The role of fruit bats in the transmission of pathogenic leptospires in Australia

Although antileptospiral antibodies and leptospiral DNA have been detected in Australian fruit bats, the role of such bats as infectious hosts for the leptospires found in rodents and humans remains unconfirmed. A cohort-design, replicated survey was recently conducted in Far North Queensland, Australia, to determine if the abundance and leptospiral status of rodents were affected by association with colonies of fruit bats (Pteropus conspicillatus spp.) via rodent contact with potentially infectious fruit-bat urine. In each of four study areas, a 'colony site' that included a fruit-bat colony and the land within 1500 m of the colony was compared with a 'control site' that held no fruit-bat colonies and was >2000 m from the nearest edge of the colony site. Rodents were surveyed, for a total of 2400 trap-nights, over six sampling sessions between September 2007 and September 2008. A low abundance of rodents but a high carriage of leptospires in the rodents present were found to be associated with proximity to a fruit-bat colony. For example, means of 0·4 and 2·3 fawn-footed melomys (Melomys cervinipes) were collected/100 trap-nights at sites with and without fruit-bat colonies, respectively (P<0·001), but the corresponding prevalences of leptospiral carriage were 100% and 3·6% (P<0·001). Such trends were consistent across all of the sampling sessions but not across all of the sampling sites. Leptospires were not isolated from fruit bats by culture, and the role of such bats in the transmission of leptospires to rodents cannot be confirmed. The data collected do, however, indicate the existence of a potential pathway for transmission of leptospires from fruit bats to rodents, via rodent contact with infectious fruit-bat urine. Fruit bats may possibly be involved in the ecology of leptospires (including emergent serovars), as disseminators of pathogens to rodent populations. Stringent quantitative risk analysis of the present and similar data, to explore their implications in terms of disease prevalence and wildlife population dynamics, is recommended.     

Comparative analysis of current diagnostic PCR assays in detecting pathogenic Leptospira isolates from environmental samples

Objective: To compare the efficiency of routine diagnostic PCR assays in detecting pathogenic Leptospira isolated from water and soils. Methods: Seven routine assays targeting six genes(lip L32, fla B, gyr B, lfb1, sec Y and lig B) were evaluated and compared on the cultures of two groups of pathogenic Leptospira from different sources. One group included 19 described reference strains recovered from infected human or animals, and another group included 22 environmental isolates from recreational and residential sites in Malaysia. The latter have been confirmed for presence of pathogenic Leptospira DNA. PCR positivity or detection sensitivity of each assay was determined and compared between the two groups. Results: Validation on reference strains showed 100.0% PCR sensitivity for all assays except lig B-PCR(95.0%) that failed to amplify Leptospira interrogans serovar Pomona. In marked contrast, there was a notable decline in sensitivity in the environmental isolates(lip L32-PCR, 95.5%; fla B-PCR, 90.9%; gyr B-PCR, 77.3%; lfb1-PCR, 59.1%; sec Y-PCRs, 40.9% G1/G2-PCR, 36.4%; lig B-PCR, 13.6%), implying a large genetic distance between the two groups, as well as nucleotide polymorphism among environmental isolates. Conclusions: High proportion of false-negative PCR results suggests a need of prudent selection of primers in detecting environmental pathogenic Leptospira. These findings offer valuable insights on the extensive biodiversity of genus Leptospira and its impact on the efficacy and development of molecular detection tool.     

Short report: prospective evaluation of a multi-test strip for the diagnoses of scrub and murine typhus, leptospirosis, dengue Fever, and Salmonella typhi infection

A multi-test strip dotblot immunoassay for the diagnosis of typhoid fever, scrub typhus, murine typhus, dengue virus infection and leptospirosis was evaluated in Thai adults presenting to hospital with acute, undifferentiated fever. The kit gave multiple positive test results in 33 of 36 patients with defined infections and was therefore not a useful admission diagnostic tool.     

一种人类免疫缺陷病毒抗体(HIV 1/2)口腔黏膜渗出液检测试剂盒(免疫层析法)的质量评价

目的对广州万孚公司生产的人类免疫缺陷病毒抗体(HIV1/2)口腔黏膜渗出液检测试剂盒(免疫层析法),检测不同来源样本的能力进行质量评价。方法分别采集1 183名受检者[包括514名HIV-1感染者、86名乙型肝炎病毒(HBV)感染者、33名丙型肝炎病毒(HCV)感染者、20名梅毒感染者,10名类风湿病人、520名正常人]的血浆样品和口腔黏膜渗出液样品,以广州万孚公司生产的人类免疫缺陷病毒抗体(HIV1/2)口腔黏膜渗出液检测试剂盒(免疫层析法)作为考核试剂,以北京玛诺生物制药有限公司的人类免疫缺陷病毒抗体口腔黏膜渗出液诊断试剂盒(胶体金法)和上海科华生物工程股份有限公司的人类免疫缺陷病毒(HIV1+2)抗体诊断试剂盒(胶体金法)分别作为参比试剂1和参比试剂2。用考核试剂和参比试剂1平行检测口腔黏膜渗出液样品,对来自同一受试者的血浆样本使用参比试剂2进行检测,采用新加坡MP生物医学亚太私人有限公司(MP Biomedicals Asia Pa-cific Pte.Ltd)的人类免疫缺陷病毒(HIV1+2)抗体免疫印迹试剂盒作为第三方试剂进行复核。评价考核试剂的阳性符合率、阴性符合率、总符合率。结果考核试剂和参比试剂1的阳性符合率为99.61%,阴性符合率为100.00%,总符合率为99.83%;与参比试剂2的阳性符合率为98.06%,阴性符合率为100.00%,总符合率均为99.15%。广州万孚公司人类免疫缺陷病毒抗体(HIV1/2)口腔黏膜渗出液检测试剂盒(免疫层析法)对口腔黏膜渗出液样本的敏感性为98.25%(95%CI:97.12%～99.38%),特异性为100%(95%CI:99.91%～100%)。结论考核试剂在口腔黏膜渗出液样本检测HIV抗体的敏感性和特异性较好。     

恙虫病东方体目视LAMP现场化检测方法的建立

目的 建立基于"染料-蜡丸"的目视LAMP检测恙螨中恙虫病东方体的方法,为恙虫病的防治提供新工具.方法 选择Ot GroEL基因作为检测靶序列,在线设计并合成LAMP引物.构建rOt-GroEL重组质粒作为阳性对照.建立基于SYBR Green I的"染料-蜡丸"目视LAMP,并联合便携式LAMP仪使其利于现场应用.结...     

Orexins and their receptors from fish to mammals: a comparative approach

Although recently discovered, orexins have been rapidly established as important neuropeptides in regulating physiological processes including food intake, sleep/wake cycles and reproduction through binding to two class B G protein-coupled receptors (OX1R and OX2R). To date, a handful of sequences for orexins and their receptors ranging from fish to mammalian species have been identified, allowing a glimpse into their evolution. Structurally, the genetic and molecular organization of the peptides and receptors amongst vertebrates are highly similar, underlining the strong evolutionary pressure that has been exerted to preserve structure and ultimately function. Furthermore, the absence of invertebrate orexin-like sequences suggests early vertebrates as the origin from which orexins evolved. With respect to the receptors, OX2R is probably evolutionary more ancient whilst OX1R is specific to mammalian species and evolved only during this later lineage. In common to all vertebrates studied, the hypothalamus remains to be the key brain region in which orexinergic neurons and fibers are localized in, establishing orexin to be an important player in regulating physiological processes especially those related to food intake and energy metabolism. To allow better understanding of the evolution of orexins and their receptors, this review will provide a comparative approach to their structures and functions in vertebrates.     

Bartonella species pathogenic for humans infect pets,free-ranging wild mammals and their ectoparasites in the Caatinga biome,Northeastern Brazil: a serological and molecular study

This study verified the occurrence of Bartonella spp. in dogs, cats, wild mammals and their ectoparasites in Petrolina and Lagoa Grande Counties, Pernambuco, located in a semi-arid region in Northeastern Brazil. Anti-Bartonella spp. antibodies were detected by indirect immunofluorescence assay (IFA) in 24.8% of dogs (27/109) and in 15% of cats (6/40). Bartonella sp. DNA was identified by PCR performed on DNA extracted from blood and ectoparasites using primers targeting Bartonella sp. gltA and ribC genes in 100% (9/9) of Pulex irritans from Cerdocyon thous, 57.4% (35/61) of P. irritans from dogs, 2.3% (1/43) of Ctenocephalides felis felis from dogs, 53.3% (24/45) of C. felis felis from cats, and 10% (1/10) of Polyplax spp. from Thrichomys apereoides. DNA sequencing identified Bartonella clarridgeiae and Bartonella henselae in C. felis felis from cats, Bartonella rochalimae in P. irritans from dog and C. thous, and Bartonella vinsoni berkhofii in P. irritans from dog.     

IgA肾病遗传学研究——现状,机遇和挑战

原发性IgA肾病(IgA nephropathy,IgAN)是最常见的肾小球肾炎,家族聚集起病及发病率的人种差异均提示遗传因素为重要致病机制之一。尽管迄今为止仍未找到明确的致病基因,但随着遗传学研究方法的改进,特别是高密度基因芯片的出现及广泛应用以及人类基因组计划(HGP)的推进,在该领域出现了许多振奋人心的研究成果。连锁分析对家族性IgA肾病基因定位至少已得到4个易感区段;关联分析提示IgAN发病可能与IgA1糖基化过程中的关键酶相关;基因表达谱研究通过对外周血白细胞和肾组织的表达谱分析,发现了一系列与IgAN起病与进展潜在相关的基因;借助IgAN动物模型,则有助于明确候选基因功能和阐明致病机制。近年来全基因组关联研究(GWAS)成为遗传学研究的热点,该方法应用高密度基因芯片,无需假设易感基因,定位微效及中效易感基因效能要强于连锁分析,最近已有2项IgAN的GWAS研究结果发表。复杂性疾病的基因定位极具挑战性,但随着遗传学研究方法的不断改进以及新技术的出现,特别是下一代测序方法的不断完善,必将加快推动IgAN致病基因定位工作。     

Neprilysin inhibition to treat heart failure: a tale of science,serendipity, and second chances

This review describes the role of neprilysin (also known as neutral endopeptidase or enkephalinase) in the degradation of natriuretic and other vasoactive peptides, including bradykinin and adrenomedullin. The initial development of neprilysin inhibitors, then angiotensin converting enzyme‐neprilysin inhibitors and, most recently, the angiotensin receptor neprilysin inhibitor (ARNI) LCZ696 (sacubitril valsartan) as an extension of the nurohumoral basis for the treatment of heart failure is also summarised. Finally, the implications of the compelling benefits of LCZ696 compared with enalapril in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM‐HF) is discussed.     

Oogenesis in adult mammals, including humans: a review

The origin of oocytes and primary follicles in ovaries of adult mammalian females has been a matter of dispute for over 100 yr. The prevailing belief that all oocytes in adult mammalian females must persist from the fetal period of life seems to be a uniquely retrogressive reproductive mechanism requiring humans to preserve their gametes from the fetal period for several decades. The utilization of modern techniques during last 10 yr clearly demonstrates that mammalian primordial germ cells originate from somatic cell precursors. This indicates that if somatic cells are precursors of germ cells, then somatic mutations can be passed on to progeny. Mitotically active germline stem cells have been described earlier in ovaries of adult prosimian primates and recently have been reported to also be present in the ovaries of adult mice. We have earlier shown that in adult human females, mesenchymal cells in the ovarian tunica albuginea undergo a mesenchymal-epithelial transition into ovarian surface epithelium cells, which differentiate sequentially into primitive granulosa and germ cells. Recently, we have reported that these structures assemble in the deeper ovarian cortex and form new follicles to replace earlier primary follicles undergoing atresia (follicular renewal). Our current observations also indicate that follicular renewal exists in rat ovaries, and human oocytes can differentiate from ovarian surface epithelium in fetal ovaries in vivo and from adult ovaries in vitro. These reports challenge the established dogma regarding the fetal origin of eggs and primary follicles in adult mammalian ovaries. Our data indicate that the pool of primary follicles in adult human ovaries does not represent a static but a dynamic population of differentiating and regressing structures. Yet, the follicular renewal may cease at a certain age, and this may predetermine the onset of the natural menopause or premature ovarian failure. A lack of follicular renewal in aging ovaries may cause an accumulation of spontaneously arising or environmentally induced genetic alterations of oocytes, and that may be why aging females have a much higher chance of having oocytes with more mutations in persisting primary follicles.     

Economic evaluation in the field of cardiology: Theory and practice

Economic evaluations figure largely in health care. Economic evaluation aims at offering structured information about the balance between costs and effects of a intervention in comparison to another intervention. Four basic types of economic evaluation studies exist: cost-minimization analysis, cost-effectiveness analysis, cost-utility analysis, and cost-benefit analysis. In deciding which types of evaluation should be used in the analysis, the aim of the analysis is determinative. This article illustrates the theory of economic evaluation and concentrates on its use within cardiology. Finally, this article describes the project "Appropriate Medical Care," a project developed by the Royal Dutch Medical Association. In this project results from cost-effectiveness analysis will be taken into consideration in forming guidelines for the treatment of coronary artery diseases.     

Fecal incontinence: a practical approach to evaluation and treatment

Fecal incontinence is a common problem and can have a major impact on the quality of life of those affected. Various disease processes affecting stool consistency, rectal sensitivity, or the anal sphincters can cause fecal incontinence. Obstetric trauma is now known to be a major cause of sphincter dysfunction. The evaluation of the patient with incontinence helps to determine the choice of therapy-medical or surgical. The two most important tests are anorectal manometry, which provides information on sphincter pressures, and rectal sensation, and anal endosonography, which is currently the test of choice for defining the anatomy of the anal sphincters. The choice of therapy depends on the etiology of incontinence, the anatomy of the sphincters, and also on the effect of incontinence on the quality of life of the patient. Control of diarrhea, regardless of the cause, should be attempted first. Biofeedback therapy is effective in the majority of patients and is particularly attractive because it is safe and well tolerated. Surgery is offered when medical therapy is unsuccessful or when the etiology is thought to respond best to surgery, such as in postobstetric trauma. Sphincter repair, for treatment of selective sphincter defects, is the best surgical option. Neoanal sphincters and implanted artificial sphincters are far less attractive because of technical difficulties and low success rate.     

Angiocidal effect of Cyclosporin A: a new therapeutic approach for pathogenic angiogenesis.

AIM: Angiogenesis is essential in the development of several disorders such as cancer, arthritis, and autoimmune diseases. Several agents prevent angiogenesis but only a few destroy established angiogenesis. In this study we tested whether local or systemic administration of Cyclosporin A (CyA) would inhibit as well as destroy established angiogenesis in an in vivo assay of angiogenesis. METHODS: We utilized an in vivo assay of angiogenesis in which an angiogenic mixture of Matrigel, FGF, VEGF, and heparin was injected subcutaneously into mice. Angiogenesis in the subcutaneous plugs was quantified by ANOVA. CyA or the vehicle for CyA was administered to the experimental or the control groups by three routes: by addition to the angiogenic mixture, by local injection into the angiogenic plug at various time points or by systemic administration at high doses. Angiogenesis was quantified by pointing method and expressed as an angiogenic index (AI). RESULTS: In control animals the subcutaneous plug of Matrigel with the angiogenic mixture revealed exuberant angiogenesis at day 4 and day 7. This angiogenesis was completely inhibited when CyA was included in the angiogenic mixture; the vehicle for CyA had no such effect. Angiogenesis that had progressed was found to regress after local subcutaneous injection of CyA at day 4 and 7. Similar regression of angiogenesis was noted when CyA was administered systemically after allowing angiogenesis to proceed for 4 days. CONCLUSIONS: Our experiments strongly suggest that CyA is both angiocidal and angiostatic in vivo. These results provide a basis for future therapy directed against established angiogenesis in malignancies and autoimmune diseases.