Septicemia Caused by Tick-borne Bacterial Pathogen Candidatus Neoehrlichia mikurensis

We have repeatedly detected Candidatus Neoehrlichia mikurensis, a bacterium first described in Rattus norvegicus rats and Ixodes ovatus ticks in Japan in 2004 in the blood of a 61-year-old man with signs of septicemia by 16S rRNA and groEL gene PCR. After 6 weeks of therapy with doxycycline and rifampin, the patient recovered

Occurrence and identification of risk areas of Ixodes ricinus-borne pathogens: a cost-effectiveness analysis in north-eastern Italy

<p>Abstract</p> <p>Background</p> <p><it>Ixodes ricinus</it>, a competent vector of several pathogens, is the tick species most frequently reported to bite humans in Europe. The majority of human cases of Lyme borreliosis (LB) and tick-borne encephalitis (TBE) occur in the north-eastern region of Italy. The aims of this study were to detect the occurrence of endemic and emergent pathogens in north-eastern Italy using adult tick screening, and to identify areas at risk of pathogen transmission. Based on our results, different strategies for tick collection and pathogen screening and their relative costs were evaluated and discussed.</p> <p>Methods</p> <p>From 2006 to 2008 adult ticks were collected in 31 sites and molecularly screened for the detection of pathogens previously reported in the same area (i.e., LB agents, TBE virus, <it>Anaplasma phagocytophilum, Rickettsia </it>spp., <it>Babesia </it>spp., "<it>Candidatus Neoehrlichia mikurensis</it>"). Based on the results of this survey, three sampling strategies were evaluated <it>a</it>-<it>posteriori</it>, and the impact of each strategy on the final results and the overall cost reductions were analyzed. The strategies were as follows: tick collection throughout the year and testing of female ticks only (strategy A); collection from April to June and testing of all adult ticks (strategy B); collection from April to June and testing of female ticks only (strategy C).</p> <p>Results</p> <p>Eleven pathogens were detected in 77 out of 193 ticks collected in 14 sites. The most common microorganisms detected were <it>Borrelia burgdorferi </it>sensu lato (17.6%), <it>Rickettsia helvetica </it>(13.1%), and "<it>Ca. N. mikurensis</it>" (10.5%). Within the <it>B. burgdorferi </it>complex, four genotypes (i.e., <it>B. valaisiana, B. garinii, B. afzelii</it>, and <it>B. burgdorferi </it>sensu stricto) were found. Less prevalent pathogens included <it>R. monacensis </it>(3.7%), TBE virus (2.1%), <it>A. phagocytophilum </it>(1.5%), <it>Bartonella </it>spp. (1%), and <it>Babesia </it>EU1 (0.5%). Co-infections by more than one pathogen were diagnosed in 22% of infected ticks. The prevalences of infection assessed using the three alternative strategies were in accordance with the initial results, with 13, 11, and 10 out of 14 sites showing occurrence of at least one pathogen, respectively. The strategies A, B, and C proposed herein would allow to reduce the original costs of sampling and laboratory analyses by one third, half, and two thirds, respectively. Strategy B was demonstrated to represent the most cost-effective choice, offering a substantial reduction of costs, as well as reliable results.</p> <p>Conclusions</p> <p>Monitoring of tick-borne diseases is expensive, particularly in areas where several zoonotic pathogens co-occur. Cost-effectiveness studies can support the choice of the best monitoring strategy, which should take into account the ecology of the area under investigation, as well as the available budget.</p

The selective peroxisome proliferator-activated receptor alpha modulator (SPPARM) paradigm : conceptual framework and therapeutic potential: A consensus statement from the International Atherosclerosis Society (IAS) and the Residual Risk Reduction Initiative (R3i) Foundation

In the era of precision medicine, treatments that target specific modifiable characteristics of high-risk patients have the potential to lower further the residual risk of atherosclerotic cardiovascular events. Correction of atherogenic dyslipidemia, however, remains a major unmet clinical need. Elevated plasma triglycerides, with or without low levels of high-density lipoprotein cholesterol (HDL-C), offer a key modifiable component of this common dyslipidemia, especially in insulin resistant conditions such as type 2 diabetes mellitus. The development of selective peroxisome proliferator-activated receptor alpha modulators (SPPARM) offers an approach to address this treatment gap. This Joint Consensus Panel appraised evidence for the first SPPARM agonist and concluded that this agent represents a novel therapeutic class, distinct from fibrates, based on pharmacological activity, and, importantly, a safe hepatic and renal profile. The ongoing PROMINENT cardiovascular outcomes trial is testing in 10,000 patients with type 2 diabetes mellitus, elevated triglycerides, and low levels of HDL-C whether treatment with this SPPARM agonist safely reduces residual cardiovascular risk.Peer reviewe

WRN Mutation Update: Mutation Spectrum, Patient Registries, and Translational Prospects: HUMAN MUTATION

Werner syndrome (WS) is a rare autosomal recessive disorder characterized by a constellation of adult onset phenotypes consistent with an acceleration of intrinsic biological aging. It is caused by pathogenic variants in the WRN gene, which encodes a multifunctional nuclear protein with exonuclease and helicase activities. WRN protein is thought to be involved in optimization of various aspects of DNA metabolism, including DNA repair, recombination, replication, and transcription. In this update, we summarize a total of 83 different WRN mutations, including eight previously unpublished mutations identified by the International Registry of Werner Syndrome (Seattle, WA) and the Japanese Werner Consortium (Chiba, Japan), as well as 75 mutations already reported in the literature. The Seattle International Registry recruits patients from all over the world to investigate genetic causes of a wide variety of progeroid syndromes in order to contribute to the knowledge of basic mechanisms of human aging. Given the unusually high prevalence of WS patients and heterozygous carriers in Japan, the major goal of the Japanese Consortium is to develop effective therapies and to establish management guidelines for WS patients in Japan and elsewhere. This review will also discuss potential translational approaches to this disorder, including those currently under investigation

Fungitoxicty of Bidens pilosa, Thymus vulgaris, Lippia alba and Rosmarinus officinalis in the in vitro development of phytophatogens fungi

Avaliou-se in vitro, a atividade fungitóxica dos extratos brutos aquosos (EBA) em diferentes concentrações isolados e em misturas de Bidens pilosa, Thymus vulgaris, Lippia alba e Rosmarinus officinalis no desenvolvimento dos fungos Alternaria alternata, Colletotrichum graminicola, Rhizoctonia solani e Sclerotium rolfsii. A avaliação foi realizada incorporando os extratos brutos aquosos (EBAs) ao meio BDA isolados e em mistura, nas concentrações 0%, 1%, 5%, 10%, 15%, 25% e 50%. Foram feitas medições diárias das colônias fúngicas até o momento em o tratamento controle cobriu 2/3 da superfície do meio de cultura. Verificou-se que a mistura de T. vulgaris com B. pilosa não teve efeito positivo, pois o EBA isolado de B. pilosa não reduziu o crescimento do fungo R. solani e em mistura reduziu o efeito do EBA de T. vulgaris. Porém, o EBAs de R. officinalis e L. alba em mistura levaram a melhores resultados, reduzindo em até 60% o crescimento de A. alternata, do que os EBAs isoladamente. O extrato isolado de T. vulgaris reduziu em até 97% o crescimento de C. graminicola. Os resultados demonstraram que os extratos brutos das plantas testadas tiveram ação fungitóxica significativa contra os quatro fitopatógenos.The fungitoxicity of aqueous crude extracts (ACE) of Bidens pilosa, Thymus vulgaris, Lippia alba and Rosmarinus officinalis was evaluated in vitro on development of Alternaria alternata, Colletotrichum graminicola, Rhizoctonia solani and Sclerotium rolfsii. The active ACE were incorporated to Potato- Dextrose-Agar (PDA) alone or in mixture, at 0%, 1%, 5%, 10%, 15%, 25% and 50% concentrations. Measurement in fungal colonies was taken daily until the control treatment covered 2/3 of the culture media. The mixtures of T. vulgaris with B. pilosa did not have positive effect because the ACE of B. pilosa did not reduce the fungal growth of R. solani and in mixture inhibited the effect ACE of T. vulgaris. However, the mixture of ACEs of R. officinalis and L. alba produced better results than isolated ACEs, with 60% of growth inhibition of A. alternata. The ACE of T. vulgaris inhibited the growth of C. graminicola at 97%. The results show that ACEs have significative fungitoxicity in the evaluated phythopathogens