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pestis fulminans [keywords]
- Being Prepared: Bioterrorism and Mass Prophylaxis: Part II. [JOURNAL ARTICLE]
- Adv Emerg Nurs J 2014 October/December; 36(4):307-317.
Although several biological agents have been recognized as presenting a significant threat to public health if used in a bioterrorist attack, those that are of greatest importance are known as the Category A agents: Bacillus anthracis (anthrax); variola major (smallpox); Yersinia pestis (plague); Francisella tularensis (tularemia); ribonucleic acid viruses (hemorrhagic fevers); and Clostridium botulinum (botulism toxin). In the previous issue, Part I of this review focused on the clinical presentation and treatment of anthrax, plague, and tularemia. In this second part of this 2-part review of these agents, the focus is on the clinical presentation and treatment of smallpox, viral hemorrhagic fevers, and botulism toxin. The utilization of mass prophylaxis to limit the morbidity and mortality associated with all these agents is also discussed along with the role emergency care personnel play in its implementation.
- Therapeutic effect of carotid artery stenting versus endarterectomy for patients with high-risk carotid stenosis. [Journal Article]
- Int J Clin Exp Med 2014; 7(9):2895-900.
To investigate therapeutic effect of carotid artery stenting versus endarterectomy for patients with high-risk carotid stenosis.A total of 130 carotid stenosis patients at high-risk of stroke were randomly divided into stenting group and endarterectomy group, including 65 patients in each group. The patients in the endarterectomy group underwent endarterectomy and those in the stenting group received carotid artery stenting for treatment.After operation, carotid intima-media thickness (IMT), plague areas and carotid artery resistance indexes in both groups decreased significantly, and the carotid artery peak blood flow velocities increased significantly and had significant differences with that before operation (P < 0.05). After operation, total cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL) values in two groups all significantly decreased, and intragroup and intergroup differences were statistically significant (P < 0.05). Postoperative three months of followed-up found that the mortality rate in stenting group was 1.5% and that in the endarterectomy group was 9.2%; the mortality rate in the stenting group was significantly lower than the endarterectomy group (P < 0.05).Compared with carotid endarterectomy, application of carotid artery stenting can effectively promote patency of blood flow in the carotid artery, and exertion of its effect is related to lowering lipid and lowering inflammatory factor expression.
- Ed focus- F-676-2013 The slowing down of renal deterioration but acceleration of cardiac hypertrophy-is estrogen receptor α a hero or villain? [JOURNAL ARTICLE]
- Am J Physiol Renal Physiol 2014 Oct 1.:ajprenal.00529.2014.
Role of estrogen receptor α (ERα) in the kidney and heart was still uncertain, although Estrogen-ER action is usually thought to function as reno- and possibly cardio-protection, which includes prevention of glomerulosclerosis and podocyte apoptosis in kidney, and atheroprotection by lowering plague formation and against endothelial dysfunction after injury, ischemia and re-perfusion. The adenine-fed rat model of Diwan showed that an adenine diet significantly decreased ERα expression in male rat kidney, but significantly increased ERα expression in the heart of both genders. Their results regarding renal function showed male adenine-fed rats had significantly more kidney function decline than female adenine-fed rats, suggesting the favorable role of ERα in the kidney. However, the results of an increased expression of ERα in the heart should be read with caution. Since an increased expression of ERα and the subsequently activating the extracellular signal-regulated kinase (ERK1/2) pathway may be attributed partly to cardiac hypertrophy. Cardiac hypertrophy, a compensation for the contraction ability of the heart, might transiently maintain the "normal" heart function; therefore, is a hero for the heart. However, cardiac hypertrophy may increase the burden of oxygen consumption and further exacerbate the severity of existence of ischemic heart disease or even worsen the "normal heart". Therefore, the net long-term effect of ERα might not be good for the heart itself.
- On Finding and Using Identifiable Parameter Combinations in Nonlinear Dynamic Systems Biology Models and COMBOS: A Novel Web Implementation. [JOURNAL ARTICLE]
- PLoS One 2014; 9(10):e110261.
Parameter identifiability problems can plague biomodelers when they reach the quantification stage of development, even for relatively simple models. Structural identifiability (SI) is the primary question, usually understood as knowing which of P unknown biomodel parameters p1,…, pi,…, pP are-and which are not-quantifiable in principle from particular input-output (I-O) biodata. It is not widely appreciated that the same database also can provide quantitative information about the structurally unidentifiable (not quantifiable) subset, in the form of explicit algebraic relationships among unidentifiable pi. Importantly, this is a first step toward finding what else is needed to quantify particular unidentifiable parameters of interest from new I-O experiments. We further develop, implement and exemplify novel algorithms that address and solve the SI problem for a practical class of ordinary differential equation (ODE) systems biology models, as a user-friendly and universally-accessible web application (app)-COMBOS. Users provide the structural ODE and output measurement models in one of two standard forms to a remote server via their web browser. COMBOS provides a list of uniquely and non-uniquely SI model parameters, and-importantly-the combinations of parameters not individually SI. If non-uniquely SI, it also provides the maximum number of different solutions, with important practical implications. The behind-the-scenes symbolic differential algebra algorithms are based on computing Gröbner bases of model attributes established after some algebraic transformations, using the computer-algebra system Maxima. COMBOS was developed for facile instructional and research use as well as modeling. We use it in the classroom to illustrate SI analysis; and have simplified complex models of tumor suppressor p53 and hormone regulation, based on explicit computation of parameter combinations. It's illustrated and validated here for models of moderate complexity, with and without initial conditions. Built-in examples include unidentifiable 2 to 4-compartment and HIV dynamics models.
- A bivalent typhoid live vector vaccine expressing both chromosomal and plasmid-encoded Y. pestis antigens fully protects against murine lethal pulmonary plague infection. [JOURNAL ARTICLE]
- Infect Immun 2014 Oct 20.
Live attenuated bacteria hold great promise as multivalent mucosal vaccines against a variety of pathogens. A major challenge of this approach has been the successful delivery of sufficient amounts of vaccine antigens to adequately prime the immune system without over-attenuating the live vaccine. Here we have used a live attenuated Salmonella enterica serovar Typhi strain to create a bivalent mucosal plague vaccine that produces both the protective F1 capsular antigen of Yersinia pestis as well as the LcrV protein required for secretion of virulence effector proteins. To reduce metabolic burden associated with the co-expression of F1 and LcrV within the live vector, we balanced expression of both antigens by combining plasmid-based expression of F1 with chromosomal expression of LcrV from three independent loci. The immunogenicity and protective efficacy of this novel vaccine were assessed in mice using a heterologous prime-boost immunization strategy, and compared to a conventional strain in which F1 and LcrV were expressed from a single low copy number plasmid. The serum antibody responses to LPS induced by the optimized bivalent vaccine were indistinguishable from those elicited by the parent strain, suggesting adequate immunogenic capacity maintained through preservation of bacterial fitness; by contrast, LPS titers were 10-fold lower in mice immunized with the conventional vaccine strain. Importantly, mice receiving the optimized bivalent vaccine were fully protected against lethal pulmonary challenge. These results demonstrate the feasibility of distributing foreign antigen expression across both chromosomal and plasmid locations within a single vaccine organism for induction of protective immunity.
- Draft Genome Sequences of Yersinia pestis Strains from the 1994 Plague Epidemic of Surat and 2002 Shimla Outbreak in India. [Journal Article]
- Indian J Microbiol 2014 Dec; 54(4):480-2.
We report the first draft genome sequences of the strains of plague-causing bacteria, Yersinia pestis, from India. These include two strains from the Surat epidemic (1994), one strain from the Shimla outbreak (2002) and one strain from the plague surveillance activity in the Deccan plateau region (1998). Genome size for all four strains is ~4.49 million bp with 139-147 contigs. Average sequencing depth for all four genomes was 21x.
- Older Siblings' Contributions to Young Child's Cognitive Skills. [JOURNAL ARTICLE]
- Econ Model 2013 Sep.:235-248.
This work finds that older siblings as well as early parenting influence young children's cognitive skills directly or indirectly, for example, Mathematics, and English. Our findings challenge a pervasive view in the economical literatures that early parenting play a dominant role in explaining child development. In economics, early environmental conditions are important to demonstrate the evolution of adolescent and adult cognitive skills (Knudsen, Heckman, Cameron, and Shonkoff, 2006; Cunha and Heckman, 2007), and it establishes causal impacts of early parental inputs and other environmental factors on cognitive and non-cognitive skills (Heckman, Stixrud, and Urzua, 2006; Borghans, Duckworth, Heckman, and Weel, 2006; Cunha, Heckman, and Schennach, 2010). Early parenting as well as older siblings should explain a diverse array of academic and social outcomes, for example, Mathematics, English, maritage and pregnancy. In fact, older siblings' characteristics are as important, if not more important, than parenting for child development. Our analysis addresses the problems of measurement error, imperfect proxies, and reverse causality that plague conventional approach in psychology. We find that older brother contributes much more than older sister to child's mathematical achievement, while older sister contributes much more to child's english achievement. Our evidence is consistent with psychology literature, for example, Hetherington (1988), Jenkins (1992), Zukow-Goldring (1995), Marshall, Garcia-Coll, Marx, McCartney, Keffe, and Rub (1997), Maynard (2002), and Brody Ge, Kim, Murry, Simons, Gibbons, Gerrard, and Conger (2003) for siblings' direct contributions to child development, Bronfenbrenner (1997), East (1998), Whiteman and Buchanan (2002), and Brody, Ge, Kim, Murry, Simons, Gibbons, Gerrard, and Conger (2003) for siblings's indirect contributions, and Reiss, Neiderhiser, Hetherington, and Plomin (2000), Feinberg and Hetherington (2001), Kowal, Kramer, Krull, and Crick (2002) for parental differential treatment.
- Detection of Rickettsia felis, Rickettsia typhi, Bartonella Species and Yersinia pestis in Fleas (Siphonaptera) from Africa. [Journal Article]
- PLoS Negl Trop Dis 2014 Oct; 8(10):e3152.
Little is known about the presence/absence and prevalence of Rickettsia spp, Bartonella spp. and Yersinia pestis in domestic and urban flea populations in tropical and subtropical African countries.Fleas collected in Benin, the United Republic of Tanzania and the Democratic Republic of the Congo were investigated for the presence and identity of Rickettsia spp., Bartonella spp. and Yersinia pestis using two qPCR systems or qPCR and standard PCR. In Xenopsylla cheopis fleas collected from Cotonou (Benin), Rickettsia typhi was detected in 1% (2/199), and an uncultured Bartonella sp. was detected in 34.7% (69/199). In the Lushoto district (United Republic of Tanzania), R. typhi DNA was detected in 10% (2/20) of Xenopsylla brasiliensis, and Rickettsia felis was detected in 65% (13/20) of Ctenocephalides felis strongylus, 71.4% (5/7) of Ctenocephalides canis and 25% (5/20) of Ctenophthalmus calceatus calceatus. In the Democratic Republic of the Congo, R. felis was detected in 56.5% (13/23) of Ct. f. felis from Kinshasa, in 26.3% (10/38) of Ct. f. felis and 9% (1/11) of Leptopsylla aethiopica aethiopica from Ituri district and in 19.2% (5/26) of Ct. f. strongylus and 4.7% (1/21) of Echidnophaga gallinacea. Bartonella sp. was also detected in 36.3% (4/11) of L. a. aethiopica. Finally, in Ituri, Y. pestis DNA was detected in 3.8% (1/26) of Ct. f. strongylus and 10% (3/30) of Pulex irritans from the villages of Wanyale and Zaa.Most flea-borne infections are neglected diseases which should be monitored systematically in domestic rural and urban human populations to assess their epidemiological and clinical relevance. Finally, the presence of Y. pestis DNA in fleas captured in households was unexpected and raises a series of questions regarding the role of free fleas in the transmission of plague in rural Africa, especially in remote areas where the flea density in houses is high.
- A Non-Stationary Relationship between Global Climate Phenomena and Human Plague Incidence in Madagascar. [Journal Article]
- PLoS Negl Trop Dis 2014 Oct; 8(10):e3155.
Plague, a zoonosis caused by Yersinia pestis, is found in Asia and the Americas, but predominantly in Africa, with the island of Madagascar reporting almost one third of human cases worldwide. Plague's occurrence is affected by local climate factors which in turn are influenced by large-scale climate phenomena such as the El Niño Southern Oscillation (ENSO). The effects of ENSO on regional climate are often enhanced or reduced by a second large-scale climate phenomenon, the Indian Ocean Dipole (IOD). It is known that ENSO and the IOD interact as drivers of disease. Yet the impacts of these phenomena in driving plague dynamics via their effect on regional climate, and specifically contributing to the foci of transmission on Madagascar, are unknown. Here we present the first analysis of the effects of ENSO and IOD on plague in Madagascar.We use a forty-eight year monthly time-series of reported human plague cases from 1960 to 2008. Using wavelet analysis, we show that over the last fifty years there have been complex non-stationary associations between ENSO/IOD and the dynamics of plague in Madagascar. We demonstrate that ENSO and IOD influence temperature in Madagascar and that temperature and plague cycles are associated. The effects on plague appear to be mediated more by temperature, but precipitation also undoubtedly influences plague in Madagascar. Our results confirm a relationship between plague anomalies and an increase in the intensity of ENSO events and precipitation.This work widens the understanding of how climate factors acting over different temporal scales can combine to drive local disease dynamics. Given the association of increasing ENSO strength and plague anomalies in Madagascar it may in future be possible to forecast plague outbreaks in Madagascar. The study gives insight into the complex and changing relationship between climate factors and plague in Madagascar.
- Evaluation of the effect of host immune status on short-term Yersinia pestis infection in fleas with implications for the enzootic host model for maintenance of Y. pestis during interepizootic periods. [Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.]
- J Med Entomol 2014 Sep; 51(5):1079-86.
Plague, a primarily flea-borne disease caused by Yersinia pestis, is characterized by rapidly spreading epizootics separated by periods of quiescence. Little is known about how and where Y. pestis persists between epizootics. It is commonly proposed, however, that Y pestis is maintained during interepizootic periods in enzootic cycles involving flea vectors and relatively resistant host populations. According to this model, while susceptible individuals serve as infectious sources for feeding fleas and subsequently die of infection, resistant hosts survive infection, develop antibodies to the plague bacterium, and continue to provide bloodmeals to infected fleas. For Y. pestis to persist under this scenario, fleas must remain infected after feeding on hosts carrying antibodies to Y. pestis. Studies of other vector-borne pathogens suggest that host immunity may negatively impact pathogen survival in the vector. Here, we report infection rates and bacterial loads for fleas (both Xenopsylla cheopis (Rothschild) and Oropsylla montana (Baker)) that consumed an infectious bloodmeal and subsequently fed on an immunized or age-matched naive mouse. We demonstrate that neither the proportion of infected fleas nor the bacterial loads in infected fleas were significantly lower within 3 d of feeding on immunized versus naive mice. Our findings thus provide support for one assumption underlying the enzootic host model of interepizootic maintenance of Y. pestis.