Occult persistence and lymphotropism of hepatitis C virus infection

Recent discovery of occult hepatitis C virus (HCV) infection persisting after spontaneous or antiviral therapy-induced resolution of hepatitis C was made possible by the introduction of nucleic acid amplification assays capable of detecting HCV RNA at sensitivities superseding those offered by clinical tests. Although individuals with this seemingly silent HCV infection are usually anti-HCV antibody reactive and have normal liver function tests, occult HCV infection has also been reported in anti-HCV-negative individuals with persistently elevated liver enzymes of unknown etiology. Studies have shown that HCV RNA can persist for years in serum, lymphomononuclear cells and liver in the absence of clinical symptoms, although histological evidence of a mild inflammatory liver injury can be occasionally encountered. Furthermore, while HCV RNA can be detected in circulating lymphoid cells in approximately 30% of cases, a short-term culture under stimulatory conditions augments HCV replication in these cells allowing detection of virus in otherwise HCV-negative cases. HCV infects different immune cell subsets, including CD4+ and CD8+ T lymphocytes, B cells and monocytes. Studies employing clonal sequencing and single-stranded conformational polymorphism analyses have revealed unique HCV variants residing in immune cells, further strengthening the notion of HCV lymphotropism. Overall, the data accumulated suggest that occult HCV infection is a common consequence of resolution of symptomatic hepatitis C and that examination of the cells of the immune system is an effective approach to diagnosis of HCV infection and its long-term persistence. Further work is required to fully realize pathogenic and epidemiological consequences of occult HCV persistence.

Radial artery access site complications during cardiac procedures,clinical implications and potential solutions: The role of nitric oxide

Percutaneous coronary intervention for the treatment of coronary artery disease is most commonly performed in the UK through the radial artery,as this is considered to be safer than the femoral approach.However,despite improvements in technology and techniques,complications can occur.The most common complication,arterial spasm,can cause intense pain and,in some cases,procedural failure.The incidence of spasm is dependent on several variables,including operator experience,artery size,and equipment used.An antispasmolytic cocktail can be applied to reduce spasm,which usually includes an exogenous nitric oxide(NO)donor(glyceryl trinitrate).NO is an endogenous local vasodilator and therefore is a potential target for anti-spasm intervention.However,systemic administration can result in unwanted side-effects,such as hypotension.A method that adopts local delivery of NO might be advantageous.This review article describes the mechanisms involved in radial artery spasm,discusses the advantages and disadvantages of current strategies to reduce spasm,and highlight the potential of NO-loaded nanoporous materials for use in this setting.

DUSP2 deletion with CRISPR/Cas9 promotes Mauthner cell axonal regeneration at the early stage of zebrafish

Axon regeneration of central neurons is a complex process that is tightly regulated by multiple extrinsic and intrinsic factors.The expression levels of distinct genes are changed after central neural system(CNS)injury and affect axon regeneration.A previous study identified dusp2 as an upregulated gene in zebrafish with spinal cord injury.Here,we found that dual specificity phosphatase 2(DUSP2)is a negative regulator of axon regeneration of the Mauthner cell(M-cell).DUSP2 is a phosphatase that mediates the dephosphorylation of JNK.In this study,we knocked out dusp2 by CRISPR/Cas9 and found that M-cell axons of dusp2(-/-)zebrafish had a better regeneration at the early stage after birth(within 8 days after birth),while those of dusp2^(+/-)zebrafish did not.Overexpression of DUSP2 in Tg(Tol 056)zebrafish by single-cell electroporation retarded the regeneration of M-cell axons.Western blotting results showed that DUSP2 knockout slightly increased the levels of phosphorylated JNK.These findings suggest that knocking out DUSP2 promoted the regeneration of zebrafish M-cell axons,possibly through enhancing JNK phosphorylation.

Intravenous morphine self-administration alters accumbal microRNA profiles in the mouse brain

A significant amount of evidence indicates that microRNAs （miRNAs） play an important role in drug addiction. The nucleus accumbens （NAc） is a critical part of the brain’s reward circuit and is involved in a variety of psychiatric disorders, including depression, anxiety, and drug addiction. However, few studies have examined the expression of miRNAs and their functional roles in the NAc under conditions of morphine addiction. In this study, mice were intravenously infused with morphine （0.01, 0.03, 0.3, 1 and 3 mg/kg/infusion） and showed inverted U-shaped response. After morphine self-administration, NAc was used to analyze the functional networks of altered miRNAs and their putative target mRNAs in the NAc following intravenous self-administration of morphine. We utilized several bioinformatics tools, including Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway mapping and CyTargetLinker. We found that 62 miRNAs were altered and exhibited differential expression patterns. The putative targets were related to diverse regulatory functions, such as neurogenesis, neurodegeneration, and synaptic plasticity, as well as the pharmacological effects of morphine （receptor internalization/endocytosis）. The present findings provide novel insights into the regulatory mechanisms of accumbal molecules under conditions of morphine addiction and identify several novel biomarkers associated with morphine addiction.

Direct Visualisation of the Depth-Dependent Mechanical Properties of Full-Thickness Articular Cartilage

Objective: The structural anisotropy of articular cartilage controls its deformation response. As proteoglycans and collagen vary with depth, simple uniaxial compression results in inhomogeneous deformation with distinct depth-dependent mechanical properties. Investigations into depth-dependent mechanical properties of articular cartilage have previously required tissue modification after specimen isolation. Such modifications include histological processes, freezing, subchondral bone removal, and fluorescent staining that may alter the tissue, limiting in vivo applicability. Design: Using a custom tissue-sectioning device, 0.1 mm thick unfixed, unstained, osetochondral samples were obtained. A customized apparatus loaded samples to 12.5%, 24%, and 29% compression in under a microscope with 10× magnification. Equilibrium load was measured after stress relaxation. Intra-tissue displacement was measured by tracing groups of cells between the different compression levels using a digital imaging program. Cell distance from the subchondral bone was measured to identify intratissue displacement and calculate strain. Results: The results reveal that stress levels and intratissue displacement increased with greater tissue compression (p p in vivo conditions and may provide an important method for analyzing the coordinated changes in cartilage composition and function due to ageing and disease.

A review of concurrent infections of malaria and dengue in Asia

Concurrent infections of malaria and dengue are when both of these mosquito-borne diseases occur simultaneously in an individual. In this review, reported cases with these co-infections in Asia are discussed. The focus is on the overlapping clinical presentations and the difficulties encountered in differential diagnosis. Also, cases reported in some special conditions, viz., pregnancy, foetal infections, and co-infections with one or more other infectious agents are highlighted. Due to similar clinical presentations of malaria and dengue, these co-infections may give rise to an incorrect diagnosis. Moreover, the treatment regimens for these co-infections are not the same as those for mono-infections.Hence, a delay in implementing the appropriate treatment regimen for these concurrent infections due to poor diagnosis can be fatal. The present review is intended to increase awareness about the clinical significance and the importance of these co-infections among clinicians, public health workers and health authorities in the Asian region. Though malaria-dengue concurrent infections are seldom reported from the Asian region, it is probably increasing particularly in the countries known to be endemic for both of the above diseases. A compulsory reporting of the incidences of malaria-dengue concurrent infections is recommended.

Anthelmintic activity of Securidaca longepedunculata(Family:Polygalaceae)root extract in mice,in vitro and in vivo

Objective:To elucidate the pharmacological bases of oral administration of Securidaca longepedunculata(S.longepedunculata) root extract as an anthelmintic in folkloric medicine. Methods:Albino mice were infected with infective third(L3) larval stage of Heligmosomoides polygyrus(H.polygyrus) by esophageal intubation.Following establishment of the adult worms in the intestine,the mice were treated with 0-2 000 mg/kg body weight(bw) of methanolic root extract of S.longepedunculata and 100 mg/kg bw of pyrantel embonate,the reference drug in vivo. Bioactivity and larvicidal effects of the extract were tested by exposing brine shrimps(Artemia salina) to 0.00-1.00 mg/mL and the L3 stage of Heligmosomoides contortus(H.contortus) and H.polygyrus to 0.00-2.50 mg/mL of the extract in vitro.Results:The percentage yield of the extract was 7.13%w/w dry matter.The brine shrimps toxicity bioassay resulted in an LC_(50) of 74.18 μ g/mL.The extract had a significant,dose-dependent larvicidal effect on the L3 stage of H.contortus and H.polygyrus with the terminal effect of 75%and 70%at the highest exposure concentrations,respectively.The extract however,did not affect the number of worm eggs per gram(epg) of fecal materials(P<0.05) and total worm burden(twb) of adult H.polygyrus in infected mice.Treatment with pyrantel embonate significant reduced both the fecal egg count and twb to 0 compared to the untreated control(P<0.05).Conclusions:These results indicate that S.longepedunculata root extract contains potent bioactive compounds and has larvicidal effect on L3 stage of H.contortus and H.polygyrus,substantiating its use as anthelmintic in alternative medicine.

Wound healing effect of methanolic leaf extract of Napoleona vogelii(Family:Lecythidaceae) in rats

Objective:To investigate the wound healing properly of Napoleona vogelii leaf extract in folkloric medicine.Methods:Roth sexes of adult albino rats(n=25) were used in this study and another group(n=30) were subjected to acute toxicity test(LD_(50)) of the plant extract.For the LD_(50),three randomized groups of 5 rats were first treated with 10,100,1 000 mg/kg body weight(bw),orally.This w as followed by a second treatment of 1500,3000,and 5 000 mg/kg bw of the leaf extract with continual monitoring of the animals for mortality or non-mortality.Incision wounds(1.3cm) were created on the skin of five groups of 5 rals using surgical blade under anesthesia.The first group was topically treated with petroleum jelly alone,group 2 was topically applied 400 mg/mL w/v of the reference drug,Neobaein,while group 3-5 were topically treated with 5-50 mg/mL w/v of the plant extract,respectively.Results:The percentage yield of the extract was 49.80%w/w dry matter.The phytochemical analysis revealed several bioactive constituents including glycosides,tannins,alkaloids,perpenoids.saponins,steroids,proteins,and carbohydrates.The LD_(50) was beyond our experimental limit and was not determined.Increased concentrations(5,20,and 50mg/mL w/v) of the extract had significant(ANOVA,P<0.05) healing effect on the incision wounds giving rise to 125%-140% while treatmentawith Neobacin resulted in 150% healing effect on the third treatment regimen compared to the control(100%).Conclusions:These data indicate that Napoleona vogelii leaf extract contains potent bioactive compounds containing wound healing activity,substantiating its use as a wound healer in folkloric medicine.

<i>In Vitro</i>Investigation of DNA Damage Induced by the DNA Cross-Linking Agents Oxaliplatin and Satraplatin in Lymphocytes of Colorectal Cancer Patients

Exposure to toxic chemicals, especially chemotherapeutic drugs, may induce several DNA lesions, including DNA interstrand crosslinks. These crosslinks are considered toxic lesions to the dividing cells since they can induce mutations, chromosomal rearrangements, and cell death. Many DNA interstrand crosslinks lesions can be generated by platinum-based chemotherapeutic agents. Satraplatin is a novel orally administered platinum-based chemotherapeutic agent. In the present study, we investigated DNA interstrand crosslinks lesions induced by oxaliplatin and satraplatin in lymphocytes obtained from colorectal cancer patients and healthy volunteers. Satraplatin demonstrated an increase in interstrand crosslinks in a dose-dependent manner in the Comet assay (p in vitro. Here, to the best of our knowledge we report for the first time evidence of DNA double strand breaks formation as a possible molecular mechanism of action for satraplatin.

A bibliometric analysis of global research output on health and human rights(1900–2017)

Background:Baseline data on global research activity on health and human rights(HHR)needs to be assessed and analyzed to identify research gaps and to prioritize funding and research agendas.Therefore,the aim of this study was to assess the growth of publications and research pattern on HHR.Methods:A bibliometric methodology was used.Literature on HHR was retrieved using SciVerse Scopus for the study period from 1900 to 2017.Nine different search scenarios with different keyword combinations were used to retrieve the required documents.All types of documents published in peer-reviewed journals,including editorials,were included.The search strategy was validated.Results:In total 6513 documents were retrieved with an h-index of 88 and an average of 9.8 citations per document.Publications on HHR field started as early as 1950 but showed a steep rise in the past two decades.Visualization of author keywords revealed that HIV/AIDS,mental health,maternal and reproductive health,violence,ethics,torture,and refugees were most commonly encountered keywords.The journal“Health and Human Rights”was most active(n=467;7.2%)in this field.However,documents that appeared in The Lancet received the highest impact(29.5 citations per document).The United States of America produced the most in this field(n=1817;27.9%).Researchers in the region of Americas participated in approximately 45%of the retrieved documents while researchers in the Eastern Mediterranean region had the least contribution(2.5%).Researchers in high-income countries contributed to approximately 78%of the retrieved documents while researchers in low-income countries contributed to less than 5%of the retrieved documents.When data were standardized by population size,the research output from high-income countries was approximately four documents per one million inhabitants.For middle-income countries,the research output was 0.3 document per one million inhabitants.For low-income countries,the research output was 0.5 document per one million inhabitants.Conclusions:Differential research productivity on HHR was seen among scholars in different world regions.World countries need to encourage and strengthen research on HHR in order to achieve the goals set in international agreements of human rights.

克山病患者心肌肠道病毒VP1结构蛋白检测

目的 探讨肠道病毒感染与克山病发病的关系。方法 应用抗柯萨奇B5病毒(Coxsackie B5 virus,CVB5)VP1蛋白单克隆抗体,采用免疫组化方法,检测黑龙江、山东、云南省克山病病区急型、亚急型、慢型、潜在型克山病死亡病例心肌标本83例,风心病10例,冠心病10例,心肌炎21例,扩张型心肌病29例,非病区非正常死亡的正常人10例,病区发病季节非克山病死亡病例13例。结果 克山病83例心肌标本中有74例VP1结构蛋白阳性,阳性率89.2％;风心病、冠心病、非正常死亡健康人VP1阳性检出率均为10％;心肌炎、扩张型心肌病VP1阳性检出率分别为66.7％和70％;病区发病季节非克山病死亡病人VP1阳性检出率为38.5％。结论 来自3省份的各型克山病死亡病例心肌标本中均能检出肠道病毒VP1结构蛋白,克山病的发生与肠道病毒感染高度相关。

颈动脉支架成形术后持续性血流动力学抑制的预测指标及其对预后的影响

目的探讨颈动脉支架成形术(carotid angioplasty stenting,CAS)术后持续性血流动力学抑制(persistent hemodynamic depression,PHD)相关的预测因子,总结对这种情况的处理经验,阐明PHD对术后患者预后的影响。方法连续收集184例患有重度颈动脉狭窄并接受CAS的患者。采用单因素分析及和二分类Logistic回归分析鉴别PHD的预测因子,同时分析PHD对术后缺血性卒中、心脏及肾脏并发症的影响。结果既往心肌梗死(P=0.04)、术中血管升压药支持(P=0.01)、钙化斑块(P=0.02)及重复血管扩张(P=0.003)是术后PHD的独立危险因素;术中血管升压药支持(P=0.003)、钙化斑块(P=0.04)、重复血管扩张(P=0.02)外,年龄>80 y(P=0.02)和女性(P=0.01)是术后需要血管升压药使用>24 h的PHD的独立危险因素。围手术期缺血性卒中、心脏并发症及肾脏并发症的发生率在3组患者中间无差别。结论老年女性、术中存在HD、钙化斑块及反复球囊扩张是PHD的预测指标。发生PHD的患者给予适当治疗后并不影响患者总体预后。

克山病患者心肌中肠道病毒抗原VP1及其基因检测

目的 进一步探讨肠道病毒感染与克山病发病的关系。方法 应用免疫组织化学等方法对克山病患者心肌组织标本进行肠道病毒检测并与其他疾病进行对比。结果 在 11例克山病患者中发现 9例病毒结构蛋白VP1阳性 ,其中 8例同时检测到病毒RNA ;而 8例缺血性心肌病仅 3例VP1阳性 ,其中 2例RNA也阳性。 3例死于其他疾病患者未发现肠道病毒。结论 克山病患者心肌组织中不仅存在肠道病毒基因RNA ,而且也有其表达的结构蛋白VP1,提示肠道病毒感染可能为克山病发病的主要原因之一。

奥氮平致代谢紊乱和心血管疾病研究进展

抗精神病药物是治疗精神分裂症（schizophrenia,SZ）及其他精神病性障碍的最主要手段,目前临床广泛使用的第二代抗精神病药物（second generation antipsychotics,SGA）,尤其是奥氮平,能够引起以肥胖和胰岛素抵抗（insulin resistance,IR）为主的代谢紊乱（metabolic disorder）,显著增加2型糖尿病和心血管疾病（cardiovascular disease,CVD）的风险[1-3]。研究发现长期使用奥氮平的患者,代谢紊乱和CVD的发生率是普通人群2~3倍[4],因此近年来,奥氮平致代谢紊乱和CVD的机制备受关注。

Persistent occult hepatitis B virus infection:Experimental findings and clinical implications

Hepatitis B virus (HBV) is a highly pathogenic virus that causes chronic liver diseases in millions of people globally. In addition to a symptomatic, serologically evident infection, occult persistent HBV carriage has been identified since nucleic acid amplification assays of enhanced sensitivity became introduced for detection of hepadnaviral genomes and their replicative intermediates. Current evidence indicates that occult HBV infection is a common and long-term consequence of resolution of acute hepatitis B. This form of residual infection is termed as secondary occult infection (SOI). The data from the woodchuck model of HBV infection indicate that exposure to small amounts of hepadnavirus can also cause primary occult infection (POI) where virus genome, but no serological makers of exposure to virus, are detectable, and the liver may not be involved. However, virus replicates at low levels in the lymphatic system in both these forms. We briefly summarize the current understanding of the nature and characteristics of occult hepadnaviral persistence as well as of its documented and expected pathological consequences.

Protein tyrosine phosphatase non-receptor type 2 andinflammatory bowel disease

Genome wide association studies have associated single nucleotide polymorphisms within the gene locus encoding protein tyrosine phosphatase non-receptor type 2(PTPN2) with the onset of inflammatory bowel disease(IBD) and other inflammatory disorders. Expression of PTPN2 is enhanced in actively inflamed intestinal tissue featuring a marked up-regulation in intestinal epithelial cells. PTPN2 deficient mice suffer from severe intestinal and systemic inflammation and display aberrant innate and adaptive immune responses. In particular, PTPN2 is involved in the regulation of inflammatory signalling cascades, and critical for protecting intestinal epithelial barrier function, regulating innate and adaptive immune responses, and finally for maintaining intestinal homeostasis. On one hand, dysfunction of PTPN2 has drastic effects on innate host defence mechanisms, including increased secretion of pro-inflammatory cytokines, limited autophagosome formation in response to invading pathogens, and disruption of the intestinal epithelial barrier. On the other hand, PTPN2 function is crucial for controlling adaptive immune functions, by regulating T cell proliferation and differentiation as well as maintaining T cell tolerance. In this way, dysfunction of PTPN2 contributes to the manifestation of IBD. The aim of this review is to present an overview of recent findings on the role of PTPN2 in intestinal homeostasis and the impact of dysfunctional PTPN2 on intestinal inflammation.

一种肝组织及其肿瘤CT扫描快速分段的新型整体解剖与强力计算方法

肝脏疾病的治疗[如肝肿瘤的射频消融和（或）放射治疗]需要正确了解肝脏结构，包括肝表面与病变的部位。本文报道了一种肝脏及其内部病灶CT扫描的新型快速分段方法与相应的计算法。由于计算是完全自动的，初始时不需要用户与分析系统间的互动。基于一个统计学模型创建的分析方法可以鉴别肝组织与其他腹部器官。系统利用梯度矢量结合了激活的边界技术以得到平滑、更自然的肝表面分段，从而可利用自动分类的方法将病理改变从肝实质中分离出来。对21个代表不同解剖与病理的数据库进行了处理与分析。特别注意得到结果的处理时间并评价其质量。

Increased plasma leptin as a novel predictor for psychopathological depressive symptoms in chronic schizophrenia

Background Depressive symptoms are often seen in schizophrenia. The overlap in presentation makes it difficult to distinguish depressive symptoms from the negative symptoms of schizophrenia. The adipokine leptin was found to be altered in both depression and schizophrenia. There are few studies focusing on the prediction of leptin in diagnosis and evaluation of depressive symptoms in schizophrenia.ObjectiveAims To assess the plasma leptin level in patients with schizophrenia and its relationships with depressive symptoms.Methods Cross-sectional studies were applied to(1) compare the levels of plasma leptin between schizophrenia(n=74) and healthy controls(n=50); and(2)investigate the relationship between plasma leptin levels and depressive subscores.Results(1) Plasma leptin levels were significantly higher in patients with schizophrenia than in healthy controls.(2) Correlation analysis revealed a significant negative association between leptin levels and the depressed factor scores on the Positive and Negative Syndrome Scale(PANSS).(3) Stepwise multiple regression analyses identified leptin as an influencing factor for depressed factor score on PANSS.Conclusion Leptin may serve as a predictor for the depressive symptoms of chronic schizophrenia.

Aquaporin-4 and spinal cord injury

Edema formation is a major problem following traumatic spinal cord injury(SCI) that acts to exacerbate secondary damage.Severity of edema correlates with reduced neurological outcome in human patients.To date, there are no effective treatments to directly resolve edema within the spinal cord.The aquaporin-4(AQP4) water channel is found on membranes of astrocytic endfeet in direct contact with blood vessels, the glia limitans in contact with the cerebrospinal fluid and ependyma around the central canal.Being so locally expressed at the interface between fluid and tissue allow AQP4 channels to play an important role in the bidirectional regulation of water homeostasis under normal conditions and following trauma.With the need to better understand the pathophysiology underlying the devastating cellular events in SCI, animal models have become an integral part of exploration.Inevitably, several injury models have been developed(contusion, compression, transection) resulting in difficult interpretation between studies with conflicting results.This is true in the case of understanding the role of AQP4 in the progression and resolution of edema following SCI, whose role is still not completely understood and is highly dependent on the type of edema present(vasogenic vs cytotoxic).Here, we discuss regulation of AQP4 in varying injury models and the effects of potential therapeutic interventions on expression, edema formation and functional recovery.Better understanding of the precise role of AQP4 following a wide range of injuries will help to understand optimal treatment timing following human SCI for prime therapeutic benefit and enhanced neurological outcome.

Adenocarcinomas after Prophylactic Surgery for Familial Adenomatous Polyposis

The incidence of familial adenomatous polyposis (FAP) is one in 7,000 to 12,000 live births. Virtually, all surgically untreated patients with FAP inevitably develop colorectal-cancer in their lifetime because they carry the adenomatous polyposis coli gene. Thus prophylactic proctocolectomy is indicated. Surgical treatment of FAP is still controversial. There are however, four surgical options: ileorectal anastomosis, restorative proctocolectomy with ileal pouch-anal anastomosis, proctocolectomy with ileostomy, and proctocolectomy with continent-ileostomy. Conventional proctocolectomy options largely lie between colectomy with ileorectal anastomosis or ileal pouch-anal anastomosis. Detractors of ileal pouch-anal anastomosis prefer ileorectal anastomosis because of better functional results and quality of life. The functional outcome of total colectomy with ileorectal anastomosis is undoubtedly far superior to that of the ileoanal pouch;however, the risk for rectal cancer is increased by 30%. Even after mucosectomy, inadvertent small mucosal residual islands remain. These residual islands carry the potential for the development of subsequent malignancy. We reviewed the literature (1975-2012) on the incidence, nature, and possible etiology of subsequent ileal-pouch and anal transit zone adenocarcinoma after prophylactic surgery procedure for FAP. To date there are 24 studies reporting 92 pouch-related cancers;15 case reports, 4 prospective and 5 retrospective studies. Twenty three of 92 cancers (25%) developed in the pouch mucosa and 69 (75%) in anal transit zone (ATZ). Current recommendation for pouch surveillance and treatment are presented. Data suggest lifetime surveillance of these patients.