply results in antiproliferative activity in vivo in neuroendocrine tumor cells,which require a high vascular supply.
文摘Objective:Afghanistan has witnessed a long-lasting 4-decade armed conflict,which together with high levels of poverty and interpersonal violence,resulted in high incidence and prevalence of mental disorders in general population,including children and adolescents.Until mid-2018,there was neither mental health care facility nor a child psychiatrist in Afghanistan.Here,we report the establishment of the first children and adolescents'mental health center(CAMHC)in Herat province of Afghanistan.Methods:In July 2018,CAMHC was initiated at Mental Health Training Center-Herat.CAMHC was initially planned by the International Assistance Mission(IAM)and Herat Public Health Directorate;and financially supported by the Tearfund UK,the United Methodist Committee on Relief and Tearfund Australia.The target population of CAMHC was children and adolescents in Herat and neighboring provinces,healthcare professionals,staff of government and non-governmental organizations,school teachers and community leaders.Results:A group of eight mental health professionals were trained and made the interdisciplinary board for diagnosis and management of mental disorders in children and adolescents.During the initial three-year period,2448 patients,including 1264(51.6%)boys and 1184(48.4%)girls,presented with mental disorders to CAMHC.Diagnosis and management of mental disorders were performed according to standard international protocols.Eighteen awareness-raising seminars were held;2000 leaflets,10000 posters,and 30000 brochures were prepared and distributed;and two short video clips were produced and broadcast via IAM website,social media and local TV channels.A database was developed to house for project data,assessment of outcomes and reporting to stakeholders.Conclusion:Establishment of CAMHC resulted in significant achievements in diagnosis and management of mental disorders among children and adolescents,healthcare staff capacity building,and awareness-raising about mental disorders.Data obtained in CAMHC offers government,mental health professionals and the community the opportunity of improving mental health in the region.
基金This study was approved by Ethical Committee of The Sapienza University of Rome(5068/2018).
文摘Background:Porto-sinusoidal vascular disease(PSVD)and portal vein thrombosis(PVT)are causes of portal hypertension characterized respectively by an intrahepatic and a pre-hepatic obstacle to the flow in the portal system.As PVT may be a consequence of PSVD,in PVT patients at presentation,a pre-existing PSVD should be suspected.In these patients the identification of an underlying PSVD would have relevant implication regarding follow-up and therapeutic management,but it could be challenging.In this setting ultrasonography may be valuable in differential diagnosis.The aim of the study was to use ultrasonography to identify parameters to discriminate between PSVD and“pure”PVT and then to suspect PVT secondary to a pre-existing PSVD.Methods:Fifty-three patients with histologically proven PSVD and forty-eight patients affected by chronic PVT were enrolled and submitted to abdominal ultrasonography with elastography by acoustic radiation force impulse(ARFI).Results:ARFI was higher and superior mesenteric vein(SMV)diameter was wider in PSVD patients than in PVT patients.Thus,a prognostic score was obtained as linear combinations of the two parameters with a good discrimination capacity between PSVD and PVT(the area under the curve=0.780;95%confidence interval:0.690-0.869).Conclusions:A score based on ARFI and SMV diameter may be useful to suspect an underlying PSVD in patients with PVT and to identify a subgroup of patients to be submitted to liver biopsy.
文摘Non-alcoholic fatty liver disease(NAFLD) represents the most common and emerging chronic liver disease worldwide. It includes a wide spectrum of liver diseasesranging from simple fatty liver to non-alcoholic steatohepatitis(NASH),which may progress to fibrosis and more severe liver complications such as cirrhosis,hepatocellular carcinoma and liver mortality. NAFLD is strongly associated with obesity,insulin resistance,hypertension,and dyslipidaemia,and is now regarded as the liver manifestation of the metabolic syndrome. The increased mortality of patients with NAFLD is primarily a result of cardiovascular disease and,to a lesser extent,to liver related diseases. Increased oxidative stress has been reported in both patients with NAFLD and patient with cardiovascular risk factors. Thus,oxidative stress represents a shared pathophysiological disorder between the two conditions. Several therapeutic strategies targeting oxidative stress reduction in patients with NAFLD have been proposed,with conflicting results. In particular,vitamin E supplementation has been suggested for the treatment of non-diabetic,non-cirrhotic adults with active NASH,although this recommendation is based only on the results of a single randomized controlled trial. Other antioxidant treatments suggested are resveratrol,silybin,L-carnitine and pentoxiphylline. No trial so far,has evaluated the cardiovascular effects of antioxidant treatment in patients with NAFLD. New,large-scale studies including as end-point also the assessment of the atherosclerosis markers are needed.
基金Supported by Grants to R.Sessa from Center for Social Disease Research,"Sapienza"University,Rome
文摘Atherosclerotic cardiovascular diseases, chronic inflam-matory diseases of multifactorial etiology, are the lead-ing cause of death worldwide. In the last decade, more infectious agents, labeled as "infectious burden", rather than any single pathogen, have been showed to con-tribute to the development of atherosclerosis through different mechanisms. Some microorganisms, such as Chlamydia pneumoniae(C. pneumoniae), human cytomegalovirus, etc. may act directly on the arterial wall contributing to endothelial dysfunction, foam cell formation, smooth muscle cell proliferation, platelet ag-gregation as well as cytokine, reactive oxygen specie, growth factor, and cellular adhesion molecule produc-tion. Others, such as Helicobacter pylori(H. pylori), in-fluenza virus, etc. may induce a systemic inflammation which in turn may damage the vascular wall(e.g., by cytokines and proteases). Moreover, another indirect mechanism by which some infectious agents(such as H. pylori, C. pneumoniae, periodontal pathogens, etc.) may play a role in the pathogenesis of atherosclero-sis is molecular mimicry. Given the complexity of the mechanisms by which each microorganism may con-tribute to atherosclerosis, defining the interplay of moreinfectious agents is far more difficult because the pro-atherogenic effect of each pathogen might be ampli-fied. Clearly, continued research and a greater aware-ness will be helpful to improve our knowledge on the complex interaction between the infectious burden and atherosclerosis.
文摘Objective:To study the genetic diversity of Murray Valley encephalitis virus(MVEV) in Australia and Papua New Guinea.Methods:MVEV envelope gene sequences were aligned using Clustal X and manual editing was performed with Bioedit.ModelTest v.3.7 was used to select the simplest evolutionary model that adequately fitted the sequence data.Maximum likelihood analysis was performed using PhyML.The phylogenetic signal of the dataset wa.s investigated by the likelihood mapping analysis.The Bayesian phylogenetic tree was built using BEAST.Results:The phylogenetic trees showed two main clades.The clade Ⅰincluding eight strains isolated from West Australia.The clade Ⅱ was characterized by at least four epidemic entries,three of which localized in Northern West Australia and one in Papua New Guinea.The estimated mean evolutionary rate value of the MVEV envelope gene wa.s0.407 × 10^(-3) substitution/site/year(95%HPD:0.623 × 10~4-0.780× 10^(-3)).Population dynamics defines a relative constant population until the year 2000.when a reduction occurred,probably due to a bottleneck.Conclusions:This study has been useful in supporting the probable connection between climate changes and viral evolution also by the vector point of view:multidisciplinary monitoring studies are important to prevent new viral epidemics inside and outside new endemic areas.
文摘The aim of this paper is to highlight the current development in the research field for helping people just exposed to Ebola virus survive(treatment) and to prevent the disease when given at various times after exposure(vaccine).Concerning the treatment,recombinant anti-Ebola monoclonal antibodies and small interfering RNAs that block the expression of essential viral proteins,are the most promising way in stopping the disease when it has already reached the humans.As far as concerns the prevention field,two candidate vaccines have clinical-grade vials available for phase 1 pre-licensure clinical trials,and demonstrated to have a 100%efficacy in studies on non human primates.Well-informed communities can reduce the main ways of spread the infection,by avoiding unprotected home-based care of people who are infected and also by completely modifying traditional burial practices that are way of diffusion of the contagion.
文摘AIM To determine factors independently influencing response to ingenol mebutate therapy and assess efficacy on clinical setting of non-hypertrophic non-hyperkeratotic actinic keratosis (AK).METHODS Consecutive patients affected by non-hypertrophic non-hyperkeratotic AKs of the face or scalp were enrolled to receive ingenol mebutate 0.015% gel on a selected skin area of 25 cm^2 for 3 consecutive days.Local skin reactions were calculated at each follow up visit using a validated composite score.Efficacy was evaluated by the comparison of clinical and dermoscopic pictures before the treatment and at day 57,and classified as complete,partial and poor response.RESULTS A number of 130 patients were enrolled,of which 101(77.7%) were treated on the face,while 29 (22.3%) on the scalp.The great majority of our study population (n = 119,91.5%) reached at least a 75% clearance of AKs and,in particular,58 patients (44.6%) achieved a complete response while 61(46.9%) a partial one.Logistic backward multivariate analysis showed that facial localization,level of local skin reaction (LSR) at day 2,the highest LSR values and level of crusts at day 8 were factors independently associated with the achievement of a complete response.CONCLUSION Ingenol mebutate 0.015% gel,when properly applied,is more effective on the face than on the scalp and efficacy is directly associated to LSR score.
基金supported by National Institute of Health andProxagent Ltd in collaboration with University of Rome "Tor Vergata
文摘Objective:To explore the genetic diversity and the modification of antibody response in the recent outbreak of Ebola Virus.Methods:Sequences retrieved from public databases,the selective pressure analysis and the homology modelling based on the all protein(nucleoprotein.VP35,VP40.soluble glycoprotein,small soluble glycoprotein.VP30,VP24 and polymerase) were used.Results:Structural proteins VP24.VP30.VP35 and VP40 showed relative conserved sequences making them suitable target candidates for antiviral treatment.On the contrary,nucleoprotein.polymerase and soluble glycoprotein have high mutation frequency.Conclusions:Data from this study point out important aspects of Ebola virus sequence variability that for epitope and vaccine design should be considered for appropriate targeting of conserved protein regions.
基金supported by the Department of Public Health and Infectious Diseases of the Faculty of Medicine-Herat University and the International Assistance Mission(IAM)一Herat officeproject was funded by the International Assistance Mission(Grant number#323,216).
文摘Objectives:Coronavirus disease 2019(COVID-19)pandemic has been associated with a great level of psychological distresses in people around the world.This study aims to assess the prevalence of depression,anxiety and stress among COVID-19 patients and identify the associated factors,in Herat Province of Afghanistan.Methods:This cross-sectional study was conducted on 459 hospitalized patients between May and September 2021.Data was collected with a structured questionnaire on depression,anxiety and stress scale,which was the validated Dari-version.Chi-square test was adopted to analyze the associations of the prevalence of the mental disorders and the factors.Results:The mean age of participants was 38.05;51.9%(238/459)were male and 84.1%(386/459)were married.Median scores for depression,anxiety and stress were 5.0,8.0,and 10.0,respectively.Gender,general health condition,nutritional status,COVID-19 clinical manifestation and concurrent comorbidities(except diabetes and hypertension)were significantly associated with mental disorders;while association between marital status and these psychological disorders was not significant.Moreover,a significant difference was observed in the level of anxiety between healthcare workers and other respondents.Conclusion:This is the first study to report the high prevalence of depression,anxiety and stress among COVID-19 patients in Herat,which indicates the negative effect of mental health for COVID-19 patients globally and highlights the need for urgent and appropriate interventions to improve mental health of people during the pandemic.
文摘The pathophysiological mechanisms that underlie the progression of human immunodeficiency virus-1(HIV-1) disease to full-blown AIDS are not well understood. Findings suggest that, during HIV-1 infection, plasma lipopolysaccharide(LPS) levels, which are used as an indicator of microbial translocation(MT), are elevated throughout the acute and chronic phases of HIV-1 disease. The translocation of bacterial products through the damaged gastrointestinal barrier into the systemic circulation has been described as a driver of immune activation. In contrast, comorbidities that are associated with HIV-1 infection have been attributed to chronic inflammation and immune system dysfunction secondary to MT or low-level HIV-1 replication in plasma and cell reservoirs. Moreover, accelerated aging is significantly associated with chronic inflammation, immune activation, and immune senescence. In this review, we aimed to investigate the role of inflammation as a pivotal marker in the pathogenesis of HIV-1 disease. We will discuss the key features of chronic inflammation and immune activation that are observed during the natural course of the disease and those features that are detected in c ART-modified infection. The review will focus on the following aspects of HIV-1 infection:(1) MT;(2) the role of residual viremia; and(3) "immune senescence" or "inflammaging." Many questions remain unanswered about the potential mechanisms that are involved in HIV-1 pathogenesis. Further studies are needed to better investigate the mechanisms that underlie immune activation and their correlation with HIV-1 disease progression.
文摘Dear Editor,Urinary incontinence(UI)is defined as involuntary leakage of urine.[1]Higa and Lopes.[2]found that nursing activities that require greater physical effort increase urinary loss among female nurses with UI,resulting in stress,humiliation,and lack of focus at work.Pelvic floor muscle exercises(PFME)should be used as a health promotion strategy for the prevention and management of UI among female nurses,especially in the time of COVID‑19 pandemic as nurses are faced with numerous tasks and stress.The use of sanitary pad is the most frequent strategy used by female nurses to manage UI during working hours,and this approach is not usually convenient for them.[2]UI affects the quality of life and sexual health of female nurses.[3]The risk factors for UI among females are aging,childbearing,increase in body mass index,anxiety,depression,and musculoskeletal disorders.
文摘Liver disease is associated with qualitative and quantitative changes in the intestinal microbiota.In cirrhotic patients the alteration in gut microbiota is characterized by an overgrowth of potentially pathogenic bacteria(i.e.,gram negative species)and a decrease in autochthonous familiae.Here we summarize the available literature on the risk of gut dysbiosis in liver cirrhosis and its clinical consequences.We therefore described the features of the complex interaction between gut microbiota and cirrhotic host,the so called"gut-liver axis",with a particular attention to the acquired risk of bacterial translocation,systemic inflammation and the relationship with systemic infections in the cirrhotic patient.Such knowledge might help to develop novel and innovative strategies for the prevention and therapy of gut dysbiosis and its complication in liver cirrhosis.
文摘Hepatitis B virus (HBV) reactivation represents an emerging cause of liver disease in patients undergoing treatment with biologic agents. In particular, the risk ofHBV reactivation is heightened by the use monoclonalantibodies, such as rituximab (anti-CD20) and alemtuzumab (anti-CD52) that cause profound and longlasting immunosuppression. Emerging data indicatethat HBV reactivation could also develop following theuse of other biologic agents, such as tumor necrosis factor (TNF)-α inhibitors. When HBV reactivation is di-agnosed, it is mandatory to suspend biologic treatmentand start antiviral agents immediately. However, preemptive antiviral therapy prior to monoclonal antibodyadministration is crucial in preventing HBV reactivationand its clinical consequences. Several lines of evidencehave shown that risk of HBV reactivation is greatlyreduced by the identifi cation of high-risk patients andthe use of prophylactic antiviral therapy. In this article, we discuss current trends in the management of HBV reactivation in immunosuppressed patients receiving biologic therapy, such as rituximab, alemtuzumab and TNF-α antagonists.
文摘Non-alcoholic fatty liver disease(NAFLD)is the most common and emerging form of chronic liver disease worldwide.It includes a wide spectrum of liver diseases ranging from simple fatty liver to steatohepatitis,which may progress to cirrhosis,liver cancer,and liver mortality.Common metabolic diseases,which are well established cardiovascular risk factors,have been associated to NAFLD and cardiovascular disease is the single most important cause of morbidity and mortality in this patient population.The pathogenesis of NAFLD appears multifactorial and many mechanisms have been proposed as possible causes of fatty liver infiltration.Management of fatty liver has become a major challenge to healthcare systems as the consequence of the increasing rates of obesity worldwide.First-line management focuses on lifestyle modifications.Moderate weight reduction either by dietary restriction or by increased habitual physical activity is safe and highly recommended.Several therapeutic interventions have been proposed.These include insulin sensitizer agents,lipid lowering drugs,antioxidants such as vitamin E and supplementation of vitamin D3.However,therapeutic strategies have been largely empirical so far,and experimental trials have mostly been carried out in uncontrolled settings with small sample sizes.Metabolic conditions such as diabetes mellitus,obesity,hypertension and hyperlipidemia,should be strongly considered and a multidisciplinary approach should be personalized for individual patients.Treatment of co-morbidities should be regarded as of paramount importance in the management of these patients.The purpose of this review is to examine different approaches for the clinical management of non-alcoholic fatty liver disease.
文摘BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is an emerging liver disease and currently the most common cause of incidental abnormal liver tests.The pathogenesis of NAFLD is multifactorial and many mechanisms that cause fatty liver infiltration,inflammation,oxidative stress and progressive fibrosis have been proposed.Obstructive sleep apnea(OSA)may be linked with the pathogenesis and the severity of NAFLD.AIM To study the association between NAFLD and OSA considering also the efficacy of continuous positive airway pressure(CPAP)treatment.METHODS A Pub Med search was conducted using the terms"non-alcoholic fatty liver disease AND(obstructive sleep apnea OR obstructive sleep disorders OR sleep apnea)".Research was limited to title/abstract of articles published in English in the last 5 years;animal and child studies,case reports,commentaries,letters,editorials and meeting abstracts were not considered.Data were extracted on a standardized data collection table which included:First author,publication year,country,study design,number of patients involved,diagnosis and severity of OSA,diagnosis of NAFLD,patient characteristics,results of the study.RESULTSIn total,132 articles were initially retrieved on Pub Med search and 77 in the last five years.After removal of irrelevant studies,13 articles were included in the qualitative analysis.There was a total of 2753 participants across all the studies with a mean age between 42 and 58 years.The proportion of males ranged from21%to 87.9%and the mean body mass index ranged from 24.0 to 49.9 kg/m2.The results of this review showed an increased prevalence of NAFLD in patients with diagnosis of OSA,even in the absence of coexisting comorbidities such as obesity or metabolic syndrome.Furthermore,the severity of NAFLD is associated with the increase in OSA severity.Effective CPAP treatment,although not always decisive,may stabilize or slow NAFLD progression with benefits on metabolic and cardiovascular functions.CONCLUSION In NAFLD patients,although asymptomatic,it is recommended to systematically perform polysomnography in order to early and better treat them before the development of potentially life threatening systemic dysfunctions.
文摘Over the last two decades, the rise in the prevalence rates of overweight and obesity explains the emergence of nonalcoholic fatty liver disease(NAFLD) as the leading cause of chronic liver disease worldwide. As described in adults, children and adolescents with fatty liver display insulin resistance, glucose intolerance, and dyslipidemia. Thus NAFLD has emerged as the hepatic component of the metabolic syndrome(MetS) and a strong cardiovascular risk factor even at a very early age. Several studies, including pediatric populations, have reported independent associations between NAFLD and markers of subclinical atherosclerosis including impaired flow-mediated vasodilation, increased carotid artery intima-media thickness, and arterial stiffness, after adjusting for cardiovascular risk factors and MetS. Also, it has been shown that NAFLD is associated with cardiac alterations, including abnormal left ventricular structure and impaired diastolic function. The duration of these subclinical abnormalities may be important, because treatment to reverse the process is most likely to be effective earlier in the disease. In the present review, we examine the current evidence on the association between NAFLD and atherosclerosis as well as between NAFLD and cardiac dysfunction in the pediatric population, and discuss briefly the possible biological mechanisms linking NAFLD and cardiovascular changes. We also address the approach to treatment for this increasingly prevalent disease, which is likely to have an important future global impact on the burden of ill health, to prevent not only end-stage liver disease but also cardiovascular disease.
文摘Lysosomal acid lipase(LAL)plays a key role in intracellular lipid metabolism.Reduced LAL activity promotes increased multi-organ lysosomal cholesterol ester storage,as observed in two recessive autosomal genetic diseases,Wolman disease and Cholesterol ester storage disease.Severe liver steatosis and accelerated liver fibrosis are common features in patients with genetic LAL deficiency.By contrast,few reliable data are available on the modulation of LAL activity in vivo and on the epigenetic and metabolic factors capable of regulating its activity in subjects without homozygous mutations of the Lipase A gene.In the last few years,a less severe and non-genetic reduction of LAL activity was reported in children and adults with non-alcoholic fatty liver disease(NAFLD),suggesting a possible role of LAL reduction in the pathogenesis and progression of the disease.Patients with NAFLD show a significant,progressive reduction of LAL activity from simple steatosis to non-alcoholic steatohepatitis and cryptogenic cirrhosis.Among cirrhosis of different etiologies,those with cryptogenic cirrhosis show the most significant reductions of LAL activity.These findings suggest that the modulation of LAL activity may become a possible new therapeutic target for patients with more advanced forms of NAFLD.Moreover,the measurement of LAL activity may represent a possible new marker of disease severity in this clinical setting.
文摘Objective: To investigate the genetic diversity of Zika virus(ZIKV) and the relationships existing among these circulating viruses worldwide. To evaluate the genetic polymorphisms harboured from ZIKV that can have an influence on the virus circulation. Methods: Three different ZIKV dataset were built. The first dataset included 63 E gene sequences, the second one 22 NS3 sequences and the third dataset was composed of 108 NS5 gene sequences. Phylogenetic and selective pressure analysis was performed. The edited nucleic acid alignment from the Envelope dataset was used to generate a conceptual translation to the corresponding peptide sequences through UGene software. Results: The phylogeographic reconstruction was able to discriminate unambiguously that the Brazilian strains are belonged to the Asian lineage. The structural analysis reveals instead the presence of the Ser residue in the Brazilian sequences(however already observed in other previously reported ZIKV infections) that could suggest the presence of a neutralization-resistant population of viruses. Conclusions: Phylogenetic, evolutionary and selective pressure analysis contributed to improve the knowledge on the circulation of ZIKV.
