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Sample records for multiple independent lyme

  1. Lyme Disease

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Lyme Disease KidsHealth > For Teens > Lyme Disease A A A ... Northwest, and the northern midwestern states. What Is Lyme Disease? People get Lyme disease through tick bites. The ...

  2. Transplantation of Human Embryonic Stem Cells in Patients with Multiple Sclerosis and Lyme Disease

    PubMed Central

    Shroff, Geeta

    2016-01-01

    Case series Patient: Male, 42 • Female, 30 Final Diagnosis: Human embryonic stem cells showed good therapeutic potential for treatment of multiple sclerosis with lyme disease Symptoms: Fatigue • weakness in limbs Medication: — Clinical Procedure: Human embryonic stem cells transplantation Specialty: Transplantology Objective: Rare disease Background: Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease in which the myelin sheath of nerve cells is damaged. It can cause delayed neurologic symptoms similar to those seen in Lyme disease (LD) patients. Thymus derived T-cells (myelin reactive) migrate to the blood brain barrier and stimulate an inflammatory cascade in the central nervous system. Cell based therapies play an important role in treating neurological diseases such as MS and LD. Case Report: Human embryonic stem cell (hESC) therapy was used to treat two patients with both MS and LD. The hESCs were administered via different routes including intramuscular, intravenous, and supplemental routes (e.g., deep spinal, caudal, intercostal through eye drops) to regenerate the injured cells. Both the patients showed remarkable improvement in their functional skills, overall stamina, cognitive abilities, and muscle strength. Furthermore, the improvement in the patients’ conditions were assessed by magnetic resonance tractography and single photon emission computed tomography (SPECT). Conclusions: Therapy with hESCs might emerge as an effective and safe treatment for patients with both MS and LD. Well-designed clinical trials and follow-up studies are needed to prove the long-term efficacy and safety of hESC therapy in the treatment of patients with MS and LD. PMID:27956736

  3. Lyme Disease Presenting with Multiple Cranial Nerve Deficits: Report of a Case

    PubMed Central

    Chaturvedi, Abhishek; Baker, Keith; Jeanmonod, Donald

    2016-01-01

    Lyme disease is a tick-transmitted multisystem inflammatory disease caused by the spirochete Borrelia burgdorferi. With more than 25,000 CDC reported cases annually, it has become the most common vector-borne disease in the United States. We report a case of 38-year-old man with Lyme disease presenting with simultaneous palsy of 3rd, 5th, 7th, 9th, and 10th cranial nerves. PMID:27635267

  4. Lyme disease

    MedlinePlus

    ... up the bacteria when they bite mice or deer that are infected with B burgdorferi . You can ... syndrome Images Lyme disease organism, Borrelia burgdorferi Tick, deer engorged on the skin Lyme disease - Borrelia burgdorferi ...

  5. Lyme carditis.

    PubMed

    Robinson, Matthew L; Kobayashi, Takaaki; Higgins, Yvonne; Calkins, Hugh; Melia, Michael T

    2015-06-01

    Lyme disease is a common disease that uncommonly affects the heart. Because of the rarity of this diagnosis and the frequent absence of other concurrent clinical manifestations of early Lyme disease, consideration of Lyme carditis demands a high level of suspicion when patients in endemic areas come to attention with cardiovascular symptoms and evidence of higher-order heart block. A majority of cases manifest as atrioventricular block. A minority of Lyme carditis cases are associated with myopericarditis. Like other manifestations of Lyme disease, carditis can readily be managed with antibiotic therapy and supportive care measures, such that affected patients almost always completely recover.

  6. Lyme Disease

    PubMed Central

    Burdge, David R.; O'Hanlon, David

    1992-01-01

    Lyme borreliosis is an infectious disease caused by the tick-transmitted spirochete Borrelia burgdorferi. To date, the only known endemic focus of Lyme disease in Canada is Long Point, Ont. A national case definition for surveillance purposes, consensus statement regarding laboratory diagnosis, and treatment guidelines have recently been developed in an attempt to standardize the approach to surveillance, diagnosis, and management of Lyme borreliosis in Canada. PMID:21221399

  7. [Lyme disease--clinical manifestations and treatment].

    PubMed

    Stock, Ingo

    2016-05-01

    Lyme disease (Lyme borreliosis) is a systemic infectious disease that can present in a variety of clinical manifestations. The disease is caused by a group of spirochaetes--Borrelia burgdorferi sensu lato or Lyme borrelia--that are transmitted to humans by the bite of Ixodes ticks. Lyme disease is the most common arthropode-borne infectious disease in many European countries including Germany. Early localized infection is typically manifested by an erythema migrans skin lesion, in rarer cases as a borrelial lymphocytoma. The most common early disseminated manifestation is (early) neuroborreliosis. In adults, neuroborreliosis appears typically as meningoradiculoneuritis. Neuroborreliosis in children, however, is typically manifested by meningitis. In addition, multiple erythema migrans lesions and Lyme carditis occur relatively frequently. The most common manifestation oflate Lyme disease is Lyme arthritis. Early manifestations (and usually also late manifestations) of Lyme disease can be treated successfully by application of suitable antibacterial agents. For the treatment of Lyme disease, doxycycline, certain penicillins such as amoxicillin and some cephalosporins (ceftriaxone, cefotaxime, cefuroxime axetil) are recommended in current guidelines. A major challenge is the treatment of chronic, non-specific disorders, i. e., posttreatment Lyme disease syndrome and "chronic Lyme disease". Prevention of Lyme disease is mainly accomplished by protecting against tick bites. Prophylactic administration of doxycycline after tick bites is generally not recommended in Germany. There is no vaccine available for human beings.

  8. Lyme Disease (For Parents)

    MedlinePlus

    ... Old Feeding Your 1- to 2-Year-Old Lyme Disease KidsHealth > For Parents > Lyme Disease A A A ... Pacific Northwest, and the northern Midwest states. About Lyme Disease Lyme disease is caused by the bacterium Borrelia ...

  9. [Lyme carditis].

    PubMed

    Błaut-Jurkowska, Justyna; Olszowska, Maria; Kaźnica-Wiatr, Magdalena; Podolec, Piotr

    2015-08-01

    Lyme disease is a multisystem infectious disease caused by the spirochete Borrelia burgdorferi. A steady increase in the number of cases is noticed both in Poland and Europe. Cardiac involvement in the course of borreliosis is relatively rare. It is estimated that it concerns about 0.5-10% of patients with Lyme disease. Cardiac involvement generally occurs in the early phase of illness. The most common manifestation of Lyme carditis are transient conduction abnormality, arrhythmias, myocarditis and pericarditis. The basic method of treatment Lyme carditis are antibiotics. The clinical course is usually benign. In most cases a complete recovery is observed. However, in a small proportion of patients dilated cardiomyopathy may occur. Furthermore, death from Lyme carditis has been reported. Lyme carditis remains a real diagnostic and therapeutic challenge for clinicians. Factors that can make the diagnosis difficult are: atypical clinical picture, negation of tick bite, the absence of erythema migrans, onset of symptoms outside the period of tick activity and negative serological results in the initial stage of the disease.

  10. Lyme Disease.

    ERIC Educational Resources Information Center

    Taylor, George C.

    1991-01-01

    This overview of the public health significance of Lyme disease includes the microbiological specifics of the infectious spirochete, the entomology and ecology of the ticks which are the primary disease carrier, the clinical aspects and treatment stages, the known epidemiological patterns, and strategies for disease control and for expanded public…

  11. Contrasting emergence of Lyme disease across ecosystems.

    PubMed

    Mysterud, Atle; Easterday, William Ryan; Stigum, Vetle Malmer; Aas, Anders Bjørnsgaard; Meisingset, Erling L; Viljugrein, Hildegunn

    2016-06-16

    Global environmental changes are causing Lyme disease to emerge in Europe. The life cycle of Ixodes ricinus, the tick vector of Lyme disease, involves an ontogenetic niche shift, from the larval and nymphal stages utilizing a wide range of hosts, picking up the pathogens causing Lyme disease from small vertebrates, to the adult stage depending on larger (non-transmission) hosts, typically deer. Because of this complexity the role of different host species for emergence of Lyme disease remains controversial. Here, by analysing long-term data on incidence in humans over a broad geographical scale in Norway, we show that both high spatial and temporal deer population density increase Lyme disease incidence. However, the trajectories of deer population sizes play an overall limited role for the recent emergence of the disease. Our study suggests that managing deer populations will have some effect on disease incidence, but that Lyme disease may nevertheless increase as multiple drivers are involved.

  12. Contrasting emergence of Lyme disease across ecosystems

    PubMed Central

    Mysterud, Atle; Easterday, William Ryan; Stigum, Vetle Malmer; Aas, Anders Bjørnsgaard; Meisingset, Erling L.; Viljugrein, Hildegunn

    2016-01-01

    Global environmental changes are causing Lyme disease to emerge in Europe. The life cycle of Ixodes ricinus, the tick vector of Lyme disease, involves an ontogenetic niche shift, from the larval and nymphal stages utilizing a wide range of hosts, picking up the pathogens causing Lyme disease from small vertebrates, to the adult stage depending on larger (non-transmission) hosts, typically deer. Because of this complexity the role of different host species for emergence of Lyme disease remains controversial. Here, by analysing long-term data on incidence in humans over a broad geographical scale in Norway, we show that both high spatial and temporal deer population density increase Lyme disease incidence. However, the trajectories of deer population sizes play an overall limited role for the recent emergence of the disease. Our study suggests that managing deer populations will have some effect on disease incidence, but that Lyme disease may nevertheless increase as multiple drivers are involved. PMID:27306947

  13. Interleukin-10 alters effector functions of multiple genes induced by Borrelia burgdorferi in macrophages to regulate Lyme disease inflammation.

    PubMed

    Gautam, Aarti; Dixit, Saurabh; Philipp, Mario T; Singh, Shree R; Morici, Lisa A; Kaushal, Deepak; Dennis, Vida A

    2011-12-01

    Interleukin-10 (IL-10) modulates inflammatory responses elicited in vitro and in vivo by Borrelia burgdorferi, the Lyme disease spirochete. How IL-10 modulates these inflammatory responses still remains elusive. We hypothesize that IL-10 inhibits effector functions of multiple genes induced by B. burgdorferi in macrophages to control concomitantly elicited inflammation. Because macrophages are essential in the initiation of inflammation, we used mouse J774 macrophages and live B. burgdorferi spirochetes as the model target cell and stimulant, respectively. First, we employed transcriptome profiling to identify genes that were induced by stimulation of cells with live spirochetes and that were perturbed by addition of IL-10 to spirochete cultures. Spirochetes significantly induced upregulation of 347 genes at both the 4-h and 24-h time points. IL-10 inhibited the expression levels, respectively, of 53 and 65 of the 4-h and 24-h genes, and potentiated, respectively, at 4 h and 24 h, 65 and 50 genes. Prominent among the novel identified IL-10-inhibited genes also validated by quantitative real-time PCR (qRT-PCR) were Toll-like receptor 1 (TLR1), TLR2, IRAK3, TRAF1, IRG1, PTGS2, MMP9, IFI44, IFIT1, and CD40. Proteome analysis using a multiplex enzyme-linked immunosorbent assay (ELISA) revealed the IL-10 modulation/and or potentiation of RANTES/CCL5, macrophage inflammatory protein 2 (MIP-2)/CXCL2, IP-10/CXCL10, MIP-1α/CCL3, granulocyte colony-stimulating factor (G-CSF)/CSF3, CXCL1, CXCL5, CCL2, CCL4, IL-6, tumor necrosis factor alpha (TNF-α), IL-1α, IL-1β, gamma interferon (IFN-γ), and IL-9. Similar results were obtained using sonicated spirochetes or lipoprotein as stimulants. Our data show that IL-10 alters effectors induced by B. burgdorferi in macrophages to control concomitantly elicited inflammatory responses. Moreover, for the first time, this study provides global insight into potential mechanisms used by IL-10 to control Lyme disease inflammation.

  14. Testing for conditional multiple marginal independence.

    PubMed

    Bilder, Christopher R; Loughin, Thomas M

    2002-03-01

    Survey respondents are often prompted to pick any number of responses from a set of possible responses. Categorical variables that summarize this kind of data are called pick any/c variables. Counts from surveys that contain a pick any/c variable along with a group variable (r levels) and stratification variable (q levels) can be marginally summarized into an r x c x q contingency table. A question that may naturally arise from this setup is to determine if the group and pick any/c variable are marginally independent given the stratification variable. A test for conditional multiple marginal independence (CMMI) can be used to answer this question. Since subjects may pick any number out of c possible responses, the Cochran (1954, Biometrics 10, 417-451) and Mantel and Haenszel (1959, Journal of the National Cancer Institute 22, 719-748) tests cannot be used directly because they assume that units in the contingency table are independent of each other. Therefore, new testing methods are developed. Cochran's test statistic is extended to r x 2 x q tables, and a modified version of this statistic is proposed to test CMMI. Its sampling distribution can be approximated through bootstrapping. Other CMMI testing methods discussed are bootstrap p-value combination methods and Bonferroni adjustments. Simulation findings suggest that the proposed bootstrap procedures and the Bonferroni adjustments consistently hold the correct size and provide power against various alternatives.

  15. [Lyme disease].

    PubMed

    Portillo, Aránzazu; Santibáñez, Sonia; Oteo, José A

    2014-02-01

    Lyme disease (LD) is a worldwide-distributed multisystemic process caused by Borrelia burgdorferi sensu lato (s.l.) and transmitted by hard ticks. In fact, it is the most common tick-borne infectious disease in the northern hemisphere. In Spain it is transmitted by Ixodes ricinus ticks and Borrelia garinii is the genoespecies of B. burgdorferi s.l. mostly involved in our area. LD is known as "the last great imitator" due to the broad clinical spectrum that may cause. Except in the case of erythema migrans (pathognomonic feature of the disease), the remaining clinical manifestations should be confirmed using microbiological tests. This review is intended to provide readers a current vision of the etiology, epidemiology, clinical manifestations, laboratory diagnosis and treatment of Lyme disease in our environment. Controversial aspects arising from the use of non-validated microbiological tests that are being used without scientific rigor are highlighted.

  16. Lyme Disease.

    PubMed

    Hu, Linden T

    2016-05-03

    This issue provides a clinical overview of Lyme disease, focusing on prevention, diagnosis, treatment, and practice improvement. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of additional science writers and physician writers.

  17. Lyme borreliosis.

    PubMed

    Steere, Allen C; Strle, Franc; Wormser, Gary P; Hu, Linden T; Branda, John A; Hovius, Joppe W R; Li, Xin; Mead, Paul S

    2016-12-15

    Lyme borreliosis is a tick-borne disease that predominantly occurs in temperate regions of the northern hemisphere and is primarily caused by the bacterium Borrelia burgdorferi in North America and Borrelia afzelii or Borrelia garinii in Europe and Asia. Infection usually begins with an expanding skin lesion, known as erythema migrans (referred to as stage 1), which, if untreated, can be followed by early disseminated infection, particularly neurological abnormalities (stage 2), and by late infection, especially arthritis in North America or acrodermatitis chronica atrophicans in Europe (stage 3). However, the disease can present with any of these manifestations. During infection, the bacteria migrate through the host tissues, adhere to certain cells and can evade immune clearance. Yet, these organisms are eventually killed by both innate and adaptive immune responses and most inflammatory manifestations of the infection resolve. Except for patients with erythema migrans, Lyme borreliosis is diagnosed based on a characteristic clinical constellation of signs and symptoms with serological confirmation of infection. All manifestations of the infection can usually be treated with appropriate antibiotic regimens, but the disease can be followed by post-infectious sequelae in some patients. Prevention of Lyme borreliosis primarily involves the avoidance of tick bites by personal protective measures.

  18. Lyme disease.

    PubMed

    Chomel, B

    2015-08-01

    Lyme disease is among the most frequently diagnosed zoonotic tick-borne diseases worldwide. The number of human cases has been on the increase since the first recognition of its aetiological agent. Lyme disease is caused by spirochete bacteria belonging to the genus Borrelia, with B. burgdorferi sensu stricto (s.s.) found in the Americas, and B. afzelii and B. garinii, in addition to B. burgdorferi s.s., in Europe and Asia. Environmental factors, such as human encroachment onto habitats favourable to ticks and their hosts, reduced deforestation, increased human outdoor activities, and climatic factors favouring a wider distribution of tick vectors, have enhanced the impact of the disease on both humans and animals. Clinical manifestations in humans include, in the early phases, erythema migrans, followed several weeks later by neuro-borreliosis (meningo-radiculitis, meningitis or meningo-encephalitis), Lyme arthritis and/or Borrelia lymphocytoma. In dogs, acute signs include fever, general malaise, lameness, lymph node enlargement and polyarthritis, as well as neuro-borreliosis in the chronic form. Diagnosis is mainly serological in both humans and animals, based on either a two-tier approach (an immunoenzymatic test followed by a Western blot confirmatory test) in humans or C(6) peptide, only in dogs. Early treatment with antibiotics, such as doxycycline or amoxicillin, for three weeks usually reduces the risk of chronic disease. Tick control, including the use of tick repellents for both humans and animals, particularly dogs, is highly reliable in preventing transmission. Vaccines are not available to prevent human infection, whereas several vaccines are available to reduce transmission and the clinical manifestations of infection in dogs.

  19. Lyme Disease: Fact or Fiction?

    MedlinePlus

    ... message, please visit this page: About CDC.gov . Lyme Disease Lyme Disease Preventing tick bites On people On pets In ... What you need to know about Lyme carditis Lyme Disease Rashes and Look-alikes Diagnosis and testing Two- ...

  20. Origin of the Lyme Dome and implications for the timing of multiple Alleghanian deformational and intrusive events in southern Connecticut

    USGS Publications Warehouse

    Walsh, G.J.; Aleinikoff, J.N.; Wintsch, R.P.

    2007-01-01

    Geologic mapping, structural analysis, and geochronology in the area of the Lyme dome, southern Connecticut provides constraints on the origin of the rocks in the core of the dome, the absolute timing of the principal deformational and thermal events attributed to Alleghanian orogenesis, and the processes that generated the dome. Detrital zircon geochronology in combination with ages on intrusive rocks brackets the deposition of quartzite in the core of the dome sometime between ca. 925 and 620 Ma. Granite and granodiorite intruded the Neoproteorozic metasedimentary rocks in the core of the dome at ca. 620 to 610 Ma. Four major early Permian events associated with the Alleghanian orogeny affected the rocks in the Lyme dome area. Syn-tectonic migmatization and widespread penetrative deformation (D1, ca. 300 - 290 Ma) included emplacement of alaskite at 290 ?? 4 Ma during regional foliation development and aluminosilicate-orthoclase metamorphic conditions. Rocks of the Avalon terrane may have wedged between Gander cover rocks and Gander basement in the core of the Lyme during D1. Limited structural evidence for diapiric uplift of the Lyme dome indicates that diapirism started late in D1 and was completed by D2 (ca. 290 - 280 Ma) when horizontal WNW contractional stresses dominated over vertical stresses. Second sillimanite metamorphism continued and syn-tectonic D2 granite pegmatite (288 ?? 4 Ma) and the Joshua Rock Granite Gniess (284 ?? 3 Ma) intruded at this time. North-northwest extension during D3 (ca. 280 - 275 Ma) led to granitic pegmatite intrusion along S3 cleavage planes and in extensional zones in boudin necks during hydraulic failure and decompression melting. Intrusion of a Westerly Granite dike at 275 ?? 4 Ma suggests that D3 extension was active, and perhaps concluding, by ca. 275 Ma. Late randomly oriented but gently dipping pegmatite dikes record a final stage of intrusion during D4 (ca. 275 - 260 Ma), and a switch from NNW extension to vertical

  1. Lyme Disease-Causing Borrelia Species Encode Multiple Lipoproteins Homologous to Peptide-Binding Proteins of ABC-Type Transporters

    PubMed Central

    Kornacki, Jon A.; Oliver, Donald B.

    1998-01-01

    To identify cell envelope proteins of Borrelia burgdorferi, the causative agent of Lyme disease, we constructed a library of B. burgdorferi genes fused to the Escherichia coli phoA gene, which expresses enzymatically active alkaline phosphatase. One such gene, oppA-1, encodes a predicted polypeptide with significant similarities to various peptide-binding proteins of ABC-type transporters. Immediately downstream of oppA-1 are two genes, oppA-2 and oppA-3, whose predicted polypeptide products show strong similarities in their amino acid sequences to OppA-1, including a sequence that resembles the most highly conserved region in peptide-binding proteins. By labeling with [3H]palmitate, OppA-1, OppA-2, and OppA-3 were shown to be lipoproteins. DNA hybridization analysis showed that the oppA-1 oppA-2 oppA-3 region is located on the linear chromosome of B. burgdorferi, and the genes are conserved among different Borrelia species that cause Lyme disease (B. burgdorferi, B. garinii, and B. afzelli), suggesting that all three homologous genes are important to the maintenance of Lyme disease spirochetes in one or more of their hosts. PMID:9712756

  2. Lyme disease antibody

    MedlinePlus

    ... JavaScript. The Lyme disease blood test looks for antibodies in the blood to the bacteria that causes ... needed. A laboratory specialist looks for Lyme disease antibodies in the blood sample using the ELISA test . ...

  3. Lyme disease (image)

    MedlinePlus

    Lyme disease is an acute inflammatory disease characterized by skin changes, joint inflammation and symptoms similar to the ... that is caused by the bacterium Borrelia burgdorferi . Lyme disease is transmitted by the bite of a deer ...

  4. Lyme Disease (For Kids)

    MedlinePlus

    ... Emergency Room? What Happens in the Operating Room? Lyme Disease KidsHealth > For Kids > Lyme Disease A A A What's in this article? Ticks ... and summer, you might hear about something called Lyme disease. It has nothing to do with limes, but ...

  5. Lyme disease in Oregon.

    PubMed

    Doggett, J Stone; Kohlhepp, Sue; Gresbrink, Robert; Metz, Paul; Gleaves, Curt; Gilbert, David

    2008-06-01

    The incidence of Lyme disease in Oregon is calculated from cases reported to the Oregon State Health Division. We reviewed the exposure history of reported cases of Lyme disease and performed field surveys for infected Ixodes pacificus ticks. The incidence of Lyme disease correlated with the distribution of infected I. pacificus ticks.

  6. Multiple caliper arms capable of independent movement

    SciTech Connect

    Deaton, J.G.

    1992-02-11

    This patent describes a multiple arm caliper tool system for use in a well borehole. It comprises: an elongate tool body that adapted to be lowered and retrieved along a well borehole; at least a pari of caliper arms, each of the arms being a piston isolating the chamber; and means for compressing the hydraulic fluid within the chamber so that hydraulic fluid in the chamber is brought to a specified pressure wherein the hydraulic fluid acts on all of the push rods extending into the chamber.

  7. Hyperosmia in Lyme disease.

    PubMed

    Puri, Basant K; Monro, Jean A; Julu, Peter O O; Kingston, Michele C; Shah, Mussadiq

    2014-08-01

    Neurological involvement in Lyme disease has been reported to include meningitis, cranial neuropathy and radiculoneuritis. While it is known that in some cases of asceptic meningitis patients may develop hyperosmia, the association between hyperosmia and Lyme disease has not previously been studied. Objective To carry out the first systematic study to ascertain whether hyperosmia is also a feature of Lyme disease. Method A questionnaire regarding abnormal sensory sensitivity in respect of the sense of smell was administered to 16 serologically positive Lyme disease patients and to 18 control subjects. Results The two groups were matched in respect of age, sex and body mass. None of the 34 subjects was suffering from migraine. Eight (50%) of the Lyme patients and none (0%) of the controls suffered from hyperosmia (p=0.0007). Conclusion This first systematic controlled study showed that Lyme disease is associated with hyperosmia.

  8. Manifestations of Lyme carditis.

    PubMed

    Kostić, Tomislav; Momčilović, Stefan; Perišić, Zoran D; Apostolović, Svetlana R; Cvetković, Jovana; Jovanović, Andriana; Barać, Aleksandra; Šalinger-Martinović, Sonja; Tasić-Otašević, Suzana

    2017-04-01

    The first data of Lyme carditis, a relatively rare manifestation of Lyme disease, were published in eighties of the last century. Clinical manifestations include syncope, light-headedness, fainting, shortness of breath, palpitations, and/or chest pain. Atrioventricular (AV) electrical block of varying severity presents the most common conduction disorder in Lyme carditis. Although is usually mild, AV block can fluctuates rapidly and progress from a prolonged P-R interval to a His-Purkinje block within minutes to hours and days. Rarely, Lyme disease may be the cause of endocarditis, while some studies and reports, based on serological and/or molecular investigations, have suggested possible influence of Borrelia burgdorferi on degenerative cardiac valvular disease. Myocarditis, pericarditis, pancarditis, dilated cardiomyopathy, and heart failure have also been described as possible manifestations of Lyme carditis. The clinical course of Lyme carditis is generally mild, short term, and in most cases, completely reversible after adequate antibiotic treatment.

  9. Lyme disease in athletes.

    PubMed

    DuPrey, Kevin M

    2015-01-01

    Lyme disease, a bacterial infection transmitted by ticks, is the most common vector-borne disease in the northern hemisphere. Athletes who train or compete in wooded environments in endemic regions are at increased risk of contracting Lyme disease. Variability in clinical presentation, masquerading symptoms, and limitations in testing may lead to misdiagnosis. Early diagnosis and treatment result in full recovery for most patients with Lyme disease; however symptoms may persist for months to years, especially when diagnosis is delayed. This article reviews the epidemiology, clinical manifestations, diagnosis, treatment, and prevention of Lyme disease, with focus on the athletic population.

  10. The paradox of the binomial Ixodes ricinus activity and the observed unimodal Lyme borreliosis season in Hungary.

    PubMed

    Trájer, A; Bede-Fazekas, Á; Hufnagel, L; Bobvos, J; Páldy, A

    2014-01-01

    The change of ambient temperature plays a key role in determining the run of the annual Lyme season. Our aim was to explain the apparent contradiction between the annual unimodal Lyme borreliosis incidence and the bimodal Ixodes ricinus tick activity run--both observed in Hungary--by distinguishing the temperature-dependent seasonal human and tick activity, the temperature-independent factors, and the multiplicative effect of human outdoor activity in summer holiday, using data from Hungary in the period of 1998-2012. This separation was verified by modeling the Lyme incidence based on the separated factors, and comparing the run of the observed and modeled incidence. We demonstrated the bimodality of tick season by using the originally unimodal Lyme incidence data. To model the outdoor human activity, the amount of camping guest nights was used, which showed an irregular run from mid-June to September. The human outdoor activity showed a similar exponential correlation with ambient temperature to that what the relative incidence did. It was proved that summer holiday has great influence on Lyme incidence.

  11. Ocular Lyme borreliosis as a rare presentation of unilateral vision loss.

    PubMed

    Patterson-Fortin, Jeffrey; Kohli, Anita; Suarez, Maria J; Miller, P Elliott

    2016-04-25

    Ocular Lyme borreliosis is a rare manifestation of Lyme disease. We describe a case of an 80-year-old woman who presented with a 1-month history of unilateral painless central vision loss. Based on a temporal artery biopsy, she was initially diagnosed with giant cell arteritis and treated with a 3-day course of high-dose intravenous steroids. A more detailed history uncovered multiple previous treatments for Lyme disease and residence in an endemic Lyme area. The patient was subsequently diagnosed with ocular Lyme borreliosis and treated with intravenous antibiotics. After 5 weeks of treatment, unilateral vision loss did not progress and optic disc oedema resolved.

  12. Chronic Lyme disease.

    PubMed

    Lantos, Paul M

    2015-06-01

    Chronic Lyme disease is a poorly defined diagnosis that is usually given to patients with prolonged, unexplained symptoms or with alternative medical diagnoses. Data do not support the proposition that chronic, treatment-refractory infection with Borrelia burgdorferi is responsible for the many conditions that get labeled as chronic Lyme disease. Prolonged symptoms after successful treatment of Lyme disease are uncommon, but in rare cases may be severe. Prolonged courses of antibiotics neither prevent nor ameliorate these symptoms and are associated with considerable harm.

  13. [Lyme arthritis, Lyme carditis and other presentations potentially associated to Lyme disease].

    PubMed

    Begon, E

    2007-01-01

    Lyme disease or Lyme borreliosis is the most common tick-transmitted disease in the Northern hemisphere and is caused by Borrelia burgdorferi spirochetes. Lyme disease commonly begins with a characteristic skin lesion, erythema migrans. Weeks or months later, the patients may have neurologic, joint, or cardiac abnormalities. Some patients may still present persistent deep fatigue and various unspecific symptoms after standard courses of antibiotic treatment for Lyme disease. This constellation of symptoms has been variously referred to as "chronic Lyme disease", or "post-Lyme disease syndrome". The first French National Consensus Conference on Lyme Disease was the reason to review all aspects of articular and cardiac manifestations of Lyme disease after a synthesis of recent literature. The involvement of Borrelia species in chronic Lyme disease and other pathologies is discussed.

  14. American Lyme Disease Foundation

    MedlinePlus

    ... from our website. How to Make Donations and Contributions to Support the ALDF The American Lyme Disease ... and much more. Read MORE>> The thanks and contributions we receive from many of those who have ...

  15. Lyme disease in children.

    PubMed

    Sood, Sunil K

    2015-06-01

    The diagnosis and management of Lyme disease in children is similar to that in adults with a few clinically relevant exceptions. The use of doxycycline as an initial empiric choice is to be avoided for children 8 years old and younger. Children may present with insidious onset of elevated intracranial pressure during acute disseminated Lyme disease; prompt diagnosis and treatment of this condition is important to prevent loss of vision. Children who acquire Lyme disease have an excellent prognosis even when they present with the late disseminated manifestation of Lyme arthritis. Guidance on the judicious use of serologic tests is provided. Pediatricians and family practitioners should be familiar with the prevention and management of tick bites, which are common in children.

  16. Lyme disease and conservation

    USGS Publications Warehouse

    Ginsberg, H.

    1994-01-01

    Lyme disease is a tick-borne illness that is wide-spread in North America, especially in the northeastern and northcentral United States. This disease could negatively influence efforts to conserve natural populations in two ways: (1) the disease could directly affect wild animal health; and (2) tick control efforts could adversely affect natural populations and communities. Lyme disease affects several domestic animals, but symptoms have been reported in only a few wild species. Direct effects of Lyme disease on wild animal populations have not been reported, but the disease should be considered as a possible cause in cases of unexplained population declines in endemic areas. Methods available to manage ticks and Lyme disease include human self-protection techniques, manipulation of habitats and hosts species populations, biological control, and pesticide applications. The diversity of available techniques allows selection of approaches to minimize environmental effects by (1) emphasizing personal protection techniques, (2) carefully targeting management efforts to maximize efficiency, and (3) integrating environmentally benign techniques to improve management while avoiding broad-scale environmentally destructive approaches. The environmental effects of Lyme disease depend, to a large extent, on the methods chosen to minimize human exposure to infected ticks. Conservation biologists can help design tick management programs that effectively lower the incidence of human Lyme disease while simultaneously minimizing negative effects on natural populations.

  17. Classification of independent components of EEG into multiple artifact classes.

    PubMed

    Frølich, Laura; Andersen, Tobias S; Mørup, Morten

    2015-01-01

    In this study, we aim to automatically identify multiple artifact types in EEG. We used multinomial regression to classify independent components of EEG data, selecting from 65 spatial, spectral, and temporal features of independent components using forward selection. The classifier identified neural and five nonneural types of components. Between subjects within studies, high classification performances were obtained. Between studies, however, classification was more difficult. For neural versus nonneural classifications, performance was on par with previous results obtained by others. We found that automatic separation of multiple artifact classes is possible with a small feature set. Our method can reduce manual workload and allow for the selective removal of artifact classes. Identifying artifacts during EEG recording may be used to instruct subjects to refrain from activity causing them.

  18. Multiple Independent File Parallel I/O with HDF5

    SciTech Connect

    Miller, M. C.

    2016-07-13

    The HDF5 library has supported the I/O requirements of HPC codes at Lawrence Livermore National Labs (LLNL) since the late 90’s. In particular, HDF5 used in the Multiple Independent File (MIF) parallel I/O paradigm has supported LLNL code’s scalable I/O requirements and has recently been gainfully used at scales as large as O(106) parallel tasks.

  19. Posttreatment Lyme disease syndrome.

    PubMed

    Aucott, John N

    2015-06-01

    The prognosis following appropriate antibiotic treatment of early or late Lyme disease is favorable but can be complicated by persistent symptoms of unknown cause termed posttreatment Lyme disease syndrome (PTLDS), characterized by fatigue, musculoskeletal pain, and cognitive complaints that persist for 6 months or longer after completion of antibiotic therapy. Risk factors include delayed diagnosis, increased severity of symptoms, and presence of neurologic symptoms at time of initial treatment. Two-tier serologic testing is neither sensitive nor specific for diagnosis of PTLDS because of variability in convalescent serologic responses after treatment of early Lyme disease. Optimal treatment of PTLDS awaits more precise understanding of the pathophysiologic mechanisms involved in this illness and future treatment trials.

  20. Lyme disease: why the controversy?

    PubMed

    Beaman, M H

    2016-12-01

    Some Australians have become convinced of the existence of locally acquired Lyme disease (LD). The history of LD, since its recognition in the early 1970s, is reviewed as a model for investigative approaches to unknown syndromes. Australian Management Guidelines for LD include the requirement for diagnostic testing by National Association of Testing Authorities-accredited laboratories using Therapeutic Goods Administration-licensed tests, which result in the efficient diagnosis of LD in overseas travellers. Despite this, patients who have not left Australia pay many thousands of dollars for non-specialist consultations and testing at overseas laboratories. Unproven long-term therapy with multiple antibiotics has resulted in serious complications, including allergies, line sepsis, pancreatitis and pseudomembranous colitis. Studies have shown that LD vectors are not found in Australia, and Lyme Borrelia has not been found in Australian vectors, animals or patients with autochthonous illnesses. I propose that (i) A non-controversial name for the chronic syndrome should be adopted, 'Australian Multisystem Disorder'. (ii) Research funding should enable the development of a consensus case definition and studies of the epidemiology of this syndrome with laboratory investigations to identify an aetiology and surrogate markers of disease. Prospective, randomised treatment studies could then be undertaken using ethical protocols.

  1. Lyme disease - what to ask your doctor

    MedlinePlus

    What to ask your doctor about Lyme disease; Lyme borreliosis - questions; Bannwarth syndrome - questions ... I am treated with antibiotics? How can my doctor diagnose me with Lyme disease? Can I be ...

  2. Lyme Disease Data

    MedlinePlus

    ... the northeast and upper Midwest. Lyme Disease Data File To facilitate the public health and research community’s ... 207KB] ––Right–click the link and select “save”. File Formats Help: How do I view different file ...

  3. Dystrophin contains multiple independent membrane-binding domains.

    PubMed

    Zhao, Junling; Kodippili, Kasun; Yue, Yongping; Hakim, Chady H; Wasala, Lakmini; Pan, Xiufang; Zhang, Keqing; Yang, Nora N; Duan, Dongsheng; Lai, Yi

    2016-09-01

    Dystrophin is a large sub-sarcolemmal protein. Its absence leads to Duchenne muscular dystrophy (DMD). Binding to the sarcolemma is essential for dystrophin to protect muscle from contraction-induced injury. It has long been thought that membrane binding of dystrophin depends on its cysteine-rich (CR) domain. Here, we provide in vivo evidence suggesting that dystrophin contains three additional membrane-binding domains including spectrin-like repeats (R)1-3, R10-12 and C-terminus (CT). To systematically study dystrophin membrane binding, we split full-length dystrophin into ten fragments and examined subcellular localizations of each fragment by adeno-associated virus-mediated gene transfer. In skeletal muscle, R1-3, CR domain and CT were exclusively localized at the sarcolemma. R10-12 showed both cytosolic and sarcolemmal localization. Importantly, the CR-independent membrane binding was conserved in murine and canine muscles. A critical function of the CR-mediated membrane interaction is the assembly of the dystrophin-associated glycoprotein complex (DGC). While R1-3 and R10-12 did not restore the DGC, surprisingly, CT alone was sufficient to establish the DGC at the sarcolemma. Additional studies suggest that R1-3 and CT also bind to the sarcolemma in the heart, though relatively weak. Taken together, our study provides the first conclusive in vivo evidence that dystrophin contains multiple independent membrane-binding domains. These structurally and functionally distinctive membrane-binding domains provide a molecular framework for dystrophin to function as a shock absorber and signaling hub. Our results not only shed critical light on dystrophin biology and DMD pathogenesis, but also provide a foundation for rationally engineering minimized dystrophins for DMD gene therapy.

  4. [Message from Lyme].

    PubMed

    Wahlberg, P

    1993-01-01

    The background to the discovery of Lyme disease teaches a salutary lesson. The symptoms and signs of this disease had been observed by doctors for a century, particularly in the Scandinavian countries, without anybody being able to draw the right conclusions. The first patients were identified in the USA by their relatives or by themselves. Recognition of their plight by the medical profession was chiefly due to the patients' tenacity. We must remember to pay attention to what patients tell us; they may often be right, even when they seem to be wrong. Where fact and theory are incompatible, it is theory, not fact, that needs to be amended. In all likelihood, we all from time to time observe disorders in our patients that are inconsistent with established scientific models, but which we nevertheless attempt to squeeze into these models. Such an approach is not uncommon in the history of medicine. The message from Lyme calls for humility and reflexion.

  5. New World cattle show ancestry from multiple independent domestication events

    PubMed Central

    McTavish, Emily Jane; Decker, Jared E.; Schnabel, Robert D.; Taylor, Jeremy F.; Hillis, David M.

    2013-01-01

    Previous archeological and genetic research has shown that modern cattle breeds are descended from multiple independent domestication events of the wild aurochs (Bos primigenius) ∼10,000 y ago. Two primary areas of domestication in the Middle East/Europe and the Indian subcontinent resulted in taurine and indicine lines of cattle, respectively. American descendants of cattle brought by European explorers to the New World beginning in 1493 generally have been considered to belong to the taurine lineage. Our analyses of 47,506 single nucleotide polymorphisms show that these New World cattle breeds, as well as many related breeds of cattle in southern Europe, actually exhibit ancestry from both the taurine and indicine lineages. In this study, we show that, although European cattle are largely descended from the taurine lineage, gene flow from African cattle (partially of indicine origin) contributed substantial genomic components to both southern European cattle breeds and their New World descendants. New World cattle breeds, such as Texas Longhorns, provide an opportunity to study global population structure and domestication in cattle. Following their introduction into the Americas in the late 1400s, semiferal herds of cattle underwent between 80 and 200 generations of predominantly natural selection, as opposed to the human-mediated artificial selection of Old World breeding programs. Our analyses of global cattle breed population history show that the hybrid ancestry of New World breeds contributed genetic variation that likely facilitated the adaptation of these breeds to a novel environment. PMID:23530234

  6. Widespread transmission of independent cancer lineages within multiple bivalve species

    PubMed Central

    Metzger, Michael J.; Villalba, Antonio; Carballal, María J.; Iglesias, David; Sherry, James; Reinisch, Carol; Muttray, Annette F.; Baldwin, Susan A.; Goff, Stephen P.

    2016-01-01

    Most cancers arise from oncogenic changes in the genomes of somatic cells, and while the cells may migrate by metastasis, they remain within that single individual. Natural transmission of cancer cells from one individual to another has been observed in two distinctive cases in mammals (Tasmanian devils1 and dogs2,3), but these are generally considered to be rare exceptions in nature. The discovery of transmissible cancer in soft-shell clams (Mya arenaria)4 suggested that this phenomenon might be more widespread. Here we analyzed disseminated neoplasia in mussels (Mytilus trossulus), cockles (Cerastoderma edule), and golden carpet shell clams (Polititapes aureus) and found that neoplasias in all three species are attributable to independent transmissible cancer lineages. In mussels and cockles, the cancer lineages are derived from their respective host species, but unexpectedly, cancer cells in P. aureus are all derived from Venerupis corrugata, a different species living in the same geographic area. No cases of disseminated neoplasia have thus far been found in V. corrugata from the same region. These findings show that transmission of cancer cells in the marine environment is common in multiple species, that it has originated many times, and that while most transmissible cancers were found spreading within the species of origin, cross-species transmission of cancer cells can occur. PMID:27338791

  7. New World cattle show ancestry from multiple independent domestication events.

    PubMed

    McTavish, Emily Jane; Decker, Jared E; Schnabel, Robert D; Taylor, Jeremy F; Hillis, David M

    2013-04-09

    Previous archeological and genetic research has shown that modern cattle breeds are descended from multiple independent domestication events of the wild aurochs (Bos primigenius) ∼10,000 y ago. Two primary areas of domestication in the Middle East/Europe and the Indian subcontinent resulted in taurine and indicine lines of cattle, respectively. American descendants of cattle brought by European explorers to the New World beginning in 1493 generally have been considered to belong to the taurine lineage. Our analyses of 47,506 single nucleotide polymorphisms show that these New World cattle breeds, as well as many related breeds of cattle in southern Europe, actually exhibit ancestry from both the taurine and indicine lineages. In this study, we show that, although European cattle are largely descended from the taurine lineage, gene flow from African cattle (partially of indicine origin) contributed substantial genomic components to both southern European cattle breeds and their New World descendants. New World cattle breeds, such as Texas Longhorns, provide an opportunity to study global population structure and domestication in cattle. Following their introduction into the Americas in the late 1400s, semiferal herds of cattle underwent between 80 and 200 generations of predominantly natural selection, as opposed to the human-mediated artificial selection of Old World breeding programs. Our analyses of global cattle breed population history show that the hybrid ancestry of New World breeds contributed genetic variation that likely facilitated the adaptation of these breeds to a novel environment.

  8. Embodying Multiplicity: The Independent Contemporary Dancer's Moving Identity

    ERIC Educational Resources Information Center

    Roche, Jenny

    2011-01-01

    In this article, I argue for an acknowledgement of the significance of the dancer's role in the creation of independent contemporary dance. I propose the term "moving identity" to outline the independent contemporary dancer's "way of moving" which could be perceived as the accumulation of various factors including training approaches,…

  9. Prevention of Lyme borreliosis.

    PubMed

    Wormser, Gary P

    2005-06-01

    Lyme borreliosis, the most common tick-borne disease in both North America and Europe, is acquired through the bite of certain tick species in the genus Ixodes. The number of Ixodes ticks in the environment can be reduced by relatively simple interventions such as removing leaf litter and brush, which increases exposure of the tick to sun and air and takes advantage of the tick's vulnerability to desiccation, or by application of acaricides to property. Deer elimination or exclusion, application of topical acaricides to mice or deer, and application of systemic acaricides to deer are more complex approaches. However, none of these methods for reducing tick numbers, nor any of the recommended personal prevention measures, such as reducing the amount of exposed skin, use of tick repellents on exposed skin or clothing, and frequent tick checks to remove attached ticks expeditiously, has been demonstrated to decrease significantly the incidence of Lyme borreliosis in humans. Only two strategies have been shown to do so. A recombinant outer surface protein A (OspA) vaccine was approximately 80% effective in clinical trials in the United States, and a single 200 mg dose of doxycycline given within 72 hours of an I. scapularis tick bite, was shown to be 87% effective. The OspA vaccine is no longer manufactured due to poor sales. Consequently, single-dose doxycycline prophylaxis is rapidly gaining acceptance in the United States. Limiting single-dose doxycycline to just the highest risk tick bites can be accomplished if the health care provider has learned to differentiate engorged from unengorged I. scapularis ticks. Limitations of single-dose doxycycline prophylaxis are that the majority of patients with Lyme borreliosis do not recall a tick bite, and that there is no evidence that other Ixodes transmitted infections, such as human granulocytic ehrlichiosis, would be prevented. A safe, effective, inexpensive and well-accepted vaccine would be welcome.

  10. Epidemiology of Lyme disease.

    PubMed

    Mead, Paul S

    2015-06-01

    Lyme disease is the most common vector-borne illness in North America and Europe. The etiologic agent, Borrelia burgdorferi sensu lato, is transmitted to humans by certain species of Ixodes ticks, which are found widely in temperate regions of the Northern hemisphere. Clinical features are diverse, but death is rare. The risk of human infection is determined by the geographic distribution of vector tick species, ecologic factors that influence tick infection rates, and human behaviors that promote tick bite. Rates of infection are highest among children 5 to 15 years old and adults older than 50 years.

  11. New insights into Lyme disease.

    PubMed

    Peacock, Brandon N; Gherezghiher, Teshome B; Hilario, Jennifer D; Kellermann, Gottfried H

    2015-08-01

    Lyme borreliosis is transmitted through the bite of a tick that is infected by the bacterial spirochete Borrelia burgdorferi. Clinical manifestation of the disease can lead to heart conditions, neurological disorders, and inflammatory disorders. Oxidative stress has been implicated in the pathogenesis of many human diseases. The aim of this study was to investigate the mechanisms of oxidative stress and intracellular communication in Lyme borreliosis patients. Mitochondrial superoxide and cytosolic ionized calcium was measured in peripheral blood mononuclear cells (PBMCs) of Lyme borreliosis patients and healthy controls. Mitochondrial superoxide levels were significantly higher (p<0.0001) in Lyme borreliosis patients (n=32) as compared to healthy controls (n=30). Significantly low (p<0.0001) levels of cytosolic ionized calcium were also observed in Lyme borreliosis patients (n=11) when compared to healthy controls (n=11). These results indicate that there is an imbalance of reactive oxygen species and cytosolic calcium in Lyme borreliosis patients. The results further suggest that oxidative stress and interrupted intracellular communication may ultimately contribute to a condition of mitochondrial dysfunction in the immune cells of Lyme borreliosis patients.

  12. Epitope-Specific Evolution of Human B Cell Responses to Borrelia burgdorferi VlsE Protein from Early to Late Stages of Lyme Disease.

    PubMed

    Jacek, Elzbieta; Tang, Kevin S; Komorowski, Lars; Ajamian, Mary; Probst, Christian; Stevenson, Brian; Wormser, Gary P; Marques, Adriana R; Alaedini, Armin

    2016-02-01

    Most immunogenic proteins of Borrelia burgdorferi, the causative agent of Lyme disease, are known or expected to contain multiple B cell epitopes. However, the kinetics of the development of human B cell responses toward the various epitopes of individual proteins during the course of Lyme disease has not been examined. Using the highly immunogenic VlsE as a model Ag, we investigated the evolution of humoral immune responses toward its immunodominant sequences in 90 patients with a range of early to late manifestations of Lyme disease. The results demonstrate the existence of asynchronous, independently developing, Ab responses against the two major immunogenic regions of the VlsE molecule in the human host. Despite their strong immunogenicity, the target epitopes were inaccessible to Abs on intact spirochetes, suggesting a lack of direct immunoprotective effect. These observations document the association of immune reactivity toward specific VlsE sequences with different phases of Lyme disease, demonstrating the potential use of detailed epitope mapping of Ags for staging of the infection, and offer insights regarding the pathogen's possible immune evasion mechanisms.

  13. Lyme Disease in South America?

    DTIC Science & Technology

    1991-01-01

    20889-5044 ELEMENT NO. NO. NO. ACCESSION NO. 11 TITLE (include Security Classification) Lyme disease in South America? 12. PERSONAL AUTHOR(S) Need JI...secretor state and susceptilty to recurrent 002~2 IS500’) h101i o()52iil i0i urinary, tract Infection in ssiimcn. BNIJ 1982.285>7 Lyme Disease in South...antiboy in human serum. I an irbo19;22347 tial vectors. 7. arbour AG. The diagnosis of Lyme disease ; rewards and perils. Ann j Intern Med 1989:110:501

  14. Lyme Borreliosis and Skin

    PubMed Central

    Vasudevan, Biju; Chatterjee, Manas

    2013-01-01

    Lyme disease is a multisystem illness which is caused by the strains of spirochete Borrelia burgdorferi sensu lato and transmitted by the tick, Ixodes. Though very commonly reported from the temperate regions of the world, the incidence has increased worldwide due to increasing travel and changing habitats of the vector. Few cases have been reported from the Indian subcontinent too. Skin manifestations are the earliest to occur, and diagnosing these lesions followed by appropriate treatment, can prevent complications of the disease, which are mainly neurological. The three main dermatological manifestations are erythema chronicum migrans, borrelial lymphocytoma and acrodermatitis chronica atrophicans. Many other dermatological conditions including morphea, lichen sclerosus and lately B cell lymphoma, have been attributed to the disease. Immunofluorescence and polymerase reaction tests have been developed to overcome the problems for diagnosis. Culture methods are also used for diagnosis. Treatment with Doxycycline is the mainstay of management, though prevention is of utmost importance. Vaccines against the condition are still not very successful. Hence, the importance of recognising the cutaneous manifestations early, to prevent systemic complications which can occur if left untreated, can be understood. This review highlights the cutaneous manifestations of Lyme borreliosis and its management. PMID:23723463

  15. No Geographic Correlation between Lyme Disease and Death Due to 4 Neurodegenerative Disorders, United States, 2001-2010.

    PubMed

    Forrester, Joseph D; Kugeler, Kiersten J; Perea, Anna E; Pastula, Daniel M; Mead, Paul S

    2015-11-01

    Associations between Lyme disease and certain neurodegenerative diseases have been proposed, but supportive evidence for an association is lacking. Similar geographic distributions would be expected if 2 conditions were etiologically linked. Thus, we compared the distribution of Lyme disease cases in the United States with the distributions of deaths due to Alzheimer disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Parkinson disease; no geographic correlations were identified. Lyme disease incidence per US state was not correlated with rates of death due to ALS, MS, or Parkinson disease; however, an inverse correlation was detected between Lyme disease and Alzheimer disease. The absence of a positive correlation between the geographic distribution of Lyme disease and the distribution of deaths due to Alzheimer disease, ALS, MS, and Parkinson disease provides further evidence that Lyme disease is not associated with the development of these neurodegenerative conditions.

  16. Lyme disease: considerations for dentistry.

    PubMed

    Heir, G M; Fein, L A

    1996-01-01

    Although Lyme disease has spread rapidly and it is difficult to diagnose, a review of the dental literature does not reveal many references to this illness. Dental practitioners must be aware of the systemic effects of this often multiorgan disorder. Its clinical manifestations may include facial and dental pain, facial nerve palsy, headache, temporomandibular joint pain, and masticatory muscle pain. The effects precipitated when performing dental procedures on a patient with Lyme disease must also be considered. This study discusses the epidemiology and diagnosis of Lyme disease, its prevention, and factors to consider when making a differential diagnosis. Dental care of the patient with Lyme disease and currently available treatments also are considered. Three case reports are presented.

  17. Laboratory aspects of Lyme borreliosis.

    PubMed Central

    Barbour, A G

    1988-01-01

    Lyme borreliosis (Lyme disease), a common tick-borne disorder of people and domestic animals in North America and Europe, is caused by the spirochete Borrelia burgdorferi. Following the discovery and initial propagation of this agent in 1981 came revelations that other tick-associated infectious disorders are but different forms of Lyme borreliosis. A challenge for the clinician and microbiology laboratory is confirmation that a skin rash, a chronic meningitis, an episode of myocarditis, or an arthritic joint is the consequence of B. burgdorferi infection. The diagnosis of Lyme borreliosis may be established by (i) directly observing the spirochete in host fluid or tissue, (ii) recovering the etiologic spirochete from the patient in culture medium or indirectly through inoculation of laboratory animals, or (iii) carrying out serologic tests with the patient's serum or cerebrospinal fluid. The last method, while lacking in discriminatory power, is the most efficacious diagnostic assay for most laboratories at present. Images PMID:3069200

  18. Treatment of Lyme borreliosis

    PubMed Central

    2009-01-01

    Borrelia burgdorferi sensu lato is the causative agent of Lyme borreliosis in humans. This inflammatory disease can affect the skin, the peripheral and central nervous system, the musculoskeletal and cardiovascular system and rarely the eyes. Early stages are directly associated with viable bacteria at the site of inflammation. The pathogen-host interaction is complex and has been elucidated only in part. B. burgdorferi is highly susceptible to antibiotic treatment and the majority of patients profit from this treatment. Some patients develop chronic persistent disease despite repeated antibiotics. Whether this is a sequel of pathogen persistence or a status of chronic auto-inflammation, auto-immunity or a form of fibromyalgia is highly debated. Since vaccination is not available, prevention of a tick bite or chemoprophylaxis is important. If the infection is manifest, then treatment strategies should target not only the pathogen by using antibiotics but also the chronic inflammation by using anti-inflammatory drugs. PMID:20067594

  19. Reconciling catch differences from multiple fishery independent gill net surveys

    USGS Publications Warehouse

    Kraus, Richard T.; Vandergoot, Christopher; Kocovsky, Patrick M.; Rogers, Mark W.; Cook, H. Andrew; Brenden, Travis O.

    2017-01-01

    Fishery independent gill net surveys provide valuable demographic information for population assessment and resource management, but relative to net construction, the effects of ancillary species, and environmental variables on focal species catch rates are poorly understood. In response, we conducted comparative deployments with three unique, inter-agency, survey gill nets used to assess walleye Sander vitreus in Lake Erie. We used an information-theoretic approach with Akaike’s second-order information criterion (AICc) to evaluate linear mixed models of walleye catch as a function of net type (multifilament and two types of monofilament netting), mesh size (categorical), Secchi depth, temperature, water depth, catch of ancillary species, and interactions among selected variables. The model with the greatest weight of evidence showed that walleye catches were positively associated with potential prey and intra-guild predators and negatively associated with water depth and temperature. In addition, the multifilament net had higher average walleye catches than either of the two monofilament nets. Results from this study both help inform decisions about proposed gear changes to stock assessment surveys in Lake Erie, and advance our understanding of how multispecies associations explain variation in gill net catches. Of broader interest to fishery-independent gill net studies, effects of abiotic variables and ancillary species on focal specie’s catch rates were small in comparison with net characteristics of mesh size or twine type.

  20. Multiple independent introductions of Plasmodium falciparum in South America

    PubMed Central

    Yalcindag, Erhan; Elguero, Eric; Arnathau, Céline; Durand, Patrick; Akiana, Jean; Anderson, Timothy J.; Aubouy, Agnes; Balloux, François; Besnard, Patrick; Bogreau, Hervé; Carnevale, Pierre; D'Alessandro, Umberto; Fontenille, Didier; Gamboa, Dionicia; Jombart, Thibaut; Le Mire, Jacques; Leroy, Eric; Maestre, Amanda; Mayxay, Mayfong; Ménard, Didier; Musset, Lise; Newton, Paul N.; Nkoghé, Dieudonné; Noya, Oscar; Ollomo, Benjamin; Rogier, Christophe; Veron, Vincent; Wide, Albina; Zakeri, Sedigheh; Carme, Bernard; Legrand, Eric; Chevillon, Christine; Ayala, Francisco J.; Renaud, François; Prugnolle, Franck

    2012-01-01

    The origin of Plasmodium falciparum in South America is controversial. Some studies suggest a recent introduction during the European colonizations and the transatlantic slave trade. Other evidence—archeological and genetic—suggests a much older origin. We collected and analyzed P. falciparum isolates from different regions of the world, encompassing the distribution range of the parasite, including populations from sub-Saharan Africa, the Middle East, Southeast Asia, and South America. Analyses of microsatellite and SNP polymorphisms show that the populations of P. falciparum in South America are subdivided in two main genetic clusters (northern and southern). Phylogenetic analyses, as well as Approximate Bayesian Computation methods suggest independent introductions of the two clusters from African sources. Our estimates of divergence time between the South American populations and their likely sources favor a likely introduction from Africa during the transatlantic slave trade. PMID:22203975

  1. New haptophyte lineages and multiple independent colonizations of freshwater ecosystems.

    PubMed

    Simon, Marianne; López-García, Purificación; Moreira, David; Jardillier, Ludwig

    2013-04-01

    The diversity and ecological relevance of small haptophytes in marine systems is increasingly recognized. Similar investigations in freshwater remain scarce, despite some recent studies showing the existence of divergent haptophyte lineages and indicating that these microalgae can occur at high abundance in lakes. We studied the diversity of haptophytes in a wide variety of marine, salty continental and, most particularly, freshwater environments by amplifying, cloning and sequencing 18S rRNA genes. For this purpose, we designed two sets of primers specific for the two recognized haptophyte classes, Prymnesiophyceae and Pavlovophyceae. We detected pavlovophyte sequences only in freshwater systems as well as several novel prymnesiophyte phylotypes in both freshwater and marine environments. In addition, we retrieved a cluster of sequences (HAP-3) from the Marmara Sea branching deeply in the haptophyte tree with no clear affiliation to either of the two recognized classes. Five of the freshwater prymnesiophyte phylotypes detected formed a divergent monophyletic group (EV) without close described representatives that branched within the Isochrysidales, a group of generally marine and most often calcifying coccolithophorids. The presence of several sequences of freshwater haptophytes scattered among marine taxa in phylogenetic trees confirms the occurrence of several independent haptophyte transitions between marine and freshwater environments.

  2. Delivering multiple independent RIB simultaneously: Technical and operational challenges

    NASA Astrophysics Data System (ADS)

    Morton, A. C.

    2016-06-01

    ISAC is an ISOL-type facility at which RIB are produced by direct reactions of 480 MeV protons from TRIUMFs main cyclotron on thick targets. Like other ISOL-type facilities, ISAC is limited to the production and delivery of a single RIB at any given time. ARIEL, the Advanced Rare-IsotopE Laboratory, will provide for the production and delivery of, ultimately, two additional RIB, the first produced by photofission on actinide targets using electrons from a new superconducting electron linac and the second by direct and indirect reactions with protons from TRIUMFs main cyclotron. This will allow for the simultaneous delivery of three independent RIB to experimental areas at ARIEL and ISAC. The shift from single-user to multi-user operation will introduce significant technical and operational challenges that RIB facilities have not yet had to address. Almost all aspects of facility operation will become more complex as the first RIB from ARIEL targets become available.

  3. Post-Lyme disease syndrome.

    PubMed

    Ścieszka, Joanna; Dąbek, Józefa; Cieślik, Paweł

    2015-01-01

    About 10% of patients with Lyme disease continue to experience musculoskeletal pain and cognitive dysfunction after recommended antibiotic treatment. This condition is called post-Lyme disease syndrome (PLDS) or post-treatment Lyme disease syndrome. These two terms are used interchangeably. The pathogenesis of PLDS has been controversial. The hypothesis that patients with PLDS may harbor hidden reservoirs of Borrelia burgdorferi after their initial antibiotic treatment is difficult to accept. The prospective, double-blind studies contradict this point of view. Also, recently published research applying xenodiagnosis to PLDS supports the opinion that PLDS most likely has an autoimmune background. Lengthy courses of antibiotics are not justified in patients with PLDS because of the lack of benefit, and they are fraught with hazards. Most patients with PLDS recover from persistent symptoms with time. However, it can take months before they feel completely well.

  4. Post-Lyme disease syndrome

    PubMed Central

    Dąbek, Józefa; Cieślik, Paweł

    2015-01-01

    About 10% of patients with Lyme disease continue to experience musculoskeletal pain and cognitive dysfunction after recommended antibiotic treatment. This condition is called post-Lyme disease syndrome (PLDS) or post-treatment Lyme disease syndrome. These two terms are used interchangeably. The pathogenesis of PLDS has been controversial. The hypothesis that patients with PLDS may harbor hidden reservoirs of Borrelia burgdorferi after their initial antibiotic treatment is difficult to accept. The prospective, double-blind studies contradict this point of view. Also, recently published research applying xenodiagnosis to PLDS supports the opinion that PLDS most likely has an autoimmune background. Lengthy courses of antibiotics are not justified in patients with PLDS because of the lack of benefit, and they are fraught with hazards. Most patients with PLDS recover from persistent symptoms with time. However, it can take months before they feel completely well. PMID:27407225

  5. Multiple correlation computer program determines relationships between several independent and dependent variables

    NASA Technical Reports Server (NTRS)

    Kaspar, H.; Newsbaum, J. B.

    1967-01-01

    Relationships between independent and dependent variables are determined by multiple correlation computer program. This is applied to research and experimental design and development of complex hardware and components that require test programs.

  6. Recognising and understanding Lyme disease.

    PubMed

    Pearson, Sandra

    2014-09-09

    Lyme disease is the most common vector-borne disease in the northern hemisphere and its incidence is rising, leading to increased public health concerns. It is important to understand the nature of the disease because this defines the limitations of current understanding and knowledge. Significant uncertainties in diagnostics and treatment remain. There is an important role for the nurse in raising awareness, giving advice on prevention and correct tick removal, and in recognising signs of Lyme disease to assist access to prompt medical attention. Increased awareness, further research, improved diagnostics and advances in therapeutics are urgently required.

  7. Forest fragmentation and Lyme disease

    EPA Science Inventory

    Lyme disease is the most commonly reported vectorborne disease in the United States. It is associated with human exposure to infected Ixodes ticks which exist even in degraded forest and herbaceous habitat. We provide an overview of the epidemiology, ecology and landscape charact...

  8. Neurological Complications of Lyme Disease

    MedlinePlus

    ... after a tick bite, include decreased concentration, irritability, memory and sleep disorders, and nerve damage in the arms and legs. × Definition Lyme disease is caused by a bacterial organism that is transmitted to humans via the bite of an infected tick. Most ...

  9. [Post-Lyme disease syndrome].

    PubMed

    Błaut-Jurkowska, Justyna; Jurkowski, Marcin

    2016-02-01

    Lyme disease is a chronic infectious disease caused by the bacteria, spirochete of the Borrelia type. Skin, nervous system, musculoskeletal system and heart may be involved in the course of the disease. The prognosis for properly treated Lyme disease is usually good. However, in about 5% of patients so called Post-Lyme disease syndrome (PLSD) develops. It is defined as a syndrome of subjective symptoms persisting despite proper treatment of Borrelia burgdorferi infection. The most common symptoms include: fatigue, muscle and joint pain, and problems with memory and concentration. Pathogenesis of PLDS remains unknown. The differential diagnosis should include neurological, rheumatic and mental diseases. Till now there is no causative treatment of PLDS. In relieving symptom rehabilitation, painkillers, anti-inflammatory and antidepressants medicines are recommended. Emotional and psychological supports are also necessary. Non-specific symptoms reported by patients with post- Lyme disease syndrome raise the suspicion of other pathologies. This can lead to misdiagnosis and implementation of unnecessary, potentially harmful to the patient's therapy. An increase in tick-borne diseases needs to increase physicians awareness of these issues.

  10. Lyme Disease Comes to Camp.

    ERIC Educational Resources Information Center

    Peterson, Michael

    1989-01-01

    Describes one summer camp's plan for dealing with Lyme disease. Describes the disease and the deer tick. Recommends avoiding tick exposure through clothing, frequent examination, showers, and avoiding high grass and brushy areas, and using chemical insect repellents and chemicals to kill ticks in deer mouse nests. (DHP)

  11. [Winged scapula in lyme borreliosis].

    PubMed

    Rausch, V; Königshausen, M; Gessmann, J; Schildhauer, T A; Seybold, D

    2016-06-01

    Here we present the case of a young patient with one-sided winged scapula and lyme borreliosis. This disease can be very delimitating in daily life. If non-operative treatment fails, dynamic or static stabilization of the scapula can be a therapeutic option.

  12. Scintigraphic evaluation of Lyme disease: Gallium-67 imaging of Lyme myositis

    SciTech Connect

    Kengen, R.A.; v.d. Linde, M.; Sprenger, H.G.; Piers, D.A. )

    1989-10-01

    A patient suffering from Lyme disease had cardiac conduction abnormalities, symptoms of arthritis, and myalgia. A Ga-67 image showed evidence of endomyocarditis, but intense skeletal muscle uptake pointed to Lyme myositis. Reference is made to two other case reports of Lyme myositis.

  13. Hypersensitivity to ticks and Lyme disease risk.

    PubMed

    Burke, Georgine; Wikel, Stephen K; Spielman, Andrew; Telford, Sam R; McKay, Kathleen; Krause, Peter J

    2005-01-01

    Although residents of Lyme disease-endemic regions describe frequent exposure to ticks, Lyme disease develops in relatively few. To determine whether people who experience cutaneous hypersensitivity against tick bite have fewer episodes of Lyme disease than those who do not, we examined several factors that might restrict the incidence of Lyme disease among residents of Block Island, Rhode Island. Of 1,498 study participants, 27% (95% confidence interval [CI] 23%-31%) reported > or = 1 tick bites, and 17% (95% CI 13%-21%) reported itch associated with tick bite in the previous year. Borrelia burgdorferi infected 23% (95% CI 20%-26%) of 135 nymphal Ixodes scapularis (I. dammini) ticks. The likelihood of Lyme disease infection decreased with >3 reports of tick-associated itch (odds ratio 0.14, 95% CI 0.94-0.03, p = 0.01). Prior exposure to uninfected vector ticks protects residents of disease-endemic sites from Lyme disease.

  14. Clinical Manifestations and Treatment of Lyme Disease.

    PubMed

    Sanchez, Joyce L

    2015-12-01

    Lyme disease is the most common tick-borne illness in the United States and is also seen in areas of Europe and Asia. The growing deer and Ixodes species tick populations in many areas underscore the importance of clinicians to properly recognize and treat the different stages of Lyme disease. Controversy regarding the cause and management of persistent symptoms following treatment of Lyme disease persists and is highlighted in this review.

  15. Photonic generation and independent steering of multiple RF signals for software defined radars.

    PubMed

    Ghelfi, Paolo; Laghezza, Francesco; Scotti, Filippo; Serafino, Giovanni; Pinna, Sergio; Bogoni, Antonella

    2013-09-23

    As the improvement of radar systems claims for digital approaches, photonics is becoming a solution for software defined high frequency and high stability signal generation. We report on our recent activities on the photonic generation of flexible wideband RF signals, extending the proposed architecture to the independent optical beamforming of multiple signals. The scheme has been tested generating two wideband signals at 10 GHz and 40 GHz, and controlling their independent delays at two antenna elements. Thanks to the multiple functionalities, the proposed scheme allows to improve the effectiveness of the photonic approach, reducing its cost and allowing flexibility, extremely wide bandwidth, and high stability.

  16. Variability in results from negative binomial models for Lyme disease measured at different spatial scales.

    PubMed

    Tran, Phoebe; Waller, Lance

    2015-01-01

    Lyme disease has been the subject of many studies due to increasing incidence rates year after year and the severe complications that can arise in later stages of the disease. Negative binomial models have been used to model Lyme disease in the past with some success. However, there has been little focus on the reliability and consistency of these models when they are used to study Lyme disease at multiple spatial scales. This study seeks to explore how sensitive/consistent negative binomial models are when they are used to study Lyme disease at different spatial scales (at the regional and sub-regional levels). The study area includes the thirteen states in the Northeastern United States with the highest Lyme disease incidence during the 2002-2006 period. Lyme disease incidence at county level for the period of 2002-2006 was linked with several previously identified key landscape and climatic variables in a negative binomial regression model for the Northeastern region and two smaller sub-regions (the New England sub-region and the Mid-Atlantic sub-region). This study found that negative binomial models, indeed, were sensitive/inconsistent when used at different spatial scales. We discuss various plausible explanations for such behavior of negative binomial models. Further investigation of the inconsistency and sensitivity of negative binomial models when used at different spatial scales is important for not only future Lyme disease studies and Lyme disease risk assessment/management but any study that requires use of this model type in a spatial context.

  17. WAIS-III and WMS-III performance in chronic Lyme disease.

    PubMed

    Keilp, John G; Corbera, Kathy; Slavov, Iordan; Taylor, Michael J; Sackeim, Harold A; Fallon, Brian A

    2006-01-01

    There is controversy regarding the nature and degree of intellectual and memory deficits in chronic Lyme disease. In this study, 81 participants with rigorously diagnosed chronic Lyme disease were administered the newest revisions of the Wechsler Adult Intelligence Scale (WAIS-III) and Wechsler Memory Scale (WMS-III), and compared to 39 nonpatients. On the WAIS-III, Lyme disease participants had poorer Full Scale and Performance IQ's. At the subtest level, differences were restricted to Information and the Processing Speed subtests. On the WMS-III, Lyme disease participants performed more poorly on Auditory Immediate, Immediate, Auditory Delayed, Auditory Recognition Delayed, and General Memory indices. Among WMS-III subtests, however, differences were restricted to Logical Memory (immediate and delayed) and Family Pictures (delayed only), a Visual Memory subtest. Discriminant analyses suggest deficits in chronic Lyme are best characterized as a combination of memory difficulty and diminished processing speed. Deficits were modest, between one-third and two-thirds of a standard deviation, consistent with earlier studies. Depression severity had a weak relationship to processing speed, but little other association to test performance. Deficits in chronic Lyme disease are consistent with a subtle neuropathological process affecting multiple performance tasks, although further work is needed to definitively rule out nonspecific illness effects.

  18. Helping Three Persons with Multiple Disabilities Acquire Independent Dressing Through Assistive Technology

    ERIC Educational Resources Information Center

    Lancioni, Giulio E.; O'Reilly, Mark F.; Singh, Nirbhay N.; Sigafoos, Jeff; Oliva, Doretta; Campodonico, Francesca; Groeneweg, Jop

    2007-01-01

    Enabling persons with intellectual or multiple disabilities to carry out personal care tasks (such as washing and dressing) independent of guidance from parents or staff members and without prolonged interruptions is often difficult, particularly with persons whose disabilities also include visual impairments. Attempts were recently made to curb…

  19. Datafish Multiphase Data Mining Technique to Match Multiple Mutually Inclusive Independent Variables in Large PACS Databases.

    PubMed

    Kelley, Brendan P; Klochko, Chad; Halabi, Safwan; Siegal, Daniel

    2016-06-01

    Retrospective data mining has tremendous potential in research but is time and labor intensive. Current data mining software contains many advanced search features but is limited in its ability to identify patients who meet multiple complex independent search criteria. Simple keyword and Boolean search techniques are ineffective when more complex searches are required, or when a search for multiple mutually inclusive variables becomes important. This is particularly true when trying to identify patients with a set of specific radiologic findings or proximity in time across multiple different imaging modalities. Another challenge that arises in retrospective data mining is that much variation still exists in how image findings are described in radiology reports. We present an algorithmic approach to solve this problem and describe a specific use case scenario in which we applied our technique to a real-world data set in order to identify patients who matched several independent variables in our institution's picture archiving and communication systems (PACS) database.

  20. Sexual transmission of Lyme disease: challenging the tickborne disease paradigm.

    PubMed

    Stricker, Raphael B; Middelveen, Marianne J

    2015-01-01

    Lyme disease caused by the spirochete Borrelia burgdorferi has become a major worldwide epidemic. In this article, we explore the clinical, epidemiological and experimental evidence for sexual transmission of Lyme disease in animal models and humans. Although the likelihood of sexual transmission of the Lyme spirochete remains speculative, the possibility of Lyme disease transmission via intimate human contact merits further study.

  1. Sunburn and Lyme Disease: Two Preventable Injuries.

    ERIC Educational Resources Information Center

    Pavlicin, Karen M.

    1995-01-01

    Stresses the importance of educating campers and staff about the dangers of overexposure to the sun and the transmission of Lyme disease. Discusses the importance of using an appropriate sunscreen and avoiding outdoor activities during peak hours of sunlight. Discusses how Lyme disease is transmitted, the life cycle of a tick, and how to remove…

  2. Lyme neuroborreliosis-epidemiology, diagnosis and management.

    PubMed

    Koedel, Uwe; Fingerle, Volker; Pfister, Hans-Walter

    2015-08-01

    Lyme disease, caused by the Borrelia burgdorferi bacterium, is the most common vector-borne disease in the northern hemisphere. The clinical presentation varies with disease stage, and neurological manifestations (often referred to as Lyme neuroborreliosis) are reported in up to 12% of patients with Lyme disease. Most aspects of the epidemiology, clinical manifestation and treatment of Lyme neuroborreliosis are well known and accepted; only the management of so-called chronic Lyme disease is surrounded by considerable controversy. This term is used for disparate patient groups, including those who have untreated late-stage infection (for example, late neuroborreliosis), those with subjective symptoms that persist after treatment (termed 'post-treatment Lyme disease syndrome' [PTLDS]), and those with unexplained subjective complaints that may or may not be accompanied by positive test results for B. burgdorferi infection in serum (here called 'chronic Lyme disease'). The incidence of PTLDS is still a matter of debate, and its pathogenesis is unclear, but there is evidence that these patients do not have ongoing B. burgdorferi infection and, thus, do not benefit from additional antibiotic therapy. Chronic Lyme disease lacks an accepted clinical definition, and most patients who receive this diagnosis have other illnesses. Thus, a careful diagnostic work-up is needed to ensure proper treatment.

  3. Sinus pause in association with Lyme carditis.

    PubMed

    Oktay, A Afsin; Dibs, Samer R; Friedman, Harvey

    2015-06-01

    Lyme disease is the most prevalent tick-borne disease in the United States. It is caused by the spirochete Borrelia burgdorferi. Cardiac involvement is seen in 4% to 10% of patients with Lyme disease. The principal manifestation of Lyme carditis is self-limited conduction system disease, with predominant involvement of the atrioventricular node. On rare occasions, Lyme carditis patients present with other conduction system disorders such as bundle branch block, intraventricular conduction delay, and supraventricular or ventricular tachycardia. We report the unusual case of a 59-year-old man who presented with new-onset symptomatic sinus pauses one month after hiking in upstate New York. To our knowledge, this is the first case report from North America that describes the relationship between symptomatic sinus pause and Lyme carditis.

  4. Lyme disease: neurology, neurobiology, and behavior.

    PubMed

    Halperin, John J

    2014-05-01

    The Lyme disease controversy can be largely linked to the misconception that neurobehavioral effects of illness constitute evidence of nervous system infection. Appropriate differentiation between neuroborreliosis (nervous system Borrelia burgdorferi infection) and Lyme encephalopathy (altered nervous system function in individuals with systemic but not nervous system infection)-or encephalopathies of other etiologies-would lessen the controversy considerably, as the attribution of nonspecific symptoms to supposed ongoing central nervous system infection is a major factor perpetuating the debate. Epidemiologic considerations suggest that the entities referred to as "posttreatment Lyme disease" and "chronic Lyme disease" may not actually exist but rather reflect anchoring bias, linking common, nonspecific symptoms to an antecedent medical event. On the other hand, there are data suggesting possible mechanisms by which posttreatment Lyme disease could occur.

  5. Sinus Pause in Association with Lyme Carditis

    PubMed Central

    Dibs, Samer R.; Friedman, Harvey

    2015-01-01

    Lyme disease is the most prevalent tick-borne disease in the United States. It is caused by the spirochete Borrelia burgdorferi. Cardiac involvement is seen in 4% to 10% of patients with Lyme disease. The principal manifestation of Lyme carditis is self-limited conduction system disease, with predominant involvement of the atrioventricular node. On rare occasions, Lyme carditis patients present with other conduction system disorders such as bundle branch block, intraventricular conduction delay, and supraventricular or ventricular tachycardia. We report the unusual case of a 59-year-old man who presented with new-onset symptomatic sinus pauses one month after hiking in upstate New York. To our knowledge, this is the first case report from North America that describes the relationship between symptomatic sinus pause and Lyme carditis. PMID:26175640

  6. Diagnostic impact of routine Lyme serology in recent-onset arthritis: results from the ESPOIR cohort

    PubMed Central

    Guellec, Dewi; Narbonne, Valérie; Cornec, Divi; Marhadour, Thierry; Varache, Sophie; Dougados, Maxime; Daurès, Jean Pierre; Jousse-Joulin, Sandrine; Devauchelle-Pensec, Valérie; Saraux, Alain

    2016-01-01

    Objectives Lyme disease may be considered by rheumatologists in patients with recent-onset arthritis, even in the absence of suggestive symptoms. The aim of this study was to determine the diagnostic impact of routine Lyme serology in a French cohort of patients with recent-onset arthritis affecting at least 2 joints. Methods We performed an ancillary study of a French prospective multicentre cohort established to monitor clinical, biological and radiographic data in patients with inflammatory arthritis in at least 2 joints, lasting for 6 weeks to 6 months. Borrelia IgM and IgG antibodies were sought routinely at baseline, using ELISA tests, independently from the physician's strategy for detecting a spirochetal infection. We recorded the proportion of patients with a final diagnosis of Lyme arthritis and evaluated the diagnostic performance of Lyme serology in this particular context. The clinical and biological characteristics of patients according to the Lyme serology results were analysed. Results Of 810 patients, 657 (81.1%) were negative for IgM and IgG antibodies, 91 (11.2%) had only IgM antibodies, 49 (6%) had only IgG antibodies, and 13 (1.6%) had IgG and IgM antibodies. Thus, 7.6% had IgG positivity, consistent with exposure to Borrelia infection. IgG positivity was significantly more prevalent in the North and North-East regions of France (χ2=14.6, p<0.001). No patients received a definite diagnosis of Lyme arthritis. Conclusions This study does not support routine Lyme serological testing in patients with recent-onset inflammatory arthritis affecting more than 1 joint. PMID:26819751

  7. [Lyme disease: how widespread is the problem?].

    PubMed

    van der Horst, Henriëtte E

    2014-01-01

    Lyme disease is the cause of a lot of anxiety and discussion. Patients are demanding more preventive actions to avoid tick bites, and earlier and better diagnosis of Lyme disease. However, only a minority of people bitten by a tick go on to develop Lyme disease. Although physician delay may lead to a late diagnosis of disseminated Lyme disease, these patients are still treatable and even in bad cases, symptoms will subside within a few years. While we know that serious complications of late disseminated Lyme, e.g. neuroborreliosis, are very rare, there is still uncertainty about how often Lyme disease occurs, and how often the diagnosis is delayed. The high prevalence of seropositive people in the population suggests that many people clear the infection without any symptoms and without any treatment. Some decades ago mononucleosis infectiosa also had a bad reputation but this largely disappeared when it became clear that recovery is the rule. Lyme disease may also shed its reputation once the facts are known.

  8. Does Lyme disease exist in Australia?

    PubMed

    Collignon, Peter J; Lum, Gary D; Robson, Jennifer Mb

    2016-11-07

    There is no convincing evidence that classic Lyme disease occurs in Australia, nor is there evidence that the causative agent, Borrelia burgdorferi, is found in Australian animals or ticks. Lyme disease, however, can be acquired overseas but diagnosed in Australia; most people presenting with laboratory-confirmed Lyme disease in Australia were infected in Europe. Despite the lack of evidence that Lyme disease can be acquired in Australia, growing numbers of patients, their supporters, and some politicians demand diagnoses and treatment according to the protocols of the "chronic Lyme disease" school of thought. Antibiotic therapy for chronic "Lyme disease-like illness" can cause harm to both the individual (eg, cannula-related intravenous sepsis) and the broader community (increased antimicrobial resistance rates). Until there is strong evidence from well performed clinical studies that bacteria present in Australia cause a chronic debilitating illness that responds to prolonged antibiotics, treating patients with "Lyme disease-like illness" with prolonged antibiotic therapy is unjustified, and is likely to do much more harm than good.

  9. Identification of multiple independent horizontal gene transfers into poxviruses using a comparative genomics approach

    PubMed Central

    2008-01-01

    Background Poxviruses are important pathogens of humans, livestock and wild animals. These large dsDNA viruses have a set of core orthologs whose gene order is extremely well conserved throughout poxvirus genera. They also contain many genes with sequence and functional similarity to host genes which were probably acquired by horizontal gene transfer. Although phylogenetic trees can indicate the occurrence of horizontal gene transfer and even uncover multiple events, their use may be hampered by uncertainties in both the topology and the rooting of the tree. We propose to use synteny conservation around the horizontally transferred gene (HTgene) to distinguish between single and multiple events. Results Here we devise a method that incorporates comparative genomic information into the investigation of horizontal gene transfer, and we apply this method to poxvirus genomes. We examined the synteny conservation around twenty four pox genes that we identified, or which were reported in the literature, as candidate HTgenes. We found support for multiple independent transfers into poxviruses for five HTgenes. Three of these genes are known to be important for the survival of the virus in or out of the host cell and one of them increases susceptibility to some antiviral drugs. Conclusion In related genomes conserved synteny information can provide convincing evidence for multiple independent horizontal gene transfer events even in the absence of a robust phylogenetic tree for the HTgene. PMID:18304319

  10. Diagnosis and treatment of Lyme arthritis.

    PubMed

    Arvikar, Sheila L; Steere, Allen C

    2015-06-01

    In the United States, Lyme arthritis is the most common feature of late-stage Borrelia burgdorferi infection, usually beginning months after the initial bite. In some, earlier phases are asymptomatic and arthritis is the presenting manifestation. Patients with Lyme arthritis have intermittent or persistent attacks of joint swelling and pain in 1 or a few large joints. Serologic testing is the mainstay of diagnosis. Synovial fluid polymerase chain reaction for B burgdorferi DNA is often positive before treatment, but is not a reliable marker of spirochetal eradication after therapy. This article reviews the clinical manifestations, diagnosis, and management of Lyme arthritis.

  11. Testing Multiple Psychological Processes for Common Neural Mechanisms Using EEG and Independent Component Analysis.

    PubMed

    Wessel, Jan R

    2016-03-08

    Temporal independent component analysis (ICA) is applied to an electrophysiological signal mixture (such as an EEG recording) to disentangle the independent neural source signals-independent components-underlying said signal mixture. When applied to scalp EEG, ICA is most commonly used either as a pre-processing step (e.g., to isolate physiological processes from non-physiological artifacts), or as a data-reduction step (i.e., to focus on one specific neural process with increased signal-to-noise ratio). However, ICA can be used in an even more powerful way that fundamentally expands the inferential utility of scalp EEG. The core assumption of EEG-ICA-namely, that individual independent components represent separable neural processes-can be leveraged to derive the following inferential logic: If a specific independent component shows activity related to multiple psychological processes within the same dataset (e.g., elicited by different experimental events), it follows that those psychological processes involve a common, non-separable neural mechanism. As such, this logic allows testing a class of hypotheses that is beyond the reach of regular EEG analyses techniques, thereby crucially increasing the inferential utility of the EEG. In the current article, this logic will be referred to as the 'common independent process identification' (CIPI) approach. This article aims to provide a tutorial into the application of this powerful approach, targeted at researchers that have a basic understanding of standard EEG analysis. Furthermore, the article aims to exemplify the usage of CIPI by outlining recent studies that successfully applied this approach to test neural theories of mental functions.

  12. Lyme Disease Frequently Asked Questions (FAQ)

    MedlinePlus

    ... the following year. What is a surveillance case definition? Reporting of all nationally notifiable diseases, including Lyme disease, is based on standard surveillance case definitions developed by the Council of State and Territorial ...

  13. Lyme disease in Canada: Focus on children.

    PubMed

    Onyett, Heather

    2014-08-01

    Lyme disease, the most common tick-borne infection in Canada and much of the United States, is caused by the bacteria Borrelia burgdorferi. Peak incidence for Lyme disease is among children five to nine years of age and older adults (55 to 59 years of age). The bacteria are transmitted through the bite of infected black-legged ticks of the Ixodes species. The primary hosts of black-legged ticks are mice and other rodents, small mammals, birds (which are reservoirs for B burgdorferi) and white-tailed deer. Geographical distribution of Ixodes ticks is expanding in Canada and an increasing number of cases of Lyme disease are being reported. The present practice point reviews the epidemiology, clinical presentation, diagnosis, management and prevention of Lyme disease, with a focus on children.

  14. Lyme disease in Canada: Focus on children

    PubMed Central

    Onyett, Heather

    2014-01-01

    Lyme disease, the most common tick-borne infection in Canada and much of the United States, is caused by the bacteria Borrelia burgdorferi. Peak incidence for Lyme disease is among children five to nine years of age and older adults (55 to 59 years of age). The bacteria are transmitted through the bite of infected black-legged ticks of the Ixodes species. The primary hosts of black-legged ticks are mice and other rodents, small mammals, birds (which are reservoirs for B burgdorferi) and white-tailed deer. Geographical distribution of Ixodes ticks is expanding in Canada and an increasing number of cases of Lyme disease are being reported. The present practice point reviews the epidemiology, clinical presentation, diagnosis, management and prevention of Lyme disease, with a focus on children. PMID:25332678

  15. Radiation of the Nod-independent Aeschynomene relies on multiple allopolyploid speciation events.

    PubMed

    Arrighi, Jean-François; Chaintreuil, Clémence; Cartieaux, Fabienne; Cardi, C; Rodier-Goud, M; Brown, Spencer C; Boursot, Marc; D'Hont, Angélique; Dreyfus, Bernard; Giraud, Eric

    2014-03-01

    • The semi-aquatic legumes belonging to the genus Aeschynomene constitute a premium system for investigating the origin and evolution of unusual symbiotic features such as stem nodulation and the presence of a Nod-independent infection process. This latter apparently arose in a single Aeschynomene lineage. But how this unique Nod-independent group then radiated is not yet known. • We have investigated the role of polyploidy in Aeschynomene speciation via a case study of the pantropical A. indica and then extended the analysis to the other Nod-independent species. For this, we combined SSR genotyping, genome characterization through flow cytometry, chromosome counting, FISH and GISH experiments, molecular phylogenies using ITS and single nuclear gene sequences, and artificial hybridizations. • These analyses demonstrate the existence of an A. indica polyploid species complex comprising A. evenia (C. Wright) (2n = 2x = 20), A. indica L. s.s. (2n = 4x = 40) and a new hexaploid form (2n = 6x = 60). This latter contains the two genomes present in the tetraploid (A. evenia and A. scabra) and another unidentified genome. Two other species, A. pratensis and A. virginica, are also shown to be of allopolyploid origin. • This work reveals multiple hybridization/polyploidization events, thus highlighting a prominent role of allopolyploidy in the radiation of the Nod-independent Aeschynomene.

  16. Development of a Multiantigen Panel for Improved Detection of Borrelia burgdorferi Infection in Early Lyme Disease

    PubMed Central

    Panas, Michael W.; Mao, Rong; Delanoy, Michelle; Flanagan, John J.; Binder, Steven R.; Rebman, Alison W.; Montoya, Jose G.; Soloski, Mark J.; Steere, Allen C.; Dattwyler, Raymond J.; Arnaboldi, Paul M.; Aucott, John N.

    2015-01-01

    The current standard for laboratory diagnosis of Lyme disease in the United States is serologic detection of antibodies against Borrelia burgdorferi. The Centers for Disease Control and Prevention recommends a two-tiered testing algorithm; however, this scheme has limited sensitivity for detecting early Lyme disease. Thus, there is a need to improve diagnostics for Lyme disease at the early stage, when antibiotic treatment is highly efficacious. We examined novel and established antigen markers to develop a multiplex panel that identifies early infection using the combined sensitivity of multiple markers while simultaneously maintaining high specificity by requiring positive results for two markers to designate a positive test. Ten markers were selected from our initial analysis of 62 B. burgdorferi surface proteins and synthetic peptides by assessing binding of IgG and IgM to each in a training set of Lyme disease patient samples and controls. In a validation set, this 10-antigen panel identified a higher proportion of early-Lyme-disease patients as positive at the baseline or posttreatment visit than two-tiered testing (87.5% and 67.5%, respectively; P < 0.05). Equivalent specificities of 100% were observed in 26 healthy controls. Upon further analysis, positivity on the novel 10-antigen panel was associated with longer illness duration and multiple erythema migrans. The improved sensitivity and comparable specificity of our 10-antigen panel compared to two-tiered testing in detecting early B. burgdorferi infection indicates that multiplex analysis, featuring the next generation of markers, could advance diagnostic technology to better aid clinicians in diagnosing and treating early Lyme disease. PMID:26447113

  17. Development of a Multiantigen Panel for Improved Detection of Borrelia burgdorferi Infection in Early Lyme Disease.

    PubMed

    Lahey, Lauren J; Panas, Michael W; Mao, Rong; Delanoy, Michelle; Flanagan, John J; Binder, Steven R; Rebman, Alison W; Montoya, Jose G; Soloski, Mark J; Steere, Allen C; Dattwyler, Raymond J; Arnaboldi, Paul M; Aucott, John N; Robinson, William H

    2015-12-01

    The current standard for laboratory diagnosis of Lyme disease in the United States is serologic detection of antibodies against Borrelia burgdorferi. The Centers for Disease Control and Prevention recommends a two-tiered testing algorithm; however, this scheme has limited sensitivity for detecting early Lyme disease. Thus, there is a need to improve diagnostics for Lyme disease at the early stage, when antibiotic treatment is highly efficacious. We examined novel and established antigen markers to develop a multiplex panel that identifies early infection using the combined sensitivity of multiple markers while simultaneously maintaining high specificity by requiring positive results for two markers to designate a positive test. Ten markers were selected from our initial analysis of 62 B. burgdorferi surface proteins and synthetic peptides by assessing binding of IgG and IgM to each in a training set of Lyme disease patient samples and controls. In a validation set, this 10-antigen panel identified a higher proportion of early-Lyme-disease patients as positive at the baseline or posttreatment visit than two-tiered testing (87.5% and 67.5%, respectively; P < 0.05). Equivalent specificities of 100% were observed in 26 healthy controls. Upon further analysis, positivity on the novel 10-antigen panel was associated with longer illness duration and multiple erythema migrans. The improved sensitivity and comparable specificity of our 10-antigen panel compared to two-tiered testing in detecting early B. burgdorferi infection indicates that multiplex analysis, featuring the next generation of markers, could advance diagnostic technology to better aid clinicians in diagnosing and treating early Lyme disease.

  18. Phylogeographic and population genetic analyses reveal multiple species of Boa and independent origins of insular dwarfism.

    PubMed

    Card, Daren C; Schield, Drew R; Adams, Richard H; Corbin, Andrew B; Perry, Blair W; Andrew, Audra L; Pasquesi, Giulia I M; Smith, Eric N; Jezkova, Tereza; Boback, Scott M; Booth, Warren; Castoe, Todd A

    2016-09-01

    Boa is a Neotropical genus of snakes historically recognized as monotypic despite its expansive distribution. The distinct morphological traits and color patterns exhibited by these snakes, together with the wide diversity of ecosystems they inhabit, collectively suggest that the genus may represent multiple species. Morphological variation within Boa also includes instances of dwarfism observed in multiple offshore island populations. Despite this substantial diversity, the systematics of the genus Boa has received little attention until very recently. In this study we examined the genetic structure and phylogenetic relationships of Boa populations using mitochondrial sequences and genome-wide SNP data obtained from RADseq. We analyzed these data at multiple geographic scales using a combination of phylogenetic inference (including coalescent-based species delimitation) and population genetic analyses. We identified extensive population structure across the range of the genus Boa and multiple lines of evidence for three widely-distributed clades roughly corresponding with the three primary land masses of the Western Hemisphere. We also find both mitochondrial and nuclear support for independent origins and parallel evolution of dwarfism on offshore island clusters in Belize and Cayos Cochinos Menor, Honduras.

  19. Lyme disease: a case report of a 17-year-old male with fatal Lyme carditis.

    PubMed

    Yoon, Esther C; Vail, Eric; Kleinman, George; Lento, Patrick A; Li, Simon; Wang, Guiqing; Limberger, Ronald; Fallon, John T

    2015-01-01

    Lyme disease is a systemic infection commonly found in the northeastern, mid-Atlantic, and north-central regions of the United States. Of the many systemic manifestations of Lyme disease, cardiac involvement is uncommon and rarely causes mortality. We describe a case of a 17-year-old adolescent who died unexpectedly after a 3-week viral-like syndrome. Postmortem examination was remarkable for diffuse pancarditis characterized by extensive infiltrates of lymphocytes and focal interstitial fibrosis. In the cardiac tissue, Borrelia burgdorferi was identified via special stains, immunohistochemistry, and polymerase chain reaction. The findings support B. burgdorferi as the causative agent for his fulminant carditis and that the patient suffered fatal Lyme carditis. Usually, Lyme carditis is associated with conduction disturbances and is a treatable condition. Nevertheless, few cases of mortality have been reported in the literature. Here, we report a rare example of fatal Lyme carditis in an unsuspected patient.

  20. Isolation of live Borrelia burgdorferi sensu lato spirochaetes from patients with undefined disorders and symptoms not typical for Lyme borreliosis.

    PubMed

    Rudenko, N; Golovchenko, M; Vancova, M; Clark, K; Grubhoffer, L; Oliver, J H

    2016-03-01

    Lyme borreliosis is a multisystem disorder with a diverse spectrum of clinical manifestations, caused by spirochaetes of the Borrelia burgdorferi sensu lato complex. It is an infectious disease that can be successfully cured by antibiotic therapy in the early stages; however, the possibility of the appearance of persistent signs and symptoms of disease following antibiotic treatment is recognized. It is known that Lyme borreliosis mimics multiple diseases that were never proven to have a spirochaete aetiology. Using complete modified Kelly-Pettenkofer medium we succeeded in cultivating live B. burgdorferi sensu lato spirochaetes from samples taken from people who suffered from undefined disorders, had symptoms not typical for Lyme borreliosis, but who had undergone antibiotic treatment due to a suspicion of having Lyme disease even though they were seronegative. We report the first recovery of live B. burgdorferi sensu stricto from residents of southeastern USA and the first successful cultivation of live Borrelia bissettii-like strain from residents of North America. Our results support the fact that B. bissettii is responsible for human Lyme borreliosis worldwide along with B. burgdorferi s.s. The involvement of new spirochaete species in Lyme borreliosis changes the understanding and recognition of clinical manifestations of this disease.

  1. Case studies of technology for adults with multiple disabilities to make telephone calls independently.

    PubMed

    Lancioni, Giulio E; Singh, Nirbhay N; O'Reilly, Mark F; Sigafoos, Jeff; Boccasini, Adele; La Martire, Maria L; Lang, Russell

    2014-08-01

    Recent literature has shown the possibility of enabling individuals with multiple disabilities to make telephone calls independently via computer-aided telephone technology. These two case studies assessed a modified version of such technology and a commercial alternative to it for a woman and a man with multiple disabilities, respectively. The modified version used in Study 1 (a) presented the names of the persons available for a call and (b) reminded the participant of the response she needed to perform (i.e., pressing a microswitch) if she wanted to call any of those names/persons. The commercial device used in Study 2 was a Galaxy S3 (Samsung) equipped with the S-voice module, which allowed the participant to activate phone calls by uttering the word "Call" followed by the name of the persons he wanted to call. The results of the studies showed that the participants learned to make phone calls independently using the technology/device available. Implications of the results are discussed.

  2. Multiple and independent origins of short seeded alleles of GS3 in rice

    PubMed Central

    Takano-Kai, Noriko; Jiang, Hui; Powell, Adrian; McCouch, Susan; Takamure, Itsuro; Furuya, Naruto; Doi, Kazuyuki; Yoshimura, Atsushi

    2013-01-01

    GRAIN SIZE 3 (GS3) is a cloned gene that is related to seed length. Here we report the discovery of new deletion alleles at the GS3 locus, each of which confer short seed. We selected ten short seeded cultivars from a collection of 282 diverse cultivars. Sequence analysis across the GS3 gene in these ten cultivars identified three novel alleles and a known allele that contain several independent deletion(s) in the fifth exon of GS. These independent deletion variants each resulted in a frameshift mutation that caused a premature stop codon, and they were functionally similar to one another. Each coded for a truncated gene product that behaved as an incomplete dominant allele and conferred a short seeded phenotype. Haplotype analysis of these sequence variants indicated that two of the variants were of japonica origin, and two were from indica. Transformation experiments demonstrated that one of the deletion alleles of GS3 decrease the cell number in the upper epidermis of the glume, resulting in a significant reduction in seed length. The multiple and independent origins of these short seeded alleles indicate that farmers and early breeders imposed artificial selection favoring short seeds. PMID:23641184

  3. Evidence for Multiple Mediator Complexes in Yeast Independently Recruited by Activated Heat Shock Factor

    PubMed Central

    Anandhakumar, Jayamani; Moustafa, Yara W.; Chowdhary, Surabhi; Kainth, Amoldeep S.

    2016-01-01

    Mediator is an evolutionarily conserved coactivator complex essential for RNA polymerase II transcription. Although it has been generally assumed that in Saccharomyces cerevisiae, Mediator is a stable trimodular complex, its structural state in vivo remains unclear. Using the “anchor away” (AA) technique to conditionally deplete select subunits within Mediator and its reversibly associated Cdk8 kinase module (CKM), we provide evidence that Mediator's tail module is highly dynamic and that a subcomplex consisting of Med2, Med3, and Med15 can be independently recruited to the regulatory regions of heat shock factor 1 (Hsf1)-activated genes. Fluorescence microscopy of a scaffold subunit (Med14)-anchored strain confirmed parallel cytoplasmic sequestration of core subunits located outside the tail triad. In addition, and contrary to current models, we provide evidence that Hsf1 can recruit the CKM independently of core Mediator and that core Mediator has a role in regulating postinitiation events. Collectively, our results suggest that yeast Mediator is not monolithic but potentially has a dynamic complexity heretofore unappreciated. Multiple species, including CKM-Mediator, the 21-subunit core complex, the Med2-Med3-Med15 tail triad, and the four-subunit CKM, can be independently recruited by activated Hsf1 to its target genes in AA strains. PMID:27185874

  4. The increasing risk of Lyme disease in Canada.

    PubMed

    Bouchard, Catherine; Leonard, Erin; Koffi, Jules Konan; Pelcat, Yann; Peregrine, Andrew; Chilton, Neil; Rochon, Kateryn; Lysyk, Tim; Lindsay, L Robbin; Ogden, Nicholas Hume

    2015-07-01

    There is an increasing risk of Lyme disease in Canada due to range expansion of the tick vector, Ixodes scapularis. The objectives of this article are to i) raise public awareness with the help of veterinarians on the emerging and expanding risk of Lyme disease across Canada, ii) review the key clinical features of Lyme disease in dogs, and iii) provide recommendations for veterinarians on the management of Lyme disease in dogs.

  5. What Teachers Need to Know about Lyme Disease

    ERIC Educational Resources Information Center

    Cook, Lysandra

    2009-01-01

    Although widely misunderstood, Lyme disease is the most prevalent vector borne disease in the United States. Children are the most at-risk group for Lyme disease, which can impact every system in the body. It can produce the musculo-skeletal, neurologic, psychiatric, opthalmologic, and cardiac symptoms. The symptoms of Lyme disease can have a…

  6. Epidemiology of Lyme disease in low-incidence states.

    PubMed

    Forrester, Joseph D; Brett, Meghan; Matthias, James; Stanek, Danielle; Springs, Chasisity Brown; Marsden-Haug, Nicola; Oltean, Hanna; Baker, JoDee Summers; Kugeler, Kiersten J; Mead, Paul S; Hinckley, Alison

    2015-09-01

    Lyme disease is the most common vector-borne disease in the U.S. Surveillance data from four states with a low-incidence of Lyme disease was evaluated. Most cases occurred after travel to high-incidence Lyme disease areas. Cases without travel-related exposure in low-incidence states differed epidemiologically; misdiagnosis may be common in these areas.

  7. Geographic Distribution and Expansion of Human Lyme Disease, United States.

    PubMed

    Kugeler, Kiersten J; Farley, Grace M; Forrester, Joseph D; Mead, Paul S

    2015-08-01

    Lyme disease occurs in specific geographic regions of the United States. We present a method for defining high-risk counties based on observed versus expected number of reported human Lyme disease cases. Applying this method to successive periods shows substantial geographic expansion of counties at high risk for Lyme disease.

  8. Multiple independent autonomous hydraulic oscillators driven by a common gravity head.

    PubMed

    Kim, Sung-Jin; Yokokawa, Ryuji; Lesher-Perez, Sasha Cai; Takayama, Shuichi

    2015-06-15

    Self-switching microfluidic circuits that are able to perform biochemical experiments in a parallel and autonomous manner, similar to instruction-embedded electronics, are rarely implemented. Here, we present design principles and demonstrations for gravity-driven, integrated, microfluidic pulsatile flow circuits. With a common gravity head as the only driving force, these fluidic oscillator arrays realize a wide range of periods (0.4 s-2 h) and flow rates (0.10-63 μl min(-1)) with completely independent timing between the multiple oscillator sub-circuits connected in parallel. As a model application, we perform systematic, parallel analysis of endothelial cell elongation response to different fluidic shearing patterns generated by the autonomous microfluidic pulsed flow generation system.

  9. Multiple independent autonomous hydraulic oscillators driven by a common gravity head

    PubMed Central

    Kim, Sung-Jin; Yokokawa, Ryuji; Lesher-Perez, Sasha Cai; Takayama, Shuichi

    2015-01-01

    Self-switching microfluidic circuits that are able to perform biochemical experiments in a parallel and autonomous manner similar to instruction-embedded electronics, are rarely implemented. Here, we present design principles and demonstrations for gravity-driven, integrated, microfluidic pulsatile flow circuits. With a common gravity-head as the only driving force, these fluidic oscillator arrays realize a wide range of periods (0.4 s – 2 h) and flow rates (0.10 – 63 μL min−1) with completely independent timing between the multiple oscillator sub-circuits connected in parallel. As a model application, we perform systematic, parallel analysis of endothelial cell elongation response to different fluidic shearing patterns generated by the autonomous microfluidic pulsed flow generation system. PMID:26073884

  10. Markerless view-independent registration of multiple distorted projectors on extruded surfaces using an uncalibrated camera.

    PubMed

    Sajadi, Behzad; Majumder, Aditi

    2009-01-01

    In this paper, we present the first algorithm to geometrically register multiple projectors in a view-independent manner (i.e. wallpapered) on a common type of curved surface, vertically extruded surface, using an uncalibrated camera without attaching any obtrusive markers to the display screen. Further, it can also tolerate large non-linear geometric distortions in the projectors as is common when mounting short throw lenses to allow a compact set-up. Our registration achieves sub-pixel accuracy on a large number of different vertically extruded surfaces and the image correction to achieve this registration can be run in real time on the GPU. This simple markerless registration has the potential to have a large impact on easy set-up and maintenance of large curved multi-projector displays, common for visualization, edutainment, training and simulation applications.

  11. Immunogenetic Markers Definition in Latvian Patients with Lyme Borreliosis and Lyme Neuroborreliosis.

    PubMed

    Kovalchuka, Lilija; Cvetkova, Svetlana; Trofimova, Julija; Eglite, Jelena; Gintere, Sandra; Lucenko, Irina; Oczko-Grzesik, Barbara; Viksna, Ludmila; Krumina, Angelika

    2016-12-01

    The aim of this study was to determine the human leukocyte antigen (HLA)-DRB1 alleles in two groups of patients in Latvia: patients with Lyme borreliosis and patients with Lyme neuroborreliosis. The study included 216 patients with Lyme borreliosis, 29 patients with Lyme neuroborreliosis and 282 control persons. All surveyed persons were residents of Latvia. The HLA-DR genotyping was performed by polymerase chain reaction- sequence specific primer (PCR-SSP). The predisposition to the Lyme borreliosis is associated with the HLA-DRB1*07, -DRB1*17(03), -DRB1*04, -DRB1*15(02) alleles. The allele -DRB1*11(05), -DRB1*14(06) and -DRB1*13(06) were significantly more frequent in controls. In-group with Lyme neuroborreliosis differences were found for the -DRB1*07 and -DRB1*04 alleles, but only HLA-DRB1*07 allele was statistically significant after Bonferroni correction and associated with Lyme neuroborreliosis in Latvian patients.

  12. Immunogenetic Markers Definition in Latvian Patients with Lyme Borreliosis and Lyme Neuroborreliosis

    PubMed Central

    Kovalchuka, Lilija; Cvetkova, Svetlana; Trofimova, Julija; Eglite, Jelena; Gintere, Sandra; Lucenko, Irina; Oczko-Grzesik, Barbara; Viksna, Ludmila; Krumina, Angelika

    2016-01-01

    The aim of this study was to determine the human leukocyte antigen (HLA)-DRB1 alleles in two groups of patients in Latvia: patients with Lyme borreliosis and patients with Lyme neuroborreliosis. The study included 216 patients with Lyme borreliosis, 29 patients with Lyme neuroborreliosis and 282 control persons. All surveyed persons were residents of Latvia. The HLA-DR genotyping was performed by polymerase chain reaction- sequence specific primer (PCR-SSP). The predisposition to the Lyme borreliosis is associated with the HLA-DRB1*07, -DRB1*17(03), -DRB1*04, -DRB1*15(02) alleles. The allele -DRB1*11(05), -DRB1*14(06) and -DRB1*13(06) were significantly more frequent in controls. In-group with Lyme neuroborreliosis differences were found for the -DRB1*07 and -DRB1*04 alleles, but only HLA-DRB1*07 allele was statistically significant after Bonferroni correction and associated with Lyme neuroborreliosis in Latvian patients. PMID:27916969

  13. An Unrecognized Rash Progressing to Lyme Carditis: Important Features and Recommendations Regarding Lyme Disease.

    PubMed

    Lee, Shawn; Singla, Montish

    2016-01-01

    We present a case report of 46-year-old man with no medical history, who complained of extreme fatigue, near-syncope, and palpitations. He initially presented in complete heart block. A transvenous pacemaker was placed in the emergency department, and he was started empirically on Ceftriaxone for Lyme disease. He was admitted and over the course of the next few days, his rhythm regressed to Mobitz type I first-degree atrioventricular block and then to normal sinus rhythm. This case report highlights some important features regarding Lyme carditis, a rare presentation of early disseminated Lyme disease (seen in a few weeks to months after the initial tick bite). In 25%-30% of patients, the characteristic targetoid rash may not be seen, a likely culprit of the disease not being detected early and progressing to disseminated disease. The most common cardiac complaint of Lyme disease is palpitations, occurring in 6.6% of patients, which may not accurately reflect progression into disseminated Lyme disease because it is a nonspecific finding. Conduction abnormality, occurring in 1.8% of patients, is a more specific finding of Borrelia invading cardiac tissue. Finally, this case report highlights a recommendation that patients with confirmed Lyme disease or those presenting with cardiac abnormalities or symptoms who have an atypical profile for a cardiac event should be screened with a 12-lead electrocardiogram, Lyme serology, and be considered for antibiotic therapy with the possibility of temporary pacing.

  14. [Acute atrioventricular block in chronic Lyme disease].

    PubMed

    Wagner, Vince; Zima, Endre; Gellér, László; Merkely, Béla

    2010-09-26

    The tick bite transmitted Lyme disease is one of the most common antropozoonosis, about 10 000 new infections are reported in Hungary each year. The progress and clinical presentation can vary, and carditis can occur in later stages. A serologically verified Lyme disease caused third degree atrioventricular block in young male presenting with presyncope. Based on the tick-bites mentioned a few weeks prior to hospital admission, Lyme carditis was considered with the administration of antibiotics and monitor observation. Typical skin lesions were not recognized and laboratory findings showed no pathology. An electrophysiological study recorded a predominant supra-His atrioventricular block. Total regression of conduction could be detected later and the serological tests established an underlying Lyme disease. Currently no definite treatment recommendation is available for the potentially reversible Lyme carditis. The tick bite seemed to be the key on our way to diagnosis; however, serological tests proved the disease to be older than one year. A detailed medical history and serological tests are essential in identifying the cause and pacemaker implantation can be avoided.

  15. Physical activity, social support, and depression: possible independent and indirect associations in persons with multiple sclerosis.

    PubMed

    Suh, Yoojin; Weikert, Madeline; Dlugonski, Deirdre; Sandroff, Brian; Motl, Robert W

    2012-01-01

    The present study examined the pattern of associations among physical activity, social support, mobility disability, perceived stress, and depressive symptoms in relapsing-remitting MS (RRMS). Persons (N = 218) with RRMS completed a battery of questionnaires that was sent and returned through the United States Postal Service (USPS). Bivariate correlation analysis indicated that physical activity and social support were both inversely associated with depressive symptoms (r's = -0.288 and -0.386, p ≤ 0.05, respectively). Multiple linear regression analysis indicated that physical activity (β = -0.21, p = 0.002) and social support (β = -0.37, p = 0.0001) were independently associated with depressive symptoms. Path analysis confirmed that the associations between physical activity and social support with depressive symptoms were indirect via mobility disability and perceived stress. Collectively, the evidence indicates that physical activity and social support are independently and indirectly associated with depression via mobility disability and perceived stress in relapsing-remitting MS. This supports the design of interventions and programs that target physical activity and social support for reducing depressive symptoms among persons with MS.

  16. Singlet oxygen signatures are detected independent of light or chloroplasts in response to multiple stresses.

    PubMed

    Mor, Avishai; Koh, Eugene; Weiner, Lev; Rosenwasser, Shilo; Sibony-Benyamini, Hadas; Fluhr, Robert

    2014-05-01

    The production of singlet oxygen is typically associated with inefficient dissipation of photosynthetic energy or can arise from light reactions as a result of accumulation of chlorophyll precursors as observed in fluorescent (flu)-like mutants. Such photodynamic production of singlet oxygen is thought to be involved in stress signaling and programmed cell death. Here we show that transcriptomes of multiple stresses, whether from light or dark treatments, were correlated with the transcriptome of the flu mutant. A core gene set of 118 genes, common to singlet oxygen, biotic and abiotic stresses was defined and confirmed to be activated photodynamically by the photosensitizer Rose Bengal. In addition, induction of the core gene set by abiotic and biotic selected stresses was shown to occur in the dark and in nonphotosynthetic tissue. Furthermore, when subjected to various biotic and abiotic stresses in the dark, the singlet oxygen-specific probe Singlet Oxygen Sensor Green detected rapid production of singlet oxygen in the Arabidopsis (Arabidopsis thaliana) root. Subcellular localization of Singlet Oxygen Sensor Green fluorescence showed its accumulation in mitochondria, peroxisomes, and the nucleus, suggesting several compartments as the possible origins or targets for singlet oxygen. Collectively, the results show that singlet oxygen can be produced by multiple stress pathways and can emanate from compartments other than the chloroplast in a light-independent manner. The results imply that the role of singlet oxygen in plant stress regulation and response is more ubiquitous than previously thought.

  17. Serum YKL-40: a new independent prognostic marker for skeletal complications in patients with multiple myeloma.

    PubMed

    Mylin, Anne K; Abildgaard, Niels; Johansen, Julia S; Heickendorff, Lene; Kreiner, Svend; Waage, Anders; Turesson, Ingemar; Gimsing, Peter

    2015-01-01

    In a time of increasing treatment options for multiple myeloma bone disease, risk factors predicting progression need to be elucidated. This study investigated the value of serum YKL-40, previously shown to be associated with radiographic progression of bone destruction, as a predictor for time to clinical progression, i.e. skeletal-related events (SREs), in 230 newly diagnosed patients with multiple myeloma receiving intravenous bisphosphonates. Serum concentrations of YKL-40 and biochemical bone markers (CTX-MMP, CTX-I, PINP) were measured at diagnosis. Patients were evaluated every third month for SRE and at 9 and 24 months for radiographic progression. Elevated serum YKL-40 was seen in 47% of patients and associated with high-risk disease (International Staging System stage III; p < 0.001), increased bone resorption (serum CTX/MMP; p < 0.001) and early radiographic progression at 9 months (p = 0.01). Serum YKL-40 together with serum CTX-MMP/PINP ratio and World Health Organization status were independent predictors of time to first SRE.

  18. Visuospatial Attention to Single and Multiple Objects Is Independently Impaired in Parkinson's Disease

    PubMed Central

    Norton, Daniel J.; Nguyen, Victoria A.; Lewis, Michaela F.; Reynolds, Gretchen O.; Somers, David C.; Cronin-Golomb, Alice

    2016-01-01

    Parkinson’s disease (PD) is associated with deficits in visuospatial attention. It is as yet unknown whether these attentional deficits begin at a perceptual level or instead reflect disruptions in oculomotor or higher-order processes. In the present study, non-demented individuals with PD and matched normal control adults (NC) participated in two tasks requiring sustained visuospatial attention, both based on a multiple object tracking paradigm. Eye tracking was used to ensure central fixation. In Experiment 1 (26 PD, 21 NC), a pair of identical red dots (one target, one distractor) rotated randomly for three seconds at varied speeds. The task was to maintain the identity of the sole target, which was labeled prior to each trial. PD were less accurate than NC overall (p = .049). When considering only trials where fixation was maintained, however, there was no significant group difference, suggesting that the deficit’s origin is closely related to oculomotor processing. To determine whether PD had additional impairment in multifocal attention, in Experiment 2 (25 PD, 15 NC), two targets were presented along with distractors at a moderate speed, along with a control condition in which dots remained stationary. PD were less accurate than NC for moving (p = 0.02) but not stationary targets. This group difference remained significant when considering only trials where fixation was maintained, suggesting the source of the PD deficit was independent from oculomotor processing. Taken together, the results implicate separate mechanisms for single vs. multiple object tracking deficits in PD. PMID:26963388

  19. Lyme disease update for the general dermatologist.

    PubMed

    Godar, Desiree A; Laniosz, Valerie; Wetter, David A

    2015-02-01

    Lyme disease is an Ixodes tick-borne illness that may arise from different species of the Borrelia spirochete and may be propagated in various hosts. Humans are considered dead-end hosts in this propagation cycle but may have a range of Lyme disease characteristics as a result of borrelial infection. Lyme disease has varied cutaneous manifestations, and the approach to diagnosis and treatment is based on the patient, the region, and suspected coinfection with another tick-borne illness. An understanding of the distribution of the Ixodes tick, its vectors, and the most likely dermatologic presentation based on these factors allows the dermatologist to make appropriate testing and treatment recommendations. Our aim is to simplify this approach for the treating practitioner.

  20. Lyme carditis. Electrophysiologic and histopathologic study

    SciTech Connect

    Reznick, J.W.; Braunstein, D.B.; Walsh, R.L.; Smith, C.R.; Wolfson, P.M.; Gierke, L.W.; Gorelkin, L.; Chandler, F.W.

    1986-11-01

    To further define the nature of Lyme carditis, electrophysiologic study and endomyocardial biopsy were performed in a patient with Lyme disease, whose principal cardiac manifestation was high-degree atrioventricular block. Intracardiac recording demonstrated supra-Hisian block and complete absence of an escape mechanism. Gallium 67 scanning demonstrated myocardial uptake, and right ventricular endomyocardial biopsy revealed active lymphocytic myocarditis. A structure compatible with a spirochetal organism was demonstrated in one biopsy specimen. It is concluded that Lyme disease can produce active myocarditis, as suggested by gallium 67 imaging and confirmed by endomyocardial biopsy. Furthermore, the presence of high-grade atrioventricular block in this disease requires aggressive management with temporary pacemaker and corticosteroid therapy.

  1. Texas Occurrence of Lyme Disease and Its Neurological Manifestations.

    PubMed

    Dandashi, Jad A; Nizamutdinov, Damir; Dayawansa, Samantha; Fonkem, Ekokobe; Huang, Jason H

    2016-06-01

    Today, Lyme disease is the most commonly reported tick-borne disease in the United States and Europe. The culprits behind Lyme disease are the Borrelia species of bacteria. In the USA, Borrelia burgdorferi causes the majority of cases, while in Europe and Asia Borrelia afzelii and Borrelia garinii carry the greatest burden of disease. The clinical manifestations of Lyme disease have been identified as early localized, early disseminated, and late chronic. The neurological effects of Lyme disease include both peripheral and central nervous systems involvement, including focal nerve abnormalities, cranial neuropathies, painful radiculoneuritis, meningitis, and/or toxic metabolic encephalopathy, known as Lyme encephalopathy. Given the geographic predominance of Lyme disease in the Northeast and Midwest of the USA, no major studies have been conducted regarding Southern states. Between 2005 and 2014, the Center for Disease Control has reported 582 confirmed cases of Lyme disease in Texas. Because of the potential for increased incidence and prevalence in Texas, it has become essential for research and clinical efforts to be diverted to the region. The Texas A&M College of Veterinary Medicine and Biomedical Sciences Lyme Lab has been investigating the ecology of Lyme disease in Texas and developing a pan-specific serological test for Lyme diagnosis. This report aimed to exposure materials and raise awareness of Lyme disease to healthcare providers.

  2. Achieving molecular diagnostics for Lyme disease.

    PubMed

    Eshoo, Mark W; Schutzer, Steven E; Crowder, Christopher D; Carolan, Heather E; Ecker, David J

    2013-11-01

    Early Lyme disease is often difficult to diagnose. Left untreated, symptoms can last for many years leading to chronic health problems. Serological tests for the presence of antibodies that react to Borrelia burgdorferi antigens are generally used to support a clinical diagnosis. Due to the biologically delayed antibody response, serology is negative in many patients in the initial 3 weeks after infection and a single test cannot be used to demonstrate active disease, although certain specialized tests provide strong correlation. Because of these limitations there exists a need for better diagnostics for Lyme disease that can detect Borrelia genomic material at the onset of symptoms.

  3. Multiple, independent colonizations of the Hawaiian Archipelago by the family Dolichopodidae (Diptera)

    PubMed Central

    Goodman, Kari Roesch; Evenhuis, Neal; Bartošová-Sojková, Pavla

    2016-01-01

    The family Dolichopodidae forms two of the four largest evolutionary radiations in the Hawaiian Islands across all flies: Campsicnemus (183 spp) and the Eurynogaster complex (66 spp). They also include a small radiation of Conchopus (6 spp). A handful of other dolichopodid species are native to the islands in singleton lineages or small radiations. This study provides a phylogenetic perspective on the colonization history of the dolichopodid fauna in the islands. We generated a multi-gene data set including representatives from 11 of the 14 endemic Hawaiian dolichopodid genera to examine the history of colonization to the islands, and analyzed it using Bayesian and maximum likelihood phylogenetic methods. We used a subset of the data that included Conchopus and the eight genera comprising the Eurynogaster complex to estimate the first phylogenetic hypothesis for these endemic groups, then used Beast to estimate their age of arrival to the archipelago. The Eurynogaster complex, Campsicnemus and Conchopus are clearly the result of independent colonizations. The results strongly support the Eurynogaster complex as a monophyletic group, and also supports the monophyly of 4 of the 8 described genera within the complex (Adachia, Arciellia, Uropachys and Eurynogaster). Members of the family Dolichopodidae have been dispersing over vast distances to colonize the Hawaiian Archipelago for millions of years, leading to multiple independent evolutionary diversification events. The Eurynogaster complex arrived in the Hawaiian Archipelago 11.8 Ma, well before the arrival of Campsicnemus (4.5 Ma), and the even more recent Conchopus (1.8 Ma). Data presented here demonstrate that the Hawaiian Dolichopodidae both disperse and diversify easily, a rare combination that lays the groundwork for field studies on the reproductive isolating mechanisms and ecological partitioning of this group. PMID:27896033

  4. Management approaches for suspected and established Lyme disease used at the Lyme disease diagnostic center.

    PubMed

    Wormser, Gary P; McKenna, Donna; Nowakowski, John

    2016-01-14

    2015 marks the 27th year that the Lyme Disease Diagnostic Center, located in New York State in the United States, has provided care for patients with suspected or established deer tick-transmitted infections. There are five deer tick-transmitted infectious in this geographic area of which Lyme disease is the most common.For patients with erythema migrans, we do not obtain any laboratory testing. However, if the patient is febrile at the time of the visit or reports rigors and high-grade fevers, we consider the possibility of a co-infection and order pertinent laboratory tests.Our preferred management for Lyme disease-related facial palsy and/or radiculopathy is a 2-week course of doxycycline. Patients who are hospitalized for Lyme meningitis are usually treated at least initially with ceftriaxone. We have not seen convincing cases of encephalitis or myelitis solely due to Borrelia burgdorferi infection in the absence of laboratory evidence of concomitant deer tick virus infection (Powassan virus). We have also never seen Lyme encephalopathy or a diffuse axonal peripheral neuropathy and suggest that these entities are either very rare or nonexistent.We have found that Lyme disease rarely presents with fever without other objective clinical manifestations. Prior cases attributed to Lyme disease may have overlooked an asymptomatic erythema migrans skin lesion or the diagnosis may have been based on nonspecific IgM seroreactivity. More research is needed on the appropriate management and significance of IgG seropositivity in asymptomatic patients who have no history of Lyme disease.

  5. Domain loss has independently occurred multiple times in plant terpene synthase evolution

    PubMed Central

    Hillwig, Matthew L.; Xu, Meimei; Toyomasu, Tomonobu; Tiernan, Mollie S.; Wei, Gao; Cui, Guanghong; Huang, Luqi; Peters, Reuben J.

    2011-01-01

    SUMMARY The extensive family of plant terpene synthases (TPSs) generally has a bi-domain structure, yet phylogenetic analyses consistently indicate that these evolved from larger diterpene synthases. In particular, that duplication of the diterpene synthase genes required for gibberellin phytohormone biosynthesis provided an early predecessor, whose loss of a ~220 amino acid “internal sequence element” (now recognized as the γ domain) gave rise to the precursor of modern mono- and sesqui-TPSs found in all higher plants. Intriguingly, TPSs are conserved by taxonomic relationships rather than function, demonstrating that such functional radiation has occurred both repeatedly and relatively recently, yet phylogenetic analyses assume that “internal/γ” domain loss represents a single evolutionary event. Here we provide evidence that such loss was not a singular event, but rather has occurred multiple times. Specifically, we provide an example of a bi-domain diterpene synthase, from Salvia miltiorrhiza, along with a sesquiterpene synthase from Triticum aestivum (wheat) that is not only closely related to diterpene synthases, but retains the ent-kaurene synthase activity relevant to the ancestral gibberellin metabolic function. Indeed, while the wheat sesquiterpene synthase clearly no longer contains the “internal/γ” domain, it is closely related to rice diterpene synthase genes that retain the ancestral tri-domain structure. Thus, these findings provide examples of key evolutionary intermediates underlying the bi-domain structure observed in the expansive plant TPS gene family, as well as indicating that “internal/γ” domain loss has independently occurred multiple times, highlighting the complex evolutionary history of this important enzymatic family. PMID:21999670

  6. The behavior of multiple independent managers and ecological traits interact to determine prevalence of weeds.

    PubMed

    Coutts, Shaun R; Yokomizo, Hiroyuki; Buckley, Yvonne M

    2013-04-01

    Management of damaging invasive plants is often undertaken by multiple decision makers, each managing only a small part of the invader's population. As weeds can move between properties and re-infest eradicated sites from unmanaged sources, the dynamics of multiple decision makers plays a significant role in weed prevalence and invasion risk at the landscape scale. We used a spatially explicit agent-based simulation to determine how individual agent behavior, in concert with weed population ecology, determined weed prevalence. We compared two invasive grass species that differ in ecology, control methods, and costs: Nassella trichotoma (serrated tussock) and Eragrostis curvula (African love grass). The way decision makers reacted to the benefit of management had a large effect on the extent of a weed. If benefits of weed control outweighed the costs, and either net benefit was very large or all agents were very sensitive to net benefits, then agents tended to act synchronously, reducing the pool of infested agents available to spread the weed. As N. trichotoma was more damaging than E. curvula and had more effective control methods, agents chose to manage it more often, which resulted in lower prevalence of N. trichotoma. A relatively low number of agents who were intrinsically less motivated to control weeds led to increased prevalence of both species. This was particularly apparent when long-distance dispersal meant each infested agent increased the invasion risk for a large portion of the landscape. In this case, a small proportion of land mangers reluctant to control, regardless of costs and benefits, could lead to the whole landscape being infested, even when local control stopped new infestations. Social pressure was important, but only if it was independent of weed prevalence, suggesting that early access to information, and incentives to act on that information, may be crucial in stopping a weed from infesting large areas. The response of our model to both

  7. Analysis with the exome array identifies multiple new independent variants in lipid loci.

    PubMed

    Kanoni, Stavroula; Masca, Nicholas G D; Stirrups, Kathleen E; Varga, Tibor V; Warren, Helen R; Scott, Robert A; Southam, Lorraine; Zhang, Weihua; Yaghootkar, Hanieh; Müller-Nurasyid, Martina; Couto Alves, Alexessander; Strawbridge, Rona J; Lataniotis, Lazaros; An Hashim, Nikman; Besse, Céline; Boland, Anne; Braund, Peter S; Connell, John M; Dominiczak, Anna; Farmaki, Aliki-Eleni; Franks, Stephen; Grallert, Harald; Jansson, Jan-Håkan; Karaleftheri, Maria; Keinänen-Kiukaanniemi, Sirkka; Matchan, Angela; Pasko, Dorota; Peters, Annette; Poulter, Neil; Rayner, Nigel W; Renström, Frida; Rolandsson, Olov; Sabater-Lleal, Maria; Sennblad, Bengt; Sever, Peter; Shields, Denis; Silveira, Angela; Stanton, Alice V; Strauch, Konstantin; Tomaszewski, Maciej; Tsafantakis, Emmanouil; Waldenberger, Melanie; Blakemore, Alexandra I F; Dedoussis, George; Escher, Stefan A; Kooner, Jaspal S; McCarthy, Mark I; Palmer, Colin N A; Hamsten, Anders; Caulfield, Mark J; Frayling, Timothy M; Tobin, Martin D; Jarvelin, Marjo-Riitta; Zeggini, Eleftheria; Gieger, Christian; Chambers, John C; Wareham, Nick J; Munroe, Patricia B; Franks, Paul W; Samani, Nilesh J; Deloukas, Panos

    2016-09-15

    It has been hypothesized that low frequency (1-5% minor allele frequency (MAF)) and rare (<1% MAF) variants with large effect sizes may contribute to the missing heritability in complex traits. Here, we report an association analysis of lipid traits (total cholesterol, LDL-cholesterol, HDL-cholesterol triglycerides) in up to 27 312 individuals with a comprehensive set of low frequency coding variants (ExomeChip), combined with conditional analysis in the known lipid loci. No new locus reached genome-wide significance. However, we found a new lead variant in 26 known lipid association regions of which 16 were >1000-fold more significant than the previous sentinel variant and not in close LD (six had MAF <5%). Furthermore, conditional analysis revealed multiple independent signals (ranging from 1 to 5) in a third of the 98 lipid loci tested, including rare variants. Addition of our novel associations resulted in between 1.5- and 2.5-fold increase in the proportion of heritability explained for the different lipid traits. Our findings suggest that rare coding variants contribute to the genetic architecture of lipid traits.

  8. IP-MSA: Independent order of progressive multiple sequence alignments using different substitution matrices

    NASA Astrophysics Data System (ADS)

    Boraik, Aziz Nasser; Abdullah, Rosni; Venkat, Ibrahim

    2014-12-01

    Multiple sequence alignment (MSA) is an essential process for many biological sequence analyses. There are many algorithms developed to solve MSA, but an efficient computation method with very high accuracy is still a challenge. Progressive alignment is the most widely used approach to compute the final MSA. In this paper, we present a simple and effective progressive approach. Based on the independent order of sequences progressive alignment which proposed in QOMA, this method has been modified to align the whole sequences to maximize the score of MSA. Moreover, in order to further improve the accuracy of the method, we estimate the similarity of any pair of input sequences by using their percent identity, and based on this measure, we choose different substitution matrices during the progressive alignment. In addition, we have included horizontal information to alignment by adjusting the weights of amino acid residues based on their neighboring residues. The experimental results have been tested on popular benchmark of global protein sequences BAliBASE 3.0 and local protein sequences IRMBASE 2.0. The results of the proposed approach outperform the original method in QOMA in terms of sum-of-pair score and column score by up to 14% and 7% respectively.

  9. Report for simultaneous, multiple independently steered beam study for Airborne Electronically Steerable Phased Array (AESPA) program

    NASA Technical Reports Server (NTRS)

    1978-01-01

    Design concepts of an array for the formation of multiple, simultaneous, independently pointed beams for satellite communication links were investigated through tradeoffs of various approaches which were conceived as possible solutions to the problem. After the preferred approach was selected, a more detailed design was configured and is presented as a candidate system that should be given further consideration for development leading to a preliminary design. This array uses an attenuator and a phase shifter with every element. The aperture excitation necessary to form the four beams is calculated and then placed across the array using these devices. Pattern analysis was performed for two beam and four beam cases with numerous patterns being presented. Parameter evaluation shown includes pointing accuracy and beam shape, sidelobe characteristics, gain control, and beam normalization. It was demonstrated that a 4 bit phase shifter and a 6 bit, 30 dB attenuator were sufficient to achieve adequate pattern performances. The phase amplitude steered multibeam array offers the flexibility of 1 to 4 beams with an increase in gain of 6 dB if only one beam is selected.

  10. The independent association of mean platelet volume with overall survival in multiple myeloma

    PubMed Central

    Zhuang, Qiang; Xiang, Lina; Xu, Hanyan; Fang, Fang; Xing, Chongyun; Liang, Bin; Yu, Kang; Feng, Jianhua

    2016-01-01

    We retrospectively analyzed the association between mean platelet volume (MPV) and prognosis in 62 newly diagnosed multiple myeloma (MM) patients. The associations between MPV and clinical characteristics were assessed. The log-rank test and the Cox proportional hazards model were used to evaluate the effect of MPV on survival. A MPV value of 8.50 fl was considered to be the optimal cut-off value for prognosis. MPV was associated with IgA isotype (P=0.012), serum creatinine concentration > 176.8 μmol/L (P=0.025) and IgH rearrangement (P=0.008). The log-rank test demonstrated that patients with low MPV experienced a shorter overall survival (OS) (P=0.0397). The multivariate analysis demonstrated that low MPV was an independent prognostic factor for OS [hazard ratio (HR)=2.44, P=0.026]. Therefore, we demonstrated that low MPV predicted an unfavorable prognosis in patients with MM. PMID:27566590

  11. [Non antibiotic treatments of Lyme borreliosis].

    PubMed

    Puéchal, X

    2007-01-01

    Non-antibiotic treatment of Lyme borreliosis is only indicated in a few specific clinical situations. In chronic Lyme arthritis, intra-articular steroids are useful to immediately relieve symptomatic joint effusion. Nevertheless, 4 studies with weak methodological evidence were convergent enough to recommend not proposing intra-articular injection before or even immediately after antibiotic treatment. The injection can only be recommended in the treatment of patients whose joint effusion persists despite 2 courses of oral antibiotherapy or one course of IV antibiotherapy. For some experts, the injection can only be made after negative PCR assessment of the joint fluid for spirochetes. This recommendation, although logical, has never been evaluated. Radiation synovectomy may be indicated in persistent synovitis after antibiotherapy and before surgical synovectomy. Further studies are mandatory to confirm the role of radiation synovectomy in the local therapy. Arthroscopic synovectomy can reduce the period of joint inflammation when persistent synovitis is associated with significant pain or limited function. Several experts recommend using the procedure only if synovitis persists after 2 months of antibiotherapy and a negative PCR joint fluid assessment. Non-steroidal anti-inflammatory drugs are often prescribed for their symptomatic effects. Experimental data is consensual on the deleterious consequences of systemic corticosteroid therapy. Corticosteroids are not indicated in Lyme's disease. In post Lyme's disease syndrome, patient complaints may lead to a multidisciplinary therapeutic management and the use of neuro-psychiatric drugs.

  12. Lyme Disease: Implications for Health Educators.

    ERIC Educational Resources Information Center

    Harbit, Maryanne Drake; Willis, Dawn

    1990-01-01

    Lyme disease may be one of the most commonly misdiagnosed diseases of this decade. Health educators should be knowledgeable about this new disease and be able to share with the public information about prevention, early signs and symptoms, and treatment of the disease (Author/IAH)

  13. Lyme disease: diagnostic issues and controversies.

    PubMed

    Aguero-Rosenfeld, Maria E; Wormser, Gary P

    2015-01-01

    The diagnosis of Lyme disease is a controversial topic. Most practitioners and scientists recognize that Lyme disease is associated with certain objective clinical manifestations supported by laboratory evidence of infection with Borrelia burgdorferi sensu lato (the etiologic agent). There are others, however, who believe that patients with Lyme disease may have a wide variety of entirely nonspecific symptoms without any objective clinical manifestation and that laboratory evidence of infection by B. burgdorferi is not required to support the diagnosis. In reality, this perspective is not evidence based and would inevitably lead to innumerable misdiagnoses, given the high frequency of medically unexplained symptoms, such as fatigue and musculoskeletal pains, in the general population. Although those espousing this viewpoint do not believe that a positive laboratory test is required, nevertheless, they often seek out and promote alternative, unapproved testing methods that frequently provide false-positive results to justify their diagnosis. Herein, we provide a brief overview of Lyme disease testing, emphasizing current usage and limitations. We also discuss the use of nonvalidated procedures and the prospects for a reduction in such testing practices in the future.

  14. Gallium-positive Lyme disease myocarditis

    SciTech Connect

    Alpert, L.I.; Welch, P.; Fisher, N.

    1985-09-01

    In the course of a work-up for fever of unknown origin associated with intermittent arrhythmias, a gallium scan was performed which revealed diffuse myocardial uptake. The diagnosis of Lyme disease myocarditis subsequently was confirmed by serologic titers. One month following recovery from the acute illness, the abnormal myocardial uptake completely resolved.

  15. Lyme Disease: A Challenge for Outdoor Educators.

    ERIC Educational Resources Information Center

    Whitcombe, Mark

    1989-01-01

    Describes signs and symptoms of Lyme disease; life cycle and feeding habits of the deer tick (Ixodes dammini), which transmits the spirochete bacterium; tick control measures; outdoor precautions; and veterinary considerations. Discusses the disease's potential impact on outdoor education, and suggests a reasoned, nonhysterical approach. Contains…

  16. Hyperglycemia Impairs Neutrophil-Mediated Bacterial Clearance in Mice Infected with the Lyme Disease Pathogen

    PubMed Central

    Javid, Ashkan; Zlotnikov, Nataliya; Pětrošová, Helena; Tang, Tian Tian; Zhang, Yang; Bansal, Anil K.; Ebady, Rhodaba; Parikh, Maitry; Ahmed, Mijhgan; Sun, Chunxiang; Newbigging, Susan; Kim, Yae Ram; Santana Sosa, Marianna; Glogauer, Michael

    2016-01-01

    Insulin-insufficient type 1 diabetes is associated with attenuated bactericidal function of neutrophils, which are key mediators of innate immune responses to microbes as well as pathological inflammatory processes. Neutrophils are central to immune responses to the Lyme pathogen Borrelia burgdorferi. The effect of hyperglycemia on host susceptibility to and outcomes of B. burgdorferi infection has not been examined. The present study investigated the impact of sustained obesity-independent hyperglycemia in mice on bacterial clearance, inflammatory pathology and neutrophil responses to B. burgdorferi. Hyperglycemia was associated with reduced arthritis incidence but more widespread tissue colonization and reduced clearance of bacterial DNA in multiple tissues including brain, heart, liver, lung and knee joint. B. burgdorferi uptake and killing were impaired in neutrophils isolated from hyperglycemic mice. Thus, attenuated neutrophil function in insulin-insufficient hyperglycemia was associated with reduced B. burgdorferi clearance in target organs. These data suggest that investigating the effects of comorbid conditions such as diabetes on outcomes of B. burgdorferi infections in humans may be warranted. PMID:27340827

  17. Emerging borreliae - Expanding beyond Lyme borreliosis.

    PubMed

    Cutler, Sally J; Ruzic-Sabljic, Eva; Potkonjak, Aleksandar

    2017-02-01

    Lyme borreliosis (or Lyme disease) has become a virtual household term to the exclusion of other forgotten, emerging or re-emerging borreliae. We review current knowledge regarding these other borreliae, exploring their ecology, epidemiology and pathological potential, for example, for the newly described B. mayonii. These bacteria range from tick-borne, relapsing fever-inducing strains detected in some soft ticks, such as B. mvumii, to those from bat ticks resembling B. turicatae. Some of these emerging pathogens remain unnamed, such as the borrelial strains found in South African penguins and some African cattle ticks. Others, such as B. microti and unnamed Iranian strains, have not been recognised through a lack of discriminatory diagnostic methods. Technical improvements in phylogenetic methods have allowed the differentiation of B. merionesi from other borrelial species that co-circulate in the same region. Furthermore, we discuss members that challenge the existing dogma that Lyme disease-inducing strains are transmitted by hard ticks, whilst the relapsing fever-inducing spirochaetes are transmitted by soft ticks. Controversially, the genus has now been split with Lyme disease-associated members being transferred to Borreliella, whilst the relapsing fever species retain the Borrelia genus name. It took some 60 years for the correlation with clinical presentations now known as Lyme borreliosis to be attributed to their spirochaetal cause. Many of the borreliae discussed here are currently considered exotic curiosities, whilst others, such as B. miyamotoi, are emerging as significant causes of morbidity. To elucidate their role as potential pathogenic agents, we first need to recognise their presence through suitable diagnostic approaches.

  18. Coordinated steroid hormone-dependent and independent expression of multiple kallikreins in breast cancer cell lines.

    PubMed

    Paliouras, Miltiadis; Diamandis, Eleftherios P

    2007-03-01

    The regulation of gene expression by steroid hormones plays an important role in the normal development and function of many organs, as well in the pathogenesis of endocrine-related cancers. Previous experiments have shown that many kallikrein genes are under steroid hormone regulation in breast cancer cell lines. We here examine the coordinated expression of multiple kallikrein genes in several breast cancer cell lines after steroid hormone stimulation. Breast cancer cell lines were treated with various steroid hormones and kallikrein (KLK/hK) expression of hK3 (prostate-specific antigen, PSA), hK5, hK6, hK7, hK8, hK10, hK11, hK13, and hK14 was analyzed at the RNA level via RT-PCR and at the protein level by immunofluorometric ELISA assays. We identified several distinct hK hormone-dependent and hormone-independent expression patterns. Hormone-specific modulation of expression was seen for several kallikreins in BT-474, MCF-7, and T-47D cell lines. hK6 was specifically up-regulated upon estradiol treatment in all three cell lines whereas PSA expression was induced by dihydrotestosterone (DHT) and norgestrel stimulation in BT-474 and T-47D. hK10, hK11, hK13, and hK14 were specifically up-regulated by DHT in T-47D and by estradiol in BT-474 cells. Bioinformatic analysis of upstream proximal promoter sequences for these hKs did not identify any recognizable hormone-response elements (HREs), suggesting that the coordinated activation of these four hKs represents a unique expression "cassette", utilizing a common hormone-dependent mechanism. We conclude that groups of human hKs are coordinately expressed in a steroid hormone-dependent manner. Our data supports clinical observations linking expression of multiple hKs with breast cancer prognosis.

  19. Iron deposition is independent of cellular inflammation in a cerebral model of multiple sclerosis

    PubMed Central

    2011-01-01

    Background Perivenular inflammation is a common early pathological feature in multiple sclerosis (MS). A recent hypothesis stated that CNS inflammation is induced by perivenular iron deposits that occur in response to altered blood flow in MS subjects. In order to evaluate this hypothesis, an animal model was developed, called cerebral experimental autoimmune encephalomyelitis (cEAE), which presents with CNS perivascular iron deposits. This model was used to investigate the relationship of iron deposition to inflammation. Methods In order to generate cEAE, mice were given an encephalitogen injection followed by a stereotactic intracerebral injection of TNF-α and IFN-γ. Control animals received encephalitogen followed by an intracerebral injection of saline, or no encephalitogen plus an intracerebral injection of saline or cytokines. Laser Doppler was used to measure cerebral blood flow. MRI and iron histochemistry were used to localize iron deposits. Additional histological procedures were used to localize inflammatory cell infiltrates, microgliosis and astrogliosis. Results Doppler analysis revealed that cEAE mice had a reduction in cerebral blood flow compared to controls. MRI revealed T2 hypointense areas in cEAE animals that spatially correlated with iron deposition around vessels and at some sites of inflammation as detected by iron histochemistry. Vessels with associated iron deposits were distributed across both hemispheres. Mice with cEAE had more iron-labeled vessels compared to controls, but these vessels were not commonly associated with inflammatory cell infiltrates. Some iron-laden vessels had associated microgliosis that was above the background microglial response, and iron deposits were observed within reactive microglia. Vessels with associated astrogliosis were more commonly observed without colocalization of iron deposits. Conclusion The findings indicate that iron deposition around vessels can occur independently of inflammation providing

  20. Folding mechanism of a multiple independently-folding domain protein: double B domain of protein A.

    PubMed

    Arora, Pooja; Hammes, Gordon G; Oas, Terrence G

    2006-10-10

    The antibody binding properties of staphylococcal protein A (SpA) can be attributed to the presence of five highly homologous domains (E, D, A, B, and C). Although the folding of the B domain of protein A (BdpA) is well-characterized, the folding behavior of this domain in the context of full-length SpA in the cell remains unexplored. The sequence of the B domain is 89 and 91% identical to those of domains A and C, respectively. We have fused B domain sequences (BBdpA) as a close approximation of the A-B or B-C portion of SpA. Circular dichroism and fluorescence-detected denaturation curves of BBdpA are experimentally indistinguishable from those of BdpA. The rate constants for folding and unfolding from NMR line shape analysis for the single- and double-domain proteins are the same within experimental uncertainties (+/-20%). These results support the designation of SpA as a multiple independently-folding domain (MIFD) protein. We develop a mathematical model that describes the folding thermodynamics and kinetics of MIFD proteins. The model depicts MIFD protein folding and unfolding as a parallel network and explicitly calculates the flux through all parallel pathways. These fluxes are combined to give a complete description of the global thermodynamics and kinetics of the folding and unfolding of MIFD proteins. The global rates for complete folding and unfolding of a MIFD protein and those of the individual domains depend on the stability of the protein. We show that the global unfolding rate of a MIFD protein may be many orders of magnitude slower than that of the constituent domains.

  1. AN INVESTIGATION OF NON-INDEPENDENCE OF COMPONENTS OF SCORES ON MULTIPLE-CHOICE TESTS. FINAL REPORT.

    ERIC Educational Resources Information Center

    ZIMMERMAN, DONALD W.; BURKHEIMER, GRAHAM J., JR.

    INVESTIGATION IS CONTINUED INTO VARIOUS EFFECTS OF NON-INDEPENDENT ERROR INTRODUCED INTO MULTIPLE-CHOICE TEST SCORES AS A RESULT OF CHANCE GUESSING SUCCESS. A MODEL IS DEVELOPED IN WHICH THE CONCEPT OF THEORETICAL COMPONENTS OF SCORES IS NOT INTRODUCED AND IN WHICH, THEREFORE, NO ASSUMPTIONS REGARDING ANY RELATIONSHIP BETWEEN SUCH COMPONENTS NEED…

  2. Lyme Disease: What the Wilderness Provider Needs to Know.

    PubMed

    Forrester, Joseph D; Vakkalanka, J Priyanka; Holstege, Christopher P; Mead, Paul S

    2015-12-01

    Lyme disease is a multisystem tickborne illness caused by the spirochete Borrelia burgdorferi and is the most common vectorborne disease in the United States. Prognosis after initiation of appropriate antibiotic therapy is typically good if treated early. Wilderness providers caring for patients who live in or travel to high-incidence Lyme disease areas should be aware of the basic biology, epidemiology, clinical manifestations, and treatment of Lyme disease.

  3. Methods to Prevent Tick Bites and Lyme Disease.

    PubMed

    Ogden, Nick H; Lindsay, L Robbin; Schofield, Steven W

    2015-12-01

    Current approaches for prevention of tick bites, Lyme disease, and other tick-borne diseases are described. Particular attention is paid to 4 risk-reduction strategies: (i) avoiding risk areas; (ii) personal protective measures that reduce the risk of tick bites or transmission of the agent of Lyme disease, Borrelia burgdorferi; (iii) reducing the number of infected ticks in the environment; and (iv) use of prophylactic antibiotic treatments following a bite to prevent clinical Lyme disease.

  4. Triple-phase bone image abnormalities in Lyme arthritis

    SciTech Connect

    Brown, S.J.; Dadparvar, S.; Slizofski, W.J.; Glab, L.B.; Burger, M. )

    1989-10-01

    Arthritis is a frequent manifestation of Lyme disease. Limited triple-phase Tc-99m MDP bone imaging of the wrists and hands with delayed whole-body images was performed in a patient with Lyme arthritis. This demonstrated abnormal joint uptake in the wrists and hands in all three phases, with increased activity seen in other affected joints on delayed whole-body images. These findings are nonspecific and have been previously described in a variety of rheumatologic conditions, but not in Lyme disease. Lyme disease should be considered in the differential diagnosis of articular and periarticular bone scan abnormalities.

  5. Lyme Disease Presenting as a Spontaneous Knee Effusion.

    PubMed

    Matzkin, Elizabeth; Suslavich, Kaytelin; Curry, Emily J

    2015-11-01

    Musculoskeletal complaints, which are frequently associated with Lyme disease, often prompt patients to see a physician. In particular, transient episodes of spontaneous knee effusion are common early in the progression of Lyme disease, and, if left untreated, 60% of patients diagnosed with the disease develop Lyme arthritis. This disease is easily treated with antibiotics; therefore, inclusion of Lyme disease in the differential diagnosis as a potential cause of a spontaneous knee effusion can prevent the development of more severe symptoms associated with the disease. However, the time required to receive test results and the inconsistencies between serum and synovial tests can complicate diagnosis of the disease.

  6. Multiple independent constraints help resolve net ecosystem carbon exchange under nutrient limitation

    NASA Astrophysics Data System (ADS)

    Thornton, P. E.; Metcalfe, D.; Oren, R.; Ricciuto, D. M.

    2014-12-01

    The magnitude, spatial distribution, and variability of land net ecosystem exchange of carbon (NEE) are important determinants of the trajectory of atmospheric carbon dioxide concentration. Independent observational constraints provide important clues regarding NEE and its component fluxes, with information available at multiple spatial scales: from cells, to leaves, to entire organisms and collections of organisms, to complex landscapes and up to continental and global scales. Experimental manipulations, ecosystem observations, and process modeling all suggest that the components of NEE (photosynthetic gains, and respiration and other losses) are controlled in part by the availability of mineral nutrients, and that nutrient limitation is a common condition in many biomes. Experimental and observational constraints at different spatial scales provide a complex and sometimes puzzling picture of the nature and degree of influence of nutrient availability on carbon cycle processes. Photosynthetic rates assessed at the cellular and leaf scales are often higher than the observed accumulation of carbon in plant and soil pools would suggest. We infer that a down-regulation process intervenes between carbon uptake and plant growth under conditions of nutrient limitation, and several down-regulation mechanisms have been hypothesized and tested. A recent evaluation of two alternative hypotheses for down-regulation in the light of whole-plant level flux estimates indicates that some plants take up and store extra carbon, releasing it to the environment again on short time scales. The mechanism of release, either as additional autotrophic respiration or as exudation belowground is unclear, but has important consequences for long-term ecosystem state and response to climate change signals. Global-scale constraints from atmospheric concentration and isotopic composition data help to resolve this question, ultimately focusing attention on land use fluxes as the most uncertain

  7. Natalizumab-Related Progressive Multifocal Leukoencephalopathy in Multiple Sclerosis: Findings from an Italian Independent Registry

    PubMed Central

    de Rossi, Nicola; Scarpazza, Cristina; Moiola, Lucia; Cosottini, Mirco; Gerevini, Simonetta; Capra, Ruggero

    2016-01-01

    Background The monoclonal antibody natalizumab (NTZ) is a highly effective treatment for patients with multiple sclerosis (MS). However, this drug is associated with increased risk of developing Progressive Multifocal Leukoencephalopathy (PML), an opportunistic infection of central nervous system (CNS) caused by the John Cunningham polyomavirus (JCV). Objective To describe the 12-month clinical course of 39 patients with MS (28 women, 11 men) who developed NTZ-related PML after a mean exposure of 39 infusions. Methods An Italian independent collaborative repository initiative collected and analyzed socio-demographic, clinical, magnetic resonance imaging (MRI) data and number of JCV-DNA copies detected on cerebrospinal fluid (CSF) samples of patients diagnosed as affected by NTZ-related PML. The evolution of disability, measured by the Expanded Disability Status Scale, was assessed at NTZ start, at PML diagnosis and after 2, 6 and 12 months from PML diagnosis. The effect of clinical and paraclinical characteristics at PML diagnosis on the final outcome was also investigated. Results Ten patients (25.6%) were diagnosed before 24 NTZ infusions. In six cases (15.4%) the PML suspect was made on the basis of highly suggestive MRI findings in absence of any detectable change of clinical conditions (asymptomatic PML). In patients with symptomatic PML, the diagnosis was quicker for those who presented with cognitive symptoms (n = 12) rather than for those with other neurological pictures (n = 21) (p = 0.003). Three patients (7.7%) died during the 12-month observation period, resulting in a survival rate of 92.3%. Asymptomatic PML, more localized brain involvement and gadolinium-enhancement detected at MRI, as well as lower viral load were associated with a better disability outcome (p-values<0.01). Conclusion Our findings support that early PML diagnosis, limited CNS involvement and initial signs of immune restoration are associated with a better outcome and higher survival

  8. Induction of lyme arthritis in LSH hamsters

    SciTech Connect

    Schmitz, J.L.; Schell, R.F.; Hejka, A.; England, D.M.; Konick, L.

    1988-09-01

    In studies of experimental Lyme disease, a major obstacle has been the unavailability of a suitable animal model. We found that irradiated LSH/Ss Lak hamsters developed arthritis after injection of Borrelia burgdorferi in the hind paws. When nonirradiated hamsters were injected in the hind paws with B. burgdorferi, acute transient synovitis was present. A diffuse neutrophilic infiltrate involved the synovia and periarticular structures. The inflammation was associated with edema, hyperemia, and granulation tissue. Numerous spirochetes were seen in the synovial and subsynovial tissues. The histopathologic changes were enhanced in irradiated hamsters. The onset and duration of the induced swelling were dependent on the dose of radiation and the inoculum of spirochetes. Inoculation of irradiated hamsters with Formalin-killed spirochetes or medium in which B. burgdorferi had grown for 7 days failed to induce swelling. This animal model should prove useful for studies of the immune response to B. burgdorferi and the pathogenesis of Lyme arthritis.

  9. Controversies in Persistent (Chronic) Lyme Disease

    PubMed Central

    2016-01-01

    The Centers for Disease Control and Prevention estimates that more than 300 000 new cases of Lyme disease occur each year in the United States and that 10% to 20% of these patients will remain symptomatic despite receiving appropriate antibiotic therapy. Many elements of the disease are poorly understood and have generated considerable controversy. This paper discusses the medical controversies related to posttreatment manifestations and their potential impact on infusion nurses. PMID:27755213

  10. Lyme borreliosis: A neglected zoonosis in Egypt.

    PubMed

    Elhelw, Rehab A; El-Enbaawy, Mona I; Samir, Ahmed

    2014-12-01

    Borrelia burgdorferi, the causal organism of Lyme borreliosis. In Egypt, available data about the occurrence of Lyme disease are scarce and no structured studies documented the presence of Lyme borreliosis in Egyptian animals and tick reservoirs verifying its zoonotic evidence. Besides, no successful trials to isolate B. burgdorferi from clinical samples have occurred. This study was conducted to investigate B. burgdorferi infection as an emerging zoonosis neglected in Egypt. A total number of 92 animals, tick and human companion specimens were collected and subjected for culture, PCR and/or serodetection. B. burgdorferi has been detected and isolated from Egyptian animal breeds. We also detected the presence of outer surface protein A gene of B. burgdorferi by PCR as well as anti-B. burgdorferi IgM by ELISA in human contacts who were suffering from fever of unknown origin. This report represents the first systematic study on animals associated with patients suffering from febrile illness to confirm the emerging of such neglected zoonosis in Egypt.

  11. Lyme disease: case report of persistent Lyme disease from Pulaski County, Virginia.

    PubMed

    Palmieri, James R; King, Scott; Case, Matthew; Santo, Arben

    2013-01-01

    A 50-year-old woman from Pulaski, Virginia, presented to a local clinic with headaches, fever, generalized joint pain, excessive thirst and fluid intake, and a progressing rash on her back. On physical examination, she had a large circular red rash on her back with a bull's-eye appearance, 16 × 18 cm in diameter. Serologic tests confirmed a diagnosis of Lyme disease. The patient could recall a walk through the woods 3 weeks prior, although she never noticed a tick on her body. Following a prolonged course of antibiotics, this case report presents a patient with ongoing symptoms consistent with post-treatment Lyme disease.

  12. Enhancing the participation and independence of students with severe physical and multiple disabilities in performing community activities.

    PubMed

    Sowers, J A; Powers, L

    1995-08-01

    The effectiveness of a multi-element approach derived from factors to increase self-determination of middle- and high-school-age students with physical and multiple disabilities was examined. The approach includes equipment and performance adaptations, brief in-school simulation training, and instruction and support for parents and home assistance providers. The intervention was instituted with 3 students; a multiple baseline design was used. Student participation and independence dramatically increased after the intervention. Results suggest that this approach may be one solution to providing students with both inclusive education and community skill and activity instruction. The impact of the intervention on student self-determination was discussed.

  13. 77 FR 6465 - Drawbridge Operation Regulations; Connecticut River, Old Lyme, CT

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-08

    ... SECURITY Coast Guard 33 CFR Part 117 Drawbridge Operation Regulations; Connecticut River, Old Lyme, CT... of the Old Saybrook-Old Lyme RR Bridge, mile 3.4, across the Connecticut River at Old Lyme... INFORMATION: The Old Saybrook-Old Lyme RR Bridge at mile 3.4, across the Connecticut River at Old...

  14. Estimation of the cumulative incidence function under multiple dependent and independent censoring mechanisms.

    PubMed

    Lok, Judith J; Yang, Shu; Sharkey, Brian; Hughes, Michael D

    2017-02-25

    Competing risks occur in a time-to-event analysis in which a patient can experience one of several types of events. Traditional methods for handling competing risks data presuppose one censoring process, which is assumed to be independent. In a controlled clinical trial, censoring can occur for several reasons: some independent, others dependent. We propose an estimator of the cumulative incidence function in the presence of both independent and dependent censoring mechanisms. We rely on semi-parametric theory to derive an augmented inverse probability of censoring weighted (AIPCW) estimator. We demonstrate the efficiency gained when using the AIPCW estimator compared to a non-augmented estimator via simulations. We then apply our method to evaluate the safety and efficacy of three anti-HIV regimens in a randomized trial conducted by the AIDS Clinical Trial Group, ACTG A5095.

  15. A Lyme Disease Case Study and Individualized Healthcare Plan

    ERIC Educational Resources Information Center

    Cavendish, Roberta

    2003-01-01

    The Atlantic and Pacific coasts are the boundaries of Lyme disease with the Northeastern and Midwestern regions of the United States continuing to report the majority of cases. New reported cases of Lyme disease doubled from 1991 to 2001 according to statistics published by the Centers for Disease Control and Prevention (CDC, 2002). Within that…

  16. TOWARDS LANDSCAPE DESIGN GUIDELINES FOR REDUCING LYME DISEASE RISK

    EPA Science Inventory

    Incidence of Lyme disease in the United States continues to grow. Low-density development is also increasing in endemic regions, raising questions about the relationship between development pattern and disease. This study sought to model Lyme disease incidence rate using quanti...

  17. "Capitalizing on Sport": Sport, Physical Education and Multiple Capitals in Scottish Independent Schools

    ERIC Educational Resources Information Center

    Horne, John; Lingard, Bob; Weiner, Gaby; Forbes, Joan

    2011-01-01

    This paper draws on a research study into the existence and use of different forms of capital--including social, cultural and physical capital--in three independent schools in Scotland. We were interested in understanding how these forms of capital work to produce and reproduce "advantage" and "privilege". Analysis is framed by…

  18. Optimising threshold levels for information transmission in binary threshold networks: Independent multiplicative noise on each threshold

    NASA Astrophysics Data System (ADS)

    Zhou, Bingchang; McDonnell, Mark D.

    2015-02-01

    The problem of optimising the threshold levels in multilevel threshold system subject to multiplicative Gaussian and uniform noise is considered. Similar to previous results for additive noise, we find a bifurcation phenomenon in the optimal threshold values, as the noise intensity changes. This occurs when the number of threshold units is greater than one. We also study the optimal thresholds for combined additive and multiplicative Gaussian noise, and find that all threshold levels need to be identical to optimise the system when the additive noise intensity is a constant. However, this identical value is not equal to the signal mean, unlike the case of additive noise. When the multiplicative noise intensity is instead held constant, the optimal threshold levels are not all identical for small additive noise intensity but are all equal to zero for large additive noise intensity. The model and our results are potentially relevant for sensor network design and understanding neurobiological sensory neurons such as in the peripheral auditory system.

  19. Cross-reactivity between Lyme and syphilis screening assays: Lyme disease does not cause false-positive syphilis screens.

    PubMed

    Patriquin, Glenn; LeBlanc, Jason; Heinstein, Charles; Roberts, Catherine; Lindsay, Robbin; Hatchette, Todd F

    2016-03-01

    Increased rates of Lyme disease and syphilis in the same geographic area prompted an assessment of screening test cross-reactivity. This study supports the previously described cross-reactivity of Lyme screening among syphilis-positive sera and reports evidence against the possibility of false-positive syphilis screening tests resulting from previous Borrelia burgdorferi infection.

  20. Lyme disease: a rigorous review of diagnostic criteria and treatment.

    PubMed

    Borchers, Andrea T; Keen, Carl L; Huntley, Arthur C; Gershwin, M Eric

    2015-02-01

    Lyme disease was originally identified in Lyme, Connecticut, based upon an unusual cluster of what appeared to be patients with juvenile rheumatoid arthritis. It was subsequently identified as a new clinical entity originally called Lyme arthritis based on the observation that arthritis was a major clinical feature. However, Lyme arthritis is now called Lyme disease based upon the understanding that the clinical features include not only arthritis, but also potential cardiac, dermatologic and neurologic findings. Lyme disease typically begins with an erythematous rash called erythema migrans (EM). Approximately 4-8% of patients develop cardiac, 11% develop neurologic and 45-60% of patients manifest arthritis. The disease is transmitted following exposure to a tick bite containing a spirochete in a genetically susceptible host. There is considerable data on spirochetes, including Borrelia burgdorferi (Bb), the original bacteria identified in this disease. Lyme disease, if an organism had not been identified, would be considered as a classic autoimmune disease and indeed the effector mechanisms are similar to many human diseases manifest as loss of tolerance. The clinical diagnosis is highly likely based upon appropriate serology and clinical manifestations. However, the serologic features are often misinterpreted and may have false positives if confirmatory laboratory testing is not performed. Antibiotics are routinely and typically used to treat patients with Lyme disease, but there is no evidence that prolonged or recurrent treatment with antibiotics change the natural history of Lyme disease. Although there are animal models of Lyme disease, there is no system that faithfully recapitulates the human disease. Further research on the effector mechanisms that lead to pathology in some individuals should be further explored to develop more specific therapy.

  1. Space-time delta-sigma modulation for reception of multiple simultaneous independent RF beams

    NASA Astrophysics Data System (ADS)

    Rong, Guoguang; Black, Bruce A.; Siahmakoun, Azad Z.

    2005-09-01

    In this paper we introduce and analyze a multiple-RF-beam beamformer in receive mode utilizing the principle of space-time delta-sigma modulation. This principle is based on sampling input signals in both time and space and converting the sampled signals into a digital format by delta-sigma conversion. Noise shaping is achieved in 2D frequency domain. We show that the modulator can receive signals of narrow and wide bandwidths with steering capability, can receive multiple beams, and establish tradeoffs between sampling in time and in space. The ability of the modulator to trade off between time and space provides an effective way to sample high frequency RF signals without down conversion. In addition, a space-time delta-sigma modulator has better performance than a solely temporal delta-sigma modulator (for the same filter order), as is typically used in communication systems to digitize the down-converted analog signals.

  2. Polarization-Independent Multiple Fano Resonances in Plasmonic Nonamers for Multimode-Matching Enhanced Multiband Second-Harmonic Generation.

    PubMed

    Liu, Shao-Ding; Leong, Eunice Sok Ping; Li, Guang-Can; Hou, Yidong; Deng, Jie; Teng, Jing Hua; Ong, Hock Chun; Lei, Dang Yuan

    2016-01-26

    Plasmonic oligomers composed of metallic nanoparticles are one class of the most promising platforms for generating Fano resonances with unprecedented optical properties for enhancing various linear and nonlinear optical processes. For efficient generation of second-harmonic emissions at multiple wavelength bands, it is critical to design a plasmonic oligomer concurrently having multiple Fano resonances spectrally matching the fundamental excitation wavelengths and multiple plasmon resonance modes coinciding with the harmonic wavelengths. Thus far, the realization of such a plasmonic oligomer remains a challenge. This study demonstrates both theoretically and experimentally that a plasmonic nonamer consisting of a gold nanocross surrounded by eight nanorods simultaneously sustains multiple polarization-independent Fano resonances in the near-infrared region and several higher-order plasmon resonances in the visible spectrum. Due to coherent amplification of the nonlinear excitation sources by the Fano resonances and efficient scattering-enhanced outcoupling by the higher-order modes, the second-harmonic emission of the nonamer is significantly increased at multiple spectral bands, and their spectral positions and radiation patterns can be flexibly manipulated by easily tuning the length of the surrounding nanorods in the nonamer. These results provide us with important implications for realizing ultrafast multichannel nonlinear optoelectronic devices.

  3. Multiple brain networks underpinning word learning from fluent speech revealed by independent component analysis.

    PubMed

    López-Barroso, Diana; Ripollés, Pablo; Marco-Pallarés, Josep; Mohammadi, Bahram; Münte, Thomas F; Bachoud-Lévi, Anne-Catherine; Rodriguez-Fornells, Antoni; de Diego-Balaguer, Ruth

    2015-04-15

    Although neuroimaging studies using standard subtraction-based analysis from functional magnetic resonance imaging (fMRI) have suggested that frontal and temporal regions are involved in word learning from fluent speech, the possible contribution of different brain networks during this type of learning is still largely unknown. Indeed, univariate fMRI analyses cannot identify the full extent of distributed networks that are engaged by a complex task such as word learning. Here we used Independent Component Analysis (ICA) to characterize the different brain networks subserving word learning from an artificial language speech stream. Results were replicated in a second cohort of participants with a different linguistic background. Four spatially independent networks were associated with the task in both cohorts: (i) a dorsal Auditory-Premotor network; (ii) a dorsal Sensory-Motor network; (iii) a dorsal Fronto-Parietal network; and (iv) a ventral Fronto-Temporal network. The level of engagement of these networks varied through the learning period with only the dorsal Auditory-Premotor network being engaged across all blocks. In addition, the connectivity strength of this network in the second block of the learning phase correlated with the individual variability in word learning performance. These findings suggest that: (i) word learning relies on segregated connectivity patterns involving dorsal and ventral networks; and (ii) specifically, the dorsal auditory-premotor network connectivity strength is directly correlated with word learning performance.

  4. Lyme Disease Coinfections in the United States.

    PubMed

    Caulfield, Adam J; Pritt, Bobbi S

    2015-12-01

    Lyme disease in North America is caused by infection with the spirochetal bacterium Borrelia burgdorferi and transmitted by Ixodes scapularis and Ixodes pacificus ticks. These ticks also have the potential to transmit a rapidly expanding list of other pathogenic bacteria, viruses, and parasites, including Anaplasma phagocytophilum, Babesia microti, deer tick (Powassan) virus, Borrelia miyamotoi, and the Ehrlichia muris-like organism. Coinfections with B burgdorferi and these other agents are often difficult to diagnose and may go untreated, and thus contribute significantly to patient morbidity and mortality from tick-borne infections.

  5. Cerebrospinal Fluid Proteome of Patients with Acute Lyme Disease

    SciTech Connect

    Angel, Thomas E.; Jacobs, Jon M.; Smith, Robert P.; Pasternack, Mark S.; Elias, Susan; Gritsenko, Marina A.; Shukla, Anil K.; Gilmore, Edward C.; McCarthy, Carol; Camp, David G.; Smith, Richard D.

    2012-10-05

    Acute Lyme disease results from transmission of and infection by the bacterium Borrelia burgdorferi following a tick bite. During acute infection, bacteria can disseminate to the central nervous system (CNS) leading to the development of Lyme meningitis. Here we have analyzed pooled cerebrospinal fluid (CSF) allowing for a deep view into the proteome for a cohort of patients with early-disseminated Lyme disease and CSF inflammation leading to the identification of proteins that reflect host responses, which are distinct for subjects with acute Lyme disease. Additionally, we analyzed individual patient samples and quantified changes in protein abundance employing label-free quantitative mass spectrometry based methods. The measured changes in protein abundances reflect the impact of acute Lyme disease on the CNS as presented in CSF. We have identified 89 proteins that differ significantly in abundance in patients with acute Lyme disease. A number of the differentially abundant proteins have been found to be localized to brain synapse and thus constitute important leads for better understanding of the neurological consequence of disseminated Lyme disease.

  6. Lyme Borreliosis in Human Patients in Florida and Georgia, USA

    PubMed Central

    Clark, Kerry L.; Leydet, Brian; Hartman, Shirley

    2013-01-01

    The aim of this study was to determine the cause of illness in several human patients residing in Florida and Georgia, USA, with suspected Lyme disease based upon EM-like skin lesions and/or symptoms consistent with early localized or late disseminated Lyme borreliosis. Using polymerase chain reaction (PCR) assays developed specifically for Lyme group Borrelia spp., followed by DNA sequencing for confirmation, we identified Borrelia burgdorferi sensu lato DNA in samples of blood and skin and also in lone star ticks (Amblyomma americanum) removed from several patients who either live in or were exposed to ticks in Florida or Georgia. This is the first report to present combined PCR and DNA sequence evidence of infection with Lyme Borrelia spp. in human patients in the southern U.S., and to demonstrate that several B. burgdorferi sensu lato species may be associated with Lyme disease-like signs and symptoms in southern states. Based on the findings of this study, we suggest that human Lyme borreliosis occurs in Florida and Georgia, and that some cases of Lyme-like illness referred to as southern tick associated rash illness (STARI) in the southern U.S. may be attributable to previously undetected B. burgdorferi sensu lato infections. PMID:23781138

  7. Hamster and Murine Models of Severe Destructive Lyme Arthritis

    PubMed Central

    Munson, Erik; Nardelli, Dean T.; Du Chateau, Brian K.; Callister, Steven M.; Schell, Ronald F.

    2012-01-01

    Arthritis is a frequent complication of infection in humans with Borrelia burgdorferi. Weeks to months following the onset of Lyme borreliosis, a histopathological reaction characteristic of synovitis including bone, joint, muscle, or tendon pain may occur. A subpopulation of patients may progress to a chronic, debilitating arthritis months to years after infection which has been classified as severe destructive Lyme arthritis. This arthritis involves focal bone erosion and destruction of articular cartilage. Hamsters and mice are animal models that have been utilized to study articular manifestations of Lyme borreliosis. Infection of immunocompetent LSH hamsters or C3H mice results in a transient synovitis. However, severe destructive Lyme arthritis can be induced by infecting irradiated hamsters or mice and immunocompetent Borrelia-vaccinated hamsters, mice, and interferon-gamma- (IFN-γ-) deficient mice with viable B. burgdorferi. The hamster model of severe destructive Lyme arthritis facilitates easy assessment of Lyme borreliosis vaccine preparations for deleterious effects while murine models of severe destructive Lyme arthritis allow for investigation of mechanisms of immunopathology. PMID:22461836

  8. Mitogen-activated protein kinase-dependent and -independent routes control shedding of transmembrane growth factors through multiple secretases.

    PubMed Central

    Montero, Juan Carlos; Yuste, Laura; Díaz-Rodríguez, Elena; Esparís-Ogando, Azucena; Pandiella, Atanasio

    2002-01-01

    Solubilization of a number of membrane proteins occurs by the action of cell-surface proteases, termed secretases. Recently, the activity of these secretases has been reported to be controlled by the extracellular signal-regulated kinases 1 and 2 (ERK1/ERK2) and the p38 mitogen-activated protein kinase (MAPK) routes. In the present paper, we show that shedding of membrane-anchored growth factors (MAGFs) may also occur through MAPK-independent routes. In Chinese-hamster ovary cells, cleavage induced by protein kinase C (PKC) stimulation was largely insensitive to inhibitors of the ERK1/ERK2 and p38 routes. Other reagents such as sorbitol or UV light stimulated MAGF cleavage independent of PKC. The action of sorbitol on cleavage was only partially prevented by the combined action of inhibitors of the p38 and ERK1/ERK2 routes, indicating that sorbitol can also stimulate shedding by MAPK-dependent and -independent routes. Studies in cells devoid of activity of the secretase tumour necrosis factor-alpha-converting enzyme (TACE) indicated that this protease had an essential role in PKC- and ERK1/ERK2-mediated shedding. However, secretases other than TACE may also cleave MAGFs since sorbitol could still induce shedding in these cells. These observations suggest that cleavage of MAGFs is a complex process in which multiple secretases, activated through different MAPK-dependent and -independent routes, are involved. PMID:11931648

  9. Multiple vacuoles in impaired tonoplast trafficking3 mutants are independent organelles.

    PubMed

    Zheng, Jiameng; Han, Sang Won; Munnik, Teun; Rojas-Pierce, Marcela

    2014-01-01

    Plant vacuoles are essential and dynamic organelles, and mechanisms of vacuole biogenesis and fusion are not well characterized. We recently demonstrated that Wortmannin, an inhibitor of Phosphatidylinositol 3-Kinase (PI3K), induces the fusion of plant vacuoles both in roots of itt3/vti11 mutant alleles and in guard cells of wild type Arabidopsis and Fava bean. Here we used Fluorescence Recovery After Photobleaching (FRAP) to demonstrate that the vacuoles in itt3/vti11 are independent organelles. Furthermore, we used fluorescent protein reporters that bind specifically to Phosphatidylinositol 3-Phosphate (PtdIns(3)P) or PtdIns(4)P to show that Wortmannin treatments that induce the fusion of vti11 vacuoles result in the loss of PtdIns(3)P from cellular membranes. These results provided supporting evidence for a critical role of PtdIns(3)P in vacuole fusion in roots and guard cells.

  10. Multiple vacuoles in impaired tonoplast trafficking3 mutants are independent organelles.

    PubMed

    Zheng, Jiameng; Won Han, Sang; Munnik, Teun; Rojas-Pierce, Marcela

    2014-08-13

    Plant vacuoles are essential and dynamic organelles, and mechanisms of vacuole biogenesis and fusion are not well characterized. We recently demonstrated that Wortmannin, an inhibitor of Phosphatidylinositol-3-Kinase (PI3K), induces the fusion of plant vacuoles both in roots of itt3/vti11 mutant alleles and in guard cells of wild type Arabidopsis and Fava bean. Here we used Fluorescence Recovery After Photobleaching (FRAP) to demonstrate that the vacuoles in itt3/vti11 are independent organelles. Furthermore, we used fluorescent protein reporters that bind specifically to Phosphatidylinositol-3-Phosphate (PtdIns(3)P) or PtdIns(4)P to show that Wortmannin treatments that induce the fusion of vti11 vacuoles result in the loss of PtdIns(3)P from cellular membranes. These results provided supporting evidence for a critical role of PtdIns(3)P in vacuole fusion in roots and guard cells.

  11. Multiple vacuoles in impaired tonoplast trafficking3 mutants are independent organelles

    PubMed Central

    Zheng, Jiameng; Han, Sang Won; Munnik, Teun; Rojas-Pierce, Marcela

    2014-01-01

    Plant vacuoles are essential and dynamic organelles, and mechanisms of vacuole biogenesis and fusion are not well characterized. We recently demonstrated that Wortmannin, an inhibitor of Phosphatidylinositol 3-Kinase (PI3K), induces the fusion of plant vacuoles both in roots of itt3/vti11 mutant alleles and in guard cells of wild type Arabidopsis and Fava bean. Here we used Fluorescence Recovery After Photobleaching (FRAP) to demonstrate that the vacuoles in itt3/vti11 are independent organelles. Furthermore, we used fluorescent protein reporters that bind specifically to Phosphatidylinositol 3-Phosphate (PtdIns(3)P) or PtdIns(4)P to show that Wortmannin treatments that induce the fusion of vti11 vacuoles result in the loss of PtdIns(3)P from cellular membranes. These results provided supporting evidence for a critical role of PtdIns(3)P in vacuole fusion in roots and guard cells. PMID:25482812

  12. Phylogeography of Asian wild rice, Oryza rufipogon, reveals multiple independent domestications of cultivated rice, Oryza sativa.

    PubMed

    Londo, Jason P; Chiang, Yu-Chung; Hung, Kuo-Hsiang; Chiang, Tzen-Yuh; Schaal, Barbara A

    2006-06-20

    Cultivated rice, Oryza sativa L., represents the world's most important staple food crop, feeding more than half of the human population. Despite this essential role in world agriculture, the history of cultivated rice's domestication from its wild ancestor, Oryza rufipogon, remains unclear. In this study, DNA sequence variation in three gene regions is examined in a phylogeographic approach to investigate the domestication of cultivated rice. Results indicate that India and Indochina may represent the ancestral center of diversity for O. rufipogon. Additionally, the data suggest that cultivated rice was domesticated at least twice from different O. rufipogon populations and that the products of these two independent domestication events are the two major rice varieties, Oryza sativa indica and Oryza sativa japonica. Based on this geographical analysis, O. sativa indica was domesticated within a region south of the Himalaya mountain range, likely eastern India, Myanmar, and Thailand, whereas O. sativa japonica was domesticated from wild rice in southern China.

  13. Maximum Likelihood Estimation of Spectra Information from Multiple Independent Astrophysics Data Sets

    NASA Technical Reports Server (NTRS)

    Howell, Leonard W., Jr.; Six, N. Frank (Technical Monitor)

    2002-01-01

    The Maximum Likelihood (ML) statistical theory required to estimate spectra information from an arbitrary number of astrophysics data sets produced by vastly different science instruments is developed in this paper. This theory and its successful implementation will facilitate the interpretation of spectral information from multiple astrophysics missions and thereby permit the derivation of superior spectral information based on the combination of data sets. The procedure is of significant value to both existing data sets and those to be produced by future astrophysics missions consisting of two or more detectors by allowing instrument developers to optimize each detector's design parameters through simulation studies in order to design and build complementary detectors that will maximize the precision with which the science objectives may be obtained. The benefits of this ML theory and its application is measured in terms of the reduction of the statistical errors (standard deviations) of the spectra information using the multiple data sets in concert as compared to the statistical errors of the spectra information when the data sets are considered separately, as well as any biases resulting from poor statistics in one or more of the individual data sets that might be reduced when the data sets are combined.

  14. Tick bites and Lyme disease: the need for timely treatment.

    PubMed

    Overstreet, Maria L

    2013-06-01

    In the United States, 30,158 people were reported as having contracted Lyme disease during 2010; 96% of the cases in 2011 were reported from 13 northeast and north-central states. Time of tick attachment is a critical factor. Prolonged attachment allows time for a bacterium to move from tick to human. Patient history and meticulous skin inspection are the most important elements used in diagnosis of Lyme disease. The most common drug for treatment is doxycycline. Ticks find their hosts by several senses: odor, moisture, heat, and vibration. Avoidance of tick-infested areas, such as wooded areas and leaf piles, is paramount in preventing Lyme disease.

  15. Water uptake is independent of the inferred composition of secondary aerosols derived from multiple biogenic VOCs

    NASA Astrophysics Data System (ADS)

    Alfarra, M. R.; Good, N.; Wyche, K. P.; Hamilton, J. F.; Monks, P. S.; Lewis, A. C.; McFiggans, G.

    2013-12-01

    We demonstrate that the water uptake properties derived from sub- and super-saturated measurements of chamber-generated biogenic secondary organic aerosol (SOA) particles are independent of their degree of oxidation, determined using both online and offline methods. SOA particles are formed from the photooxidation of five structurally different biogenic VOCs, representing a broad range of emitted species and their corresponding range of chemical reactivity: α-pinene, β-caryophyllene, limonene, myrcene and linalool. The fractional contribution of mass fragment 44 to the total organic signal (f44) is used to characterise the extent of oxidation of the formed SOA as measured online by an aerosol mass spectrometer. Results illustrate that the values of f44 are dependent on the precursor, the extent of photochemical ageing as well as on the initial experimental conditions. SOA generated from a single biogenic precursor should therefore not be used as a general proxy for biogenic SOA. Similarly, the generated SOA particles exhibit a range of hygroscopic properties, depending on the precursor, its initial mixing ratio and photochemical ageing. The activation behaviour of the formed SOA particles show no temporal trends with photochemical ageing. The average κ values derived from the HTDMA and CCNc are generally found to cover the same range for each precursor under two different initial mixing ratio conditions. A positive correlation is observed between the hygroscopicity of particles of a single size and f44 for α-pinene, β-caryophyllene, linalool and myrcene, but not for limonene SOA. The investigation of the generality of this relationship reveals that α-pinene, limonene, linalool and myrcene are all able to generate particles with similar hygroscopicity (κHTDMA ~0.1) despite f44 exhibiting a relatively wide range of values (~4 to 11%). Similarly, κCCN is found to be independent of f44. The same findings are also true when sub- and super-saturated water uptake

  16. Water uptake is independent of the inferred composition of secondary aerosols derived from multiple biogenic VOCs

    NASA Astrophysics Data System (ADS)

    Alfarra, M. R.; Good, N.; Wyche, K. P.; Hamilton, J. F.; Monks, P. S.; Lewis, A. C.; McFiggans, G. B.

    2013-04-01

    We demonstrate that the water uptake properties derived from sub- and super-saturated measurements of chamber-generated biogenic secondary organic aerosol (SOA) particles are independent of their degree of oxidation determined using both online and offline methods. SOA particles are formed from the photooxidation of five structurally different biogenic VOCs representing a broad range of emitted species and their corresponding range of chemical reactivity: α-pinene, β-caryophyllene, limonene, myrcene and linalool. The fractional contribution of mass fragment 44 to the total organic signal (f44) is used to characterise the extent of oxidation of the formed SOA as measured online by an aerosol mass spectrometer. Results illustrate that the values of f44 are dependent on the precursor, the extent of photochemical ageing as well as on the initial experimental conditions. SOA generated from a single biogenic precursor should therefore not be used as a general proxy for biogenic SOA. Similarly, the generated SOA particles exhibit a range of hygroscopic properties depending on the precursor, its initial mixing ratio and photochemical ageing. The activation behaviour of the formed SOA particles show no temporal trends with photochemical ageing. The average κ values derived from the HTDMA and CCNc are generally found to cover the same range for each precursor under two different initial mixing ratio conditions. A positive correlation is observed between the hygroscopicity of particles of a single size and f44 for α-pinene, β-caryophyllene, linalool and myrcene, but not for limonene SOA. The investigation of the generality of this relationship reveal that α-pinene, limonene, linalool and myrcene are all able to generate particles with similar hygroscopicity (κHTDMA ~0.1) despite f44 exhibiting a relatively wide range of values (~4 to 11%). Similarly, κCCN is found to be independent of f44. The same findings are also true when sub- and super-saturated water uptake

  17. Evolving Perspectives on Lyme Borreliosis in Canada

    PubMed Central

    Sperling, JLH; Middelveen, MJ; Klein, D; Sperling, FAH

    2012-01-01

    With cases now documented in every province, Lyme borreliosis (LB) is emerging as a serious public health risk in Canada. Controversy over the contribution of LB to the burden of chronic disease is maintained by difficulty in capturing accurate Canadian statistics, especially early clinical cases of LB. The use of dogs as sentinel species demon-strates that potential contact with Borrelia burgdorferi spirochetes, as detected by C6 peptide, extends across the country. Dissemination of infected ticks by migratory birds and rapid establishment of significant levels of infection have been well described. Canadian public health response has focused on identification of established populations of the tick vectors, Ixodes scapularis and I. pacificus, on the assumption that these are the only important vectors of the disease across Canada. Strains of B. burgdorferi circulating in Canada and the full range of their reservoir species and coinfections remain to be explored. Ongoing surveys and historical records demonstrate that Borrelia-positive Ixodes species are regu-larly present in regions of Canada that have previously been considered to be outside of the ranges of these species in re-cent modeling efforts. We present data demonstrating that human cases of LB are found across the nation. Consequently, physician education and better early diagnoses are needed to prevent long term sequelae. An international perspective will be paramount for developing improved Canadian guidelines that recognize the complexity and diversity of Lyme borreliosis. PMID:23091570

  18. Blastocystis Mitochondrial Genomes Appear to Show Multiple Independent Gains and Losses of Start and Stop Codons

    PubMed Central

    Jacob, Alison S.; Andersen, Lee O’Brien; Bitar, Paulina Pavinski; Richards, Vincent P.; Shah, Sarah; Stanhope, Michael J.; Stensvold, C. Rune; Clark, C. Graham

    2016-01-01

    Complete mitochondrion-related organelle (MRO) genomes of several subtypes (STs) of the unicellular stramenopile Blastocystis are presented. Complete conservation of gene content and synteny in gene order is observed across all MRO genomes, comprising 27 protein coding genes, 2 ribosomal RNA genes, and 16 transfer RNA (tRNA) genes. Despite the synteny, differences in the degree of overlap between genes were observed between subtypes and also between isolates within the same subtype. Other notable features include unusual base-pairing mismatches in the predicted secondary structures of some tRNAs. Intriguingly, the rps4 gene in some MRO genomes is missing a start codon and, based on phylogenetic relationships among STs, this loss has happened twice independently. One unidentified open reading frame (orf160) is present in all MRO genomes. However, with the exception of ST4 where the feature has been lost secondarily, orf160 contains variously one or two in-frame stop codons. The overall evidence suggests that both the orf160 and rps4 genes are functional in all STs, but how they are expressed remains unclear. PMID:27811175

  19. Multiple major disease-associated clones of Legionella pneumophila have emerged recently and independently.

    PubMed

    David, Sophia; Rusniok, Christophe; Mentasti, Massimo; Gomez-Valero, Laura; Harris, Simon R; Lechat, Pierre; Lees, John; Ginevra, Christophe; Glaser, Philippe; Ma, Laurence; Bouchier, Christiane; Underwood, Anthony; Jarraud, Sophie; Harrison, Timothy G; Parkhill, Julian; Buchrieser, Carmen

    2016-11-01

    Legionella pneumophila is an environmental bacterium and the leading cause of Legionnaires' disease. Just five sequence types (ST), from more than 2000 currently described, cause nearly half of disease cases in northwest Europe. Here, we report the sequence and analyses of 364 L. pneumophila genomes, including 337 from the five disease-associated STs and 27 representative of the species diversity. Phylogenetic analyses revealed that the five STs have independent origins within a highly diverse species. The number of de novo mutations is extremely low with maximum pairwise single-nucleotide polymorphisms (SNPs) ranging from 19 (ST47) to 127 (ST1), which suggests emergences within the last century. Isolates sampled geographically far apart differ by only a few SNPs, demonstrating rapid dissemination. These five STs have been recombining recently, leading to a shared pool of allelic variants potentially contributing to their increased disease propensity. The oldest clone, ST1, has spread globally; between 1940 and 2000, four new clones have emerged in Europe, which show long-distance, rapid dispersal. That a large proportion of clinical cases is caused by recently emerged and internationally dispersed clones, linked by convergent evolution, is surprising for an environmental bacterium traditionally considered to be an opportunistic pathogen. To simultaneously explain recent emergence, rapid spread and increased disease association, we hypothesize that these STs have adapted to new man-made environmental niches, which may be linked by human infection and transmission.

  20. A 2.9 ps equivalent resolution interpolating time counter based on multiple independent coding lines

    NASA Astrophysics Data System (ADS)

    Szplet, R.; Jachna, Z.; Kwiatkowski, P.; Rozyc, K.

    2013-03-01

    We present the design, operation and test results of a time counter that has an equivalent resolution of 2.9 ps, a measurement uncertainty at the level of 6 ps, and a measurement range of 10 s. The time counter has been implemented in a general-purpose reprogrammable device Spartan-6 (Xilinx). To obtain both high precision and wide measurement range the counting of periods of a reference clock is combined with a two-stage interpolation within a single period of the clock signal. The interpolation involves a four-phase clock in the first interpolation stage (FIS) and an equivalent coding line (ECL) in the second interpolation stage (SIS). The ECL is created as a compound of independent discrete time coding lines (TCL). The number of TCLs used to create the virtual ECL has an effect on its resolution. We tested ECLs made from up to 16 TCLs, but the idea may be extended to a larger number of lines. In the presented time counter the coarse resolution of the counting method equal to 2 ns (period of the 500 MHz reference clock) is firstly improved fourfold in the FIS and next even more than 400 times in the SIS. The proposed solution allows us to overcome the technological limitation in achievable resolution and improve the precision of conversion of integrated interpolators based on tapped delay lines.

  1. Assessement of Land Biophysical Activity Over Multiple Years From a Sensor Independent Product

    NASA Astrophysics Data System (ADS)

    Nadine, G.; Bernard, P.; Frederic, M.; Malcolm, T.; Michel, V. M.; Alan, B.; Thomas, L.; Jean-Luc, W.

    2004-12-01

    In the context of scientific research concerning global change issues, remote sensing products have been demonstrated to be essential tools to monitor the characteristics of both land surfaces and their temporal evolution. The biophysical activities on land surfaces are documented from spectral measurements made in space. Advances in the understanding of radiation transfer and availability of higher performance instruments have lead to the development of a new generation of geophysical products able to provide reliable, accurate information on the state and evolution of terrestrial environments. Specifically, a series of optimized algorithms have been developed to estimate the Fraction of Absorbed Photosynthetically Active Radiation (FAPAR) for various instruments. Such an approach allows the synergistic use of FAPAR products derived from different sensors and the construction of global FAPAR time series independent from the life time of these specific sensors. This paper will present inter-comparison procedure and results from the exercise conducted with SeaWiFS and MERIS (ENVISAT) global product. A study of European land surfaces response against 2003 drought will be illustrated.

  2. Genetic code deviations in the ciliates: evidence for multiple and independent events.

    PubMed Central

    Tourancheau, A B; Tsao, N; Klobutcher, L A; Pearlman, R E; Adoutte, A

    1995-01-01

    In several species of ciliates, the universal stop codons UAA and UAG are translated into glutamine, while in the euplotids, the glutamine codon usage is normal, but UGA appears to be translated as cysteine. Because the emerging position of this monophyletic group in the eukaryotic lineage is relatively late, this deviant genetic code represents a derived state of the universal code. The question is therefore raised as to how these changes arose within the evolutionary pathways of the phylum. Here, we have investigated the presence of stop codons in alpha tubulin and/or phosphoglycerate kinase gene coding sequences from diverse species of ciliates scattered over the phylogenetic tree constructed from 28S rRNA sequences. In our data set, when deviations occur they correspond to in frame UAA and UAG coding for glutamine. By combining these new data with those previously reported, we show that (i) utilization of UAA and UAG codons occurs to different extents between, but also within, the different classes of ciliates and (ii) the resulting phylogenetic pattern of deviations from the universal code cannot be accounted for by a scenario involving a single transition to the unusual code. Thus, contrary to expectations, deviations from the universal genetic code have arisen independently several times within the phylum. PMID:7621837

  3. Multiple Independent Fusions of Glucose-6-Phosphate Dehydrogenase with Enzymes in the Pentose Phosphate Pathway

    PubMed Central

    Stover, Nicholas A.; Dixon, Thomas A.; Cavalcanti, Andre R. O.

    2011-01-01

    Fusions of the first two enzymes in the pentose phosphate pathway, glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconolactonase (6PGL), have been previously described in two distant clades, chordates and species of the malarial parasite Plasmodium. We have analyzed genome and expressed sequence data from a variety of organisms to identify the origins of these gene fusion events. Based on the orientation of the domains and range of species in which homologs can be found, the fusions appear to have occurred independently, near the base of the metazoan and apicomplexan lineages. Only one of the two metazoan paralogs of G6PD is fused, showing that the fusion occurred after a duplication event, which we have traced back to an ancestor of choanoflagellates and metazoans. The Plasmodium genes are known to contain a functionally important insertion that is not seen in the other apicomplexan fusions, highlighting this as a unique characteristic of this group. Surprisingly, our search revealed two additional fusion events, one that combined 6PGL and G6PD in an ancestor of the protozoan parasites Trichomonas and Giardia, and another fusing G6PD with phosphogluconate dehydrogenase (6PGD) in a species of diatoms. This study extends the range of species known to contain fusions in the pentose phosphate pathway to many new medically and economically important organisms. PMID:21829610

  4. Multiple independent colonization of the Canary Islands by the winged grasshopper genus Sphingonotus Fieber, 1852.

    PubMed

    Husemann, Martin; Deppermann, Jana; Hochkirch, Axel

    2014-12-01

    Volcanic archipelagos represent ideal systems to study processes of colonization, differentiation and speciation. The Canary Islands are one of the best studied archipelagos, being composed of seven main islands with a well-known geological history. Most taxa have colonized these islands stepwise from the African or Iberian mainland from east to west, following their geological origin as well as the predominating wind direction and ocean currents. Furthermore, within-island radiations have been reported for several taxa. The grasshopper genus Sphingonotus is species-rich and occurs with nine fully winged species on the Canary Islands, seven of which are endemic to single or few islands. We inferred a phylogeny of these species and their North African and Iberian relatives based upon sequences of three mitochondrial genes and one nuclear gene of 136 specimens. Surprisingly, our results suggest that almost all Sphingonotus species colonized the archipelago independently from the mainland and nearly no inter-island colonization occurred. Despite their strong flight capabilities, only one pair of endemic species are closely related (S. sublaevis from Gran Canary and S. pachecoi from Lanzarote). Moreover, no within-island speciation events were detected. We hypothesize that passive wind dispersal from the African mainland was the main driver of the colonization process and that most Sphingonotus species are not able to cover inter-island distances by active flight. This, together with strong intrageneric niche overlap might explain the lack of within-island speciation in this taxon.

  5. Multiple independent defective suppressor-mutator transposon insertions in Arabidopsis: a tool for functional genomics.

    PubMed Central

    Tissier, A F; Marillonnet, S; Klimyuk, V; Patel, K; Torres, M A; Murphy, G; Jones, J D

    1999-01-01

    A new system for insertional mutagenesis based on the maize Enhancer/Suppressor-mutator (En/Spm) element was introduced into Arabidopsis. A single T-DNA construct carried a nonautonomous defective Spm (dSpm) element with a phosphinothricin herbicide resistance (BAR) gene, a transposase expression cassette, and a counterselectable gene. This construct was used to select for stable dSpm transpositions. Treatments for both positive (BAR) and negative selection markers were applicable to soil-grown plants, allowing the recovery of new transpositions on a large scale. To date, a total of 48,000 lines in pools of 50 have been recovered, of which approximately 80% result from independent insertion events. DNA extracted from these pools was used in reverse genetic screens, either by polymerase chain reaction (PCR) using primers from the transposon and the targeted gene or by the display of insertions whereby inverse PCR products of insertions from the DNA pools are spotted on a membrane that is then hybridized with the probe of interest. By sequencing PCR-amplified fragments adjacent to insertion sites, we established a sequenced insertion-site database of 1200 sequences. This database permitted a comparison of the chromosomal distribution of transpositions from various T-DNA locations. PMID:10521516

  6. Multiple major disease-associated clones of Legionella pneumophila have emerged recently and independently

    PubMed Central

    David, Sophia; Rusniok, Christophe; Mentasti, Massimo; Gomez-Valero, Laura; Harris, Simon R.; Lechat, Pierre; Lees, John; Ginevra, Christophe; Glaser, Philippe; Ma, Laurence; Bouchier, Christiane; Underwood, Anthony; Jarraud, Sophie; Harrison, Timothy G.; Parkhill, Julian; Buchrieser, Carmen

    2016-01-01

    Legionella pneumophila is an environmental bacterium and the leading cause of Legionnaires’ disease. Just five sequence types (ST), from more than 2000 currently described, cause nearly half of disease cases in northwest Europe. Here, we report the sequence and analyses of 364 L. pneumophila genomes, including 337 from the five disease-associated STs and 27 representative of the species diversity. Phylogenetic analyses revealed that the five STs have independent origins within a highly diverse species. The number of de novo mutations is extremely low with maximum pairwise single-nucleotide polymorphisms (SNPs) ranging from 19 (ST47) to 127 (ST1), which suggests emergences within the last century. Isolates sampled geographically far apart differ by only a few SNPs, demonstrating rapid dissemination. These five STs have been recombining recently, leading to a shared pool of allelic variants potentially contributing to their increased disease propensity. The oldest clone, ST1, has spread globally; between 1940 and 2000, four new clones have emerged in Europe, which show long-distance, rapid dispersal. That a large proportion of clinical cases is caused by recently emerged and internationally dispersed clones, linked by convergent evolution, is surprising for an environmental bacterium traditionally considered to be an opportunistic pathogen. To simultaneously explain recent emergence, rapid spread and increased disease association, we hypothesize that these STs have adapted to new man-made environmental niches, which may be linked by human infection and transmission. PMID:27662900

  7. Multiple independent origins of mitochondrial control region duplications in the order Psittaciformes

    PubMed Central

    Schirtzinger, Erin E.; Tavares, Erika S.; Gonzales, Lauren A.; Eberhard, Jessica R.; Miyaki, Cristina Y.; Sanchez, Juan J.; Hernandez, Alexis; Müeller, Heinrich; Graves, Gary R.; Fleischer, Robert C.; Wright, Timothy F.

    2012-01-01

    Mitochondrial genomes are generally thought to be under selection for compactness, due to their small size, consistent gene content, and a lack of introns or intergenic spacers. As more animal mitochondrial genomes are fully sequenced, rearrangements and partial duplications are being identified with increasing frequency, particularly in birds (Class Aves). In this study, we investigate the evolutionary history of mitochondrial control region states within the avian order Psittaciformes (parrots and cockatoos). To this aim, we reconstructed a comprehensive multi-locus phylogeny of parrots, used PCR of three diagnostic fragments to classify the mitochondrial control region state as single or duplicated, and mapped these states onto the phylogeny. We further sequenced 44 selected species to validate these inferences of control region state. Ancestral state reconstruction using a range of weighting schemes identified six independent origins of mitochondrial control region duplications within Psittaciformes. Analysis of sequence data showed that varying levels of mitochondrial gene and tRNA homology and degradation were present within a given clade exhibiting duplications. Levels of divergence between control regions within an individual varied from 0–10.9% with the differences occurring mainly between 51 and 225 nucleotides 3′ of the goose hairpin in domain I. Further investigations into the fates of duplicated mitochondrial genes, the potential costs and benefits of having a second control region, and the complex relationship between evolutionary rates, selection, and time since duplication are needed to fully explain these patterns in the mitochondrial genome. PMID:22543055

  8. Integrative taxonomy of root-knot nematodes reveals multiple independent origins of mitotic parthenogenesis

    PubMed Central

    Janssen, Toon; Karssen, Gerrit; Topalović, Olivera; Coyne, Danny; Bert, Wim

    2017-01-01

    During sampling of several Coffea arabica plantations in Tanzania severe root galling, caused by a root-knot nematode was observed. From pure cultures, morphology and morphometrics of juveniles and females matched perfectly with Meloidogyne africana, whereas morphology of the males matched identically with those of Meloidogyne decalineata. Based on their Cox1 sequence, however, the recovered juveniles, females and males were confirmed to belong to the same species, creating a taxonomic conundrum. Adding further to this puzzle, re-examination of M. oteifae type material showed insufficient morphological evidence to maintain its status as a separate species. Consequently, M. decalineata and M. oteifae are synonymized with M. africana, which is herewith redescribed based on results of light and scanning electron microscopy, ribosomal and mitochondrial DNA sequences, isozyme electrophoresis, along with bionomic and cytogenetic features. Multi-gene phylogenetic analysis placed M. africana outside of the three major clades, together with M. coffeicola, M. ichinohei and M. camelliae. This phylogenetic position was confirmed by several morphological features, including cellular structure of the spermatheca, egg mass position, perineal pattern and head shape. Moreover, M. africana was found to be a polyphagous species, demonstrating that “early-branching” Meloidogyne spp. are not as oligophagous as had previously been assumed. Cytogenetic information indicates M. africana (2n = 21) and M. ardenensis (2n = 51–54) to be a triploid mitotic parthenogenetic species, revealing at least four independent origins of mitotic parthenogenesis within the genus Meloidogyne. Furthermore, M. mali (n = 12) was found to reproduce by amphimixis, indicating that amphimictic species with a limited number of chromosomes are widespread in the genus, potentially reflecting the ancestral state of the genus. The wide variation in chromosome numbers and associated changes in reproduction modes

  9. Preserved levels of uninvolved immunoglobulins are independently associated with favorable outcome in patients with symptomatic multiple myeloma.

    PubMed

    Kastritis, E; Zagouri, F; Symeonidis, A; Roussou, M; Sioni, A; Pouli, A; Delimpasi, S; Katodritou, E; Michalis, E; Michael, M; Hatzimichael, E; Vassou, A; Repousis, P; Christophoridou, A; Kartasis, Z; Stefanoudaki, E; Megalakaki, C; Giannouli, S; Kyrtsonis, M-C; Konstantopoulos, K; Spyroupoulou-Vlachou, M; Terpos, E; Dimopoulos, M A

    2014-10-01

    Suppression of uninvolved immunoglobulins is common in multiple myeloma (MM) but the prognostic significance of this phenomenon has not been assessed. We evaluated the prognostic significance of the preservation of uninvolved immunoglobulins in 1755 consecutive, unselected, patients with newly diagnosed, symptomatic MM with pre-therapy immunoglobulin levels measured by nephelometry. Suppression of at least one uninvolved immunoglobulin was observed in 87% of patients and was more common in patients with immunoglobulin A myeloma, those aged over 65 years, in patients with advanced-International Staging System (ISS) stage, extensive-bone marrow infiltration, anemia, low platelet counts, high levels of serum M-monoclonal protein or renal dysfunction. Patients with preserved immunoglobulins had a better survival than patients with suppressed immunoglobulins (median survival 55 vs 41.5 months, P<0.001). In multivariate analysis, preservation of uninvolved immunoglobulins was independently associated with better survival (hazard ratio: 0.781, 95% confidence interval: 0.618-0.987, P=0.039); irrespective of the treatment. In a subset of 500 patients, which were strictly followed for disease progression, preservation of uninvolved immunoglobulins was associated with a significantly longer progression-free survival (60 vs 25 months, P<0.001), independently of other common prognostic factors. In conclusion, preservation of uninvolved immunoglobulins in newly diagnosed patients with symptomatic MM was independently associated with long term disease control and improved survival.

  10. Fine-scale mapping of 8q24 locus identifies multiple independent risk variants for breast cancer.

    PubMed

    Shi, Jiajun; Zhang, Yanfeng; Zheng, Wei; Michailidou, Kyriaki; Ghoussaini, Maya; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Lush, Michael; Milne, Roger L; Shu, Xiao-Ou; Beesley, Jonathan; Kar, Siddhartha; Andrulis, Irene L; Anton-Culver, Hoda; Arndt, Volker; Beckmann, Matthias W; Zhao, Zhiguo; Guo, Xingyi; Benitez, Javier; Beeghly-Fadiel, Alicia; Blot, William; Bogdanova, Natalia V; Bojesen, Stig E; Brauch, Hiltrud; Brenner, Hermann; Brinton, Louise; Broeks, Annegien; Brüning, Thomas; Burwinkel, Barbara; Cai, Hui; Canisius, Sander; Chang-Claude, Jenny; Choi, Ji-Yeob; Couch, Fergus J; Cox, Angela; Cross, Simon S; Czene, Kamila; Darabi, Hatef; Devilee, Peter; Droit, Arnaud; Dork, Thilo; Fasching, Peter A; Fletcher, Olivia; Flyger, Henrik; Fostira, Florentia; Gaborieau, Valerie; García-Closas, Montserrat; Giles, Graham G; Grip, Mervi; Guenel, Pascal; Haiman, Christopher A; Hamann, Ute; Hartman, Mikael; Miao, Hui; Hollestelle, Antoinette; Hopper, John L; Hsiung, Chia-Ni; Ito, Hidemi; Jakubowska, Anna; Johnson, Nichola; Torres, Diana; Kabisch, Maria; Kang, Daehee; Khan, Sofia; Knight, Julia A; Kosma, Veli-Matti; Lambrechts, Diether; Li, Jingmei; Lindblom, Annika; Lophatananon, Artitaya; Lubinski, Jan; Mannermaa, Arto; Manoukian, Siranoush; Le Marchand, Loic; Margolin, Sara; Marme, Frederik; Matsuo, Keitaro; McLean, Catriona; Meindl, Alfons; Muir, Kenneth; Neuhausen, Susan L; Nevanlinna, Heli; Nord, Silje; Børresen-Dale, Anne-Lise; Olson, Janet E; Orr, Nick; van den Ouweland, Ans M W; Peterlongo, Paolo; Choudary Putti, Thomas; Rudolph, Anja; Sangrajrang, Suleeporn; Sawyer, Elinor J; Schmidt, Marjanka K; Schmutzler, Rita K; Shen, Chen-Yang; Hou, Ming-Feng; Shrubsole, Matha J; Southey, Melissa C; Swerdlow, Anthony; Hwang Teo, Soo; Thienpont, Bernard; Toland, Amanda E; Tollenaar, Robert A E M; Tomlinson, Ian; Truong, Therese; Tseng, Chiu-Chen; Wen, Wanqing; Winqvist, Robert; Wu, Anna H; Har Yip, Cheng; Zamora, Pilar M; Zheng, Ying; Floris, Giuseppe; Cheng, Ching-Yu; Hooning, Maartje J; Martens, John W M; Seynaeve, Caroline; Kristensen, Vessela N; Hall, Per; Pharoah, Paul D P; Simard, Jacques; Chenevix-Trench, Georgia; Dunning, Alison M; Antoniou, Antonis C; Easton, Douglas F; Cai, Qiuyin; Long, Jirong

    2016-09-15

    Previous genome-wide association studies among women of European ancestry identified two independent breast cancer susceptibility loci represented by single nucleotide polymorphisms (SNPs) rs13281615 and rs11780156 at 8q24. A fine-mapping study across 2.06 Mb (chr8:127,561,724-129,624,067, hg19) in 55,540 breast cancer cases and 51,168 controls within the Breast Cancer Association Consortium was conducted. Three additional independent association signals in women of European ancestry, represented by rs35961416 (OR = 0.95, 95% CI = 0.93-0.97, conditional p = 5.8 × 10(-6) ), rs7815245 (OR = 0.94, 95% CI = 0.91-0.96, conditional p = 1.1 × 10(-6) ) and rs2033101 (OR = 1.05, 95% CI = 1.02-1.07, conditional p = 1.1 × 10(-4) ) were found. Integrative analysis using functional genomic data from the Roadmap Epigenomics, the Encyclopedia of DNA Elements project, the Cancer Genome Atlas and other public resources implied that SNPs rs7815245 in Signal 3, and rs1121948 in Signal 5 (in linkage disequilibrium with rs11780156, r(2)  = 0.77), were putatively functional variants for two of the five independent association signals. The results highlighted multiple 8q24 variants associated with breast cancer susceptibility in women of European ancestry.

  11. Borrelia burgdorferi infection and Lyme disease in children.

    PubMed

    Esposito, Susanna; Bosis, Samantha; Sabatini, Caterina; Tagliaferri, Laura; Principi, Nicola

    2013-03-01

    Lyme disease is a multisystem disease that frequently affects children. It is caused by a group of related spirochetes, Borrelia burgdorferi sensu lato, that are transmitted by ticks belonging to species of the genus Ixodes. The clinical characteristics of Lyme disease in pediatrics resemble those observed in adults, although the symptoms may last for a shorter time and the outcome may be better. However, identifying Lyme disease in children can be significantly more difficult because some of its signs and symptoms can be similar to those of other common pediatric clinical manifestations. Finally, the diagnostic and therapeutic approach to childhood Lyme disease is frequently not codified, and guidelines specifically prepared for adults are used for children without having been validated. This review of the currently available data will evaluate what may be the best approach to the diagnosis and treatment of B. burgdorferi infection and disease in the pediatric population.

  12. 96. Connecticut River Bridge. Old Lyme, New London Co., CT. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    96. Connecticut River Bridge. Old Lyme, New London Co., CT. Sec. 4209, MP 106.89. - Northeast Railroad Corridor, Amtrak Route between New York/Connecticut & Connecticut/Rhode Island State Lines, New Haven, New Haven County, CT

  13. 104. Connecticut River Bridge draw span. Old Lyme, New London ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    104. Connecticut River Bridge draw span. Old Lyme, New London Co., CT. Sec. 4209, MP 106.89. - Northeast Railroad Corridor, Amtrak Route between New York/Connecticut & Connecticut/Rhode Island State Lines, New Haven, New Haven County, CT

  14. 98. Connecticut River Bridge. Old Lyme, New London Co., CT. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    98. Connecticut River Bridge. Old Lyme, New London Co., CT. Sec. 4209, MP 106.89. - Northeast Railroad Corridor, Amtrak Route between New York/Connecticut & Connecticut/Rhode Island State Lines, New Haven, New Haven County, CT

  15. 101. Connecticut River Bridge. Old Lyme, New London Co., CT. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    101. Connecticut River Bridge. Old Lyme, New London Co., CT. Sec. 4209, MP 106.89. - Northeast Railroad Corridor, Amtrak Route between New York/Connecticut & Connecticut/Rhode Island State Lines, New Haven, New Haven County, CT

  16. 97. Connecticut River Bridge. Old Lyme, New London Co., CT. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    97. Connecticut River Bridge. Old Lyme, New London Co., CT. Sec. 4209, MP 106.89. - Northeast Railroad Corridor, Amtrak Route between New York/Connecticut & Connecticut/Rhode Island State Lines, New Haven, New Haven County, CT

  17. 102. Connecticut River Bridge. Old Lyme, New London Co., CT. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    102. Connecticut River Bridge. Old Lyme, New London Co., CT. Sec. 4209, MP 106.89. - Northeast Railroad Corridor, Amtrak Route between New York/Connecticut & Connecticut/Rhode Island State Lines, New Haven, New Haven County, CT

  18. 99. Connecticut River Bridge. Old Lyme, New London Co., CT. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    99. Connecticut River Bridge. Old Lyme, New London Co., CT. Sec. 4209, MP 106.89. - Northeast Railroad Corridor, Amtrak Route between New York/Connecticut & Connecticut/Rhode Island State Lines, New Haven, New Haven County, CT

  19. 100. Connecticut River Bridge. Old Lyme, New London Co., CT. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    100. Connecticut River Bridge. Old Lyme, New London Co., CT. Sec. 4209, MP 106.89. - Northeast Railroad Corridor, Amtrak Route between New York/Connecticut & Connecticut/Rhode Island State Lines, New Haven, New Haven County, CT

  20. 103. Connecticut River Bridge draw span. Old Lyme, New London ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    103. Connecticut River Bridge draw span. Old Lyme, New London Co., CT. Sec. 4209, MP 106.89. - Northeast Railroad Corridor, Amtrak Route between New York/Connecticut & Connecticut/Rhode Island State Lines, New Haven, New Haven County, CT

  1. Possible relationship between degenerative cardiac valvular pathology and lyme disease.

    PubMed

    Canver, C C; Chanda, J; DeBellis, D M; Kelley, J M

    2000-07-01

    We report an unusual clinical presentation of Lyme carditis in a previously healthy 20-year-old black woman without any epidemiologic history of Lyme disease, fulminant in nature, involving a heart valve necessitating emergent mitral valve replacement, and requiring further surgical intervention because of the development of pericardial effusion and tamponade. A dilated right ventricle with normal contractility and severe tricuspid regurgitation with increase in the right atrial size diagnosed later remains under close surveillance.

  2. Chronic lyme disease: psychogenic fantasy or somatic infection?

    PubMed Central

    Mervine, Phyllis

    2003-01-01

    Sigal and Hassett published an article about Lyme disease in the EHP Supplements (Sigal and Hassett 2002), suggesting that chronic Lyme disease is "psychogenic." I do not think that Sigal and Hassett, non-psychiatrists, are qualified to speak about psychiatric matters. I, however, actually have had the disease, which they characterize as "medically unexplained," for over 25 years and have 15 years of experience as a patient advocate and educator. I beg to differ. PMID:12573917

  3. Vaccination against Lyme disease: Are we ready for it?

    PubMed

    Kaaijk, Patricia; Luytjes, Willem

    2016-03-03

    Lyme disease is the most common tick-borne illness in the Northern hemisphere and is caused by spirochetes of the Borrelia burgdorferi sensu lato complex. A first sign of Borrelia infection is a circular skin rash, erythema migrans, but it can develop to more serious manifestations affecting skin, nervous system, joints, and/or heart. The marked increase in Lyme disease incidence over the past decades, the severity of the disease, and the associated high medical costs of, in particular, the persistent forms of Lyme disease requires adequate measures for control. Vaccination would be the most effective intervention for prevention, but at present no vaccine is available. In the 1990s, 2 vaccines against Lyme disease based on the OspA protein from the predominant Borrelia species of the US showed to be safe and effective in clinical phase III studies. However, failed public acceptance led to the demise of these monovalent OspA-based vaccines. Nowadays, public seem to be more aware of the serious health problems that Lyme disease can cause and seem more ready for the use of a broadly protective vaccine. This article discusses several aspects that should be considered to enable the development and implementation of a vaccine to prevent Lyme disease successfully.

  4. Assessing peridomestic entomological factors as predictors for Lyme disease

    USGS Publications Warehouse

    Connally, N.P.; Ginsberg, H.S.; Mather, T.N.

    2006-01-01

    The roles of entomologic risk factors, including density of nymphal blacklegged ticks (Ixodes scapularis), prevalence of nymphal infection with the etiologic agent (Borrelia burgdorferi), and density of infected nymphs, in determining the risk of human Lyme disease were assessed at residences in the endemic community of South Kingstown, RI. Nymphs were sampled between May and July from the wooded edge around 51 and 47 residential properties in 2002 and 2003, respectively. Nymphs were collected from all residences sampled. Tick densities, infection rates, and densities of infected nymphs were all significantly higher around homes reporting Lyme disease histories in 2003, while only infection rates were significantly higher in 2002. However, densities of infected nymphs did not significantly predict the probability of Lyme disease at a residence (by logistic regression) in either year. There were no significant differences in entomologic risk factors between homes with state-confirmed Lyme disease histories and homes with self-reported cases (not reported to the state health department). Therefore, although entomologic risk factors tended to be higher at residences with cases of Lyme disease, entomological indices, in the absence of human behavior measures, were not useful predictors of Lyme disease at the scale of individual residences in a tick-endemic community.

  5. [Lyme borreliosis: follow up criteria after antibiotherapy?].

    PubMed

    Christmann, D

    2007-01-01

    The post therapeutic follow-up of Lyme borreliosis is managed according to clinical and serological data. The evolution of antibody rates is such that it doesn't constitute the best element to rely on for follow-up. Indeed, after a sometimes transitory increase of this rate during or after antibiotherapy, the decrease is very slow, sometimes several months, and often incomplete. The follow-up should thus be made according to clinical symptoms and their resolution. Resolution of some but not all symptoms must lead to discussing two options. The first is that of administrating a complementary antibiotherapy with a different mode of action than the first antibiotic used. The second is that this may be due to recontamination, especially in highly endemic zones, given that antibodies present have no protecting effect. In this case, a new antibiotherapy must of course be initiated.

  6. A nonlocal spatial model for Lyme disease

    NASA Astrophysics Data System (ADS)

    Yu, Xiao; Zhao, Xiao-Qiang

    2016-07-01

    This paper is devoted to the study of a nonlocal and time-delayed reaction-diffusion model for Lyme disease with a spatially heterogeneous structure. In the case of a bounded domain, we first prove the existence of the positive steady state and a threshold type result for the disease-free system, and then establish the global dynamics for the model system in terms of the basic reproduction number. In the case of an unbound domain, we obtain the existence of the disease spreading speed and its coincidence with the minimal wave speed. At last, we use numerical simulations to verify our analytic results and investigate the influence of model parameters and spatial heterogeneity on the disease infection risk.

  7. Histopathology of Lyme arthritis in LSH hamsters

    SciTech Connect

    Hejka, A.; Schmitz, J.L.; England, D.M.; Callister, S.M.; Schell, R.F.

    1989-05-01

    The authors studied the histopathologic evolution of arthritis in nonirradiated and irradiated hamsters infected with Borrelia burgdorferi. Nonirradiated hamsters injected in the hind paws with B. burgdorferi developed an acute inflammatory reaction involving the synovium, periarticular soft tissues, and dermis. This acute inflammatory reaction was short-lived and was replaced by a mild chronic synovitis as the number of detectable spirochetes in the synovium, periarticular soft tissues, and perineurovascular areas diminished. Exposing hamsters to radiation before inoculation with B. burgdorferi exacerbated and prolonged the acute inflammatory phase. Spirochetes also persisted longer in the periarticular soft tissues. A major histopathologic finding was destructive and erosive bone changes of the hind paws, which resulted in deformation of the joints. These studies should be helpful in defining the immune mechanism participating in the onset, progression, and resolution of Lyme arthritis.

  8. Swimming Dynamics of the Lyme Disease Spirochete

    NASA Astrophysics Data System (ADS)

    Vig, Dhruv K.; Wolgemuth, Charles W.

    2012-11-01

    The Lyme disease spirochete, Borrelia burgdorferi, swims by undulating its cell body in the form of a traveling flat wave, a process driven by rotating internal flagella. We study B. burgdorferi’s swimming by treating the cell body and flagella as linearly elastic filaments. The dynamics of the cell are then determined from the balance between elastic and resistive forces and moments. We find that planar, traveling waves only exist when the flagella are effectively anchored at both ends of the bacterium and that these traveling flat waves rotate as they undulate. The model predicts how the undulation frequency is related to the torque from the flagellar motors and how the stiffness of the cell body and flagella affect the undulations and morphology.

  9. An assistive device designed to convey independent donning of a shuttle lock trans-tibial prosthesis for a multiple limb amputee.

    PubMed

    Tamir, E; Heim, M; Oppenheim, U; Siev-Ner, I

    2003-04-01

    This contribution describes a simple device designed to convey independent donning of a shuttle lock trans-tibial prosthesis for a multiple limb amputee. The device is made of a post with a shuttle lock mechanism at one end and a plate covered by rubber at the other end. This device enables correct positioning of the silicone liner and independent attachment to the prosthesis.

  10. Novel Diagnosis of Lyme Disease: Potential for CAM Intervention

    PubMed Central

    Hebroni, Frank; Raphael, Yaniv; Erde, Jonathan; Raxlen, Bernard

    2009-01-01

    Lyme disease (LD) is the most common tick-borne disease in the northern hemisphere, producing a wide range of disabling effects on multiple human targets, including the skin, the nervous system, the joints and the heart. Insufficient clinical diagnostic methods, the necessity for prompt antibiotic treatment along with the pervasive nature of infection impel the development and establishment of new clinical diagnostic tools with increased accuracy, sensitivity and specificity. The goal of this article is 4-fold: (i) to detail LD infection and pathology, (ii) to review prevalent diagnostic methods, emphasizing inherent problems, (iii) to introduce the usage of in vivo induced antigen technology (IVIAT) in clinical diagnostics and (iv) to underscore the relevance of a novel comprehensive LD diagnostic approach to practitioners of Complementary and Alternative Medicine (CAM). Utilization of this analytical method will increase the accuracy of the diagnostic process and abridge the time to treatment, with antibiotics, herbal medicines and nutritional supplements, resulting in improved quality of care and disease prognosis. PMID:18955246

  11. Controller design for delay-independent stability of linear time-invariant vibration systems with multiple delays

    NASA Astrophysics Data System (ADS)

    Mahmoodi Nia, Payam; Sipahi, Rifat

    2013-07-01

    One of the critical parameters that can deteriorate the effectiveness of active vibration control (AVC) is the delay in sensors. Especially, in remote sensing where delays are large, and in high-speed applications with even small delays, instability can be inevitable. This paper presents algebraic approaches to design controllers in order to achieve stability regardless of the amount of delays for AVC applications modeled by linear time-invariant systems with "multiple" constant delays. The approaches are based on a nonconservative framework, and can identify the regions in the controller gain space where delay-independent stability (DIS) is achievable. With these controllers, we demonstrate via simulations that vibration suppression, within certain excitation frequency bands, can be improved or be as effective as those in AVC applications without delays.

  12. Design of temperature-independent arrayed waveguide gratings based on the combination of multiple types of waveguide.

    PubMed

    Huang, Huamao; Ho, Seng-Tiong; Huang, Dexiu; Tu, Yongming; Liu, Wen

    2010-06-01

    We develop a design theory for a temperature-independent arrayed waveguide grating (TI-AWG) based on the combination of multiple types of waveguide. Each type of waveguide has a path-length difference between adjacent arrayed waveguides, and the path-length difference ratio is introduced as tuning parameter. A TI-AWG with Si wire and slot waveguides is given as an example. The thermal spectra shift of the TI-AWG can be tuned from redshift to blueshift in an ultralarge range, and the modified interference order can be reduced or enhanced. The device size is about one-fifth that of the narrow-wide-wire design that uses a combination of narrow and wide Si wire waveguides. The results are verified by the simulation of prototype devices via a two-dimensional finite-difference time-domain program.

  13. Amplification of the multidrug resistance gene pfmdr1 in Plasmodium falciparum has arisen as multiple independent events.

    PubMed

    Triglia, T; Foote, S J; Kemp, D J; Cowman, A F

    1991-10-01

    The multidrug resistance (MDR) phenotype in mammalian tumor cells can involve amplification of mdr genes that results in overexpression of the protein product termed P-glycoprotein. Chloroquine resistance (CQR) in Plasmodium falciparum has similarities with the MDR phenotype in tumor cells, and some isolates of P. falciparum have amplified levels of the pfmdr1 gene. To investigate the nature and origin of pfmdr1 amplicons, we have cloned large regions of a 110-kb amplicon from the CQR cloned isolate B8 by using the yeast artificial chromosome system. We have identified and sequenced the breakpoints of the amplicon by a novel method employing inverted polymerase chain reaction that is applicable to analysis of any large-scale repeat. We show that the five copies of the amplicon in this isolate are in a head to tail configuration. A string of 30 A's flank the breakpoints on each side of the amplified segment, suggesting a mechanism for the origin of the tandem amplification. Polymerase chain reaction analysis with oligonucleotides that cross the B8 breakpoint has shown in 26 independent CQR isolates, 16 of which contain amplified copies of pfmdr1, that amplification of the pfmdr1 gene in P. falciparum has arisen as multiple independent events. These results suggest that this region of the genome is under strong selective pressure.

  14. Bi-allelic inactivation is more prevalent at relapse in multiple myeloma, identifying RB1 as an independent prognostic marker.

    PubMed

    Chavan, S S; He, J; Tytarenko, R; Deshpande, S; Patel, P; Bailey, M; Stein, C K; Stephens, O; Weinhold, N; Petty, N; Steward, D; Rasche, L; Bauer, M; Ashby, C; Peterson, E; Ali, S; Ross, J; Miller, V A; Stephens, P; Thanendrarajan, S; Schinke, C; Zangari, M; van Rhee, F; Barlogie, B; Mughal, T I; Davies, F E; Morgan, G J; Walker, B A

    2017-02-24

    The purpose of this study is to identify prognostic markers and treatment targets using a clinically certified sequencing panel in multiple myeloma. We performed targeted sequencing of 578 individuals with plasma cell neoplasms using the FoundationOne Heme panel and identified clinically relevant abnormalities and novel prognostic markers. Mutational burden was associated with maf and proliferation gene expression groups, and a high-mutational burden was associated with a poor prognosis. We identified homozygous deletions that were present in multiple myeloma within key genes, including CDKN2C, RB1, TRAF3, BIRC3 and TP53, and that bi-allelic inactivation was significantly enriched at relapse. Alterations in CDKN2C, TP53, RB1 and the t(4;14) were associated with poor prognosis. Alterations in RB1 were predominantly homozygous deletions and were associated with relapse and a poor prognosis which was independent of other genetic markers, including t(4;14), after multivariate analysis. Bi-allelic inactivation of key tumor suppressor genes in myeloma was enriched at relapse, especially in RB1, CDKN2C and TP53 where they have prognostic significance.

  15. Insights into hemolytic uremic syndrome: segregation of three independent predisposition factors in a large, multiple affected pedigree.

    PubMed

    Esparza-Gordillo, Jorge; Jorge, Elena Goicoechea de; Garrido, Cynthia Abarrategui; Carreras, Luis; López-Trascasa, Margarita; Sánchez-Corral, Pilar; de Córdoba, Santiago Rodríguez

    2006-04-01

    Mutations in the complement regulators factor H, membrane cofactor protein (MCP), and factor I are associated with atypical hemolytic uremic syndrome (aHUS, MIM 235400), suggesting that the disease develops as a consequence of the inefficient protection of the renal endothelium from damage by the complement system. Incomplete penetrance of the disease in individuals carrying these mutations is, however, relatively frequent. Here, we report the identification of a large, multiple affected aHUS pedigree in which there is independent segregation of three different aHUS risk factors: a MCP missense mutation (c.-598C>T; Pro165Ser) that decreases MCP expression on the cell surface, a dinucleotide insertion in the coding sequence of factor I (c.-1610insAT) that introduces a premature stop codon in the factor I protein, and the MCPggaac SNP haplotype block that was previously shown to decrease the transcription activity from the MCP promoter. Interestingly, individuals affected by aHUS in the pedigree are only those who have inherited the three aHUS risk factors. These data show an additive effect for mutations in MCP and factor I and provide definitive support to the conclusion that aHUS results from a defective protection of cellular surfaces from complement activation. Furthermore, they help to explain the incomplete penetrance of the disease, illustrating that concurrence of multiple hits in complement regulatory proteins may be necessary to significantly impair host tissue protection and to confer susceptibility to aHUS.

  16. Description of Lyme disease-like syndrome in Brazil. Is it a new tick borne disease or Lyme disease variation?

    PubMed

    Mantovani, E; Costa, I P; Gauditano, G; Bonoldi, V L N; Higuchi, M L; Yoshinari, N H

    2007-04-01

    An emerging clinical entity that reproduces clinical manifestations similar to those observed in Lyme disease (LD) has been recently under discussion in Brazil. Due to etiological and laboratory particularities it is named LD-like syndrome or LD imitator syndrome. The condition is considered to be a zoonosis transmitted by ticks of the genus Amblyomma, possibly caused by interaction of multiple fastidious microorganisms originating a protean clinical picture, including neurological, osteoarticular and erythema migrans-like lesions. When peripheral blood of patients with LD-like syndrome is viewed under a dark-field microscope, mobile uncultivable spirochete-like bacteria are observed. PCR carried out with specific or conservative primers to recognize Borrelia burgdorferi sensu stricto or the genus Borrelia has been negative in ticks and in biological samples. Two different procedures, respectively involving hematoxylin and eosin staining of cerebrospinal fluid and electron microscopy analysis of blood, have revealed spirochetes not belonging to the genera Borrelia, Leptospira or Treponema. Surprisingly, co-infection with microorganisms resembling Mycoplasma and Chlamydia was observed on one occasion by electron microscopy analysis. We discuss here the possible existence of a new tick-borne disease in Brazil imitating LD, except for a higher frequency of recurrence episodes observed along prolonged clinical follow-up.

  17. Unorthodox Alternative Therapies Marketed to Treat Lyme Disease

    PubMed Central

    Lantos, Paul M.; Shapiro, Eugene D.; Auwaerter, Paul G.; Baker, Phillip J.; Halperin, John J.; McSweegan, Edward; Wormser, Gary P.

    2015-01-01

    Background. Some patients with medically unexplained symptoms or alternative medical diagnoses suspect that they chronically suffer from the tick-borne infection Lyme disease. These patients are commonly targeted by providers of alternative therapies. This study was designed to identify and characterize the range of unorthodox alternative therapies advertised to patients with a diagnosis of Lyme disease. Methods. Internet searches using the Google search engine were performed to identify the websites of clinics and services that marketed nonantimicrobial therapies for Lyme disease. We subsequently used the PubMed search engine to identify any scientific studies evaluating such treatments for Lyme disease. Websites were included in our review so long as they advertised a commercial, nonantimicrobial product or service that specifically mentioned utility for Lyme disease. Websites with patient testimonials (such as discussion groups) were excluded unless the testimonial appeared as marketing on a commercial site. Results. More than 30 alternative treatments were identified, which fell into several broad categories: these included oxygen and reactive oxygen therapy; energy and radiation-based therapies; nutritional therapy; chelation and heavy metal therapy; and biological and pharmacological therapies ranging from certain medications without recognized therapeutic effects on Borrelia burgdorgeri to stem cell transplantation. Review of the medical literature did not substantiate efficacy or, in most cases, any rationale for the advertised treatments. Conclusions. Providers of alternative therapies commonly target patients who believe they have Lyme disease. The efficacy of these unconventional treatments for Lyme disease is not supported by scientific evidence, and in many cases they are potentially harmful. PMID:25852124

  18. Update on persistent symptoms associated with Lyme disease

    PubMed Central

    Oliveira, Carlos R.; Shapiro, Eugene D.

    2015-01-01

    Purpose of review Lyme disease, caused by Borrelia burgdorferi, is the most common vector-borne illness in the United States. The pathogenesis, ecology, and epidemiology of Lyme disease have been well described, and antimicrobial treatment is very effective. There has been controversy about whether infection can persist and cause chronic symptoms despite treatment with antimicrobials. This review summarizes recent studies that have addressed this issue. Recent findings The pathogenesis of persistent nonspecific symptoms in patients who were treated for Lyme disease is poorly understood, and the validity of results of attempts to demonstrate persistent infection with B. burgdorferi has not been established. One study attempted to use xenodiagnosis to detect B. burgdorferi in patients who have been treated for Lyme disease. Another study assessed whether repeated episodes of erythema migrans were due to the same or different strains of B. burgdorferi. A possible cause of persistent arthritis in some treated patients is slow clearance of nonviable organisms that may lead to prolonged inflammation. The results of all of these studies continue to provide evidence that viable B. burgdorferi do not persist in patients who receive conventional antimicrobial treatment for Lyme disease. Summary Patients with persistent symptoms possibly associated with Lyme disease often provide a challenge for clinicians. Recent studies have provided additional evidence that viable B. burgdorferi do not persist after conventional treatment with antimicrobials, indicating that ongoing symptoms in patients who received conventional treatment for Lyme disease should not be attributed to persistent active infection. Video abstract http://links.lww.com/MOP/A23 PMID:25490690

  19. Scientific Library Presents Three-Part Program on the Dangers of Lyme Disease | Poster

    Cancer.gov

    As spring arrives and the weather turns warmer, ticks will soon reappear—and with them, Lyme disease. The northeast portion of the United States is home to the majority of Lyme disease incidents, and Maryland is one of the 14 states in which 95% of confirmed Lyme disease cases occurred in 2015.

  20. 76 FR 35978 - Drawbridge Operation Regulations; Connecticut River, Old Lyme, CT

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-21

    ... SECURITY Coast Guard 33 CFR Part 117 Drawbridge Operation Regulations; Connecticut River, Old Lyme, CT... of the Amtrak Railroad Bridge at mile 3.4, across the Connecticut River at Old Lyme, Connecticut. The... INFORMATION: The Amtrak Railroad Bridge, across the Connecticut River at mile 3.4, at Old Lyme,...

  1. Lyme neuroborreliosis in a patient treated with TNF-alpha inhibitor.

    PubMed

    Merkac, Maja Ivartnik; Tomazic, Janez; Strle, Franc

    2015-12-01

    A 57-year-old woman, receiving TNF-alpha inhibitor adalimumab for psoriasis, presented with early Lyme neuroborreliosis (Bannwarth's syndrome). Discontinuation of adalimumab and 14-day therapy with ceftriaxone resulted in a smooth course and favorable outcome of Lyme borreliosis. This is the first report on Lyme neuroborreliosis in a patient treated with TNF-alpha inhibitor.

  2. Lysosomal β-glucuronidase regulates Lyme and rheumatoid arthritis severity.

    PubMed

    Bramwell, Kenneth K C; Ma, Ying; Weis, John H; Chen, Xinjian; Zachary, James F; Teuscher, Cory; Weis, Janis J

    2014-01-01

    Lyme disease, caused by the spirochete Borrelia burgdorferi, is the most prevalent arthropod-borne illness in the United States and remains a clinical and social challenge. The spectrum of disease severity among infected patients suggests that host genetics contribute to pathogenic outcomes, particularly in patients who develop arthritis. Using a forward genetics approach, we identified the lysosomal enzyme β-glucuronidase (GUSB), a member of a large family of coregulated lysosomal enzymes, as a key regulator of Lyme-associated arthritis severity. Severely arthritic C3H mice possessed a naturally occurring hypomorphic allele, Gusbh. C57BL/6 mice congenic for the C3H Gusb allele were prone to increased Lyme-associated arthritis severity. Radiation chimera experiments revealed that resident joint cells drive arthritis susceptibility. C3H mice expressing WT Gusb as a transgene were protected from severe Lyme arthritis. Importantly, the Gusbh allele also exacerbated disease in a serum transfer model of rheumatoid arthritis. A known GUSB function is the prevention of lysosomal accumulation of glycosaminoglycans (GAGs). Development of Lyme and rheumatoid arthritis in Gusbh-expressing mice was associated with heightened accumulation of GAGs in joint tissue. We propose that GUSB modulates arthritis pathogenesis by preventing accumulation of proinflammatory GAGs within inflamed joint tissue, a trait that may be shared by other lysosomal exoglycosidases.

  3. Will Culling White-Tailed Deer Prevent Lyme Disease?

    PubMed

    Kugeler, K J; Jordan, R A; Schulze, T L; Griffith, K S; Mead, P S

    2016-08-01

    White-tailed deer play an important role in the ecology of Lyme disease. In the United States, where the incidence and geographic range of Lyme disease continue to increase, reduction of white-tailed deer populations has been proposed as a means of preventing human illness. The effectiveness of this politically sensitive prevention method is poorly understood. We summarize and evaluate available evidence regarding the effect of deer reduction on vector tick abundance and human disease incidence. Elimination of deer from islands and other isolated settings can have a substantial impact on the reproduction of blacklegged ticks, while reduction short of complete elimination has yielded mixed results. To date, most studies have been conducted in ecologic situations that are not representative to the vast majority of areas with high human Lyme disease risk. Robust evidence linking deer control to reduced human Lyme disease risk is lacking. Currently, there is insufficient evidence to recommend deer population reduction as a Lyme disease prevention measure, except in specific ecologic circumstances.

  4. The psychoimmunology of lyme/tick-borne diseases and its association with neuropsychiatric symptoms.

    PubMed

    Bransfield, Robert C

    2012-01-01

    Disease progression of neuropsychiatric symptoms in Lyme/tick-borne diseases can be better understood by greater attention to psychoimmunology. Although there are multiple contributors that provoke and weaken the immune system, infections and persistent infections are significant causes of pathological immune reactions. Immune mediated ef-fects are a significant contributor to the pathophysiological processes and disease progression. These immune effects in-clude persistent inflammation with cytokine effects and molecular mimicry and both of these mechanisms may be present at the same time in persistent infections. Sickness syndrome associated with interferon treatment and autoimmune limbic encephalopathies are models to understand inflammatory and molecular mimicry effects upon neuropsychiatric symp-toms. Progressive inflammatory reactions have been proposed as a model to explain disease progression in depression, psychosis, dementia, epilepsy, autism and other mental illnesses and pathophysiological changes have been associated with oxidative stress, excitotoxicity, changes in homocysteine metabolism and altered tryptophan catabolism. Lyme dis-ease has been associated with the proinflammatory cytokines IL-6, IL-8, IL-12, IL-18 and interferon-gamma, the chemokines CXCL12 and CXCL13 and increased levels proinflammatory lipoproteins. Borrelia burgdorferi surface gly-colipids and flagella antibodies appear to elicit anti-neuronal antibodies and anti-neuronal antibodies and Borrelia burgdorferi lipoproteins can disseminate from the periphery to inflame the brain. Autism spectrum disorders associated with Lyme/tick-borne diseases may be mediated by a combination of inflammatory and molecular mimicry mechanisms. Greater interaction is needed between infectious disease specialists, immunologists and psychiatrists to benefit from this awareness and to further understand these mechanisms.

  5. The Psychoimmunology of Lyme/Tick-Borne Diseases and its Association with Neuropsychiatric Symptoms

    PubMed Central

    Bransfield, Robert C

    2012-01-01

    Disease progression of neuropsychiatric symptoms in Lyme/tick-borne diseases can be better understood by greater attention to psychoimmunology. Although there are multiple contributors that provoke and weaken the immune system, infections and persistent infections are significant causes of pathological immune reactions. Immune mediated ef-fects are a significant contributor to the pathophysiological processes and disease progression. These immune effects in-clude persistent inflammation with cytokine effects and molecular mimicry and both of these mechanisms may be present at the same time in persistent infections. Sickness syndrome associated with interferon treatment and autoimmune limbic encephalopathies are models to understand inflammatory and molecular mimicry effects upon neuropsychiatric symp-toms. Progressive inflammatory reactions have been proposed as a model to explain disease progression in depression, psychosis, dementia, epilepsy, autism and other mental illnesses and pathophysiological changes have been associated with oxidative stress, excitotoxicity, changes in homocysteine metabolism and altered tryptophan catabolism. Lyme dis-ease has been associated with the proinflammatory cytokines IL-6, IL-8, IL-12, IL-18 and interferon-gamma, the chemokines CXCL12 and CXCL13 and increased levels proinflammatory lipoproteins. Borrelia burgdorferi surface gly-colipids and flagella antibodies appear to elicit anti-neuronal antibodies and anti-neuronal antibodies and Borrelia burgdorferi lipoproteins can disseminate from the periphery to inflame the brain. Autism spectrum disorders associated with Lyme/tick-borne diseases may be mediated by a combination of inflammatory and molecular mimicry mechanisms. Greater interaction is needed between infectious disease specialists, immunologists and psychiatrists to benefit from this awareness and to further understand these mechanisms. PMID:23091569

  6. Characterization of Lyme borreliosis isolates from patients with erythema migrans and neuroborreliosis in southern Sweden.

    PubMed

    Ornstein, K; Berglund, J; Nilsson, I; Norrby, R; Bergström, S

    2001-04-01

    Southern Sweden is an area of Lyme borreliosis (LB) endemicity, with an incidence of 69 cases per 100,000 inhabitants. The most frequent clinical manifestations are erythema migrans (77%) and neuroborreliosis (16%). There was no record of human Borrelia strains being isolated from patients in this region before the prospective study reported here. Borrelia spirochetes were isolated from skin and cerebrospinal fluid (CSF) from LB patients living in the region. A total of 39 strains were characterized by OspA serotype analysis, species-specific PCR, and signature nucleotide analysis of the 16S rRNA gene. Of 33 skin isolates, 31 (93.9%) were Borrelia afzelii strains and 2 (6.1%) were Borrelia garinii strains. Of six CSF isolates, five (83.3%) were B. garinii and one (16.7%) was B. afzelii. Neither Borrelia burgdorferi sensu stricto strains nor multiple infections were observed. The B. afzelii isolates were of OspA serotype 2. Three B. garinii strains were of OspA serotype 5, and the remaining four strains were of OspA serotype 6. All of the B. garinii strains belonged to the same 16S ribosomal DNA ribotype class. Our findings agree with earlier findings from other geographic regions in Europe where B. afzelii and B. garinii have been recovered predominantly from skin and CSF cultures, respectively. To further study the possible presence in Sweden of the genotype B. burgdorferi sensu stricto, which is known to be present in Europe and to occur predominantly in patients with Lyme arthritis, molecular detection of Borrelia-specific DNA in synovial samples from Lyme arthritis patients should be performed.

  7. Clinical determinants of Lyme borreliosis, babesiosis, bartonellosis, anaplasmosis, and ehrlichiosis in an Australian cohort

    PubMed Central

    Mayne, Peter J

    2015-01-01

    Background Borrelia burgdorferi is the causative agent of Lyme borreliosis. This spirochete, along with Babesia, Bartonella, Anaplasma, Ehrlichia, and the Rickettsia spp. are recognized tick-borne pathogens. In this study, the clinical manifestation of these zoonoses in Australia is described. Methods The clinical presentation of 500 patients over the course of 5 years was examined. Evidence of multisystem disease and cranial nerve neuropathy was sought. Supportive laboratory evidence of infection was examined. Results Patients from every state of Australia presented with a wide range of symptoms of disease covering multiple systems and a large range of time intervals from onset. Among these patients, 296 (59%) were considered to have a clinical diagnosis of Lyme borreliosis and 273 (54% of the 500) tested positive for the disease, the latter not being a subset of the former. In total, 450 (90%) had either clinical evidence for or laboratory proof of borrelial infection, and the great majority of cases featured neurological symptoms involving the cranial nerves, thus mimicking features of the disease found in Europe and Asia, as distinct from North America (where extracutaneous disease is principally an oligoarticular arthritis). Only 83 patients (17%; number [n]=492) reported never leaving Australia. Of the 500 patients, 317 (63%) had clinical or laboratory-supported evidence of coinfection with Babesia or Bartonella spp. Infection with A. phagocytophilum was detected in three individuals, and Ehrlichia chaffeensis was detected in one individual who had never traveled outside Australia. In the cohort, 30 (11%; n=279) had positive rickettsial serology. Conclusion The study suggests that there is a considerable presence of borreliosis in Australia, and a highly significant burden of coinfections accompanying borreliosis transmission. The concept sometimes advanced of a “Lyme-like illness” on the continent needs to be re-examined as the clinical interplay between

  8. Testing the role of genetic factors across multiple independent invasions of the shrub Scotch broom (Cytisus scoparius).

    PubMed

    Kang, Ming; Buckley, Yvonne M; Lowe, Andrew J

    2007-11-01

    Knowledge of the introduction history of invasive plants informs on theories of invasiveness and assists in the invasives management. For the highly successful invasive shrub Scotch broom, Cytisus scoparius, we analysed a combination of nuclear and chloroplast microsatellites for eight native source regions and eight independent invasion events in four countries across three continents. We found that two exotic Australian populations came from different sources, one of which was derived from multiple native populations, as was an invasive sample from California. An invasive population from New Zealand appeared to be predominantly sourced from a single population, either from the native or exotic ranges. Four invasive populations from Chile were genetically differentiated from the native range samples analysed here and so their source of introduction could not be confirmed, but high levels of differentiation between the Chilean populations suggested a combination of different sources. This extensive global data set of replicated introductions also enabled tests of key theories of invasiveness in relation to genetic diversity. We conclude that invasive populations have similar levels of high genetic diversity to native ranges; levels of admixture may vary across invasive populations so admixture does not appear to have been an essential requirement for invasion; invasive and native populations exhibit similar level of genetic structure indicating similar gene flow dynamics for both types of populations. High levels of diversity and multiple source populations for invasive populations observed here discount founder effects or drift as likely explanations for previously observed seed size differences between ranges. The high levels of genetic diversity, differential and source admixture identified for most exotic populations are likely to limit the ability to source biocontrol agents from the native region of origin of invasive populations.

  9. Lyme Carditis: A Case Involving the Conduction System and Mitral Valve.

    PubMed

    Patel, Lakir D; Schachne, Jay S

    2017-02-01

    Lyme disease is the most common tick-borne infection in the Northern hemisphere. Cardiac manifestations of Lyme disease typically include variable atrioventricular nodal block and rarely structural heart pathology. The incidence of Lyme carditis may be underestimated based on current reporting practices of confirmed cases. This case of a 59-year-old man with Lyme carditis demonstrates the unique presentation of widespread conduction system disease, mitral regurgitation, and suspected ischemic disease. Through clinical data, electrocardiograms, and cardiac imaging, we show the progression, and resolution, of a variety of cardiac symptoms attributable to infection with Lyme. [Full article available at http://rimed.org/rimedicaljournal-2017-02.asp].

  10. The application of independent component analysis with projection method to two-task fMRI data over multiple subjects

    NASA Astrophysics Data System (ADS)

    Li, Rui; Hui, Mingqi; Yao, Li; Chen, Kewei; Long, Zhiying

    2011-03-01

    Spatial Independent component analysis (sICA) has been successfully used to analyze functional magnetic resonance (fMRI) data. However, the application of ICA was limited in multi-task fMRI data due to the potential spatial dependence between task-related components. Long et al. (2009) proposed ICA with linear projection (ICAp) method and demonstrated its capacity to solve the interaction among task-related components in multi-task fMRI data of single subject. However, it's unclear that how to perform ICAp over a group of subjects. In this study, we proposed a group analysis framework on multi-task fMRI data by combining ICAp with the temporal concatenation method reported by Calhoun (2001). The results of real fMRI experiment containing multiple visual processing tasks demonstrated the feasibility and effectiveness of the group ICAp method. Moreover, compared to the GLM method, the group ICAp method is more sensitive to detect the regions specific to each task.

  11. Light-effect transistor (LET) with multiple independent gating controls for optical logic gates and optical amplification

    NASA Astrophysics Data System (ADS)

    Marmon, Jason; Rai, Satish; Wang, Kai; Zhou, Weilie; Zhang, Yong

    2016-03-01

    Modern electronics are developing electronic-optical integrated circuits, while their electronic backbone, e.g. field-effect transistors (FETs), remains the same. However, further FET down scaling is facing physical and technical challenges. A light-effect transistor (LET) offers electronic-optical hybridization at the component level, which can continue Moore’s law to quantum region without requiring a FET’s fabrication complexity, e.g. physical gate and doping, by employing optical gating and photoconductivity. Multiple independent gates are therefore readily realized to achieve unique functionalities without increasing chip space. Here we report LET device characteristics and novel digital and analog applications, such as optical logic gates and optical amplification. Prototype CdSe-nanowire-based LETs show output and transfer characteristics resembling advanced FETs, e.g. on/off ratios up to ~1.0x106 with a source-drain voltage of ~1.43 V, gate-power of ~260 nW, and subthreshold swing of ~0.3 nW/decade (excluding losses). Our work offers new electronic-optical integration strategies and electronic and optical computing approaches.

  12. Design of experiments with multiple independent variables: a resource management perspective on complete and reduced factorial designs.

    PubMed

    Collins, Linda M; Dziak, John J; Li, Runze

    2009-09-01

    An investigator who plans to conduct an experiment with multiple independent variables must decide whether to use a complete or reduced factorial design. This article advocates a resource management perspective on making this decision, in which the investigator seeks a strategic balance between service to scientific objectives and economy. Considerations in making design decisions include whether research questions are framed as main effects or simple effects; whether and which effects are aliased (confounded) in a particular design; the number of experimental conditions that must be implemented in a particular design and the number of experimental subjects the design requires to maintain the desired level of statistical power; and the costs associated with implementing experimental conditions and obtaining experimental subjects. In this article 4 design options are compared: complete factorial, individual experiments, single factor, and fractional factorial. Complete and fractional factorial designs and single-factor designs are generally more economical than conducting individual experiments on each factor. Although relatively unfamiliar to behavioral scientists, fractional factorial designs merit serious consideration because of their economy and versatility.

  13. Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer

    PubMed Central

    Bojesen, Stig E; Pooley, Karen A; Johnatty, Sharon E; Beesley, Jonathan; Michailidou, Kyriaki; Tyrer, Jonathan P; Edwards, Stacey L; Pickett, Hilda A; Shen, Howard C; Smart, Chanel E; Hillman, Kristine M; Mai, Phuong L; Lawrenson, Kate; Stutz, Michael D; Lu, Yi; Karevan, Rod; Woods, Nicholas; Johnston, Rebecca L; French, Juliet D; Chen, Xiaoqing; Weischer, Maren; Nielsen, Sune F; Maranian, Melanie J; Ghoussaini, Maya; Ahmed, Shahana; Baynes, Caroline; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; McGuffog, Lesley; Barrowdale, Daniel; Lee, Andrew; Healey, Sue; Lush, Michael; Tessier, Daniel C; Vincent, Daniel; Bacot, Françis; Vergote, Ignace; Lambrechts, Sandrina; Despierre, Evelyn; Risch, Harvey A; González-Neira, Anna; Rossing, Mary Anne; Pita, Guillermo; Doherty, Jennifer A; Álvarez, Nuria; Larson, Melissa C; Fridley, Brooke L; Schoof, Nils; Chang-Claude, Jenny; Cicek, Mine S; Peto, Julian; Kalli, Kimberly R; Broeks, Annegien; Armasu, Sebastian M; Schmidt, Marjanka K; Braaf, Linde M; Winterhoff, Boris; Nevanlinna, Heli; Konecny, Gottfried E; Lambrechts, Diether; Rogmann, Lisa; Guénel, Pascal; Teoman, Attila; Milne, Roger L; Garcia, Joaquin J; Cox, Angela; Shridhar, Vijayalakshmi; Burwinkel, Barbara; Marme, Frederik; Hein, Rebecca; Sawyer, Elinor J; Haiman, Christopher A; Wang-Gohrke, Shan; Andrulis, Irene L; Moysich, Kirsten B; Hopper, John L; Odunsi, Kunle; Lindblom, Annika; Giles, Graham G; Brenner, Hermann; Simard, Jacques; Lurie, Galina; Fasching, Peter A; Carney, Michael E; Radice, Paolo; Wilkens, Lynne R; Swerdlow, Anthony; Goodman, Marc T; Brauch, Hiltrud; García-Closas, Montserrat; Hillemanns, Peter; Winqvist, Robert; Dürst, Matthias; Devilee, Peter; Runnebaum, Ingo; Jakubowska, Anna; Lubinski, Jan; Mannermaa, Arto; Butzow, Ralf; Bogdanova, Natalia V; Dörk, Thilo; Pelttari, Liisa M; Zheng, Wei; Leminen, Arto; Anton-Culver, Hoda; Bunker, Clareann H; Kristensen, Vessela; Ness, Roberta B; Muir, Kenneth; Edwards, Robert; Meindl, Alfons; Heitz, Florian; Matsuo, Keitaro; du Bois, Andreas; Wu, Anna H; Harter, Philipp; Teo, Soo-Hwang; Schwaab, Ira; Shu, Xiao-Ou; Blot, William; Hosono, Satoyo; Kang, Daehee; Nakanishi, Toru; Hartman, Mikael; Yatabe, Yasushi; Hamann, Ute; Karlan, Beth Y; Sangrajrang, Suleeporn; Kjaer, Susanne Krüger; Gaborieau, Valerie; Jensen, Allan; Eccles, Diana; Høgdall, Estrid; Shen, Chen-Yang; Brown, Judith; Woo, Yin Ling; Shah, Mitul; Azmi, Mat Adenan Noor; Luben, Robert; Omar, Siti Zawiah; Czene, Kamila; Vierkant, Robert A; Nordestgaard, Børge G; Flyger, Henrik; Vachon, Celine; Olson, Janet E; Wang, Xianshu; Levine, Douglas A; Rudolph, Anja; Weber, Rachel Palmieri; Flesch-Janys, Dieter; Iversen, Edwin; Nickels, Stefan; Schildkraut, Joellen M; Silva, Isabel Dos Santos; Cramer, Daniel W; Gibson, Lorna; Terry, Kathryn L; Fletcher, Olivia; Vitonis, Allison F; van der Schoot, C Ellen; Poole, Elizabeth M; Hogervorst, Frans B L; Tworoger, Shelley S; Liu, Jianjun; Bandera, Elisa V; Li, Jingmei; Olson, Sara H; Humphreys, Keith; Orlow, Irene; Blomqvist, Carl; Rodriguez-Rodriguez, Lorna; Aittomäki, Kristiina; Salvesen, Helga B; Muranen, Taru A; Wik, Elisabeth; Brouwers, Barbara; Krakstad, Camilla; Wauters, Els; Halle, Mari K; Wildiers, Hans; Kiemeney, Lambertus A; Mulot, Claire; Aben, Katja K; Laurent-Puig, Pierre; van Altena, Anne M; Truong, Thérèse; Massuger, Leon F A G; Benitez, Javier; Pejovic, Tanja; Perez, Jose Ignacio Arias; Hoatlin, Maureen; Zamora, M Pilar; Cook, Linda S; Balasubramanian, Sabapathy P; Kelemen, Linda E; Schneeweiss, Andreas; Le, Nhu D; Sohn, Christof; Brooks-Wilson, Angela; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Cybulski, Cezary; Henderson, Brian E; Menkiszak, Janusz; Schumacher, Fredrick; Wentzensen, Nicolas; Marchand, Loic Le; Yang, Hannah P; Mulligan, Anna Marie; Glendon, Gord; Engelholm, Svend Aage; Knight, Julia A; Høgdall, Claus K; Apicella, Carmel; Gore, Martin; Tsimiklis, Helen; Song, Honglin; Southey, Melissa C; Jager, Agnes; van den Ouweland, Ans M W; Brown, Robert; Martens, John W M; Flanagan, James M; Kriege, Mieke; Paul, James; Margolin, Sara; Siddiqui, Nadeem; Severi, Gianluca; Whittemore, Alice S; Baglietto, Laura; McGuire, Valerie; Stegmaier, Christa; Sieh, Weiva; Müller, Heiko; Arndt, Volker; Labrèche, France; Gao, Yu-Tang; Goldberg, Mark S; Yang, Gong; Dumont, Martine; McLaughlin, John R; Hartmann, Arndt; Ekici, Arif B; Beckmann, Matthias W; Phelan, Catherine M; Lux, Michael P; Permuth-Wey, Jenny; Peissel, Bernard; Sellers, Thomas A; Ficarazzi, Filomena; Barile, Monica; Ziogas, Argyrios; Ashworth, Alan; Gentry-Maharaj, Aleksandra; Jones, Michael; Ramus, Susan J; Orr, Nick; Menon, Usha; Pearce, Celeste L; Brüning, Thomas; Pike, Malcolm C; Ko, Yon-Dschun; Lissowska, Jolanta; Figueroa, Jonine; Kupryjanczyk, Jolanta; Chanock, Stephen J; Dansonka-Mieszkowska, Agnieszka; Jukkola-Vuorinen, Arja; Rzepecka, Iwona K; Pylkäs, Katri; Bidzinski, Mariusz; Kauppila, Saila; Hollestelle, Antoinette; Seynaeve, Caroline; Tollenaar, Rob A E M; Durda, Katarzyna; Jaworska, Katarzyna; Hartikainen, Jaana M; Kosma, Veli-Matti; Kataja, Vesa; Antonenkova, Natalia N; Long, Jirong; Shrubsole, Martha; Deming-Halverson, Sandra; Lophatananon, Artitaya; Siriwanarangsan, Pornthep; Stewart-Brown, Sarah; Ditsch, Nina; Lichtner, Peter; Schmutzler, Rita K; Ito, Hidemi; Iwata, Hiroji; Tajima, Kazuo; Tseng, Chiu-Chen; Stram, Daniel O; van den Berg, David; Yip, Cheng Har; Ikram, M Kamran; Teh, Yew-Ching; Cai, Hui; Lu, Wei; Signorello, Lisa B; Cai, Qiuyin; Noh, Dong-Young; Yoo, Keun-Young; Miao, Hui; Iau, Philip Tsau-Choong; Teo, Yik Ying; McKay, James; Shapiro, Charles; Ademuyiwa, Foluso; Fountzilas, George; Hsiung, Chia-Ni; Yu, Jyh-Cherng; Hou, Ming-Feng; Healey, Catherine S; Luccarini, Craig; Peock, Susan; Stoppa-Lyonnet, Dominique; Peterlongo, Paolo; Rebbeck, Timothy R; Piedmonte, Marion; Singer, Christian F; Friedman, Eitan; Thomassen, Mads; Offit, Kenneth; Hansen, Thomas V O; Neuhausen, Susan L; Szabo, Csilla I; Blanco, Ignacio; Garber, Judy; Narod, Steven A; Weitzel, Jeffrey N; Montagna, Marco; Olah, Edith; Godwin, Andrew K; Yannoukakos, Drakoulis; Goldgar, David E; Caldes, Trinidad; Imyanitov, Evgeny N; Tihomirova, Laima; Arun, Banu K; Campbell, Ian; Mensenkamp, Arjen R; van Asperen, Christi J; van Roozendaal, Kees E P; Meijers-Heijboer, Hanne; Collée, J Margriet; Oosterwijk, Jan C; Hooning, Maartje J; Rookus, Matti A; van der Luijt, Rob B; van Os, Theo A M; Evans, D Gareth; Frost, Debra; Fineberg, Elena; Barwell, Julian; Walker, Lisa; Kennedy, M John; Platte, Radka; Davidson, Rosemarie; Ellis, Steve D; Cole, Trevor; Paillerets, Brigitte Bressac-de; Buecher, Bruno; Damiola, Francesca; Faivre, Laurence; Frenay, Marc; Sinilnikova, Olga M; Caron, Olivier; Giraud, Sophie; Mazoyer, Sylvie; Bonadona, Valérie; Caux-Moncoutier, Virginie; Toloczko-Grabarek, Aleksandra; Gronwald, Jacek; Byrski, Tomasz; Spurdle, Amanda B; Bonanni, Bernardo; Zaffaroni, Daniela; Giannini, Giuseppe; Bernard, Loris; Dolcetti, Riccardo; Manoukian, Siranoush; Arnold, Norbert; Engel, Christoph; Deissler, Helmut; Rhiem, Kerstin; Niederacher, Dieter; Plendl, Hansjoerg; Sutter, Christian; Wappenschmidt, Barbara; Borg, Åke; Melin, Beatrice; Rantala, Johanna; Soller, Maria; Nathanson, Katherine L; Domchek, Susan M; Rodriguez, Gustavo C; Salani, Ritu; Kaulich, Daphne Gschwantler; Tea, Muy-Kheng; Paluch, Shani Shimon; Laitman, Yael; Skytte, Anne-Bine; Kruse, Torben A; Jensen, Uffe Birk; Robson, Mark; Gerdes, Anne-Marie; Ejlertsen, Bent; Foretova, Lenka; Savage, Sharon A; Lester, Jenny; Soucy, Penny; Kuchenbaecker, Karoline B; Olswold, Curtis; Cunningham, Julie M; Slager, Susan; Pankratz, Vernon S; Dicks, Ed; Lakhani, Sunil R; Couch, Fergus J; Hall, Per; Monteiro, Alvaro N A; Gayther, Simon A; Pharoah, Paul D P; Reddel, Roger R; Goode, Ellen L; Greene, Mark H; Easton, Douglas F; Berchuck, Andrew; Antoniou, Antonis C; Chenevix-Trench, Georgia; Dunning, Alison M

    2013-01-01

    TERT-locus single nucleotide polymorphisms (SNPs) and leucocyte telomere measures are reportedly associated with risks of multiple cancers. Using the iCOGs chip, we analysed ~480 TERT-locus SNPs in breast (n=103,991), ovarian (n=39,774) and BRCA1 mutation carrier (11,705) cancer cases and controls. 53,724 participants have leucocyte telomere measures. Most associations cluster into three independent peaks. Peak 1 SNP rs2736108 minor allele associates with longer telomeres (P=5.8×10−7), reduced estrogen receptor negative (ER-negative) (P=1.0×10−8) and BRCA1 mutation carrier (P=1.1×10−5) breast cancer risks, and altered promoter-assay signal. Peak 2 SNP rs7705526 minor allele associates with longer telomeres (P=2.3×10−14), increased low malignant potential ovarian cancer risk (P=1.3×10−15) and increased promoter activity. Peak 3 SNPs rs10069690 and rs2242652 minor alleles increase ER-negative (P=1.2×10−12) and BRCA1 mutation carrier (P=1.6×10−14) breast and invasive ovarian (P=1.3×10−11) cancer risks, but not via altered telomere length. The cancer-risk alleles of rs2242652 and rs10069690 respectively increase silencing and generate a truncated TERT splice-variant. PMID:23535731

  14. Time-independent description of rapidly driven systems in the presence of friction: multiple scale perturbation approach.

    PubMed

    Shit, Anindita; Chattopadhyay, Sudip; Chaudhuri, Jyotipratim Ray

    2012-03-01

    The dynamics of a classical system driven by a rapidly oscillating field (with frequency ω) in the presence of friction has been investigated using the multiple scale perturbation theory (MSPT). By exploiting the idea of separation of time scales, the slow motion has been computed in a systematic expansion in the inverse of ω to the order ω(-3). This perturbation series can be viewed as a generalization of the calculation presented by Landau and Lifshitz for Kapitza's pendulum (where the point of suspension is moved periodically) in the presence of friction. The radiation induced dynamics of the system is found to be described by an effective time-independent potential with friction that controls the slow motion. The explicit appearance of friction in our computed effective potential is a manifestation of the dynamical effect due to the fast motion. The present study demonstrates that MSPT can be used to understand and predict the classical dynamics of a driven system in the presence of friction.

  15. Abnormalities in Chromosomes 1q and 13 Independently Correlate With Factors of Poor Prognosis in Multiple Myeloma

    PubMed Central

    Kim, Miyoung; Ju, Young-Su; Lee, Eun Jin; Kang, Hee Jung; Kim, Han-Sung; Cho, Hyoun Chan; Kim, Hyo Jung; Kim, Jung-Ah; Lee, Dong Soon

    2016-01-01

    Background We comprehensively profiled cytogenetic abnormalities in multiple myeloma (MM) and analyzed the relationship between cytogenetic abnormalities of undetermined prognostic significance and established prognostic factors. Methods The karyotype of 333 newly diagnosed MM cases was analyzed in association with established prognostic factors. Survival analysis was also performed. Results MM with abnormal karyotypes (41.1%) exhibited high international scoring system (ISS) stage, frequent IgA type, elevated IgG or IgA levels, elevated calcium levels, elevated creatine (Cr) levels, elevated β2-microglobulin levels, and decreased Hb levels. Structural abnormalities in chromosomes 1q, 4, and 13 were independently associated with elevated levels of IgG or IgA, calcium, and Cr, respectively. Chromosome 13 abnormalities were associated with poor prognosis and decreased overall survival. Conclusions This is the first study to demonstrate that abnormalities in chromosomes 1q, 4, and 13 are associated with established factors for poor prognosis, irrespective of the presence of other concurrent chromosomal abnormalities. Chromosome 13 abnormalities have a prognostic impact on overall survival in association with elevated Cr levels. Frequent centromeric breakpoints appear to be related to MM pathogenesis. PMID:27578511

  16. Gene microarray assessment of multiple genes and signal pathways involved in androgen-dependent prostate cancer becoming androgen independent.

    PubMed

    Liu, Jun-Bao; Dai, Chun-Mei; Su, Xiao-Yun; Cao, Lu; Qin, Rui; Kong, Qing-Bo

    2014-01-01

    To study the gene expression change and possible signal pathway during androgen-dependent prostate cancer (ADPC) becoming androgen-independent prostate cancer (AIPC), an LNCaP cell model of AIPC was established using flutamide in combination with androgen-free environment inducement, and differential expression genes were screened by microarray. Then the biological process, molecular function and KEGG pathway of differential expression genes are analyzed by Molecule Annotation System (MAS). By comparison of 12,207 expression genes, 347 expression genes were acquired, of which 156 were up-ragulated and 191 down-regulated. After analyzing the biological process and molecule function of differential expression genes, these genes are found to play crucial roles in cell proliferation, differntiation, cell cycle control, protein metabolism and modification and other biological process, serve as signal molecules, enzymes, peptide hormones, cytokines, cytoskeletal proteins and adhesion molecules. The analysis of KEGG show that the relevant genes of AIPC transformation participate in glutathione metabolism, cell cycle, P53 signal pathway, cytochrome P450 metabolism, Hedgehog signal pathway, MAPK signal pathway, adipocytokines signal pathway, PPAR signal pathway, TGF-β signal pathway and JAK-STAT signal pathway. In conclusion, during the process of ADPC becoming AIPC, it is not only one specific gene or pathway, but multiple genes and pathways that change. The findings above lay the foundation for study of AIPC mechanism and development of AIPC targeting drugs.

  17. Nervous system Lyme disease, chronic Lyme disease, and none of the above.

    PubMed

    Halperin, John J

    2016-03-01

    Lyme borreliosis, infection with the tick-borne spirochete Borrelia burgdorferi sensu lato, causes nervous system involvement in 10-15 % of identified infected individuals. Not unlike the other well-known spirochetosis, syphilis, infection can be protracted, but is microbiologically curable in virtually all patients, regardless of disease duration. Diagnosis relies on 2-tier serologic testing, which after the first 4-6 weeks of infection is both highly sensitive and specific. After this early, acute phase, serologic testing should rely only on IgG reactivity. Nervous system involvement most commonly presents with meningitis, cranial neuritis and radiculoneuritis, but can also present with a broader array of peripheral nervous system manifestations. Central nervous system infection typically elicits a cerebrospinal fluid pleocytosis and, often, intrathecal production of specific antibody, findings that should not be expected in disease not affecting the CNS. Treatment with recommended courses of oral or, when necessary, parenteral antibiotics is highly effective. The attribution of chronic, non-specific symptoms to "chronic Lyme disease", in the absence of specific evidence of ongoing B. burgdorferi infection, is inappropriate and unfortunate, leading not only to unneeded treatment and its associated complications, but also to missed opportunities for more appropriate management of patients' often disabling symptoms.

  18. Detecting Lyme disease using antibody-functionalized carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Dailey, Jennifer; Lerner, Mitchell; Goldsmith, Brett; Brisson, Dustin; Johnson, A. T. Charlie

    2011-03-01

    We combine antibodies for Lyme flagellar protein with carbon nanotube transistors to create an electronic sensor capable of definitive detection of Lyme disease. Over 35,000 cases of Lyme disease are reported in the United States each year, of which more than 23 percent are originally misdiagnosed. Rational design of the coupling of the biological system to the electronic system gives us a flexible sensor platform which we can apply to several biological systems. By coupling these antibodies to carbon nanotubes in particular, we allow for fast, sensitive, highly selective, electronic detection. Unlike antibody or biomarker detection, bacterial protein detection leads to positive identification of both early and late stage bacterial infections, and is easily expandable to environmental monitoring.

  19. Methods for control of tick vectors of Lyme Borreliosis

    USGS Publications Warehouse

    Jaenson, T.G.T.; Fish, D.; Ginsberg, H.S.; Gray, J.S.; Mather, T.N.; Piesman, J.

    1991-01-01

    During the IVth International Conference on Lyme Borreliosis in Stockholm, 1990, a workshop on control of Lyme disease vectors briefly reviewed: basic ecological principles for tick control; biocontrol of ticks; chemical control, including the use of repellents and use of permethrin-treated rodent nest material; tick control by habitat modification; and reduction of tick host availability. It was concluded that, although much research work remains, Lyme borreliosis is to a large extent a preventable infection. Avoidance of heavily tick-infested areas, personal protection using proper clothing, and prompt removal of attached ticks remain the most effective protective measures. Many other prophylactic measures are available and could be efficiently integrated into schemes to reduce the abundance of vectors. However, since the ecology of the infection varies greatly between different localities it may be necessary to apply different combinations of control methods in different endemic regions.

  20. [Lyme disease acrodermitis chronica atrophicans: misleading vascular signs].

    PubMed

    Blaise, S; Fiandrino, G; Satger, B; Carpentier, P-H

    2014-05-01

    Lyme disease acrodermatitis chronica atrophicans is a tertiary form of Lyme borrelliosis. It occurs at least six months, but also up to several years, after a tick bite. This rare condition is probably underestimated because of the difficult diagnosis. Clinical presentations of acrodermatitis chronic atrophicans are quite variable depending upon the duration of the disease. Complimentary explorations are difficult to interpret and rarely specific. Only rare configurations allow formal diagnosis of Borrelia burgdoferi infection. We present a patient who exhibited an atypical clinical presentation of Lyme disease acrodermatitis chronic atrophicans. The clinical outcome was quite favorable with treatment, confirming the diagnosis. Such treatments, which are well tolerated and highly effective, are essential since an untreated disease can lead to potentially severe neurological involvement.

  1. Vaccination against Lyme disease: past, present, and future.

    PubMed

    Embers, Monica E; Narasimhan, Sukanya

    2013-01-01

    Lyme borreliosis is a zoonotic disease caused by Borrelia burgdorferi sensu lato bacteria transmitted to humans and domestic animals by the bite of an Ixodes spp. tick (deer tick). Despite improvements in diagnostic tests and public awareness of Lyme disease, the reported cases have increased over the past decade to approximately 30,000 per year. Limitations and failed public acceptance of a human vaccine, comprised of the outer surface A (OspA) lipoprotein of B. burgdorferi, led to its demise, yet current research has opened doors to new strategies for protection against Lyme disease. In this review we discuss the enzootic cycle of B. burgdorferi, and the unique opportunities it poses to block infection or transmission at different levels. We present the correlates of protection for this infectious disease, the pros and cons of past vaccination strategies, and new paradigms for future vaccine design that would include elements of both the vector and the pathogen.

  2. Cerebrospinal fluid proteome of patients with acute Lyme disease

    PubMed Central

    Angel, Thomas E.; Jacobs, Jon M.; Smith, Robert P.; Pasternack, Mark S.; Elias, Susan; Gritsenko, Marina A.; Shukla, Anil; Gilmore, Edward C.; McCarthy, Carol; Camp, David G.; Smith, Richard D.; Warren, H. Shaw

    2012-01-01

    During acute Lyme disease, bacteria can disseminate to the central nervous system (CNS) leading to the development of meningitis and other neurologic symptoms. Here we have analyzed pooled cerebrospinal fluid (CSF) allowing a deep view into the proteome for patients diagnosed with early-disseminated Lyme disease and CSF inflammation. Additionally, we analyzed individual patient samples and quantified differences in protein abundance employing label-free quantitative mass spectrometry based methods. We identified 108 proteins that differ significantly in abundance in patients with acute Lyme disease from controls. Comparison between infected patients and control subjects revealed differences in proteins in the CSF associated with cell death localized to brain synapses and others that likely originate from brain parenchyma. PMID:22900834

  3. Antiscience and ethical concerns associated with advocacy of Lyme disease

    PubMed Central

    Auwaerter, Paul G; Bakken, Johan S; Dattwyler, Raymond J; Dumler, J Stephen; Halperin, John J; McSweegan, Edward; Nadelman, Robert B; O’Connell, Susan; Shapiro, Eugene D; Sood, Sunil K; Steere, Allen C; Weinstein, Arthur; Wormser, Gary P

    2015-01-01

    Advocacy for Lyme disease has become an increasingly important part of an antiscience movement that denies both the viral cause of AIDS and the benefits of vaccines and that supports unproven (sometimes dangerous) alternative medical treatments. Some activists portray Lyme disease, a geographically limited tick-borne infection, as a disease that is insidious, ubiquitous, difficult to diagnose, and almost incurable; they also propose that the disease causes mainly non-specific symptoms that can be treated only with long-term antibiotics and other unorthodox and unvalidated treatments. Similar to other antiscience groups, these advocates have created a pseudoscientific and alternative selection of practitioners, research, and publications and have coordinated public protests, accused opponents of both corruption and conspiracy, and spurred legislative efforts to subvert evidence-based medicine and peer-reviewed science. The relations and actions of some activists, medical practitioners, and commercial bodies involved in Lyme disease advocacy pose a threat to public health. PMID:21867956

  4. Survey on the subject of equine Lyme borreliosis.

    PubMed

    Gall, Yvonne; Pfister, Kurt

    2006-05-01

    According to the results of a questionnaire on equine Lyme borreliosis addressing veterinarians in Germany, the existence of the disease was confirmed by more than half of the 118 participants. Practitioners who regarded Borrelia burgdorferi as a pathogen of horses seemed to be more sensitized in terms of the number of annually diagnosed cases as well as the frequency of occurrence of tick infestation with equine patients or prophylactic treatments against ectoparasites by horse owners. Chronically poor performance and diverse orthopaedic problems were the clinical symptoms most often leading to a Lyme borreliosis suspicion. The tentative diagnoses were predominantly confirmed by serology. Antibiotics (and anti-inflammatory agents) were mainly used for therapy. Whereas horse owners repeatedly asked for examination of their horses, and some veterinarians asserted equine Lyme borreliosis to be an underestimated problem in the horse population, others stated the disease was often enough misdiagnosed.

  5. Lyme disease associated neuroretinitis - Case report.

    PubMed

    Vanya, Melinda; Fejes, Imre; Jako, Maria; Tula, Areta; Terhes, Gabriella; Janaky, Marta; Bartfai, Gyorgy

    2015-12-01

    We describe a rare case of Lyme disease complicated by unilateral neuroretinitis in the right eye. We report a case of a 27-year-old woman with blurred vision on her right eye. Because of the suspicion of optic neuritis (multiplex sclerosis) neurological examination was ordered. Surprisingly, computer tomography of the brain revealed incomplete empty sella, which generally results not monocular, but bilateral optic nerve swelling. Opthalmological examination (ophthalmoscopy and optical coherence tomography) indicated not only monocular optic nerve, but retinal oedema next to the temporal part of the right optic disk. Visual evoked potentials (VEP) demonstrated no P100 latency delay and mild differences between the amplitudes of the responses of the left and right eye. Optical coherence tomography (OCT) demonstrated the swelling of the optic nerve head and oedematous retina at the temporal part of the disk. Suspicion of an inflammatory cause of visual disturbance blood tests was ordered. Doxycycline treatment was ordered till the result of the blood test arrived. The Western blot and ELISA test were positive for Borrelia burgdorferi sensu lato. Following one week corticosteroide and ceftriaxone treatments, the patient displayed a clinical improvement. Unilateral neuroretinitis with optic disk swelling due to neuroborreliosis is a rare complication and in many cases it is difficult to distinguish between inflammatory and ischemic lesions. Further difficulty in the diagnosis can occur when intracranial alterations such as empty sella is demonstrated by CT examination.

  6. [Lyme disease: prophylaxis after tick bite].

    PubMed

    Patey, O

    2007-01-01

    Lyme disease is a bacterial infection caused by Borrelia burgdorferi, which is transmitted by infected ticks. The transmission depends on several factors, especially on the duration of the tick's presence in the host body (the nymph which is smaller than the adults and thus less visible, is in this case the most frequently involved) and on whether the tick is infected or not. The interpretation of results in the few available studies is made difficult by the lack of information obtained (due to difficulty to collect information and examination costs). The comparison is made even more difficult by the difference between Borrelia ticks species in various regions. Today, the best methods are preventive: protective clothing, tick repellents, checking and removal of ticks after a journey in an endemic zone, and in case of tick bite, regular examination of the bite site during the following weeks in order to initiate an early curative treatment if ECM is diagnosed. The currently available data seems to be insufficient to suggest systematic antimicrobial prophylaxis in case of tick bite.

  7. Precipitation and the occurrence of lyme disease in the Northeastern United States

    USGS Publications Warehouse

    McCabe, G.J.; Bunnell, J.E.

    2004-01-01

    The occurrence of Lyme disease is a growing concern in the United States, and various studies have been performed to understand the factors related to Lyme disease occurrence. In the United States, Lyme disease has occurred most frequently in the northeastern United States. Positive correlations between the number of cases of Lyme disease reported in the northeastern United States during the 1992-2002 period indicate that late spring/early summer precipitation was a significant climate factor affecting the occurrence of Lyme disease. When late spring/early summer precipitation was greater than average, the occurrence of Lyme disease was above average, possibly due to increased tick activity and survival rate during wet conditions. Temperature did not seem to explain the variability in Lyme disease reports for the northeastern United States. ?? Mary Ann Liebert, Inc.

  8. Lyme Disease: A Case Report with Typical and Atypical Lesions

    PubMed Central

    Sharma, Anuj; Guleria, Sandesh; Sharma, Reena; Sharma, Anita

    2017-01-01

    Lyme disease is a multisystem infectious disease caused by the spirochete “Borrelia burgdorferi,” which is transmitted by “Ixodes” tick, with skin being the most common and earliest organ to be affected. Diagnosis of erythema chronicum migrans (ECM), which is the characteristic lesion of early disease, may help in early treatment and prevention of complications. Here, we are reporting a case of Lyme disease in a 10-year-old young boy from a non-endemic zone of Himachal Pradesh, who presented with typical as well as atypical ECM lesions. The clinical diagnosis was confirmed serologically, and the child was treated successfully with doxycycline.

  9. [Bilateral peripheral facial paralysis secondary to Lyme disease].

    PubMed

    Zapater Latorre, E; Castillo Ruiz, A; Alba García, J R; Armengot Carceller, M; Sancho Rieger, J; Basterra Alegría, J

    2004-01-01

    Simultaneous bilateral facial paralisis (SBFP) occurs in 0.3-2% of all facial paralisis. We report a case of SBFP in association with Lyme disease. A review of literature about SBFP is made, studing specially the one caused by Borrelia burgdorferi. We present a diagnostic guideline of SBFP. Suspect diagnosis of Lyme disease is based on clinical and epidemiological criteria. Culture isolation of this bacteria is difficult, therefore serologic testing is required. Neuroborreliosis treatment is intravenous Ceftriaxone or Cefotaxime. Oral Doxycycline is useful in the treatment of neuritis without central nervous system involvement.

  10. Country, Sex, EDSS Change and Therapy Choice Independently Predict Treatment Discontinuation in Multiple Sclerosis and Clinically Isolated Syndrome

    PubMed Central

    Jokubaitis, Vilija G.; Trojano, Maria; Izquierdo, Guillermo; Grand’Maison, François; Oreja-Guevara, Celia; Boz, Cavit; Lugaresi, Alessandra; Girard, Marc; Grammond, Pierre; Iuliano, Gerardo; Fiol, Marcela; Cabrera-Gomez, Jose Antonio; Fernandez-Bolanos, Ricardo; Giuliani, Giorgio; Lechner-Scott, Jeannette; Cristiano, Edgardo; Herbert, Joseph; Petkovska-Boskova, Tatjana; Bergamaschi, Roberto; van Pesch, Vincent; Moore, Fraser; Vella, Norbert; Slee, Mark; Santiago, Vetere; Barnett, Michael; Havrdova, Eva; Young, Carolyn; Sirbu, Carmen-Adella; Tanner, Mary; Rutherford, Michelle; Butzkueven, Helmut

    2012-01-01

    Objectives We conducted a prospective study, MSBASIS, to assess factors leading to first treatment discontinuation in patients with a clinically isolated syndrome (CIS) and early relapsing-remitting multiple sclerosis (RRMS). Methods The MSBASIS Study, conducted by MSBase Study Group members, enrols patients seen from CIS onset, reporting baseline demographics, cerebral magnetic resonance imaging (MRI) features and Expanded Disability Status Scale (EDSS) scores. Follow-up visits report relapses, EDSS scores, and the start and end dates of MS-specific therapies. We performed a multivariable survival analysis to determine factors within this dataset that predict first treatment discontinuation. Results A total of 2314 CIS patients from 44 centres were followed for a median of 2.7 years, during which time 1247 commenced immunomodulatory drug (IMD) treatment. Ninety percent initiated IMD after a diagnosis of MS was confirmed, and 10% while still in CIS status. Over 40% of these patients stopped their first IMD during the observation period. Females were more likely to cease medication than males (HR 1.36, p = 0.003). Patients treated in Australia were twice as likely to cease their first IMD than patients treated in Spain (HR 1.98, p = 0.001). Increasing EDSS was associated with higher rate of IMD cessation (HR 1.21 per EDSS unit, p<0.001), and intramuscular interferon-β-1a (HR 1.38, p = 0.028) and subcutaneous interferon-β-1a (HR 1.45, p = 0.012) had higher rates of discontinuation than glatiramer acetate, although this varied widely in different countries. Onset cerebral MRI features, age, time to treatment initiation or relapse on treatment were not associated with IMD cessation. Conclusion In this multivariable survival analysis, female sex, country of residence, EDSS change and IMD choice independently predicted time to first IMD cessation. PMID:22768046

  11. Multiple Independent Emergences of Type 2 Vaccine-Derived Polioviruses during a Large Outbreak in Northern Nigeria

    PubMed Central

    Shaw, Jing; Jorba, Jaume; Bukbuk, David; Adu, Festus; Gumede, Nicksy; Pate, Muhammed Ali; Abanida, Emmanuel Ade; Gasasira, Alex; Iber, Jane; Chen, Qi; Vincent, Annelet; Chenoweth, Paul; Henderson, Elizabeth; Wannemuehler, Kathleen; Naeem, Asif; Umami, Rifqiyah Nur; Nishimura, Yorihiro; Shimizu, Hiroyuki; Baba, Marycelin; Adeniji, Adekunle; Williams, A. J.; Kilpatrick, David R.; Oberste, M. Steven; Wassilak, Steven G.; Tomori, Oyewale; Pallansch, Mark A.; Kew, Olen

    2013-01-01

    Since 2005, a large poliomyelitis outbreak associated with type 2 circulating vaccine-derived poliovirus (cVDPV2) has occurred in northern Nigeria, where immunization coverage with trivalent oral poliovirus vaccine (tOPV) has been low. Phylogenetic analysis of P1/capsid region sequences of isolates from each of the 403 cases reported in 2005 to 2011 resolved the outbreak into 23 independent type 2 vaccine-derived poliovirus (VDPV2) emergences, at least 7 of which established circulating lineage groups. Virus from one emergence (lineage group 2005-8; 361 isolates) was estimated to have circulated for over 6 years. The population of the major cVDPV2 lineage group expanded rapidly in early 2009, fell sharply after two tOPV rounds in mid-2009, and gradually expanded again through 2011. The two major determinants of attenuation of the Sabin 2 oral poliovirus vaccine strain (A481 in the 5′-untranslated region [5′-UTR] and VP1-Ile143) had been replaced in all VDPV2 isolates; most A481 5′-UTR replacements occurred by recombination with other enteroviruses. cVDPV2 isolates representing different lineage groups had biological properties indistinguishable from those of wild polioviruses, including efficient growth in neuron-derived HEK293 cells, the capacity to cause paralytic disease in both humans and PVR-Tg21 transgenic mice, loss of the temperature-sensitive phenotype, and the capacity for sustained person-to-person transmission. We estimate from the poliomyelitis case count and the paralytic case-to-infection ratio for type 2 wild poliovirus infections that ∼700,000 cVDPV2 infections have occurred during the outbreak. The detection of multiple concurrent cVDPV2 outbreaks in northern Nigeria highlights the risks of cVDPV emergence accompanying tOPV use at low rates of coverage in developing countries. PMID:23408630

  12. Synergistic and independent actions of multiple terminal nucleotidyl transferases in the 3' tailing of small RNAs in Arabidopsis.

    PubMed

    Wang, Xiaoyan; Zhang, Shuxin; Dou, Yongchao; Zhang, Chi; Chen, Xuemei; Yu, Bin; Ren, Guodong

    2015-04-01

    All types of small RNAs in plants, piwi-interacting RNAs (piRNAs) in animals and a subset of siRNAs in Drosophila and C. elegans are subject to HEN1 mediated 3' terminal 2'-O-methylation. This modification plays a pivotal role in protecting small RNAs from 3' uridylation, trimming and degradation. In Arabidopsis, HESO1 is a major enzyme that uridylates small RNAs to trigger their degradation. However, U-tail is still present in null hen1 heso1 mutants, suggesting the existence of (an) enzymatic activities redundant with HESO1. Here, we report that UTP: RNA uridylyltransferase (URT1) is a functional paralog of HESO1. URT1 interacts with AGO1 and plays a predominant role in miRNA uridylation when HESO1 is absent. Uridylation of miRNA is globally abolished in a hen1 heso1 urt1 triple mutant, accompanied by an extensive increase of 3'-to-5' trimming. In contrast, disruption of URT1 appears not to affect the heterochromatic siRNA uridylation. This indicates the involvement of additional nucleotidyl transferases in the siRNA pathway. Analysis of miRNA tailings in the hen1 heso1 urt1 triple mutant also reveals the existence of previously unknown enzymatic activities that can add non-uridine nucleotides. Importantly, we show HESO1 may also act redundantly with URT1 in miRNA uridylation when HEN1 is fully competent. Taken together, our data not only reveal a synergistic action of HESO1 and URT1 in the 3' uridylation of miRNAs, but also independent activities of multiple terminal nucleotidyl transferases in the 3' tailing of small RNAs and an antagonistic relationship between uridylation and trimming. Our results may provide further insight into the mechanisms of small RNA 3' end modification and stability control.

  13. Lyme disease risk in dogs in New Brunswick

    PubMed Central

    Bjurman, Natalie K.; Bradet, Gina; Lloyd, Vett K.

    2016-01-01

    This study assessed the seroprevalence of anti-Borrelia burgdorferi antibodies in New Brunswick dogs. Testing of 699 serum samples from dogs across the province revealed a 6% province-wide seropositivity, more than 6 times higher than that found in 2008. The rapid increase in seropositivity indicates increased Lyme disease risk to both canine and human health. PMID:27587892

  14. Lyme Disease in Hispanics, United States, 2000–2013

    PubMed Central

    Starr, J. Andrew; Kugeler, Kiersten J.; Mead, Paul S.

    2016-01-01

    Hispanics comprise a growing portion of the US population and might have distinct risk factors for tickborne diseases. During 2000–2013, a total of 5,473 Lyme disease cases were reported among Hispanics through national surveillance. Hispanics were more likely than non-Hispanics to have signs of disseminated infection and onset during fall months. PMID:26889721

  15. Effects of Forest Fragmentation on Human Risk of Lyme Disease

    EPA Science Inventory

    Percent forest-herbaceous edge repeatedly explained most of the variability in reported Lyme disease rates within a rural-to-urban study gradient across central Maryland and southeastern Pennsylvania. A one-percent increase in forest-herbaceous edge was associated with an increas...

  16. Lyme Disease in Hispanics, United States, 2000-2013.

    PubMed

    Nelson, Christina A; Starr, J Andrew; Kugeler, Kiersten J; Mead, Paul S

    2016-03-01

    Hispanics comprise a growing portion of the US population and might have distinct risk factors for tickborne diseases. During 2000-2013, a total of 5,473 Lyme disease cases were reported among Hispanics through national surveillance. Hispanics were more likely than non-Hispanics to have signs of disseminated infection and onset during fall months.

  17. Ticks Carrying Lyme Disease Confirmed in Eastern National Parks

    MedlinePlus

    ... html Ticks Carrying Lyme Disease Confirmed in Eastern National Parks U.S. National Park Service and CDC advise using insect repellents on ... Planning a hiking trip in an eastern U.S. national park? Better pack tick repellent -- a new study found ...

  18. Differential risk for Lyme disease along hiking trail, Germany.

    PubMed

    Richter, Dania; Matuschka, Franz-Rainer

    2011-09-01

    To estimate relative risk for exposure to ticks infected with Lyme disease-causing spirochetes in different land-use types along a trail in Germany, we compared tick density and spirochete prevalence on ruminant pasture with that on meadow and fallow land. Risk was significantly lower on pasture than on meadow and fallow land.

  19. Bell palsy in lyme disease-endemic regions of canada: a cautionary case of occult bilateral peripheral facial nerve palsy due to Lyme disease.

    PubMed

    Ho, Karen; Melanson, Michel; Desai, Jamsheed A

    2012-09-01

    Lyme disease caused by the spirochete Borrelia burgdorferi is a multisystem disorder characterized by three clinical stages: dermatologic, neurologic, and rheumatologic. The number of known Lyme disease-endemic areas in Canada is increasing as the range of the vector Ixodes scapularis expands into the eastern and central provinces. Southern Ontario, Nova Scotia, southern Manitoba, New Brunswick, and southern Quebec are now considered Lyme disease-endemic regions in Canada. The use of field surveillance to map risk and endemic regions suggests that these geographic areas are growing, in part due to the effects of climate warming. Peripheral facial nerve palsy is the most common neurologic abnormality in the second stage of Lyme borreliosis, with up to 25% of Bell palsy (idiopathic peripheral facial nerve palsy) occurring due to Lyme disease. Here we present a case of occult bilateral facial nerve palsy due to Lyme disease initially diagnosed as Bell palsy. In Lyme disease-endemic regions of Canada, patients presenting with unilateral or bilateral peripheral facial nerve palsy should be evaluated for Lyme disease with serologic testing to avoid misdiagnosis. Serologic testing should not delay initiation of appropriate treatment for presumed Bell palsy.

  20. Association of immune response to endothelial cell growth factor with early disseminated and late manifestations of Lyme disease but not posttreatment Lyme disease syndrome.

    PubMed

    Tang, Kevin S; Klempner, Mark S; Wormser, Gary P; Marques, Adriana R; Alaedini, Armin

    2015-12-01

    Endothelial cell growth factor has been recently proposed as a potential autoantigen in manifestations of Lyme disease that are thought to involve immune-mediated mechanisms. Our findings indicate that a humoral immune response to this protein is not associated with posttreatment Lyme disease syndrome.

  1. Association of Immune Response to Endothelial Cell Growth Factor With Early Disseminated and Late Manifestations of Lyme Disease but Not Posttreatment Lyme Disease Syndrome

    PubMed Central

    Tang, Kevin S.; Klempner, Mark S.; Wormser, Gary P.; Marques, Adriana R.; Alaedini, Armin

    2015-01-01

    Endothelial cell growth factor has been recently proposed as a potential autoantigen in manifestations of Lyme disease that are thought to involve immune-mediated mechanisms. Our findings indicate that a humoral immune response to this protein is not associated with posttreatment Lyme disease syndrome. PMID:26219695

  2. Lyme disease: the promise of Big Data, companion diagnostics and precision medicine.

    PubMed

    Stricker, Raphael B; Johnson, Lorraine

    2016-01-01

    Lyme disease caused by the spirochete Borrelia burgdorferi has become a major worldwide epidemic. Recent studies based on Big Data registries show that >300,000 people are diagnosed with Lyme disease each year in the USA, and up to two-thirds of individuals infected with B. burgdorferi will fail conventional 30-year-old antibiotic therapy for Lyme disease. In addition, animal and human evidence suggests that sexual transmission of the Lyme spirochete may occur. Improved companion diagnostic tests for Lyme disease need to be implemented, and novel treatment approaches are urgently needed to combat the epidemic. In particular, therapies based on the principles of precision medicine could be modeled on successful "designer drug" treatment for HIV/AIDS and hepatitis C virus infection featuring targeted protease inhibitors. The use of Big Data registries, companion diagnostics and precision medicine will revolutionize the diagnosis and treatment of Lyme disease.

  3. A tale of two syndromes: Lyme disease preceding postural orthostatic tachycardia syndrome.

    PubMed

    Noyes, Adam M; Kluger, Jeffrey

    2015-01-01

    The pathogenesis of postural orthostatic tachycardia syndrome (POTS) is poorly understood. However, it has been suggested that altered immune activity or denervation of the autonomic system following illness may be an important trigger. Patients infected with Lyme disease have a small incidence of post-Lyme disease syndrome that share similar characteristics to POTS. We report a short series of two women who present with persistent symptoms of orthostatic intolerance consistent with POTS after treated Lyme disease.

  4. Intentions to receive a potentially available Lyme disease vaccine in an urban sample

    PubMed Central

    Fogel, Joshua; Kusz, Martin

    2016-01-01

    Objectives: The only human Lyme disease vaccine of LYMErix was voluntarily removed from the market in the United States in 2002 for a number of reasons. A new human Lyme disease vaccine is currently being developed. We would like any future approved human Lyme disease vaccine to be of interest and marketable to consumers. Methods: We surveyed 714 participants to determine variables associated with intentions to receive a Lyme disease vaccine. Predictor variables included demographics, protection motivational theory, Lyme disease knowledge, Lyme disease preventive behaviors, beliefs and perceived health. Results: We found in multivariate linear regression analyses that Asian/Asian American race/ethnicity (p < 0.001), South Asian race/ethnicity (p = 0.01) and coping appraisal variables of response efficacy (p < 0.001) and self-efficacy (p < 0.001) were each significantly associated with increased intentions. The belief that vaccines are typically not safe was significantly associated with decreased intentions (p = 0.03). Conclusions: Asian/Asian American and South Asian race/ethnicities have a strong interest in receiving a Lyme disease vaccine. Although pharmaceutical companies may benefit by advertising a Lyme disease vaccine to Asian/Asian Americans and South Asians, marketers need to address and use approaches to interest those from other race/ethnicities. Also, marketers need to address the erroneous belief that vaccines are typically not safe in order to interest those with such beliefs to use a Lyme disease vaccine. PMID:27551427

  5. Third-degree heart block associated with lyme carditis: review of published cases.

    PubMed

    Forrester, Joseph D; Mead, Paul

    2014-10-01

    Lyme carditis is an uncommon manifestation of Lyme disease that most commonly involves some degree of atrioventricular conduction blockade. Third-degree conduction block is the most severe form and can be fatal if untreated. Systematic review of the medical literature identified 45 published cases of third-degree conduction block associated with Lyme carditis in the United States. Median patient age was 32 years, 84% of patients were male, and 39% required temporary pacing. Recognizing patient groups more likely to develop third-degree heart block associated with Lyme carditis is essential to providing prompt and appropriate therapy.

  6. Geographic Expansion of Lyme Disease in the Southeastern United States, 2000-2014.

    PubMed

    Lantos, Paul M; Nigrovic, Lise E; Auwaerter, Paul G; Fowler, Vance G; Ruffin, Felicia; Brinkerhoff, R Jory; Reber, Jodi; Williams, Carl; Broyhill, James; Pan, William K; Gaines, David N

    2015-12-01

    Background.  The majority of Lyme disease cases in the United States are acquired on the east coast between northern Virginia and New England. In recent years the geographic extent of Lyme disease has been expanding, raising the prospect of Lyme disease becoming endemic in the southeast. Methods.  We collected confirmed and probable cases of Lyme disease from 2000 through 2014 from the Virginia Department of Health and North Carolina Department of Public Health and entered them in a geographic information system. We performed spatial and spatiotemporal cluster analyses to characterize Lyme disease expansion. Results.  There was a marked increase in Lyme disease cases in Virginia, particularly from 2007 onwards. Northern Virginia experienced intensification and geographic expansion of Lyme disease cases. The most notable area of expansion was to the southwest along the Appalachian Mountains with development of a new disease cluster in the southern Virginia mountain region. Conclusions.  The geographic distribution of Lyme disease cases significantly expanded in Virginia between 2000 and 2014, particularly southward in the Virginia mountain ranges. If these trends continue, North Carolina can expect autochthonous Lyme disease transmission in its mountain region in the coming years.

  7. Co-feeding transmission facilitates strain coexistence in Borrelia burgdorferi, the Lyme disease agent.

    PubMed

    States, S L; Huang, C I; Davis, S; Tufts, D M; Diuk-Wasser, M A

    2016-12-26

    Coexistence of multiple tick-borne pathogens or strains is common in natural hosts and can be facilitated by resource partitioning of the host species, within-host localization, or by different transmission pathways. Most vector-borne pathogens are transmitted horizontally via systemic host infection, but transmission may occur in the absence of systemic infection between two vectors feeding in close proximity, enabling pathogens to minimize competition and escape the host immune response. In a laboratory study, we demonstrated that co-feeding transmission can occur for a rapidly-cleared strain of Borrelia burgdorferi, the Lyme disease agent, between two stages of the tick vector Ixodes scapularis while feeding on their dominant host, Peromyscus leucopus. In contrast, infections rapidly became systemic for the persistently infecting strain. In a field study, we assessed opportunities for co-feeding transmission by measuring co-occurrence of two tick stages on ears of small mammals over two years at multiple sites. Finally, in a modeling study, we assessed the importance of co-feeding on R0, the basic reproductive number. The model indicated that co-feeding increases the fitness of rapidly-cleared strains in regions with synchronous immature tick feeding. Our results are consistent with increased diversity of B. burgdorferi in areas of higher synchrony in immature feeding - such as the midwestern United States. A higher relative proportion of rapidly-cleared strains, which are less human pathogenic, would also explain lower Lyme disease incidence in this region. Finally, if co-feeding transmission also occurs on refractory hosts, it may facilitate the emergence and persistence of new pathogens with a more limited host range.

  8. Adaptation and Evaluation of a Multi-Criteria Decision Analysis Model for Lyme Disease Prevention.

    PubMed

    Aenishaenslin, Cécile; Gern, Lise; Michel, Pascal; Ravel, André; Hongoh, Valérie; Waaub, Jean-Philippe; Milord, François; Bélanger, Denise

    2015-01-01

    Designing preventive programs relevant to vector-borne diseases such as Lyme disease (LD) can be complex given the need to include multiple issues and perspectives into prioritizing public health actions. A multi-criteria decision aid (MCDA) model was previously used to rank interventions for LD prevention in Quebec, Canada, where the disease is emerging. The aim of the current study was to adapt and evaluate the decision model constructed in Quebec under a different epidemiological context, in Switzerland, where LD has been endemic for the last thirty years. The model adaptation was undertaken with a group of Swiss stakeholders using a participatory approach. The PROMETHEE method was used for multi-criteria analysis. Key elements and results of the MCDA model are described and contrasted with the Quebec model. All criteria and most interventions of the MCDA model developed for LD prevention in Quebec were directly transferable to the Swiss context. Four new decision criteria were added, and the list of proposed interventions was modified. Based on the overall group ranking, interventions targeting human populations were prioritized in the Swiss model, with the top ranked action being the implementation of a large communication campaign. The addition of criteria did not significantly alter the intervention rankings, but increased the capacity of the model to discriminate between highest and lowest ranked interventions. The current study suggests that beyond the specificity of the MCDA models developed for Quebec and Switzerland, their general structure captures the fundamental and common issues that characterize the complexity of vector-borne disease prevention. These results should encourage public health organizations to adapt, use and share MCDA models as an effective and functional approach to enable the integration of multiple perspectives and considerations in the prevention and control of complex public health issues such as Lyme disease or other vector

  9. Adaptation and Evaluation of a Multi-Criteria Decision Analysis Model for Lyme Disease Prevention

    PubMed Central

    Aenishaenslin, Cécile; Gern, Lise; Michel, Pascal; Ravel, André; Hongoh, Valérie; Waaub, Jean-Philippe; Milord, François; Bélanger, Denise

    2015-01-01

    Designing preventive programs relevant to vector-borne diseases such as Lyme disease (LD) can be complex given the need to include multiple issues and perspectives into prioritizing public health actions. A multi-criteria decision aid (MCDA) model was previously used to rank interventions for LD prevention in Quebec, Canada, where the disease is emerging. The aim of the current study was to adapt and evaluate the decision model constructed in Quebec under a different epidemiological context, in Switzerland, where LD has been endemic for the last thirty years. The model adaptation was undertaken with a group of Swiss stakeholders using a participatory approach. The PROMETHEE method was used for multi-criteria analysis. Key elements and results of the MCDA model are described and contrasted with the Quebec model. All criteria and most interventions of the MCDA model developed for LD prevention in Quebec were directly transferable to the Swiss context. Four new decision criteria were added, and the list of proposed interventions was modified. Based on the overall group ranking, interventions targeting human populations were prioritized in the Swiss model, with the top ranked action being the implementation of a large communication campaign. The addition of criteria did not significantly alter the intervention rankings, but increased the capacity of the model to discriminate between highest and lowest ranked interventions. The current study suggests that beyond the specificity of the MCDA models developed for Quebec and Switzerland, their general structure captures the fundamental and common issues that characterize the complexity of vector-borne disease prevention. These results should encourage public health organizations to adapt, use and share MCDA models as an effective and functional approach to enable the integration of multiple perspectives and considerations in the prevention and control of complex public health issues such as Lyme disease or other vector

  10. Concordant species delimitation from multiple independent evidence: A case study with the Pachytriton brevipes complex (Caudata: Salamandridae).

    PubMed

    Wu, Yunke; Murphy, Robert W

    2015-11-01

    Mitochondrial DNA (mtDNA) sequence data are widely used to delimit species. However, owing to its strict maternal inheritance in most species, mtDNA tracks female dispersion and dispersal only. The accuracy of mtDNA-derived species delimitation is often not explicitly tested using other independent evidence, such as nuclear DNA (nDNA) data, morphological data, or ecological data. Because species are independent evolutionary lineages that can form testable hypotheses, we present a multi-evidence case study on species delimitation that combines statistical approaches with spatially explicit ecological analysis. Montane salamanders of the Pachytriton brevipes complex (Salamandridae) from southeastern China exhibit conservative morphology and variable color patterning that impede species diagnosis. Recent studies proposed splitting P. brevipes into four species based on deep mtDNA divergence but also found discordance between mtDNA and nDNA trees. In this study, we test evolutionary independence of these hypothesized species lineages using two coalescent-based Bayesian methods (Bayes factor and BP&P). Despite significant conflict between mtDNA gene tree and the species phylogeny, the results reinforce the inference of at least four species in the complex as opposed to the one species recognized for over 130 years. Correlative ecological niche modeling and statistical analysis of environmental data indicate that suitable habitats for each species are isolated by incompatible intervening lowland regions, so the likelihood of gene flow among species is very low, which means species lineages should maintain their evolutionary independence. We demonstrate that concordance among independent evidence confirms species status, which forms the basis for accurate assessment of regional biodiversity.

  11. Lyme borreliosis: reviewing potential vaccines, clinical aspects and health economics.

    PubMed

    Šmit, Renata; Postma, Maarten J

    2015-01-01

    Lyme borreliosis (LB) is a multisystem infectious disease with a growing burden in many parts of North America, Asia and Europe. Persistent infection of LB can usually be treated effectively with antibiotic therapy, but it may be followed by post-treatment Lyme disease syndrome. Therefore, it is important to begin with treatment in the early phase of the disease. Vaccination shows potential as the most effective way of preventing LB and reducing its burden in these continents. It is concluded that there is a need for continuous effort in research from all perspectives on LB, especially regarding prevention with novel vaccines, their development, clinical efficacy and cost-effectiveness. This review may help to further develop (cost-) effective strategies for prevention and control of the disease to reduce its burden and achieve population-wide health benefits.

  12. Borrelia miyamotoi disease (BMD): Neither Lyme disease nor relapsing fever

    PubMed Central

    Telford, Sam R.; Goethert, Heidi K.; Molloy, Philip; Berardi, Victor; Chowdri, Hanumara Ram; Gugliotta, Joseph L.; Lepore, Timothy J.

    2015-01-01

    Synopsis Borrelia miyamotoi disease (BMD) is a newly recognized borreliosis globally transmitted by ticks of the Ixodes persulcatus species complex. Once considered to be a tick symbiont with no public health implications, B. miyamotoi is increasingly being recognized as the agent of a nonspecific febrile illness often misdiagnosed as acute Lyme disease without rash, or as ehrlichiosis. The frequency of its diagnosis in the northeastern U.S. is similar to that of HGA. A diagnosis of BMD may be confirmed by PCR analysis of acute blood samples, or by seroconversion using a recombinant GlpQ enzyme immunoassay. As with Lyme disease or HGA, BMD is successfully treated with oral doxycycline or amoxicillin. PMID:26593262

  13. Serum Inflammatory Mediators as Markers of Human Lyme Disease Activity

    PubMed Central

    Soloski, Mark J.; Crowder, Lauren A.; Lahey, Lauren J.; Wagner, Catriona A.

    2014-01-01

    Chemokines and cytokines are key signaling molecules that orchestrate the trafficking of immune cells, direct them to sites of tissue injury and inflammation and modulate their states of activation and effector cell function. We have measured, using a multiplex-based approach, the levels of 58 immune mediators and 7 acute phase markers in sera derived from of a cohort of patients diagnosed with acute Lyme disease and matched controls. This analysis identified a cytokine signature associated with the early stages of infection and allowed us to identify two subsets (mediator-high and mediator-low) of acute Lyme patients with distinct cytokine signatures that also differed significantly (p<0.0005) in symptom presentation. In particular, the T cell chemokines CXCL9 (MIG), CXCL10 (IP-10) and CCL19 (MIP3B) were coordinately increased in the mediator-high group and levels of these chemokines could be associated with seroconversion status and elevated liver function tests (p = 0.027 and p = 0.021 respectively). There was also upregulation of acute phase proteins including CRP and serum amyloid A. Consistent with the role of CXCL9/CXCL10 in attracting immune cells to the site of infection, CXCR3+ CD4 T cells are reduced in the blood of early acute Lyme disease (p = 0.01) and the decrease correlates with chemokine levels (p = 0.0375). The levels of CXCL9/10 did not relate to the size or number of skin lesions but elevated levels of serum CXCL9/CXCL10 were associated with elevated liver enzymes levels. Collectively these results indicate that the levels of serum chemokines and the levels of expression of their respective chemokine receptors on T cell subsets may prove to be informative biomarkers for Lyme disease and related to specific disease manifestations. PMID:24740099

  14. CCL19 as a Chemokine Risk Factor for Posttreatment Lyme Disease Syndrome: a Prospective Clinical Cohort Study.

    PubMed

    Aucott, John N; Soloski, Mark J; Rebman, Alison W; Crowder, Lauren A; Lahey, Lauren J; Wagner, Catriona A; Robinson, William H; Bechtold, Kathleen T

    2016-09-01

    Approximately 10% to 20% of patients optimally treated for early Lyme disease develop persistent symptoms of unknown pathophysiology termed posttreatment Lyme disease syndrome (PTLDS). The objective of this study was to investigate associations between PTLDS and immune mediator levels during acute illness and at several time points following treatment. Seventy-six participants with physician-documented erythema migrans and 26 healthy controls with no history of Lyme disease were enrolled. Sixty-four cytokines, chemokines, and inflammatory markers were measured at each visit for a total of 6 visits over 1 year. An operationalized definition of PTLDS incorporating symptoms and functional impact was applied at 6 months and 1 year following treatment completion, and clinical outcome groups were defined as the return-to-health, symptoms-only, and PTLDS groups. Significance analysis of microarrays identified 7 of the 64 immune mediators to be differentially regulated by group. Generalized logit regressions controlling for potential confounders identified posttreatment levels of the T-cell chemokine CCL19 to be independently associated with clinical outcome group. Receiver operating characteristic analysis identified a CCL19 cutoff of >111.67 pg/ml at 1 month following treatment completion to be 82% sensitive and 83% specific for later PTLDS. We speculate that persistently elevated CCL19 levels among participants with PTLDS may reflect ongoing, immune-driven reactions at sites distal to secondary lymphoid tissue. Our findings suggest the relevance of CCL19 both during acute infection and as an immunologic risk factor for PTLDS during the posttreatment phase. Identification of a potential biomarker predictor for PTLDS provides the opportunity to better understand its pathophysiology and to develop early interventions in the context of appropriate and specific clinical information.

  15. CCL19 as a Chemokine Risk Factor for Posttreatment Lyme Disease Syndrome: a Prospective Clinical Cohort Study

    PubMed Central

    Soloski, Mark J.; Rebman, Alison W.; Crowder, Lauren A.; Wagner, Catriona A.; Robinson, William H.; Bechtold, Kathleen T.

    2016-01-01

    Approximately 10% to 20% of patients optimally treated for early Lyme disease develop persistent symptoms of unknown pathophysiology termed posttreatment Lyme disease syndrome (PTLDS). The objective of this study was to investigate associations between PTLDS and immune mediator levels during acute illness and at several time points following treatment. Seventy-six participants with physician-documented erythema migrans and 26 healthy controls with no history of Lyme disease were enrolled. Sixty-four cytokines, chemokines, and inflammatory markers were measured at each visit for a total of 6 visits over 1 year. An operationalized definition of PTLDS incorporating symptoms and functional impact was applied at 6 months and 1 year following treatment completion, and clinical outcome groups were defined as the return-to-health, symptoms-only, and PTLDS groups. Significance analysis of microarrays identified 7 of the 64 immune mediators to be differentially regulated by group. Generalized logit regressions controlling for potential confounders identified posttreatment levels of the T-cell chemokine CCL19 to be independently associated with clinical outcome group. Receiver operating characteristic analysis identified a CCL19 cutoff of >111.67 pg/ml at 1 month following treatment completion to be 82% sensitive and 83% specific for later PTLDS. We speculate that persistently elevated CCL19 levels among participants with PTLDS may reflect ongoing, immune-driven reactions at sites distal to secondary lymphoid tissue. Our findings suggest the relevance of CCL19 both during acute infection and as an immunologic risk factor for PTLDS during the posttreatment phase. Identification of a potential biomarker predictor for PTLDS provides the opportunity to better understand its pathophysiology and to develop early interventions in the context of appropriate and specific clinical information. PMID:27358211

  16. A case of reversible third-degree AV block due to Lyme carditis.

    PubMed

    Timmer, Stefan A J; Boswijk, Dirk J; Kimman, Geert P; Germans, Tjeerd

    2016-01-01

    The most common manifestation of Lyme carditis is a varying degree of atrioventricular (AV) conduction block. This case describes a 45-year-old male with third-degree AV block due to Lyme carditis. Treatment with intravenous antibiotics resulted in complete normalization of AV conduction, thereby averting permanent pacemaker implantation.

  17. The Prevalence and Incidence of Clinical and Asymptomatic Lyme Borreliose in a Population at Risk.

    ERIC Educational Resources Information Center

    Fahrer, Heinz; And Others

    1993-01-01

    Blood samples and questionnaires from 950 Swiss orienteers revealed positive antibodies for Lyme borreliosis in 248 (26.1%) of subjects, compared to 3.9-6.0% in 2 control groups. Six months later a second blood sample from 755 participants showed that 45 had seroconverted from negative to positive. Although positive Lyme seriology was common,…

  18. Enhancing Lyme Disease Surveillance by Using Administrative Claims Data, Tennessee, USA.

    PubMed

    Clayton, Joshua L; Jones, Stephen G; Dunn, John R; Schaffner, William; Jones, Timothy F

    2015-09-01

    Lyme disease is underreported in the United States. We used insurance administrative claims data to determine the value of such data in enhancing case ascertainment in Tennessee during January 2011-June 2013. Although we identified ≈20% more cases of Lyme disease (5/year), the method was resource intensive and not sustainable in this low-incidence state.

  19. Effects of landscape fragmentation and climate on Lyme disease incidence in the northeastern United States.

    PubMed

    Tran, Phoebe Minh; Waller, Lance

    2013-12-01

    Lyme disease is the most frequently reported vector borne illness in the United States, and incidences are increasing steadily year after year. This study explores the influence of landscape (e.g., land use pattern and landscape fragmentation) and climatic factors (e.g., temperature and precipitation) at a regional scale on Lyme disease incidence. The study area includes thirteen states in the Northeastern United States. Lyme disease incidence at county level for the period of 2002-2006 was linked with several key landscape and climatic variables in a negative binomial regression model. Results show that Lyme disease incidence has a relatively clear connection with regional landscape fragmentation and temperature. For example, more fragmentation between forests and residential areas results in higher local Lyme disease incidence. This study also indicates that, for the same landscape, some landscape variables derived at a particular scale show a clearer connection to Lyme disease than do others. In general, the study sheds more light on connections between Lyme disease incidence and climate and landscape patterns at the regional scale. Integrating findings of this regional study with studies at a local scale will further refine understanding of the pattern of Lyme disease as well as increase our ability to predict, prevent, and respond to disease.

  20. Lyme Disease in West Virginia: An Assessment of Distribution and Clinicians' Knowledge of Disease and Surveillance.

    PubMed

    Singh, Sarah; Parker, David; Mark-Carew, Miguella; White, Robert; Fisher, Melanie

    2016-01-01

    Lyme disease case misclassification, a top public health concern, may be attributed to the current disconnect between clinical diagnosis and surveillance. This study examines Lyme disease distribution in West Virginia (WV) and determines clinicians' knowledge of both disease and surveillance. Lyme disease surveillance data for 2013 were obtained from the WV Bureau for Public Health. A validated survey, distributed to clinicians at an academic medical center, assessed clinicians' knowledge of disease diagnosis and surveillance. There were 297 adult Lyme disease cases of which 83 were confirmed. Clinician survey responses resulted in a correct response rate of 70% for Lyme disease knowledge questions. Fewer than half of all clinicians were aware of the surveillance criteria for confirming Lyme disease cases. Neither medical specialty nor previous treatment of patients with Lyme disease were significantly associated with clinicians' knowledge of the disease. Clinicians in WV are familiar with symptoms and clinical management of Lyme disease. However, they are less knowledgeable about diagnosis and public health surveillance comprising reporting and confirming cases of the disease. Clinicians and public health authorities should collaborate more closely to promote education and awareness as a key step to successfully reducing the burden of Lymne disease.

  1. Proceedings of the 2nd workshop on lyme disease in the Southeast

    SciTech Connect

    Apperson, C.S.; Levine, J.F.; Snoddy, E.L.

    1993-12-31

    This volume provides author prepared abstracts of oral presentation at the Second Workshop on Lyme Disease in the Southeast head in Raleigh, North Carolina September 7-9, 1993. The 33 presentations covered various aspects of the epidemic including geographical distribution of various species of ticks, transmission risks, Lyme Disease epidemiology, and taxonomic aspects.

  2. Environmental and life-style risk factors for Lyme disease in children.

    PubMed

    Klein, J D; Eppes, S C; Hunt, P

    1996-07-01

    Risk factors for Lyme disease and/or infection with Borrelia burgdorferi in children are not defined. A case-control study was performed using Lyme disease patients from our Lyme Clinic population. Age- and sex-matched controls from the same neighborhood were identified by the Lyme patients' families. A site visit was made to each case/control neighborhood. Twenty-four environmental variables, especially the ecologic characteristics of the home environment were examined. Forty-five items were surveyed by parent questionnaire, including certain "high-risk" activities and behaviors, whether ticks or certain animals were present on the property, and whether antitick measures were used. Control subjects had serologic assays for antibodies to B. burgdorferi. Forty-four Lyme disease patients and 44 well-matched control subjects participated; 2 controls were seropositive. Significant associations with Lyme disease were found for deer ticks in the home environment, ground cover containing moist humus, and leaf litter in the yard. Among the 45 items related to life-style, there was no correlation with Lyme disease for the use of any antitick measures or for any childhood activities; in fact, an inverse correlation was observed for camping and fishing. We conclude that conditions in the immediate home environment, including certain ecologic factors that favor the presence of Ixodes ticks, are associated with an increased risk for Lyme disease in children.

  3. The impact of multiple concussions on emotional distress, post-concussive symptoms, and neurocognitive functioning in active duty United States marines independent of combat exposure or emotional distress.

    PubMed

    Spira, James L; Lathan, Corinna E; Bleiberg, Joseph; Tsao, Jack W

    2014-11-15

    Controversy exists as to whether the lingering effects of concussion on emotional, physical, and cognitive symptoms is because of the effects of brain trauma or purely to emotional factors such as post-traumatic stress disorder or depression. This study examines the independent effects of concussion on persistent symptoms. The Defense Automated Neurobehavioral Assessment, a clinical decision support tool, was used to assess neurobehavioral functioning in 646 United States Marines, all of whom were fit for duty. Marines were assessed for concussion history, post-concussive symptoms, emotional distress, neurocognitive functioning, and deployment history. Results showed that a recent concussion or ever having experienced a concussion was associated with an increase in emotional distress, but not with persistent post-concussive symptoms (PPCS) or neurocognitive functioning. Having had multiple lifetime concussions, however, was associated with greater emotional distress, PPCS, and reduced neurocognitive functioning that needs attention and rapid discrimination, but not for memory-based tasks. These results are independent of deployment history, combat exposure, and symptoms of post-traumatic stress disorder and depression. Results supported earlier findings that a previous concussion is not generally associated with post-concussive symptoms independent of covariates. In contrast with other studies that failed to find a unique contribution for concussion to PPCS, however, evidence of recent and multiple concussion was seen across a range of emotional distress, post-concussive symptoms, and neurocognitive functioning in this study population. Results are discussed in terms of implications for assessing concussion on return from combat.

  4. Testing for shared biogeographic history in the lower Central American freshwater fish assemblage using comparative phylogeography: concerted, independent, or multiple evolutionary responses?

    PubMed Central

    Bagley, Justin C; Johnson, Jerald B

    2014-01-01

    A central goal of comparative phylogeography is determining whether codistributed species experienced (1) concerted evolutionary responses to past geological and climatic events, indicated by congruent spatial and temporal patterns (“concerted-response hypothesis”); (2) independent responses, indicated by spatial incongruence (“independent-response hypothesis”); or (3) multiple responses (“multiple-response hypothesis”), indicated by spatial congruence but temporal incongruence (“pseudocongruence”) or spatial and temporal incongruence (“pseudoincongruence”). We tested these competing hypotheses using DNA sequence data from three livebearing fish species codistributed in the Nicaraguan depression of Central America (Alfaro cultratus, Poecilia gillii, and Xenophallus umbratilis) that we predicted might display congruent responses due to co-occurrence in identical freshwater drainages. Spatial analyses recovered different subdivisions of genetic structure for each species, despite shared finer-scale breaks in northwestern Costa Rica (also supported by phylogenetic results). Isolation-with-migration models estimated incongruent timelines of among-region divergences, with A. cultratus and Xenophallus populations diverging over Miocene–mid-Pleistocene while P. gillii populations diverged over mid-late Pleistocene. Approximate Bayesian computation also lent substantial support to multiple discrete divergences over a model of simultaneous divergence across shared spatial breaks (e.g., Bayes factor [B10] = 4.303 for Ψ [no. of divergences] > 1 vs. Ψ = 1). Thus, the data support phylogeographic pseudoincongruence consistent with the multiple-response hypothesis. Model comparisons also indicated incongruence in historical demography, for example, support for intraspecific late Pleistocene population growth was unique to P. gillii, despite evidence for finer-scale population expansions in the other taxa. Empirical tests for phylogeographic congruence

  5. Clustering of Two Genes Putatively Involved in Cyanate Detoxification Evolved Recently and Independently in Multiple Fungal Lineages

    PubMed Central

    Elmore, M. Holly; McGary, Kriston L.; Wisecaver, Jennifer H.; Slot, Jason C.; Geiser, David M.; Sink, Stacy; O’Donnell, Kerry; Rokas, Antonis

    2015-01-01

    Fungi that have the enzymes cyanase and carbonic anhydrase show a limited capacity to detoxify cyanate, a fungicide employed by both plants and humans. Here, we describe a novel two-gene cluster that comprises duplicated cyanase and carbonic anhydrase copies, which we name the CCA gene cluster, trace its evolution across Ascomycetes, and examine the evolutionary dynamics of its spread among lineages of the Fusarium oxysporum species complex (hereafter referred to as the FOSC), a cosmopolitan clade of purportedly clonal vascular wilt plant pathogens. Phylogenetic analysis of fungal cyanase and carbonic anhydrase genes reveals that the CCA gene cluster arose independently at least twice and is now present in three lineages, namely Cochliobolus lunatus, Oidiodendron maius, and the FOSC. Genome-wide surveys within the FOSC indicate that the CCA gene cluster varies in copy number across isolates, is always located on accessory chromosomes, and is absent in FOSC’s closest relatives. Phylogenetic reconstruction of the CCA gene cluster in 163 FOSC strains from a wide variety of hosts suggests a recent history of rampant transfers between isolates. We hypothesize that the independent formation of the CCA gene cluster in different fungal lineages and its spread across FOSC strains may be associated with resistance to plant-produced cyanates or to use of cyanate fungicides in agriculture. PMID:25663439

  6. Organic Anion Transporter 1 Is Inhibited by Multiple Mechanisms and Shows a Transport Mode Independent of Exchange.

    PubMed

    Hotchkiss, Adam G; Gao, Tiandai; Khan, Usman; Berrigan, Liam; Li, Mansong; Ingraham, Leslie; Pelis, Ryan M

    2015-12-01

    The mechanism by which drugs inhibit organic anion transporter 1 (OAT1) was examined. OAT1 was stably expressed in Chinese hamster ovary (CHO) cells, and para-aminohippurate (PAH) and 6-carboxyfluorescein were the substrates. Most compounds (10 of 14) inhibited competitively, increasing the Michaelis constant (Km) without affecting the maximal transport rate (Jmax). Others were mixed-type (lowering Jmax and increasing Km) or noncompetitive (lowering Jmax only) inhibitors. The interaction of a noncompetitive inhibitor (telmisartan) with OAT1 was examined further. Binding of telmisartan to OAT1 was observed, but translocation was not. Telmisartan did not alter the plasma membrane expression of OAT1, indicating that it lowers Jmax by reducing the turnover number. PAH transport after telmisartan treatment and its washout recovered faster in the presence of 10% fetal bovine serum in the washout buffer, indicating that binding of telmisartan to OAT1 and its inhibitory effect are reversible. Together, these data suggest that telmisartan binds reversibly to a site distinct from substrate and stabilizes the transporter in a conformation unfavorable for translocation. In the absence of an exchangeable extracellular substrate, PAH efflux from CHO-OAT1 cells was relatively rapid. Telmisartan slowed PAH efflux, suggesting that some transporter-mediated efflux occurs independent of exchange. Although drug-drug interaction predictions at OAT1 assume competitive inhibition, these data show that OAT1 can be inhibited by other mechanisms, which could influence the accuracy of drug-drug interaction predictions at the transporter. Telmisartan was useful for examining how a noncompetitive inhibitor can alter OAT1 transport activity and for uncovering a transport mode independent of exchange.

  7. Multiple Independent Retroelement Insertions in the Promoter of a Stress Response Gene Have Variable Molecular and Functional Effects in Drosophila

    PubMed Central

    Merenciano, Miriam; Ullastres, Anna; González, Josefa

    2016-01-01

    Promoters are structurally and functionally diverse gene regulatory regions. The presence or absence of sequence motifs and the spacing between the motifs defines the properties of promoters. Recent alternative promoter usage analyses in Drosophila melanogaster revealed that transposable elements significantly contribute to promote diversity. In this work, we analyzed in detail one of the transposable element insertions, named FBti0019985, that has been co-opted to drive expression of CG18446, a candidate stress response gene. We analyzed strains from different natural populations and we found that besides FBti0019985, there are another eight independent transposable elements inserted in the proximal promoter region of CG18446. All nine insertions are solo-LTRs that belong to the roo family. We analyzed the sequence of the nine roo insertions and we investigated whether the different insertions were functionally equivalent by performing 5’-RACE, gene expression, and cold-stress survival experiments. We found that different insertions have different molecular and functional consequences. The exact position where the transposable elements are inserted matters, as they all showed highly conserved sequences but only two of the analyzed insertions provided alternative transcription start sites, and only the FBti0019985 insertion consistently affects CG18446 expression. The phenotypic consequences of the different insertions also vary: only FBti0019985 was associated with cold-stress tolerance. Interestingly, the only previous report of transposable elements inserting repeatedly and independently in a promoter region in D. melanogaster, were also located upstream of a stress response gene. Our results suggest that functional validation of individual structural variants is needed to resolve the complexity of insertion clusters. PMID:27517860

  8. Bacteriophage P2 ogr and P4 delta genes act independently and are essential for P4 multiplication.

    PubMed Central

    Halling, C; Calendar, R

    1990-01-01

    Satellite bacteriophage P4 requires the products of the late genes of a helper phage such as P2 for lytic growth. Expression of the P2 late genes is positively regulated by the P2 ogr gene in a process requiring P2 DNA replication. Transactivation of P2 late gene expression by P4 requires the P4 delta gene product and works even in the absence of P2 DNA replication. We have made null mutants of the P2 ogr and P4 delta genes. In the absence of the P4 delta gene product, P4 multiplication required both the P2 ogr protein and P2 DNA replication. In the absence of the P2 ogr gene product, P4 multiplication required the P4 delta protein. In complementation experiments, we found that the P2 ogr protein was made in the absence of P2 DNA replication but could not function unless P2 DNA replicated. We produced P4 delta protein from a plasmid and found that it complemented the null P4 delta and P2 ogr mutants. Images PMID:2193911

  9. Dimorphisms of the proteasome subunit beta type 8 gene (PSMB8) of ectothermic tetrapods originated in multiple independent evolutionary events.

    PubMed

    Huang, Ching-Huei; Tanaka, Yuta; Fujito, Naoko T; Nonaka, Masaru

    2013-11-01

    The proteasome subunit beta type 8 gene (PSMB8) encodes one of the beta subunits of the immunoproteasome responsible for the generation of peptides presented by major histocompatibility complex class I molecules. Dimorphic alleles of the PSMB8 gene, termed A and F types, based on the deduced 31st amino acid residue of the mature protein have been reported from various vertebrates. Phylogenetic analysis revealed the presence of dichotomous ancient lineages, one comprising the F-type PSMB8 of basal ray-finned fishes, and the other comprising the A-type PSMB8 of these animals and both the F- and A-type PSMB8 of Xenopus and acanthopterygians, indicating that evolutionary history of the PSMB8 dimorphism was not straightforward. We analyzed the PSMB8 gene of five reptile and one amphibian species and found both the A and F types from all six. Phylogenetic analysis indicated that the PSMB8 F type was apparently regenerated from the PSMB8 A type at least five times independently during tetrapod evolution. Genomic typing of wild individuals of geckos and newts indicated that the frequencies of the A- and F-type alleles are not highly biased in these species. Phylogenetic analysis of each exon of the reptile PSMB8 gene suggested interallelic sequence homogenization as a possible evolutionary mechanism for the apparent recurrent regeneration of PSMB8 dimorphism in tetrapods. An extremely strong balancing selection acting on PSMB8 dimorphism was implicated in an unprecedented pattern of allele evolution.

  10. Sex without sex chromosomes: genetic architecture of multiple loci independently segregating to determine sex ratios in the copepod Tigriopus californicus.

    PubMed

    Alexander, H J; Richardson, J M L; Edmands, S; Anholt, B R

    2015-12-01

    Sex-determining systems are remarkably diverse and may evolve rapidly. Polygenic sex-determination systems are predicted to be transient and evolutionarily unstable, yet examples have been reported across a range of taxa. Here, we provide the first direct evidence of polygenic sex determination in Tigriopus californicus, a harpacticoid copepod with no heteromorphic sex chromosomes. Using genetically distinct inbred lines selected for male- and female-biased clutches, we generated a genetic map with 39 SNPs across 12 chromosomes. Quantitative trait locus mapping of sex ratio phenotype (the proportion of male offspring produced by an F2 female) in four F2 families revealed six independently segregating quantitative trait loci on five separate chromosomes, explaining 19% of the variation in sex ratios. The sex ratio phenotype varied among loci across chromosomes in both direction and magnitude, with the strongest phenotypic effects on chromosome 10 moderated to some degree by loci on four other chromosomes. For a given locus, sex ratio phenotype varied in magnitude for individuals derived from different dam lines. These data, together with the environmental factors known to contribute to sex determination, characterize the underlying complexity and potential lability of sex determination, and confirm the polygenic architecture of sex determination in T. californicus.

  11. Interleukin 3-dependent and -independent mast cells stimulated with IgE and antigen express multiple cytokines

    PubMed Central

    1989-01-01

    In response to IgE and specific multivalent antigen, mast cell lines (both growth factor-dependent and -independent) induce the transcription and/or secretion of a number of cytokines having a wide spectrum of activities. We have identified IL-1, IL-3, IL-5, IL-6, IFN- gamma, GM-CSF, JE, MIP1 alpha, MIP1 beta, and TCA3 RNA in at least two of four mast cell clones. The production of these products (except JE) is activation-associated and can be induced by IgE plus antigen. In selected instances cytokine expression can also be induced by activation with Con A or phorbol ester plus ionophore, albeit to levels less than those observed with IgE plus antigen. In addition, long-term mast cell clones and primary cultures of bone marrow-derived mast cells specifically release IL-1, IL-4, and/or IL-6 bioactivity after activation. These findings suggest that in addition to their inflammatory effector function mast cells may serve as a source of growth and regulatory factors. The relationship of mast cells to cells of the T lymphocyte lineage is discussed. PMID:2473161

  12. Cytology and molecular phylogenetics of Monoblepharidomycetes provide evidence for multiple independent origins of the hyphal habit in the Fungi.

    PubMed

    Dee, Jaclyn M; Mollicone, Marilyn; Longcore, Joyce E; Roberson, Robert W; Berbee, Mary L

    2015-01-01

    The evolution of filamentous hyphae underlies an astounding diversity of fungal form and function. We studied the cellular structure and evolutionary origins of the filamentous form in the Monoblepharidomycetes (Chytridiomycota), an early-diverging fungal lineage that displays an exceptional range of body types, from crescent-shaped single cells to sprawling hyphae. To do so, we combined light and transmission electron microscopic analyses of hyphal cytoplasm with molecular phylogenetic reconstructions. Hyphae of Monoblepharidomycetes lack a complex aggregation of secretory vesicles at the hyphal apex (i.e. Spitzenkörper), have centrosomes as primary microtubule organizing centers and have stacked Golgi cisternae instead of tubular/fenestrated Golgi equivalents. The cytoplasmic distribution of actin in Monoblepharidomycetes is comparable to the arrangement observed previously in other filamentous fungi. To discern the origins of Monoblepharidomycetes hyphae, we inferred a phylogeny of the fungi based on 18S and 28S ribosomal DNA sequence data with maximum likelihood and Bayesian inference methods. We focused sampling on Monoblepharidomycetes to infer intergeneric relationships within the class and determined 78 new sequences. Analyses showed class Monoblepharidomycetes to be monophyletic and nested within Chytridiomycota. Hyphal Monoblepharidomycetes formed a clade sister to the genera without hyphae, Harpochytrium and Oedogoniomyces. A likelihood ancestral state reconstruction indicated that hyphae arose independently within the Monoblepharidomycetes lineage and in at least two other lineages. Cytological differences among monoblepharidalean and other fungal hyphae are consistent with these convergent origins.

  13. Phylogeographic Structure of the White-Footed Mouse and the Deer Mouse, Two Lyme Disease Reservoir Hosts in Québec.

    PubMed

    Fiset, Jessica; Tessier, Nathalie; Millien, Virginie; Lapointe, Francois-Joseph

    2015-01-01

    Modification of a species range is one of many consequences of climate change and is driving the emergence of Lyme disease in eastern Canada. The primary reservoir host of the bacteria responsible for Lyme disease, Borrelia burgdorferi, is the white-footed mouse (Peromyscus leucopus), whose range is rapidly shifting north into southern Québec. The deer mouse, P. maniculatus, is occurring over most Québec province and is a less competent host for B. burgdorferi. Here, we compared the phylogeographic structure of both Peromyscus species in Québec. Using a combination of multiple mitochondrial DNA markers and phylogeographic methods, we detected an ongoing and rapid expansion of P. leucopus, while P. maniculatus appears more stable. Haplotype and populations networks indicated that populations of P. maniculatus exhibit more genetic structure than P. leucopus across the study area. Furthermore, significant and consistent genetic divergences between populations of the two species on both sides of the St. Lawrence River suggest that distinct lineages of P. leucopus and P. maniculatus with different ancestral origins colonized Southern Québec following the Last Glacial Maximum. The phylogeographic structure of pathogens is expected to mirror the structure observed in their reservoir hosts. As different strains of Borrelia burgdorferi may be associated with different levels of pathogenicity and immune responses of their hosts, our results are helpful at better understanding the pattern of spread of Lyme disease in a zone of emergence, and associated risk for human populations.

  14. Phylogeographic Structure of the White-Footed Mouse and the Deer Mouse, Two Lyme Disease Reservoir Hosts in Québec

    PubMed Central

    Fiset, Jessica; Tessier, Nathalie; Millien, Virginie; Lapointe, Francois-Joseph

    2015-01-01

    Modification of a species range is one of many consequences of climate change and is driving the emergence of Lyme disease in eastern Canada. The primary reservoir host of the bacteria responsible for Lyme disease, Borrelia burgdorferi, is the white-footed mouse (Peromyscus leucopus), whose range is rapidly shifting north into southern Québec. The deer mouse, P. maniculatus, is occurring over most Québec province and is a less competent host for B. burgdorferi. Here, we compared the phylogeographic structure of both Peromyscus species in Québec. Using a combination of multiple mitochondrial DNA markers and phylogeographic methods, we detected an ongoing and rapid expansion of P. leucopus, while P. maniculatus appears more stable. Haplotype and populations networks indicated that populations of P. maniculatus exhibit more genetic structure than P. leucopus across the study area. Furthermore, significant and consistent genetic divergences between populations of the two species on both sides of the St. Lawrence River suggest that distinct lineages of P. leucopus and P. maniculatus with different ancestral origins colonized Southern Québec following the Last Glacial Maximum. The phylogeographic structure of pathogens is expected to mirror the structure observed in their reservoir hosts. As different strains of Borrelia burgdorferi may be associated with different levels of pathogenicity and immune responses of their hosts, our results are helpful at better understanding the pattern of spread of Lyme disease in a zone of emergence, and associated risk for human populations. PMID:26633555

  15. 2  ×  2 multiple-input multiple-output optical-wireless integration system based on optical independent-sideband modulation enabled by an in-phase/quadrature modulator.

    PubMed

    Li, Xinying; Yu, Jianjun

    2016-07-01

    We propose a novel and simple 2×2 multiple-input multiple-output (MIMO) optical-wireless integration system, in which optical independent-sideband modulation enabled by an in-phase/quadrature (I/Q) modulator, instead of optical polarization multiplexing, is used to assist the simultaneous generation of two wireless millimeter-wave (mm-wave) signals. Software-based digital signal processing is used to generate the driving signal for the I/Q modulator, the output of which is two independent single-sideband optical vector signals located at two sides of a large central optical carrier. Based on our proposed 2×2 MIMO optical-wireless integration system, we experimentally demonstrate the simultaneous generation and 2×2 MIMO wireless delivery of two independent 40-GHz quadrature-phase-shift-keying (QPSK) wireless mm-wave signals. Each 40-GHz QPSK wireless mm-wave signal can carry up to 4-Gbaud transmitter data with a bit-error ratio less than the hard-decision forward-error-correction threshold of 3.8×10-3.

  16. Interpretation of Ocular Melanin Drug Binding Assays. Alternatives to the Model of Multiple Classes of Independent Sites.

    PubMed

    Manzanares, José A; Rimpelä, Anna-Kaisa; Urtti, Arto

    2016-04-04

    Melanin has a high binding affinity for a wide range of drugs. The determination of the melanin binding capacity and its binding affinity are important, e.g., in the determination of the ocular drug distribution, the prediction of drug effects in the eye, and the trans-scleral drug delivery. The binding parameters estimated from a given data set vary significantly when using different isotherms or different nonlinear fitting methods. In this work, the commonly used bi-Langmuir isotherm, which assumes two classes of independent sites, is confronted with the Sips isotherm. Direct, log-log, and Scatchard plots are used, and the interpretation of the binding curves in the latter is critically analyzed. In addition to the goodness of fit, the emphasis is placed on the physical meaning of the binding parameters. The bi-Langmuir model imposes a bimodal distribution of binding energies for the sites on the melanin granules, but the actual distribution is most likely continuous and unimodal, as assumed by the Sips isotherm. Hence, the latter describes more accurately the distribution of binding energies and also the experimental results of melanin binding to drugs and metal ions. Simulations are used to show that the existence of two classes of sites cannot be confirmed on the sole basis of the shape of the binding curve in the Scatchard plot, and that serious doubts may appear on the meaning of the binding parameters of the bi-Langmuir model. Experimental results of melanin binding to chloroquine and metoprolol are used to illustrate the importance of the choice of the binding isotherm and of the method used to evaluate the binding parameters.

  17. Recent independent emergence of multiple multidrug-resistant Serratia marcescens clones within the United Kingdom and Ireland

    PubMed Central

    Moradigaravand, Danesh; Boinett, Christine J.; Martin, Veronique; Peacock, Sharon J.; Parkhill, Julian

    2016-01-01

    Serratia marcescens, a member of the Enterobacteriaceae family, is a Gram-negative bacterium responsible for a wide range of nosocomial infections. The emergence of multidrug-resistant strains is an increasing danger to public health. To design effective means to control the dissemination of S. marcescens, an in-depth analysis of the population structure and variation is required. Utilizing whole-genome sequencing, we characterized the population structure and variation, as well as the antimicrobial resistance determinants, of a systematic collection of antimicrobial-resistant S. marcescens associated with bloodstream infections in hospitals across the United Kingdom and Ireland between 2001 and 2011. Our results show that S. marcescens is a diverse species with a high level of genomic variation. However, the collection was largely composed of a limited number of clones that emerged from this diverse background within the past few decades. We identified potential recent transmissions of these clones, within and between hospitals, and showed that they have acquired antimicrobial resistance determinants for different beta-lactams, ciprofloxacin, and tetracyclines on multiple occasions. The expansion of these multidrug-resistant clones suggests that the treatment of S. marcescens infections will become increasingly difficult in the future. PMID:27432456

  18. Ancient and Novel Small RNA Pathways Compensate for the Loss of piRNAs in Multiple Independent Nematode Lineages

    PubMed Central

    Sarkies, Peter; Selkirk, Murray E.; Jones, John T.; Blok, Vivian; Boothby, Thomas; Goldstein, Bob; Hanelt, Ben; Ardila-Garcia, Alex; Fast, Naomi M.; Schiffer, Phillip M.; Kraus, Christopher; Taylor, Mark J.; Koutsovoulos, Georgios; Blaxter, Mark L.; Miska, Eric A.

    2015-01-01

    Small RNA pathways act at the front line of defence against transposable elements across the Eukaryota. In animals, Piwi interacting small RNAs (piRNAs) are a crucial arm of this defence. However, the evolutionary relationships among piRNAs and other small RNA pathways targeting transposable elements are poorly resolved. To address this question we sequenced small RNAs from multiple, diverse nematode species, producing the first phylum-wide analysis of how small RNA pathways evolve. Surprisingly, despite their prominence in Caenorhabditis elegans and closely related nematodes, piRNAs are absent in all other nematode lineages. We found that there are at least two evolutionarily distinct mechanisms that compensate for the absence of piRNAs, both involving RNA-dependent RNA polymerases (RdRPs). Whilst one pathway is unique to nematodes, the second involves Dicer-dependent RNA-directed DNA methylation, hitherto unknown in animals, and bears striking similarity to transposon-control mechanisms in fungi and plants. Our results highlight the rapid, context-dependent evolution of small RNA pathways and suggest piRNAs in animals may have replaced an ancient eukaryotic RNA-dependent RNA polymerase pathway to control transposable elements. PMID:25668728

  19. Reciprocal translocations in grass pea (Lathyrus sativus L.): pattern of transmission, detection of multiple interchanges and their independence.

    PubMed

    Talukdar, Dibyendu

    2010-01-01

    Grass pea (Lathyrus sativus L.) is a diploid crop having 2n = 14 chromosomes. Four different plant types, heterozygous for reciprocal translocation (RT), RT-1, RT-2, RT-3, and RT-4 showing pollen semisterility, were isolated in induced mutant population of three varieties of grass pea. Transmission rate of these 4 translocations was studied in advanced selfed and intercrossed progenies, whereas multiple chromosomal interchanges were detected by the pattern of chromosomal ring formation at meiosis I in the F(1) progeny of RTxRT. RT transmitted at an average of 48.89% in selfed progeny and along with normal plants, RT and translocation homozygotes produced some trisomic plants in the segregation progeny. RT-3 showing maximum frequency (68.20%) of zig-zag or alternate chromosome orientation exhibited highest transmission (55.20%). Presence of a ring of 6 or 2 rings of 4 chromosomes in F(1) double heterozygotes obtained from RTxRT suggested involvement of one common chromosome in translocations of RT-1, RT-2, and RT-4 but a different one in common between RT-2 and RT-3. No common chromosome, however, was shared by RT-3 and RT-4. Thus, 5 out of 7 chromosomes are involved in the present RTs, and one of the translocated chromosomes in RT-1 line was always associated with nucleolar organizing region.

  20. Distribution and presentation of Lyme borreliosis in Scotland - analysis of data from a national testing laboratory.

    PubMed

    Mavin, S; Watson, E J; Evans, R

    2015-01-01

    This study examines the distribution of laboratory-confirmed cases of Lyme borreliosis in Scotland and the clinical spectrum of presentations within NHS Highland. Methods General demographic data (age/sex/referring Health Board) from all cases of Lyme borreliosis serologically confirmed by the National Lyme Borreliosis Testing Laboratory from 1 January 2008 to 31 December 2013 were analysed. Clinical features of confirmed cases were ascertained from questionnaires sent to referring clinicians within NHS Highland during the study period. Results The number of laboratory-confirmed cases of Lyme borreliosis in Scotland peaked at 440 in 2010. From 2008 to 2013 the estimated average annual incidence was 6.8 per 100,000 (44.1 per 100,000 in NHS Highland). Of 594 questionnaires from NHS Highland patients: 76% had clinically confirmed Lyme borreliosis; 48% erythema migrans; 17% rash, 25% joint, 15% neurological and 1% cardiac symptoms. Only 61% could recall a tick bite. Conclusion The incidence of Lyme borreliosis may be stabilising in Scotland but NHS Highland remains an area of high incidence. Lyme borreliosis should be considered in symptomatic patients that have had exposure to ticks and not just those with a definite tick bite.

  1. Susceptibility, likelihood to be diagnosed, worry and fear for contracting Lyme disease.

    PubMed

    Fogel, Joshua; Chawla, Gurasees S

    Risk perception and psychological concerns are relevant for understanding how people view Lyme disease. This study investigates the four separate outcomes of susceptibility, likelihood to be diagnosed, worry, and fear for contracting Lyme disease. University students (n=713) were surveyed about demographics, perceived health, Lyme disease knowledge, Lyme disease preventive behaviors, Lyme disease history, and Lyme disease miscellaneous variables. We found that women were associated with increased susceptibility and fear. Asian/Asian-American race/ethnicity was associated with increased worry and fear. Perceived good health was associated with increased likelihood to be diagnosed, worry, and fear. Correct knowledge was associated with increased susceptibility and likelihood to be diagnosed. Those who typically spend a lot of time outdoors were associated with increased susceptibility, likelihood to be diagnosed, worry, and fear. In conclusion, healthcare providers and public health campaigns should address susceptibility, likelihood to be diagnosed, worry, and fear about Lyme disease, and should particularly target women and Asians/Asian-Americans to address any possible misconceptions and/or offer effective coping strategies.

  2. Chronic Lyme borreliosis in the laboratory mouse.

    PubMed Central

    Barthold, S. W.; de Souza, M. S.; Janotka, J. L.; Smith, A. L.; Persing, D. H.

    1993-01-01

    C3H/HeJ mice were inoculated intraperitoneally with 10(7) uncloned Borrelia burgdorferi at 4 weeks of age and examined on days 30, 90, 180, and 360. Spirochetes were isolated from multiple tissues at all intervals. Joint and heart disease were present in all mice at 30 days and resolved after 90 days. At 180 and 360 days, some mice had mild recurrent joint and heart disease, and most had peripheral segmental periarteritis. The protein electrophoretic migration of 360-day isolates differed from the original inoculum. The experiment was repeated with C3H/HeN and BALB/cByJ mice inoculated intradermally with 10(4) cloned B. burgdorferi. Characterization of infection and disease at 180 and 360 days were similar to those of the first experiment, but spirochetal proteins of isolates from both intervals displayed no protein variation in electrophoretic mobilities. Spirochetes isolated at 360 days were fully pathogenic in naive mice. Sera from infected mice showed an initial immunoglobulin M response, followed by a sustained immunoglobulin G response, involving IgG1, IgG2a, IgG2b and IgG3, with expanding reactivity against multiple antigens over time. These results indicate that immunocompetent mice sustain persistent infections and develop early acute joint and heart lesions that resolve and then recur intermittently. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:8362988

  3. Hemifacial Spasm From Lyme Disease: Antibiotic Treatment Points to the Cause.

    PubMed

    LeWitt, Tessa M

    A wide range of etiologies can cause hemifacial spasm (HFS), including infection. In this case report, a 44-year-old woman developed HFS and was explored surgically 7 years later. No abnormalities were found. Afterward, treatment of a surgical wound infection with an oral cephalosporin resulted in a temporary HFS remission that had never occurred previously. This antibiotic experience prompted further workup for an underlying infection, which ultimately led to diagnosis of Lyme disease. Presentation of HFS due to Lyme disease has not been reported. Because its diagnosis can be occult and antibiotic therapy can be both diagnostic and therapeutic, Lyme disease should be a consideration for cases of HFS.

  4. A critical appraisal of the mild axonal peripheral neuropathy of late neurologic Lyme disease.

    PubMed

    Wormser, Gary P; Strle, Franc; Shapiro, Eugene D; Dattwyler, Raymond J; Auwaerter, Paul G

    2017-02-01

    In older studies, a chronic distal symmetric sensory neuropathy was reported as a relatively common manifestation of late Lyme disease in the United States. However, the original papers describing this entity had notable inconsistencies and certain inexplicable findings, such as reports that this condition developed in patients despite prior antibiotic treatment known to be highly effective for other manifestations of Lyme disease. More recent literature suggests that this entity is seen rarely, if at all. A chronic distal symmetric sensory neuropathy as a manifestation of late Lyme disease in North America should be regarded as controversial and in need of rigorous validation studies before acceptance as a documented clinical entity.

  5. Whole-Genome Sequences of Two Borrelia afzelii and Two Borrelia garinii Lyme Disease Agent Isolates

    SciTech Connect

    Casjens, S.R.; Dunn, J.; Mongodin, E. F.; Qiu, W.-G.; Luft, B. J.; Fraser-Liggett, C. M.; Schutzer, S. E.

    2011-12-01

    Human Lyme disease is commonly caused by several species of spirochetes in the Borrelia genus. In Eurasia these species are largely Borrelia afzelii, B. garinii, B. burgdorferi, and B. bavariensis sp. nov. Whole-genome sequencing is an excellent tool for investigating and understanding the influence of bacterial diversity on the pathogenesis and etiology of Lyme disease. We report here the whole-genome sequences of four isolates from two of the Borrelia species that cause human Lyme disease, B. afzelii isolates ACA-1 and PKo and B. garinii isolates PBr and Far04.

  6. Whole-genome sequences of two Borrelia afzelii and two Borrelia garinii Lyme disease agent isolates.

    PubMed

    Casjens, Sherwood R; Mongodin, Emmanuel F; Qiu, Wei-Gang; Dunn, John J; Luft, Benjamin J; Fraser-Liggett, Claire M; Schutzer, Steve E

    2011-12-01

    Human Lyme disease is commonly caused by several species of spirochetes in the Borrelia genus. In Eurasia these species are largely Borrelia afzelii, B. garinii, B. burgdorferi, and B. bavariensis sp. nov. Whole-genome sequencing is an excellent tool for investigating and understanding the influence of bacterial diversity on the pathogenesis and etiology of Lyme disease. We report here the whole-genome sequences of four isolates from two of the Borrelia species that cause human Lyme disease, B. afzelii isolates ACA-1 and PKo and B. garinii isolates PBr and Far04.

  7. Health Care Costs, Utilization and Patterns of Care following Lyme Disease

    PubMed Central

    Adrion, Emily R.; Aucott, John; Lemke, Klaus W.; Weiner, Jonathan P.

    2015-01-01

    Background Lyme disease is the most frequently reported vector borne infection in the United States. The Centers for Disease Control have estimated that approximately 10% to 20% of individuals may experience Post-Treatment Lyme Disease Syndrome – a set of symptoms including fatigue, musculoskeletal pain, and neurocognitive complaints that persist after initial antibiotic treatment of Lyme disease. Little is known about the impact of Lyme disease or post-treatment Lyme disease symptoms (PTLDS) on health care costs and utilization in the United States. Objectives 1) to examine the impact of Lyme disease on health care costs and utilization, 2) to understand the relationship between Lyme disease and the probability of developing PTLDS, 3) to understand how PTLDS may impact health care costs and utilization. Methods This study utilizes retrospective data on medical claims and member enrollment for persons aged 0-64 years who were enrolled in commercial health insurance plans in the United States between 2006-2010. 52,795 individuals treated for Lyme disease were compared to 263,975 matched controls with no evidence of Lyme disease exposure. Results Lyme disease is associated with $2,968 higher total health care costs (95% CI: 2,807-3,128, p<.001) and 87% more outpatient visits (95% CI: 86%-89%, p<.001) over a 12-month period, and is associated with 4.77 times greater odds of having any PTLDS-related diagnosis, as compared to controls (95% CI: 4.67-4.87, p<.001). Among those with Lyme disease, having one or more PTLDS-related diagnosis is associated with $3,798 higher total health care costs (95% CI: 3,542-4,055, p<.001) and 66% more outpatient visits (95% CI: 64%-69%, p<.001) over a 12-month period, relative to those with no PTLDS-related diagnoses. Conclusions Lyme disease is associated with increased costs above what would be expected for an easy to treat infection. The presence of PTLDS-related diagnoses after treatment is associated with significant health care

  8. Action potential-independent and nicotinic receptor-mediated concerted release of multiple quanta at hippocampal CA3-mossy fiber synapses.

    PubMed

    Sharma, Geeta; Grybko, Michael; Vijayaraghavan, Sukumar

    2008-03-05

    Presynaptic action potential-independent transmitter release is a potential means of information transfer across synapses. We show that in the hippocampal mossy fiber boutons, activation of the alpha7-subtype of nicotinic acetylcholine receptors (alpha7-nAChRs) results in a large increase in the amplitude of spontaneous events, resulting from concerted release of multiple quanta from the mossy fiber boutons. This amplitude increase is abolished at low temperatures. Activation of alpha7-nAChRs causes a rise in intraterminal calcium at mossy fiber boutons, involving ryanodine receptors. Regulation of concerted release requires the subsequent activation of presynaptic calcium/calmodulin-dependent protein kinase II (CaMKII). Activation of CaMKII is required to drive presynaptic action potential-independent transmission at the mossy fiber-CA3 pyramidal cell synapse. The effects of alpha7-nAChR activation are mediated by biologically relevant doses of nicotine. Our results demonstrate a novel form of synaptic plasticity mediated by presynaptic alpha7-nAChRs and store calcium that is temporally different and might respond to a different history of synaptic activity than that mediated by incoming action potentials.

  9. Dynamic nature of the proximal AZFc region of the human Y chromosome: multiple independent deletion and duplication events revealed by microsatellite analysis.

    PubMed

    Balaresque, Patricia; Bowden, Georgina R; Parkin, Emma J; Omran, Ghada A; Heyer, Evelyne; Quintana-Murci, Lluis; Roewer, Lutz; Stoneking, Mark; Nasidze, Ivan; Carvalho-Silva, Denise R; Tyler-Smith, Chris; de Knijff, Peter; Jobling, Mark A

    2008-10-01

    The human Y chromosome shows frequent structural variants, some of which are selectively neutral, while others cause impaired fertility due to the loss of spermatogenic genes. The large-scale use of multiple Y-chromosomal microsatellites in forensic and population genetic studies can reveal such variants, through the absence or duplication of specific markers in haplotypes. We describe Y chromosomes in apparently normal males carrying null and duplicated alleles at the microsatellite DYS448, which lies in the proximal part of the azoospermia factor c (AZFc) region, important in spermatogenesis, and made up of "ampliconic" repeats that act as substrates for nonallelic homologous recombination (NAHR). Physical mapping in 26 DYS448 deletion chromosomes reveals that only three cases belong to a previously described class, representing independent occurrences of an approximately 1.5-Mb deletion mediated by recombination between the b1 and b3 repeat units. The remainder belong to five novel classes; none appears to be mediated through homologous recombination, and all remove some genes, but are likely to be compatible with normal fertility. A combination of deletion analysis with binary-marker and microsatellite haplotyping shows that the 26 deletions represent nine independent events. Nine DYS448 duplication chromosomes can be explained by four independent events. Some lineages have risen to high frequency in particular populations, in particular a deletion within haplogroup (hg) C(*)(xC3a,C3c) found in 18 Asian males. The nonrandom phylogenetic distribution of duplication and deletion events suggests possible structural predisposition to such mutations in hgs C and G.

  10. Making sense of unfamiliar risks in the countryside: the case of Lyme disease.

    PubMed

    Marcu, Afrodita; Uzzell, David; Barnett, Julie

    2011-05-01

    The focus of this paper is on how popular representations of the countryside provide countryside users with a discursive framework to make sense of unfamiliar countryside-based risks, taking Lyme disease as an example. Sixty-six semi-structured interviews were conducted with 82 visitors in Richmond Park, New Forest, and Exmoor National Park in the UK. The data were analysed using thematic analysis and was informed by social representations theory. The analysis indicated that a lay understanding of the risk of Lyme disease was filtered by place-attachment and the social representations of the countryside. Lyme disease was not understood primarily as a risk to health, but was instead constructed as a risk to the social and restorative practices in the context of the countryside. The findings suggest that advice about zoonoses such as Lyme disease is unlikely to cause panic, and that it should focus on the least intrusive preventative measures.

  11. Testing practices and volume of non-Lyme tickborne diseases in the United States.

    PubMed

    Connally, Neeta P; Hinckley, Alison F; Feldman, Katherine A; Kemperman, Melissa; Neitzel, David; Wee, Siok-Bi; White, Jennifer L; Mead, Paul S; Meek, James I

    2016-02-01

    Large commercial laboratories in the United States were surveyed regarding the number of specimens tested for eight tickborne diseases in 2008. Seven large commercial laboratories reported testing a total of 2,927,881 specimens nationally (including Lyme disease). Of these, 495,585 specimens (17%) were tested for tickborne diseases other than Lyme disease. In addition to large commercial laboratories, another 1051 smaller commercial, hospital, and government laboratories in four states (CT, MD, MN, and NY) were surveyed regarding tickborne disease testing frequency, practices, and results. Ninety-two of these reported testing a total of 10,091 specimens for four tickborne diseases other than Lyme disease. We estimate the cost of laboratory diagnostic testing for non-Lyme disease tickborne diseases in 2008 to be $9.6 million. These data provide a baseline to evaluate trends in tickborne disease test utilization and insight into the burden of these diseases.

  12. Current Guidelines, Common Clinical Pitfalls, and Future Directions for Laboratory Diagnosis of Lyme Disease, United States

    PubMed Central

    Moore, Andrew; Nelson, Christina; Molins, Claudia; Mead, Paul

    2016-01-01

    In the United States, Lyme disease is caused by Borrelia burgdorferi and transmitted to humans by blacklegged ticks. Patients with an erythema migrans lesion and epidemiologic risk can receive a diagnosis without laboratory testing. For all other patients, laboratory testing is necessary to confirm the diagnosis, but proper interpretation depends on symptoms and timing of illness. The recommended laboratory test in the United States is 2-tiered serologic analysis consisting of an enzyme-linked immunoassay or immunofluorescence assay, followed by reflexive immunoblotting. Sensitivity of 2-tiered testing is low (30%–40%) during early infection while the antibody response is developing (window period). For disseminated Lyme disease, sensitivity is 70%–100%. Specificity is high (>95%) during all stages of disease. Use of other diagnostic tests for Lyme disease is limited. We review the rationale behind current US testing guidelines, appropriate use and interpretation of tests, and recent developments in Lyme disease diagnostics. PMID:27314832

  13. A steroid-independent regimen of bortezomib, liposomal doxorubicin and thalidomide demonstrate high response rates in newly diagnosed multiple myeloma patients

    PubMed Central

    Sher, Taimur; Ailawadhi, Sikander; Miller, Kena C.; Manfredi, Debbie; Wood, Margaret; Tan, Wei; Wilding, Gregory; Czuczman, Myron S.; Hernandez-Ilizaliturri, Francisco J.; Hong, Fredrick; Sood, Raman; Soniwala, Saif; Lawrence, William; Jamshed, Saad; Masood, Aisha; Iancu, Daniel; Lee, Kelvin; Chanan-Khan, Asher

    2014-01-01

    Novel agents have provided new a foundation for multiple myeloma therapies. When combined with other anti-myeloma agents, these compounds significantly enhance clinical efficacy. High-dose steroids are frequently used in anti-myeloma combination regimens; however, the doses employed are often poorly tolerated, especially in patients with concurrent comorbid conditions. We hypothesized that a steroid-independent combination regimen could be developed without significant compromise of efficacy. The availability of such a regimen will be important for patients whose concurrent ailments make them poor candidates for steroid containing anti-myeloma regimens. A phase II single institute, non-randomized clinical trial was conducted to investigate a novel steroid-free three-drug combination of bortezomib (V), pegylated liposomal doxorubicin (D), and thalidomide (T), the VDT regimen. Forty-three newly diagnosed multiple myeloma patients requiring treatment were enrolled on this study. The overall response rate and complete response (CR) + near complete response (nCR) rate was 78% and 35%, respectively. Median time to progression was 29.5 months. Fatigue, rash, neuropathy, constipation and infections were the most common side effects. We concluded that VDT is a tolerable and an effective regimen capable of inducing high response rates and can be employed in patients considered to be poor candidates for steroid-based treatment regimens. PMID:21554260

  14. Experiences of patients identifying with chronic Lyme disease in the healthcare system: a qualitative study

    PubMed Central

    2014-01-01

    Background Chronic Lyme disease is a term that describes a constellation of persistent symptoms in patients with or without evidence of previous Borrelia burgdorferi infection. Patients labeled as having chronic Lyme disease have a substantial clinical burden. Little is known about chronic Lyme disease patient experiences in the healthcare system and their relationships with healthcare providers. The purpose of this study was to gather insights about the experiences of patients who carry a diagnosis of chronic Lyme disease in the United States healthcare system. Methods Qualitative, phenomenological study in 12 adult participants who identified themselves as having chronic Lyme disease. Semi-structured face-to-face in-depth interviews were conducted, 60–90 minutes in length, focusing on perceptions of disease burden and of their healthcare providers, using the dimensions of the Health Belief Model. Transcribed interviews were analyzed for emergent topics and themes in the categories of beliefs/understanding, personal history/narrative, consequences/limitations, management, and influences on care. Results Enrollment continued until theoretical saturation was obtained. Four major themes emerged from participants’ descriptions of their experiences and perceptions: 1) changes in health status and the social impact of chronic Lyme disease, 2) doubts about recovery and the future, 3) contrasting doctor-patient relationships, 4) and the use of unconventional therapies to treat chronic Lyme disease. Conclusions Participants reported a significant decline in health status associated with chronic Lyme disease and were often unsatisfied with care in conventional settings. Negative experiences were associated with reports of dismissive, patronizing, and condescending attitudes. Positive experiences were associated with providers who were reported to be attentive, optimistic, and supportive. Consultations with CAM practitioners and use of CAM therapies were common. Actively

  15. Lyme Carditis: An Interesting Trip to Third-Degree Heart Block and Back

    PubMed Central

    Marmoush, Fady; Rehman, Mobeen Ur; Gorsi, Umama; Yammine, Joseph F.

    2016-01-01

    Carditis is an uncommon presentation of the early disseminated phase of Lyme disease. We present the case of a young female who presented with erythema migrans and was found to have first-degree heart block which progressed to complete heart block within hours. After receiving ceftriaxone, there was complete resolution of the heart block in sequential fashion. Our case illustrates the importance of early recognition and anticipation of progressive cardiac conduction abnormalities in patients presenting with Lyme disease. PMID:27891258

  16. Detection of borreliae in archived sera from patients with clinically suspect Lyme disease.

    PubMed

    Lee, Sin Hang; Vigliotti, Jessica S; Vigliotti, Veronica S; Jones, William; Shearer, David M

    2014-03-11

    The diagnoses of Lyme disease based on clinical manifestations, serological findings and detection of infectious agents often contradict each other. We tested 52 blind-coded serum samples, including 20 pre-treatment and 12 post-treatment sera from clinically suspect Lyme disease patients, for the presence of residual Lyme disease infectious agents, using nested PCR amplification of a signature segment of the borrelial 16S ribosomal RNA gene for detection and direct DNA sequencing of the PCR amplicon for molecular validation. These archived sera were split from the samples drawn for the 2-tier serology tests performed by a CDC-approved laboratory, and are used as reference materials for evaluating new diagnostic reagents. Of the 12 post-treatment serum samples, we found DNA evidence of a novel borrelia of uncertain significance in one, which was also positive for the 2-tier serology test. The rest of the post-treatment sera and all 20 control sera were PCR-negative. Of the 20 pre-treatment sera from clinically suspect early Lyme disease patients, we found Borrelia miyamotoi in one which was 2-tier serology-negative, and a Borrelia burgdorferi in two-one negative and one positive for 2-tier serology. We conclude that a sensitive and reliable DNA-based test is needed to support the diagnosis of Lyme disease and Lyme disease-like borreliosis.

  17. Differences and similarities between culture-confirmed human granulocytic anaplasmosis and early lyme disease.

    PubMed

    Wormser, Gary P; Aguero-Rosenfeld, Maria E; Cox, Mary E; Nowakowski, John; Nadelman, Robert B; Holmgren, Diane; McKenna, Donna; Bittker, Susan; Zentmaier, Lois; Cooper, Denise; Liveris, Dionysios; Schwartz, Ira; Horowitz, Harold W

    2013-03-01

    Lyme disease is transmitted by the bite of certain Ixodes ticks, which can also transmit Anaplasma phagocytophilum, the cause of human granulocytic anaplasmosis (HGA). Although culture can be used to identify patients infected with A. phagocytophilum and is the microbiologic gold standard, few studies have evaluated culture-confirmed patients with HGA. We conducted a prospective study in which blood culture was used to detect HGA infection in patients with a compatible clinical illness. Early Lyme disease was defined by the presence of erythema migrans. The epidemiologic, clinical, and laboratory features of 44 patients with culture-confirmed HGA were compared with those of a convenience sample of 62 patients with early Lyme disease. Coinfected patients were excluded. Patients with HGA had more symptoms (P = 0.003) and had a higher body temperature on presentation (P < 0.001) than patients with early Lyme disease. HGA patients were also more likely to have a headache, dizziness, myalgias, abdominal pain, anorexia, leukopenia, lymphopenia, thrombocytopenia, or elevated liver enzymes. A direct correlation between the number of symptoms and the duration of illness at time of presentation (rho = 0.389, P = 0.009) was observed for HGA patients but not for patients with Lyme disease. In conclusion, although there are overlapping features, culture-confirmed HGA is a more severe illness than early Lyme disease.

  18. Seroprevalence of Lyme disease and associated risk factors in rural population of Beijing.

    PubMed

    Dou, Xiangfeng; Lyu, Yanning; Jiang, Yi; Tian, Lili; Li, Xinyu; Lin, Changying; Sun, Yulan; Guan, Zengzhi; Zhang, Xiuchun; Wang, Quanyi

    2015-01-01

    A seroepidemiological survey of 801 local residents from 28 villages was conducted to assess the seroprevalence of Lyme disease and to identify the risk factors of becoming seropositive for Lyme disease in the northern suburb of Beijing. Forty-one serum samples were positive for IgG against B burgdorferi and the seroprevalence was 5.1% (41/801), indicating that Lyme disease is endemic in the rural population. In the multivariable analysis, sowing and harvesting in summer (OR, 2.377, 95% CI, 1.233-4.583), weed in the yard (OR, 1.914, 95% CI, 1.003-3.655) were positively associated with Lyme disease, while wearing protective clothes (OR, 0.173, 95% CI, 0.041-0.732) was negatively associated with Lyme disease. People living in the area are easily infected just near the house or in the cropland. They were barely diagnosed and cured. Without clear tick knowledge, the people are at high risk of exposure to tick bite and Lyme disease.

  19. An Examination of the Demographic and Environmental Variables Correlated with Lyme Disease Emergence in Virginia.

    PubMed

    Seukep, Sara E; Kolivras, Korine N; Hong, Yili; Li, Jie; Prisley, Stephen P; Campbell, James B; Gaines, David N; Dymond, Randel L

    2015-12-01

    Lyme disease is the United States' most significant vector-borne illness. Virginia, on the southern edge of the disease's currently expanding range, has experienced an increase in Lyme disease both spatially and temporally, with steadily increasing rates over the past decade and disease spread from the northern to the southwestern part of the state. This study used a Geographic Information System and a spatial Poisson regression model to examine correlations between demographic and land cover variables, and human Lyme disease from 2006 to 2010 in Virginia. Analysis indicated that herbaceous land cover is positively correlated with Lyme disease incidence rates. Areas with greater interspersion between herbaceous and forested land were also positively correlated with incidence rates. In addition, income and age were positively correlated with incidence rates. Levels of development, interspersion of herbaceous and developed land, and population density were negatively correlated with incidence rates. Abundance of forest fragments less than 2 hectares in area was not significantly correlated. Our results support some findings of previous studies on ecological variables and Lyme disease in endemic areas, but other results have not been found in previous studies, highlighting the potential contribution of new variables as Lyme disease continues to emerge southward.

  20. Bedrock Geologic Map of the Old Lyme Quadrangle, New London and Middlesex Counties, Connecticut

    USGS Publications Warehouse

    Walsh, Gregory J.; Scott, Robert B.; Aleinikoff, John N.; Armstrong, Thomas R.

    2009-01-01

    The bedrock geology of the Old Lyme quadrangle consists of Neoproterozoic and Permian gneisses and granites of the Gander and Avalon terranes, Silurian metasedimentary rocks of the Merrimack terrane, and Silurian to Devonian metasedimentary rocks of uncertain origin. The Avalon terrane rocks crop out within the Selden Neck block, and the Gander terrane rocks crop out within the Lyme dome. The Silurian to Devonian rocks crop out between these two massifs. Previous mapping in the Old Lyme quadrangle includes the work by Lawrence Lundgren, Jr. Lundgren's work provides an excellent resource for rock descriptions and detailed modal analyses of rock units that will not be duplicated in this current report. New research that was not covered in detail by Lundgren is the focus of this report and includes (1) evaluation of the rocks in the core of the Lyme dome in an effort to subdivide units in this area; (2) structural analysis of foliations and folds in and around the Lyme dome; (3) geochronology of selected units within the Lyme dome; and (4) analysis of joints and the fracture properties of the rocks.

  1. TGF-β1 of no avail as prognostic marker in lyme disease.

    PubMed

    Schumann, Julia

    2014-01-01

    Background. Within the present in vivo study using the wild type mouse strains C3H/HeN and FVB/N it was intended to (1) measure TGF-β1 expression in the course of lyme disease, (2) examine the potential correlation of TGF-β1 expression with the clinical outcome of a Borrelia infection (with a focus on lyme arthritis), (3) develop a diagnostic tool based on the endogenous factor TGF-β1 to predict the progressivity of lyme disease. Findings. In the course of lyme disease there was an increase in the serum content of active TGF-β1, which became significant 56 days post infection (p < 0.001). The serum concentration of total TGF-β1 in the course of infection initially decreased then rebounded and subsequently dropped again. Despite considerable individual variations in active TGF-β1 serum concentrations there were no identifiable dissimilarities in the clinical appearance of the mice. Likewise, no correlation could be seen between the serum content of active TGF-β1 and the severity of lyme arthritis of tibiotarsal joints of infected mice. Conclusions. The present study clearly shows that TGF-β1 is of no avail as prognostic marker in lyme disease. Hence, the search for an endogenous predictive factor, which can be determined in an easy and reliable manner, remains open.

  2. Epidemiological and clinical features of 1,149 persons with Lyme disease identified by laboratory-based surveillance in Connecticut.

    PubMed Central

    Petersen, L. R.; Sweeney, A. H.; Checko, P. J.; Magnarelli, L. A.; Mshar, P. A.; Gunn, R. A.; Hadler, J. L.

    1989-01-01

    Laboratory-based surveillance of Lyme disease in Connecticut during 1984 and 1985 identified 3,098 persons with suspected Lyme disease; 1,149 were defined as cases. Lyme disease incidence in Connecticut towns ranged from none to 1,407 cases per 100,000 population in 1985. A comparison of 1985 data with data from 1977 epidemiologic studies indicated that incidence increased by 129 percent to 453 percent in towns previously known to be endemic for Lyme disease and that Lyme disease had spread northward into towns thought to be free of Lyme disease in 1977. Children aged five to 14 years had the highest incidence. Of persons with Lyme disease, 83 percent had erythema migrans, 24 percent had arthritis, 8 percent had neurologic sequelae, and 2 percent had cardiac sequelae. The distribution of symptoms was age-dependent: case-persons less than 20 years old were almost twice as likely to have arthritis than older case-persons (35 percent versus 18 percent). Of persons with arthritis, 92 percent of those less than 20 years of age, compared to 68 percent of older persons, did not have antecedent erythema migrans. We conclude that Lyme disease is increasing in incidence and geographic distribution in Connecticut. Of those with Lyme disease, children may be more likely than adults to develop arthritis and have it as their first major disease manifestation. PMID:2683415

  3. Endotoxin-like activity associated with Lyme disease Borrelia.

    PubMed

    Fumarola, D; Munno, I; Marcuccio, C; Miragliotta, G

    1986-12-01

    The newly recognized spirochete, Borrelia burgdorferi, the causative agent of Lyme Disease, has been examined for endotoxin-like activities as measured by the standard Farmacopea Ufficiale della Republica Italiana rabbit fever test and the Limulus amoebocyte lysate assay. The suspension of heat-killed microorganism caused a febrile response at a dose of 1 X 10(8) bacteria pro kilo. Similar results were obtained in the Limulus assay where the heat-killed spirochetes stimulated formation of solid clot until the concentration of 1 X 10(5) per ml. Both in pyrogen test and in Limulus assay heat-killed Escherichia coli exhibited a higher degree of potency. These results show that LD-Borrelia possess endotoxin-like activities which could help in understanding the pathogenesis of the clinical symptomatology of the disease.

  4. Erythema chronicum migrans and lyme arthritis: field study of ticks.

    PubMed

    Wallis, R C; Brown, S E; Kloter, K O; Main, A J

    1978-10-01

    Ticks were collected during 1977 in communities east of the Connecticut River where there was a high incidence of erythema chronicum migrans and Lyme arthritis and were compared with collections from a similar area 20 km west of the river where cases of the disease were rare. Ixodes scapularis was much more abundant on the east side than on the west. Immature I. scapularis were 13 times more abundant on white-footed mice (Peromyscus leucopus), and adult I. scapularis 16 times more abundant on white-tailed deer (Odocoileus virginianus) in the east than in the west communities. In addition, all active stages in the life cycle of this tick--larvae, nymphs, and adults--both males and females, were found on humans (mostly patients) in the east communities. Both nymphs and adults were abundant on dogs and cats in this area. Attempts to recover an etiologic agent from ticks were unsuccessful.

  5. Chronic Lyme disease: it's not all in our heads.

    PubMed Central

    Morgenstern, Robert G

    2003-01-01

    Those of us with chronic Lyme disease are not at all confused, as suggested by Sigal and Hassett (2002). We know from years of experience that we have real, specific symptoms that are usually painful and disabling and include severe headaches, crippling arthritis, and heart palpitations, which lead to serious heart disease. Many of us know that our symptoms are kept in check while we are on antibiotics, but they painfully reappear when the antibiotics are withdrawn. Just because the medical community cannot detect a specific causative bacterium and managed health care companies want to maximize profits doesn't mean that those of us afflicted with this terrible condition are delusional and not truly benefiting from antibiotic treatment. We are not all crazy; we are sick and we should not be required to prove it to get medical care. PMID:12573918

  6. The seroepidemiology of Lyme borreliosis in zoo animals in Germany.

    PubMed Central

    Stoebel, K.; Schoenberg, A.; Streich, W. J.

    2003-01-01

    We conducted the first seroepidemiological study to evaluate the exposure of zoo animals to Borrelia burgdorferi s.l. in German zoos and wildlife parks. A total of 1487 individuals representing 148 ungulate and carnivore species belonging to 19 families were examined using a non-species dependent ELISA. Specific antibodies were detected in 154 (10.4%) animals; 168 (11.3%) sera produced borderline results. The percentage of seropositive individuals was related to species and origin (zoo), and increased with age of the animals. Sex and season did not influence seroprevalence. Examination of 600 ticks (Ixodes ricinus; caught from vegetation in the zoos) by darkfield microscopy and indirect immunofluorescence technique revealed infection rates within the range typical for Central Europe. The results substantiate that there is an infection risk for zoo animals. A differential diagnosis of Lyme borreliosis should be taken into account in case of suspicious clinical symptoms and possible contact to ticks. PMID:14596540

  7. SUSPECTED LYME BORRELIOSIS IN A CAPTIVE ADULT CHIMPANZEE (PAN TROGLODYTES).

    PubMed

    Wack, Allison N; Holland, Cynthia J; Lopez, Job E; Schwan, Tom G; Bronson, Ellen

    2015-06-01

    An 18-yr-old female captive-born chimpanzee (Pan troglodytes) presented with an intermittent history of inappetence, lethargy, and lower limb stiffness. No notable abnormalities were found on exam or complete blood cell count and serum biochemistry analysis. Serologic testing was strongly positive via indirect fluorescent antibody testing and Western blot for Borrelia burgdorferi. Treatment with doxycycline was initiated, and a clinical response was seen within 1 wk. Convalescent serum exhibited an eightfold increase in titer. Serologic testing was performed on several conspecifics with banked serum; while some low positive titers were present and presumed indicative of past exposure, no titer was elevated to the extent of the affected chimpanzee during its course of disease. To the authors' knowledge, this is the first report of suspected Lyme borreliosis in a great ape species, and the case originates from an area of the United States with a high incidence of human borreliosis.

  8. Migratory Passerine Birds as Reservoirs of Lyme Borreliosis in Europe

    PubMed Central

    Comstedt, Pär; Bergström, Sven; Olsen, Björn; Garpmo, Ulf; Marjavaara, Lisette; Mejlon, Hans; Barbour, Alan G.

    2006-01-01

    To define the role of birds as reservoirs and disseminators of Borrelia spirochetes, we characterized tick infestation and reservoir competence of migratory passerine birds in Sweden. A total of 1,120 immature Ixodes ricinus ticks were removed from 13,260 birds and assayed by quantitative polymerase chain reaction (PCR) for Borrelia, followed by DNA sequencing for species and genotype identification. Distributions of ticks on birds were aggregated, presumably because of varying encounters with ticks along migratory routes. Lyme borreliosis spirochetes were detected in 160 (14%) ticks. Borrelia garinii was the most common species in PCR-positive samples and included genotypes associated with human infections. Infestation prevalence with infected ticks was 5 times greater among ground-foraging birds than other bird species, but the 2 groups were equally competent in transmitting Borrelia. Migratory passerine birds host epidemiologically important vector ticks and Borrelia species and vary in effectiveness as reservoirs on the basis of their feeding behavior. PMID:16836825

  9. Community ecology and disease risk: lizards, squirrels, and the Lyme disease spirochete in California, USA.

    PubMed

    Salkeld, Daniel J; Lane, Robert S

    2010-01-01

    Vector-borne zoonotic diseases are often maintained in complex transmission cycles involving multiple vertebrate hosts and their arthropod vectors. In the state of California, U.S.A., the spirochete Borrelia burgdorferi, which causes Lyme disease, is transmitted between vertebrate hosts by the western black-legged tick, Ixodes pacificus. Several mammalian species serve as reservoir hosts of the spirochete, but levels of tick infestation, reservoir competence, and Borrelia-infection prevalence vary widely among such hosts. Here, we model the host (lizards, Peromyscus mice, Californian meadow voles, dusky-footed wood rats, and western gray squirrels), vector, and pathogen community of oak woodlands in northwestern California to determine the relative importance of different tick hosts. Observed infection prevalence of B. burgdorferi in host-seeking I. pacificus nymphs was 1.8-5.3%, and our host-community model estimated an infection prevalence of 1.6-2.2%. The western gray squirrel (Sciurus griseus) was the only source of infected nymphs. Lizards, which are refractory to Borrelia infection, are important in feeding subadult ticks but reduce disease risk (nymphal infection prevalence). Species identity is therefore critical in understanding and determining the local disease ecology.

  10. Independent and joint associations between multiple measures of the built and social environment and physical activity in a multi-ethnic urban community.

    PubMed

    Schulz, Amy; Mentz, Graciela; Johnson-Lawrence, Vicki; Israel, Barbara A; Max, Paul; Zenk, Shannon N; Wineman, Jean; Marans, Robert W

    2013-10-01

    Physical activity is associated with reduced risk of a number of health outcomes, yet fewer than half of adults in the United States report recommended levels of physical activity. Analyses of structural characteristics of the built environment as correlates of physical activity have yielded mixed results. We examine associations between multiple aspects of urban neighborhood environments and physical activity in order to understand their independent and joint effects, with a focus on the extent to which the condition of the built environment and indicators of the social environment modify associations between structural characteristics and physical activity. We use data from a stratified, multi-stage proportional probability sample of 919 non-Hispanic Black, non-Hispanic White, and Hispanic adults in an urban community, observational data from their residential neighborhoods, and census data to examine independent and joint associations of structural characteristics (e.g., street network connectivity), their condition (e.g., sidewalk condition), and social environments (e.g., territoriality) with physical activity. Our findings suggest that sidewalk condition is associated with physical activity, above and beyond structural characteristics of the built environment. Associations between some structural characteristics of the built environment and physical activity were conditional upon street condition, physical deterioration, and the proportion of parks and playgrounds in good condition. We found modest support for the hypothesis that associations between structural characteristics and physical activity are modified by aspects of the social environment. Results presented here point to the value of and need for understanding and addressing the complexity of factors that contribute to the relationships between the built and social environments and physical activity, and in turn, obesity and co-morbidities. Bringing together urban planners, public health

  11. MO-C-17A-06: Online Adaptive Re-Planning to Account for Independent Motions Between Multiple Targets During Radiotherapy of Lung Cancer

    SciTech Connect

    Liu, F; Tai, A; Ahunbay, E; Gore, E; Johnstone, C; Li, X

    2014-06-15

    Purpose: To quantify interfractional independent motions between multiple targets in radiotherapy (RT) of lung cancer, and to study the dosimetric benefits of an online adaptive replanning method to account for these variations. Methods: Ninety five diagnostic-quality daily CTs acquired for 9 lung cancer patients treated with IGRT using an in-room CT (CTVision, Siemens) were analyzed. On each daily CT set, contours of the targets (GTV, CTV, or involved nodes) and organs at risk were generated by populating the planning contours using an auto-segmentation tool (ABAS, Elekta) with manual editing. For each patient, an IMRT plan was generated based on the planning CT with a prescription dose of 60 Gy in 2Gy fractions. Three plans were generated and compared for each daily CT set: an IGRT (repositioning) plan by copying the original plan with the required shifts, an online adaptive plan by rapidly modifying the aperture shapes and segment weights of the original plan to conform to the daily anatomy, and a new fully re-optimized plan based on the daily CT using a planning system (Panther, Prowess). Results: The daily deviations of the distance between centers of masses of the targets from the plans varied daily from -10 to 8 mm with an average −0.9±4.1 mm (one standard deviation). The average CTV V100 are 99.0±0.7%, 97.9±2.8%, 99.0±0.6%, and 99.1±0.6%, and the lung V20 Gy 928±332 cc, 944±315 cc, 917±300 cc, and 891±295 cc for the original, repositioning, adaptive, and re-optimized plans, respectively. Wilcoxon signed-rank tests show that the adaptive plans are statistically significantly better than the repositioning plans and comparable with the reoptimized plans. Conclusion: There exist unpredictable, interfractional, relative volume changes and independent motions between multiple targets during lung cancer RT which cannot be accounted for by the current IGRT repositioning but can be corrected by the online adaptive replanning method.

  12. Ceftiofur-Resistant Salmonella Strains Isolated from Dairy Farms Represent Multiple Widely Distributed Subtypes That Evolved by Independent Horizontal Gene Transfer

    PubMed Central

    Alcaine, S. D.; Sukhnanand, S. S.; Warnick, L. D.; Su, W.-L.; McGann, P.; McDonough, P.; Wiedmann, M.

    2005-01-01

    Salmonella is the leading cause of known food-borne bacterial infections in the United States, with an incidence rate of approximately 15 cases per 100,000 people. The rise of antimicrobial-resistant Salmonella subtypes, including the appearance of subtypes resistant to ceftriaxone, represents a particular concern. Ceftriaxone is used to treat invasive cases of Salmonella in children and is closely related to ceftiofur, an antibiotic commonly used to treat diseases of cattle. In order to develop a better understanding of the evolution and transmission of ceftiofur resistance in Salmonella, we characterized ceftiofur-resistant and -sensitive Salmonella isolates from seven New York dairy farms. A total of 39 isolates from these seven farms were analyzed for evolutionary relatedness (by DNA sequencing of the Salmonella genes fimA, manB, and mdh), antibiotic resistance profiles, and the presence of blaCMY-2, a beta-lactamase gene associated with resistance to cephalosporins. Our data indicate that (i) resistance to ceftriaxone and ceftiofur was highly correlated with the presence of blaCMY-2; (ii) ceftiofur-resistant Salmonella strains were geographically widespread, as shown by their isolation from farms located throughout New York State; (iii) ceftiofur-resistant Salmonella strains isolated from farms represent multiple distinct subtypes and evolutionary lineages, as determined by serotyping, DNA sequence typing, and antimicrobial-resistance profiles; and (iv) ceftiofur-resistant Salmonella strains evolved by multiple independent acquisitions of an identical blaCMY-2 allele and by clonal spread of ceftiofur-resistant subtypes. PMID:16189081

  13. Dusky salamanders (Desmognathus, Plethodontidae) from the Coastal Plain: multiple independent lineages and their bearing on the molecular phylogeny of the genus.

    PubMed

    Beamer, David A; Lamb, Trip

    2008-04-01

    Recent phylogenetic reassessment of the lungless salamanders (Plethodontidae) confirmed a major life-history reversal-from direct development to an aquatic larval stage-in the dusky salamanders (Desmognathus) of eastern North America. This reversal initiated high rates of lineage accumulation, reputedly generating the species richness and ecological breath that now characterize Desmognathus. Certain important aspects of the radiation, e.g., ecomorphological evolution, have been identified through intense sampling effort of Appalachian Highland lineages. However, the research preoccupation on montane species has left overlooked a significant component of dusky salamander distribution-the Coastal Plain. We present the first molecular phylogeny for Desmognathus to incorporate extensive coverage from the Atlantic and Gulf coastal plains. We examined 38 Coastal Plain populations in conjunction with 45 additional populations, representing 16 of the 19 nominal species. Bayesian analysis of 88 mitochondrial cox1 haplotypes diagnosed eight independent population lineages within the Coastal Plain, a number at odds with the region's three currently recognized species. Desmognathus has apparently experienced a complex biogeographic history in this physiographic region, one involving multiple invasions and several ecological transitions from lotic to lentic habitats.

  14. SMAC mimetic (JP1201) sensitizes non-small cell lung cancers to multiple chemotherapy agents in an IAP dependent but TNFα independent manner

    PubMed Central

    Greer, Rachel M.; Peyton, Michael; Larsen, Jill E.; Girard, Luc; Xie, Yang; Gazdar, Adi; Harran, Patrick; Wang, Lai; Brekken, Rolf A.; Wang, Xiaodong; Minna, John D.

    2012-01-01

    Inhibitors of apoptosis proteins (IAPs) are key regulators of apoptosis and are inhibited by the second mitocondrial activator of caspases (SMAC). Previously, a small subset of TNFα-expressing non-small cell lung cancers (NSCLCs) was found to be sensitive to SMAC mimetics alone. In this study we determined if a SMAC mimetic (JP1201) could sensitize non-responsive NSCLC cell lines to standard chemotherapy. We found that JP1201 sensitized NSCLCs to doxorubicin, erlotinib, gemcitabine, paclitaxel, vinorelbine, and the combination of carboplatin with paclitaxel in a synergistic manner at clinically achievable drug concentrations. Sensitization did not occur with platinum alone. Furthermore, sensitization was specific for tumor compared to normal lung epithelial cells, increased in NSCLCs harvested after chemotherapy treatment, and did not induce TNFα secretion. Sensitization also was enhanced in vivo with increased tumor inhibition and increased survival of mice carrying xenografts. These effects were accompanied by caspase 3, 4, and 9 activation, indicating that both mitochondrial and ER stress-induced apoptotic pathways are activated by the combination of vinorelbine and JP1201. Chemotherapies that induce cell death through the mitochondrial pathway required only inhibition of XIAP for sensitization, while chemotherapies that induce cell death through multiple apoptotic pathways required inhibition of cIAP1, cIAP2, and XIAP. Therefore, the data suggest that IAP-targeted therapy using a SMAC mimetic provides a new therapeutic strategy for synergistic sensitization of NSCLCs to standard chemotherapy agents, which appears to occur independently of TNFα secretion. PMID:22049529

  15. Climate change influences on the annual onset of Lyme disease in the United States.

    PubMed

    Monaghan, Andrew J; Moore, Sean M; Sampson, Kevin M; Beard, Charles B; Eisen, Rebecca J

    2015-07-01

    Lyme disease is the most commonly reported vector-borne illness in the United States. Lyme disease occurrence is highly seasonal and the annual springtime onset of cases is modulated by meteorological conditions in preceding months. A meteorological-based empirical model for Lyme disease onset week in the United States is driven with downscaled simulations from five global climate models and four greenhouse gas emissions scenarios to project the impacts of 21st century climate change on the annual onset week of Lyme disease. Projections are made individually and collectively for the 12 eastern States where >90% of cases occur. The national average annual onset week of Lyme disease is projected to become 0.4-0.5 weeks earlier for 2025-2040 (p<0.05), and 0.7-1.9 weeks earlier for 2065-2080 (p<0.01), with the largest shifts for scenarios with the highest greenhouse gas emissions. The more southerly mid-Atlantic States exhibit larger shifts (1.0-3.5 weeks) compared to the Northeastern and upper Midwestern States (0.2-2.3 weeks) by 2065-2080. Winter and spring temperature increases primarily cause the earlier onset. Greater spring precipitation and changes in humidity partially counteract the temperature effects. The model does not account for the possibility that abrupt shifts in the life cycle of Ixodes scapularis, the primary vector of the Lyme disease spirochete Borrelia burgdorferi in the eastern United States, may alter the disease transmission cycle in unforeseen ways. The results suggest 21st century climate change will make environmental conditions suitable for earlier annual onset of Lyme disease cases in the United States with possible implications for the timing of public health interventions.

  16. Climate change influences on the annual onset of Lyme disease in the United States

    PubMed Central

    Monaghan, Andrew J.; Moore, Sean M.; Sampson, Kevin M.; Beard, Charles B.; Eisen, Rebecca J.

    2015-01-01

    Lyme disease is the most commonly reported vector-borne illness in the United States. Lyme disease occurrence is highly seasonal and the annual springtime onset of cases is modulated by meteorological conditions in preceding months. A meteorological-based empirical model for Lyme disease onset week in the United States is driven with downscaled simulations from five global climate models and four greenhouse gas emissions scenarios to project the impacts of 21st century climate change on the annual onset week of Lyme disease. Projections are made individually and collectively for the 12 eastern States where >90% of cases occur. The national average annual onset week of Lyme disease is projected to become 0.4–0.5 weeks earlier for 2025–2040 (p < 0.05), and 0.7–1.9 weeks earlier for 2065–2080 (p < 0.01), with the largest shifts for scenarios with the highest greenhouse gas emissions. The more southerly mid-Atlantic States exhibit larger shifts (1.0–3.5 weeks) compared to the Northeastern and upper Midwestern States (0.2–2.3 weeks) by 2065–2080. Winter and spring temperature increases primarily cause the earlier onset. Greater spring precipitation and changes in humidity partially counteract the temperature effects. The model does not account for the possibility that abrupt shifts in the life cycle of Ixodes scapularis, the primary vector of the Lyme disease spirochete Borrelia burgdorferi in the eastern United States, may alter the disease transmission cycle in unforeseen ways. The results suggest 21st century climate change will make environmental conditions suitable for earlier annual onset of Lyme disease cases in the United States with possible implications for the timing of public health interventions. PMID:26025268

  17. Climate change influences on the annual onset of Lyme disease in the United States

    NASA Astrophysics Data System (ADS)

    Monaghan, A. J.; Moore, S. M.; Sampson, K. M.; Beard, C. B.; Eisen, R. J.

    2015-12-01

    Lyme disease is the most commonly reported vector-borne illness in the United States. Lyme disease occurrence is highly seasonal and the annual springtime onset of cases is modulated by meteorological conditions in preceding months. A meteorological-based empirical model for Lyme disease onset week in the United States is driven with downscaled simulations from five global climate models and four greenhouse gas emissions scenarios to project the impacts of 21st century climate change on the annual onset week of Lyme disease. Projections are made individually and collectively for the 12 eastern States where >90% of cases occur. The national average annual onset week of Lyme disease is projected to become 0.4-0.5 weeks earlier for 2025-2040 (p<0.05), and 0.7-1.9 weeks earlier for 2065-2080 (p<0.01), with the largest shifts for scenarios with the highest greenhouse gas emissions. The more southerly mid-Atlantic States exhibit larger shifts (1.0-3.5 weeks) compared to the Northeastern and upper Midwestern States (0.2-2.3 weeks) by 2065-2080. Winter and spring temperature increases primarily cause the earlier onset. Greater spring precipitation and changes in humidity partially counteract the temperature effects. The model does not account for the possibility that abrupt shifts in the life cycle of Ixodes scapularis, the primary vector of the Lyme disease spirochete Borrelia burgdorferi in the eastern United States, may alter the disease transmission cycle in unforeseen ways. The results suggest 21st century climate change will make environmental conditions suitable for earlier annual onset of Lyme disease cases in the United States with possible implications for the timing of public health interventions.

  18. Characteristics of seroconversion and implications for diagnosis of post-treatment Lyme disease syndrome: acute and convalescent serology among a prospective cohort of early Lyme disease patients.

    PubMed

    Rebman, Alison W; Crowder, Lauren A; Kirkpatrick, Allison; Aucott, John N

    2015-03-01

    Two-tier serology is often used to confirm a diagnosis of Lyme disease. One hundred and four patients with physician diagnosed erythema migrans rashes had blood samples taken before and after 3 weeks of doxycycline treatment for early Lyme disease. Acute and convalescent serologies for Borrelia burgdorferi were interpreted according to the 2-tier antibody testing criteria proposed by the Centers for Disease Control and Prevention. Serostatus was compared across several clinical and demographic variables both pre- and post-treatment. Forty-one patients (39.4%) were seronegative both before and after treatment. The majority of seropositive individuals on both acute and convalescent serology had a positive IgM western blot and a negative IgG western blot. IgG seroconversion on western blot was infrequent. Among the baseline variables included in the analysis, disseminated lesions (p < 0.0001), a longer duration of illness (p < 0.0001), and a higher number of reported symptoms (p = 0.004) were highly significantly associated with positive final serostatus, while male sex (p = 0.05) was borderline significant. This variability, and the lack of seroconversion in a subset of patients, highlights the limitations of using serology alone in identifying early Lyme disease. Furthermore, these findings underline the difficulty for rheumatologists in identifying a prior exposure to Lyme disease in caring for patients with medically unexplained symptoms or fibromyalgia-like syndromes.

  19. Multi-criteria decision analysis as an innovative approach to managing zoonoses: results from a study on Lyme disease in Canada

    PubMed Central

    2013-01-01

    Background Zoonoses are a growing international threat interacting at the human-animal-environment interface and call for transdisciplinary and multi-sectoral approaches in order to achieve effective disease management. The recent emergence of Lyme disease in Quebec, Canada is a good example of a complex health issue for which the public health sector must find protective interventions. Traditional preventive and control interventions can have important environmental, social and economic impacts and as a result, decision-making requires a systems approach capable of integrating these multiple aspects of interventions. This paper presents the results from a study of a multi-criteria decision analysis (MCDA) approach for the management of Lyme disease in Quebec, Canada. MCDA methods allow a comparison of interventions or alternatives based on multiple criteria. Methods MCDA models were developed to assess various prevention and control decision criteria pertinent to a comprehensive management of Lyme disease: a first model was developed for surveillance interventions and a second was developed for control interventions. Multi-criteria analyses were conducted under two epidemiological scenarios: a disease emergence scenario and an epidemic scenario. Results In general, we observed a good level of agreement between stakeholders. For the surveillance model, the three preferred interventions were: active surveillance of vectors by flagging or dragging, active surveillance of vectors by trapping of small rodents and passive surveillance of vectors of human origin. For the control interventions model, basic preventive communications, human vaccination and small scale landscaping were the three preferred interventions. Scenarios were found to only have a small effect on the group ranking of interventions in the control model. Conclusions MCDA was used to structure key decision criteria and capture the complexity of Lyme disease management. This facilitated the

  20. Risk of Lyme disease: perceptions of residents of a Lone Star tick-infested community.

    PubMed Central

    Armstrong, P. M.; Brunet, L. R.; Spielman, A.; Telford, S. R.

    2001-01-01

    BACKGROUND: Lone Star ticks (Amblyomma americanum) have been suggested as a vector of the agent of Lyme disease (Borrelia burgdorferi sensu lato) in the USA, based on associations with an infection manifesting mainly as erythema migrans. In laboratory experiments, however, they failed to transmit B. burgdorferi sensu stricto. METHODS: In this study, carried out from 1994 to 1996, we determined the seroprevalences of B. burgdorferi (1.2%), Ehrlichia chaffeensis (7%), E. phagocytophila (0%), Rickettsia rickettsii (0%), R. typhi (0%), Coxiella burneti (0%), Francisella tularensis (0%), and Babesia microti (0%) by standard serological methods for 325 residents (97% of the total population) of Gibson Island, coastal Maryland, USA, where 15% of the residents reported having had Lyme disease within a recent 5-year span. FINDINGS: Of the 167 seronegative individuals who were followed up prospectively for 235 person-years of observation, only 2 (0.85%) seroconverted for B. burgdorferi. Of 1556 ticks submitted from residents, 95% were identified as Lone Star ticks; only 3% were deer ticks (Ixodes dammini), the main American vector of Lyme disease. B. burgdorferi s.s. infected 20% of host-seeking immature deer ticks, and borreliae ("B. lonestari") were detected in 1-2% of Lone Star ticks. Erythema migrans was noted in 65% of self-reports of Lyme disease, but many such reports indicated that the rash was present while the tick was still attached, suggesting a reaction to the bite itself rather than true Lyme disease. Sera from individuals reporting Lyme disease generally failed to react to B. burgdorferi or any other pathogen antigens. CONCLUSION: The residents of Gibson Island had an exaggerated perception of the risk of Lyme disease because they were intensely infested with an aggressively human-biting and irritating nonvector tick. In addition, a Lyme disease mimic of undescribed etiology (named Masters' disease) seems to be associated with Lone Star ticks, and may confound

  1. Lyme Borreliosis: is there a preexisting (natural) variation in antimicrobial susceptibility among Borrelia burgdorferi strains?

    PubMed Central

    Hodzic, Emir

    2015-01-01

    The development of antibiotics changed the world of medicine and has saved countless human and animal lives. Bacterial resistance/tolerance to antibiotics have spread silently across the world and has emerged as a major public health concern. The recent emergence of pan-resistant bacteria can overcome virtually any antibiotic and poses a major problem for their successful control. Selection for antibiotic resistance may take place where an antibiotic is present in the skin, gut, and other tissues of humans and animals and in the environment. Borrelia burgdorferi, the etiological agents of Lyme borreliosis, evades host immunity and establishes persistent infections in its mammalian hosts. The persistent infection poses a challenge to the effective antibiotic treatment, as demonstrated in various animal models. An increasingly heterogeneous subpopulation of replicatively attenuated spirochetes arises following treatment, and these persistent antimicrobial tolerant/resistant spirochetes are non-cultivable. The non-cultivable spirochetes resurge in multiple tissues at 12 months after treatment, with B. burgdorferi-specific DNA copy levels nearly equivalent to those found in shame-treated experimental animals. These attenuated spirochetes remain viable, but divide slowly, thereby being tolerant to antibiotics. Despite the continued non-cultivable state, RNA transcription of multiple B. burgdorferi genes was detected in host tissues, spirochetes were acquired by xenodiagnostic ticks, and spirochetal forms could be visualized within ticks and mouse tissues. A number of host cytokines were up- or down-regulated in tissues of both shame- and antibiotic-treated mice in the absence of histopathology, indicating a lack of host response to the presence of antimicrobial tolerant/resistant spirochetes. PMID:26295288

  2. Prevalence of the Lyme Disease Spirochete, Borrelia burgdorferi, in Blacklegged Ticks, Ixodes scapularis at Hamilton-Wentworth, Ontario

    PubMed Central

    Scott, John D.; Anderson, John F.; Durden, Lance A.; Smith, Morgan L.; Manord, Jodi M.; Clark, Kerry L.

    2016-01-01

    Lyme disease has emerged as a major health concern in Canada, where the etiological agent, Borrelia burgdorferi sensu lato (s.l.), a spirochetal bacterium, is typically spread by the bite of certain ticks. This study explores the presence of B. burgdorferi s.l. in blacklegged ticks, Ixodes scapularis, collected at Dundas, Ontario (a locality within the region of Hamilton-Wentworth). Using passive surveillance, veterinarians and pet groomers were asked to collect blacklegged ticks from dogs and cats with no history of travel. Additionally, I. scapularis specimens were submitted from local residents and collected by flagging. Overall, 12 (41%) of 29 blacklegged ticks were infected with B. burgdorferi s.l. Using polymerase chain reaction (PCR) and DNA sequencing, two borrelial amplicons were characterized as B. burgdorferi sensu stricto (s.s.), a genospecies pathogenic to humans and certain domestic animals. Notably, three different vertebrate hosts each had two engorged I. scapularis females removed on the same day and, likewise, one cat had three repeat occurrences of this tick species. These multiple infestations suggest that a population of I. scapularis may be established in this area. The local public health unit has been underreporting the presence of B. burgdorferi s.l.-infected I. scapularis in the area encompassing Dundas. Our findings raise concerns about the need to erect tick warning signs in parkland areas. Veterinarians, medical professionals, public health officials, and the general public must be vigilant that Lyme disease-carrying blacklegged ticks pose a public health risk in the Dundas area and the surrounding Hamilton-Wentworth region. PMID:27226771

  3. Epidemiological features and clinical manifestations of Lyme borreliosis in Korea during the period 2005-2012.

    PubMed

    Moon, Shinje; Hong, Yeongseon; Hwang, Kyu-Jam; Kim, Suyeon; Eom, Jihye; Kwon, Donghyok; Park, Ji-Hyuk; Youn, Seung-Ki; Sohn, Aeree

    2015-01-01

    Lyme borreliosis is one of the most common tick-borne infections in the northern hemisphere. However, the epidemiological features and clinical manifestations of this disease in Korea are unknown. The present study is the first to investigate the characteristics of Lyme borreliosis in Korea. We traced suspected cases of Lyme borreliosis during the period 2005-2012. Of the 16 identified patients with the disease, 11 had acquired autochthonous infection within Korea, while 5 patients were infected outside Korea. The history of past exposure was investigated in 8 of the 11 patients with autochthonous infection; 5 of these 8 patients (62.5%) were suspected to have acquired the infection in the northeastern alpine region. Clinically, of 11 patients with autochthonous infection, 6 (54.5%) showed early skin manifestations, 4 (36.4%) showed neurological manifestations, and 1 (9.1%) showed acrodermatitis chronica atrophicans. In conclusion, Lyme borreliosis could be endemic in the northeastern alpine region of Korea, and neurological and early skin manifestations are likely to be the major clinical characteristics of autochthonous Lyme borreliosis in Korea.

  4. Passive tick surveillance, dog seropositivity, and incidence of human Lyme disease

    USGS Publications Warehouse

    Johnson, Jaree L.; Ginsberg, Howard S.; Zhioua, Elyes; Whitworth, Ulysses G.; Markowski, Daniel; Hyland, Kerwin E.; Hu, Renjie

    2004-01-01

    Data on nymphal Ixodes scapularis ticks submitted by the public to the University of Rhode Island Tick Research Laboratory for testing from 1991 to 2000 were compared with human case data from the Rhode Island Department of Health to determine the efficacy of passive tick surveillance at assessing human risk of Lyme disease. Numbers of ticks submitted were highly correlated with human cases by county (r = 0.998, n = 5 counties) and by town (r = 0.916, n = 37 towns), as were the numbers of positive ticks submitted (r = 0.989 by county, r = 0.787 by town). Human cases were correlated with ticks submitted by town each year, and with positive ticks in all but 2 years. Thus, passive tick surveillance effectively assessed geographical risk of human Lyme disease. In contrast, tick submissions through time were not correlated with human cases from year to year. Dog seropositivity was significantly correlated with human cases by county in both years tested, but by town in only one of two years. Numbers of ticks submitted were correlated with dog seropositivity by county but not by town, apparently because of high variability among towns with small sample sizes. Our results suggest that passive tick surveillance, using ticks submitted by the public for Lyme spirochete testing, can be used to assess the geographical distribution of Lyme disease risk, but cannot reliably predict Lyme incidence from year to year.

  5. Multiple activation of mitogen-activated protein kinases by purified independent CCN2 modules in vascular endothelial cells and chondrocytes in culture.

    PubMed

    Kubota, S; Kawaki, H; Kondo, S; Yosimichi, G; Minato, M; Nishida, T; Hanagata, H; Miyauchi, A; Takigawa, M

    2006-12-01

    CCN2 consists of 4 distinct modules that are conserved among various CCN family protein members. From the N-terminus, insulin-like growth factor binding protein (IGFBP), von Willebrand factor type C repeat (VWC), thrombospondin type 1 repeat (TSP1) and C-terminal cysteine-knot (CT) modules are all aligned tandem therein. The multiple functionality of CCN2 is thought to be enabled by the differential use of these modules when interacting with other molecules. In this study, we independently prepared all 4 purified module proteins of human CCN2, utilizing a secretory production system with Brevibacillus choshinensis and thus evaluated the cell biological effects of such single modules. In human umbilical vascular endothelial cells (HUVECs), VWC, TSP and CT modules, as well as a full-length CCN2, were capable of efficiently activating the ERK signal transduction cascade, whereas IGFBP was not. In contrast, the IGFBP module was found to prominently activate JNK in human chondrocytic HCS-2/8 cells, while the others showed similar effects at lower levels. In addition, ERK1/2 was modestly, but significantly activated by IGFBP and VWC in those cells. No single module, but a mixture of the 4 modules provoked a significant activation of p38 MAPK in HCS-2/8 cells, which was activated by the full-length CCN2. Therefore, the signals emitted by CCN2 can be highly differential, depending upon the cell types, which are thus enabled by the tetramodular structure. Furthermore, the cell biological effects of each module on these cells were also evaluated to clarify the relationship among the modules, the signaling pathways and biological outcomes. Our present results not only demonstrate that single CCN2 modules were potent activators of the intracellular signaling cascade to yield a biological response per se, while also providing new insight into the module-wise structural and functional relationship of a prototypic CCN family member, CCN2.

  6. Common and Low Frequency Variants in MERTK Are Independently Associated with Multiple Sclerosis Susceptibility with Discordant Association Dependent upon HLA-DRB1*15:01 Status

    PubMed Central

    Binder, Michele D.; Fox, Andrew D.; Merlo, Daniel; Johnson, Laura J.; Giuffrida, Lauren; Calvert, Sarah E.; Akkermann, Rainer; Ma, Gerry Z. M.; Perera, Ashwyn A.; Gresle, Melissa M.; Laverick, Louise; Foo, Grace; Fabis-Pedrini, Marzena J.; Spelman, Timothy; Jordan, Margaret A.; Baxter, Alan G.; Foote, Simon; Butzkueven, Helmut; Kilpatrick, Trevor J.; Field, Judith

    2016-01-01

    Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. The risk of developing MS is strongly influenced by genetic predisposition, and over 100 loci have been established as associated with susceptibility. However, the biologically relevant variants underlying disease risk have not been defined for the vast majority of these loci, limiting the power of these genetic studies to define new avenues of research for the development of MS therapeutics. It is therefore crucial that candidate MS susceptibility loci are carefully investigated to identify the biological mechanism linking genetic polymorphism at a given gene to the increased chance of developing MS. MERTK has been established as an MS susceptibility gene and is part of a family of receptor tyrosine kinases known to be involved in the pathogenesis of demyelinating disease. In this study we have refined the association of MERTK with MS risk to independent signals from both common and low frequency variants. One of the associated variants was also found to be linked with increased expression of MERTK in monocytes and higher expression of MERTK was associated with either increased or decreased risk of developing MS, dependent upon HLA-DRB1*15:01 status. This discordant association potentially extended beyond MS susceptibility to alterations in disease course in established MS. This study provides clear evidence that distinct polymorphisms within MERTK are associated with MS susceptibility, one of which has the potential to alter MERTK transcription, which in turn can alter both susceptibility and disease course in MS patients. PMID:26990204

  7. CKS1B, overexpressed in aggressive disease, regulates multiple myeloma growth and survival through SKP2- and p27Kip1-dependent and -independent mechanisms

    PubMed Central

    Colla, Simona; Wu, Xiaosong; Chen, Bangzheng; Stewart, James P.; Kuehl, W. Michael; Barlogie, Bart

    2007-01-01

    Overexpression of CKS1B, a gene mapping within a minimally amplified region between 153 to 154 Mb of chromosome 1q21, is linked to a poor prognosis in multiple myeloma (MM). CKS1B binds to and activates cyclin-dependent kinases and also interacts with SKP2 to promote the ubiquitination and proteasomal degradation of p27Kip1. Overexpression of CKS1B or SKP2 contributes to increased p27Kip1 turnover, cell proliferation, and a poor prognosis in many tumor types. Using 4 MM cell lines harboring MAF-, FGFR3/MMSET-, or CCND1-activating translocations, we show that lentiviral delivery of shRNA directed against CKS1B resulted in ablation of CKS1B mRNA and protein with concomitant stabilization of p27Kip1, cell cycle arrest, and apoptosis. Although shRNA-mediated knockdown of SKP2 and forced expression of a nondegradable form of p27Kip1 (p27T187A) led to cell cycle arrest, apoptosis was modest. Of importance, while knockdown of SKP2 or overexpression of p27T187A induced cell cycle arrest in KMS28PE, an MM cell line with biallelic deletion of CDKN1B/p27Kip1, CKS1B ablation induced strong apoptosis. These data suggest that CKS1B influences myeloma cell growth and survival through SKP2- and p27Kip1-dependent and -independent mechanisms and that therapeutic strategies aimed at abolishing CKS1B function may hold promise for the treatment of high-risk disease for which effective therapies are currently lacking. PMID:17303695

  8. Ceftriaxone-induced immune hemolytic anemia as a life-threatening complication of antibiotic treatment of 'chronic Lyme disease'.

    PubMed

    De Wilde, Maarten; Speeckaert, Marijn; Callens, Rutger; Van Biesen, Wim

    2017-04-01

    'Chronic Lyme disease' is a controversial condition. As any hard evidence is lacking that unresolved systemic symptoms, following an appropriately diagnosed and treated Lyme disease, are related to a chronic infection with the tick-borne spirochaetes of the Borrelia genus, the term 'chronic Lyme disease' should be avoided and replaced by the term 'post-treatment Lyme disease syndrome.' The improper prescription of prolonged antibiotic treatments for these patients can have an impact on the community antimicrobial resistance and on the consumption of health care resources. Moreover, these treatments can be accompanied by severe complications. In this case report, we describe a life-threatening ceftriaxone-induced immune hemolytic anemia with an acute kidney injury (RIFLE-stadium F) due to a pigment-induced nephropathy in a 76-year-old woman, who was diagnosed with a so-called 'chronic Lyme disease.'

  9. Nucleic Acid Amplification Based Diagnostic of Lyme (Neuro-)borreliosis - Lost in the Jungle of Methods, Targets, and Assays?

    PubMed

    Nolte, Oliver

    2012-01-01

    Laboratory based diagnosis of infectious diseases usually relies on culture of the disease causing micro-organism, followed by identification and susceptibility testing. Since Borrelia burgdorferi sensu lato, the etiologic agent of Lyme disease or Lyme borreliosis, requires very specific culture conditions (e.g. specific liquid media, long term cul-ture) traditional bacteriology is often not done on a routine basis. Instead, confirmation of the clinical diagnosis needs ei-ther indirect techniques (like serology or measurement of cellular activity in the presence of antigens) or direct but culture independent techniques, like microscopy or nucleic acid amplification techniques (NAT), with polymerase chain reaction (PCR) being the most frequently applied NAT method in routine laboratories. NAT uses nucleic acids of the disease causing micro-organism as template for amplification, isolated from various sources of clinical specimens. Although the underlying principle, adoption of the enzymatic process running during DNA duplication prior to prokaryotic cell division, is comparatively easy, a couple of 'pitfalls' is associated with the technique itself as well as with interpretation of the results. At present, no commercial, CE-marked and sufficiently validated PCR assay is available. A number of homebrew assays have been published, which are different in terms of target (i.e. the gene targeted by the amplification primers), method (nested PCR, PCR followed by hybridization, real-time PCR) and validation criteria. Inhibitory compounds may lead to false negative results, if no appropriate internal control is included. Carry-over of amplicons, insufficient handling and workflow and/or insufficiently validated targets/primers may result in false positive results. Different targets may yield different analytical sensitivity, depending, among other factors, of the redundancy of a target gene in the genome. Per-formance characteristics (e.g. analytical sensitivity and

  10. Nucleic Acid Amplification Based Diagnostic of Lyme (Neuro-)borreliosis – Lost in the Jungle of Methods, Targets, and Assays?

    PubMed Central

    Nolte, Oliver

    2012-01-01

    Laboratory based diagnosis of infectious diseases usually relies on culture of the disease causing micro-organism, followed by identification and susceptibility testing. Since Borrelia burgdorferi sensu lato, the etiologic agent of Lyme disease or Lyme borreliosis, requires very specific culture conditions (e.g. specific liquid media, long term cul-ture) traditional bacteriology is often not done on a routine basis. Instead, confirmation of the clinical diagnosis needs ei-ther indirect techniques (like serology or measurement of cellular activity in the presence of antigens) or direct but culture independent techniques, like microscopy or nucleic acid amplification techniques (NAT), with polymerase chain reaction (PCR) being the most frequently applied NAT method in routine laboratories. NAT uses nucleic acids of the disease causing micro-organism as template for amplification, isolated from various sources of clinical specimens. Although the underlying principle, adoption of the enzymatic process running during DNA duplication prior to prokaryotic cell division, is comparatively easy, a couple of ‘pitfalls’ is associated with the technique itself as well as with interpretation of the results. At present, no commercial, CE-marked and sufficiently validated PCR assay is available. A number of homebrew assays have been published, which are different in terms of target (i.e. the gene targeted by the amplification primers), method (nested PCR, PCR followed by hybridization, real-time PCR) and validation criteria. Inhibitory compounds may lead to false negative results, if no appropriate internal control is included. Carry-over of amplicons, insufficient handling and workflow and/or insufficiently validated targets/primers may result in false positive results. Different targets may yield different analytical sensitivity, depending, among other factors, of the redundancy of a target gene in the genome. Per-formance characteristics (e.g. analytical sensitivity and

  11. Multiple sulfur and carbon isotope composition of sediments from the Belingwe Greenstone Belt (Zimbabwe): A biogenic methane regulation on mass independent fractionation of sulfur during the Neoarchean?

    NASA Astrophysics Data System (ADS)

    Thomazo, Christophe; Nisbet, Euan G.; Grassineau, Nathalie V.; Peters, Marc; Strauss, Harald

    2013-11-01

    To explore the linkage between mass-independent sulfur isotope fractionation (MIF-S) and δ13Corg excursions during the Neoarchean, as well as the contemporary redox state and biogeochemical cycling of carbon and sulfur, we report the results of a detailed carbon and multiple sulfur (δ34S, δ33S, δ36S) isotopic study of the ∼2.7 Ga Manjeri and ∼2.65 Ga Cheshire formations of the Ngezi Group (Belingwe Greenstone Belt, Zimbabwe). Multiple sulfur isotope data show non-zero Δ33S and Δ36S values for sediments older than 2.4 Ga (i.e. prior to the Great Oxidation Event, GOE), indicating MIF-S thought to be associated with low atmospheric oxygen concentration. However, in several 2.7-2.5 Ga Neoarchean localities, small-scale variations in MIF-S signal (magnitude) seem to correlate with negative excursion in δ13Corg, possibly reflecting a global connection between the relative reaction rate of different MIF-S source reaction and sulfur exit channels and the biogenic flux of methane into the atmosphere during periods of localized, microbiologically mediated, shallow surface-water oxygenation. The Manjeri Formation black shales studied here display a wide range of δ13Corg between -35.4‰ and -16.2‰ (average of -30.3 ± 6.0‰, 1σ), while the Cheshire Formation shales have δ13Corg between -47.7‰ and -35.1‰ (average -41.3 ± 3‰, 1σ). The δ34S values of sedimentary sulfides from Manjeri Formation vary between -15.15‰ and +2.37‰ (average -1.71 ± 4.76‰, 1σ), showing very small and mostly negative Δ33S values varying from -0.58‰ to 0.87‰ (average 0.02 ± 0.43‰, 1σ). Cheshire Formation black shale sulfide samples measured in this study have δ34S values ranging from -2.11‰ to 2.39‰ (average 0.25 ± 1.08‰, 1σ) and near zero and solely positive Δ33S anomalies between 0.14‰ and 1.17‰ (average 0.56 ± 0.29‰, 1σ). Moreover, Δ36S/Δ33S in the two formations are comparable with a slope of -1.38 (Manjeri Formation) and -1.67 (Cheshire

  12. Anti-Lyme Subunit Vaccines: Design and Development of Peptide-Based Vaccine Candidates.

    PubMed

    Small, Christina M; Mwangi, Waithaka; Esteve-Gassent, Maria D

    2016-01-01

    Vaccinology today has been presented with several avenues to improve protection against infectious disease. The recent employment of the reverse vaccinology technique has changed the face of vaccine development against many pathogens, including Borrelia burgdorferi, the causative agent of Lyme disease. Using this technique, genomics and in silico analyses come together to identify potentially antigenic epitopes in a high-throughput fashion. The forward methodology of vaccine development was used previously to generate the only licensed human vaccine for Lyme disease, which is no longer on the market. Using reverse vaccinology to identify new antigens and isolate specific epitopes to protect against B. burgdorferi, subunit vaccines will be generated that lack reactogenic and nonspecific epitopes, yielding more effective vaccine candidates. Additionally, novel epitopes are being utilized and are presently in the commercialization pipeline both for B. burgdorferi and other spirochaetal pathogens. The versatility and methodology of the subunit protein vaccine are described as it pertains to Lyme disease from conception to performance evaluation.

  13. Living in Limbo: Contested Narratives of Patients With Chronic Symptoms Following Lyme Disease.

    PubMed

    Rebman, Alison W; Aucott, John N; Weinstein, Eric R; Bechtold, Kathleen T; Smith, Katherine C; Leonard, Lori

    2015-12-01

    Persistent, subjective symptoms of unknown etiology following treatment for Lyme disease have been termed post-treatment Lyme disease syndrome or chronic Lyme disease (PTLDS/CLD). The objective of this study was to give primacy to the patient experience of this medically contested condition by eliciting patient illness narratives and identifying emergent issues through semistructured interviews conducted among 29 participants. We used thematic narrative analysis to identify three predominant themes: (a) Physical and social limitations lead to a "new normal" characterized by fundamental shifts of ways of being in the world, (b) disease-specific factors contribute to symptom and illness invisibility that affects social support in nuanced ways, and (c) pervasive medical uncertainty regarding PTLDS/CLD promotes an increased sense of personal responsibility for care. Similar to other contested or medically unexplained syndromes, our findings suggest that the social sequelae of PTLDS/CLD can be equally protracted as the physical effects of this illness.

  14. Human Risk of Infection with Borrelia burgdorferi, the Lyme Disease Agent, in Eastern United States

    PubMed Central

    Diuk-Wasser, Maria A.; Hoen, Anne Gatewood; Cislo, Paul; Brinkerhoff, Robert; Hamer, Sarah A.; Rowland, Michelle; Cortinas, Roberto; Vourc'h, Gwenaël; Melton, Forrest; Hickling, Graham J.; Tsao, Jean I.; Bunikis, Jonas; Barbour, Alan G.; Kitron, Uriel; Piesman, Joseph; Fish, Durland

    2012-01-01

    The geographic pattern of human risk for infection with Borrelia burgdorferi sensu stricto, the tick-borne pathogen that causes Lyme disease, was mapped for the eastern United States. The map is based on standardized field sampling in 304 sites of the density of Ixodes scapularis host-seeking nymphs infected with B. burgdorferi, which is closely associated with human infection risk. Risk factors for the presence and density of infected nymphs were used to model a continuous 8 km×8 km resolution predictive surface of human risk, including confidence intervals for each pixel. Discontinuous Lyme disease risk foci were identified in the Northeast and upper Midwest, with a transitional zone including sites with uninfected I. scapularis populations. Given frequent under- and over-diagnoses of Lyme disease, this map could act as a tool to guide surveillance, control, and prevention efforts and act as a baseline for studies tracking the spread of infection. PMID:22302869

  15. Lyme disease spirochaete Borrelia burgdorferi does not require thiamin.

    PubMed

    Zhang, Kai; Bian, Jiang; Deng, Yijie; Smith, Alexis; Nunez, Roy E; Li, Michael B; Pal, Utpal; Yu, Ai-Ming; Qiu, Weigang; Ealick, Steven E; Li, Chunhao

    2016-11-21

    Thiamin pyrophosphate (ThDP), the active form of thiamin (vitamin B1), is believed to be an essential cofactor for all living organisms(1,2). Here, we report the unprecedented result that thiamin is dispensable for the growth of the Lyme disease pathogen Borrelia burgdorferi (Bb)(3). Bb lacks genes for thiamin biosynthesis and transport as well as known ThDP-dependent enzymes(4), and we were unable to detect thiamin or its derivatives in Bb cells. We showed that eliminating thiamin in vitro and in vivo using BcmE, an enzyme that degrades thiamin, has no impact on Bb growth and survival during its enzootic infectious cycle. Finally, high-performance liquid chromatography analysis reveals that the level of thiamin and its derivatives in Ixodes scapularis ticks, the enzootic vector of Bb, is extremely low. These results suggest that by dispensing with use of thiamin, Borrelia, and perhaps other tick-transmitted bacterial pathogens, are uniquely adapted to survive in tick vectors before transmitting to mammalian hosts. To our knowledge, such a mechanism has not been reported previously in any living organisms.

  16. [Atrioventricular block caused by tick bite--Lyme's carditis].

    PubMed

    Lörincz, I; Várvölgyi, C; Lakos, A; Wórum, F; Kovács, P; Polgár, P

    1989-10-22

    The authors present the case of a 44-year-old patient who was admitted to the hospital because of AV block of degree III. Six weeks earlier a tick was removed from the left foot of the patient. Two weeks later an erythema of 8 cm in diameter, spreading peripherally as well as painful inguinal lymphadenitis developed at the site of the bite with transient arthralgia and myalgia in the region of the waist and left lower limb. After the temporary use of pacemaker, steroid and atropine therapy applied because of the pronounced bradycardia the block became of degree I on the 4th day however negative T-waves appeared in leads III, aVF, V3. By the 14th day the AV time returned to normal and the pathological signs of repolarization disappeared. Serological examinations revealed increased Borrelia burgdorferi antibody level. Lyme's carditis may be prevented by starting the antibiotic therapy at the time of the chronic erythema migrans. Upon medication the patient may recover from the carditis without remaining symptoms.

  17. Epidemiology of Lyme Disease, Nova Scotia, Canada, 2002–2013

    PubMed Central

    Johnston, B. Lynn; Schleihauf, Emily; Mask, Angela; Haldane, David; Drebot, Michael; Baikie, Maureen; Cole, Teri J.; Fleming, Sarah; Gould, Richard; Lindsay, Robbin

    2015-01-01

    Ixodes scapularis ticks, which transmit Borrelia burgdorferi, the causative agent of Lyme disease (LD), are endemic to at least 6 regions of Nova Scotia, Canada. To assess the epidemiology and prevalence of LD in Nova Scotia, we analyzed data from 329 persons with LD reported in Nova Scotia during 2002–2013. Most patients reported symptoms of early localized infection with rash (89.7%), influenza-like illness (69.6%), or both; clinician-diagnosed erythema migrans was documented for 53.2%. In a separate serosurvey, of 1,855 serum samples screened for antibodies to B. burgdorferi, 2 were borderline positive (both with an indeterminate IgG on Western blot), resulting in an estimated seroprevalence of 0.14% (95% CI 0.02%–0.51%). Although LD incidence in Nova Scotia has risen sharply since 2002 and is the highest in Canada (16/100,000 population in 2013), the estimated number of residents with evidence of infection is low, and risk is localized to currently identified LD-endemic regions. PMID:26401788

  18. Massage Therapy for Lyme Disease Symptoms: a Prospective Case Study

    PubMed Central

    Thomason, Meghan J.; Moyer, Christopher A.

    2012-01-01

    Introduction To study the effects of massage therapy (MT) on Lyme disease (LD) symptoms and affect. Methods A 21-year-old female college student previously diagnosed with LD was recruited for a prospective case study that incorporated alternating periods of treatment and nontreatment across 65 days. Her self-reported symptoms of pain, fatigue, and impairment of concentration were assessed by means of a daily diary with corresponding visual analog scales. Immediate effects of MT on affect were assessed by completion of the Positive and Negative Affect Scales before and after each treatment session. Results LD symptoms decreased during treatment periods and increased during nontreatment periods. Positive affect was increased at every MT session. Conclusions MT is a promising treatment for the symptoms pain, fatigue, and impaired concentration associated with LD. In addition, MT reliably increased positive affect. Massage therapists should consider using light-to-medium pressure MT for treatment of persons who present with a similar pattern of LD symptoms, and further research with this population is warranted. PMID:23429967

  19. Lyme disease spirochaete Borrelia burgdorferi does not require thiamin

    PubMed Central

    Zhang, Kai; Bian, Jiang; Deng, Yijie; Smith, Alexis; Nunez, Roy E.; Li, Michael B.; Pal, Utpal; Yu, Ai-Ming; Qiu, Weigang; Ealick, Steven E.; Li, Chunhao

    2016-01-01

    Thiamin pyrophosphate (ThDP), the active form of thiamin (vitamin B1), is believed to be an essential cofactor for all living organisms1,2. Here, we report the unprecedented result that thiamin is dispensable for the growth of the Lyme disease pathogen Borrelia burgdorferi (Bb)3. Bb lacks genes for thiamin biosynthesis and transport as well as known ThDP-dependent enzymes4, and we were unable to detect thiamin or its derivatives in Bb cells. We showed that eliminating thiamin in vitro and in vivo using BcmE, an enzyme that degrades thiamin, has no impact on Bb growth and survival during its enzootic infectious cycle. Finally, high-performance liquid chromatography analysis reveals that the level of thiamin and its derivatives in Ixodes scapularis ticks, the enzootic vector of Bb, is extremely low. These results suggest that by dispensing with use of thiamin, Borrelia, and perhaps other tick-transmitted bacterial pathogens, are uniquely adapted to survive in tick vectors before transmitting to mammalian hosts. To our knowledge, such a mechanism has not been reported previously in any living organisms. PMID:27869793

  20. Antagonistic Interplay between MicroRNA-155 and IL-10 during Lyme Carditis and Arthritis.

    PubMed

    Lochhead, Robert B; Zachary, James F; Dalla Rosa, Luciana; Ma, Ying; Weis, John H; O'Connell, Ryan M; Weis, Janis J

    2015-01-01

    MicroRNA-155 has been shown to play a role in immune activation and inflammation, and is suppressed by IL-10, an important anti-inflammatory cytokine. The established involvement of IL-10 in the murine model of Borrelia burgdorferi-induced Lyme arthritis and carditis allowed us to assess the interplay between IL-10 and miR-155 in vivo. As reported previously, Mir155 was highly upregulated in joints from infected severely arthritic B6 Il10-/- mice, but not in mildly arthritic B6 mice. In infected hearts, Mir155 was upregulated in both strains, suggesting a role of miR-155 in Lyme carditis. Using B. burgdorferi-infected B6, Mir155-/-, Il10-/-, and Mir155-/- Il10-/- double-knockout (DKO) mice, we found that anti-inflammatory IL-10 and pro-inflammatory miR-155 have opposite and somewhat compensatory effects on myeloid cell activity, cytokine production, and antibody response. Both IL-10 and miR-155 were required for suppression of Lyme carditis. Infected Mir155-/- mice developed moderate/severe carditis, had higher B. burgdorferi numbers, and had reduced Th1 cytokine expression in hearts. In contrast, while Il10-/- and DKO mice also developed severe carditis, hearts had reduced bacterial numbers and elevated Th1 and innate cytokine expression. Surprisingly, miR-155 had little effect on Lyme arthritis. These results show that antagonistic interplay between IL-10 and miR-155 is required to balance host defense and immune activation in vivo, and this balance is particularly important for suppression of Lyme carditis. These results also highlight tissue-specific differences in Lyme arthritis and carditis pathogenesis, and reveal the importance of IL-10-mediated regulation of miR-155 in maintaining healthy immunity.

  1. Prevalence of Lyme borrelia in Ixodes persulcatus ticks from an area with a confirmed case of Lyme disease.

    PubMed

    Murase, Yusuke; Konnai, Satoru; Githaka, Naftaly; Hidano, Arata; Taylor, Kyle; Ito, Takuya; Takano, Ai; Ando, Shuji; Kawabata, Hiroki; Tsubota, Toshio; Murata, Shiro; Ohashi, Kazuhiko

    2013-02-01

    In this study, the prevalence of Borrelia infections in Ixodes ticks from a site in Hokkaido, Japan, with confirmed cases of Lyme disease was determined by a PCR method capable of detecting and differentiating between strains of pathogenic Borrelia, with particular emphasis on Borrelia garinii (B. garinii) and Borrelia afzelli (B. afzelli), using tick-derived DNA extracts as template. A total of 338 ticks, inclusive of 284 Ixodes persulcatus (I. persulcatus), were collected by flagging vegetation in mid-spring. Ninety-eight (34.5%) of I. persulcatus tested positive for Borrelia species DNA, whereas the overall prevalence of Borrelia species in Ixodes ovatus and Haemaphysalis longicornis ticks was 19.5 and 7.7%, respectively. PCR-RFLP and sequence analysis of Borrelia rrf(5S)-rrl(23S) intergenic spacer DNA amplicons indicated that they originated from three different Borrelia species namely, B. garinii, B. afzelii and B. japonica. Among the I. persulcatus species, which is a known vector of human borreliosis, 86 were mono-infected with B. garinii, 2 ticks were mono-infected with B. afzelii and whereas 12 ticks had dual infections. Most significant, 11 of the I. persulcatus ticks were coinfected with Anaplasma phagocytophilum and B. garinii. The difference between the number of obtained and expected co-infections was significant (χ(2)=4.32, P=0.038).

  2. Lyme disease-related intracranial hypertension in children: clinical and imaging findings.

    PubMed

    Ramgopal, Sriram; Obeid, Rawad; Zuccoli, Giulio; Cleves-Bayon, Catalina; Nowalk, Andrew

    2016-03-01

    Lyme disease (LD) is a tick-borne infection that is endemic to multiple areas of the United States. Patients with LD may present with sign and symptoms of intracranial hypertension (IH). The objective of this study is to evaluate the history, clinical findings, CSF analysis, and brain imaging results in pediatric patients with increased intracranial pressure secondary to LD. A retrospective database search was performed using the International Classification of Diseases (ICD) 9/10 codes to identify patients diagnosed with LD and IH between 2004 and 2014 at a tertiary referral pediatric hospital. Clinical, laboratory and neuroimaging data for each patient were reviewed. Seven patients met inclusion criteria; mean age was 9.6 years (standard deviation 4.0 years); 4/7 patients were male. Average body mass index was 18.8 kg/m(2) (standard deviation 3.0 kg/m(2)). Fever was present in four patients. Four had a history of LD related erythema migrans. All had elevated CSF opening pressure with leukocytosis and lymphocytic predominance. MRI obtained in six patients showed contrast enhancement of various cranial nerves. Tentorial enhancement was noted in all patients. In addition, patients had widening of the optic nerve sheath (ONS), optic nerve protrusion, and flattening of the posterior globe consistent with increased intracranial pressure. All patients had resolution of their symptoms after initiation of antibiotic therapy. In endemic areas, LD should be included in the differential of IH. MRI can help distinguish IH due to LD from its idiopathic form due to the presence of tentorial and cranial nerve enhancement in the former in addition to abnormal CSF showing leukocytosis with lymphocyte predominance.

  3. Borrelia burgdorferi, the Causative Agent of Lyme Disease, Forms Drug-Tolerant Persister Cells

    PubMed Central

    Sharma, Bijaya; Brown, Autumn V.; Matluck, Nicole E.; Hu, Linden T.

    2015-01-01

    Borrelia burgdorferi is the causative agent of Lyme disease, which affects an estimated 300,000 people annually in the United States. When treated early, the disease usually resolves, but when left untreated, it can result in symptoms such as arthritis and encephalopathy. Treatment of the late-stage disease may require multiple courses of antibiotic therapy. Given that antibiotic resistance has not been observed for B. burgdorferi, the reason for the recalcitrance of late-stage disease to antibiotics is unclear. In other chronic infections, the presence of drug-tolerant persisters has been linked to recalcitrance of the disease. In this study, we examined the ability of B. burgdorferi to form persisters. Killing growing cultures of B. burgdorferi with antibiotics used to treat the disease was distinctly biphasic, with a small subpopulation of surviving cells. Upon regrowth, these cells formed a new subpopulation of antibiotic-tolerant cells, indicating that these are persisters rather than resistant mutants. The level of persisters increased sharply as the culture transitioned from the exponential to stationary phase. Combinations of antibiotics did not improve killing. Daptomycin, a membrane-active bactericidal antibiotic, killed stationary-phase cells but not persisters. Mitomycin C, an anticancer agent that forms adducts with DNA, killed persisters and eradicated growing and stationary cultures of B. burgdorferi. Finally, we examined the ability of pulse dosing an antibiotic to eliminate persisters. After addition of ceftriaxone, the antibiotic was washed away, surviving persisters were allowed to resuscitate, and the antibiotic was added again. Four pulse doses of ceftriaxone killed persisters, eradicating all live bacteria in the culture. PMID:26014929

  4. Evolutionary aspects of emerging Lyme disease in Canada.

    PubMed

    Ogden, N H; Feil, E J; Leighton, P A; Lindsay, L R; Margos, G; Mechai, S; Michel, P; Moriarty, T J

    2015-11-01

    In North America, Lyme disease (LD) is a tick-borne zoonosis caused by the spirochete bacterium Borrelia burgdorferi sensu stricto, which is maintained by wildlife. Tick vectors and bacteria are currently spreading into Canada and causing increasing numbers of cases of LD in humans and raising a pressing need for public health responses. There is no vaccine, and LD prevention depends on knowing who is at risk and informing them how to protect themselves from infection. Recently, it was found in the United States that some strains of B. burgdorferi sensu stricto cause severe disease, whereas others cause mild, self-limiting disease. While many strains occurring in the United States also occur in Canada, strains in some parts of Canada are different from those in the United States. We therefore recognize a need to identify which strains specific to Canada can cause severe disease and to characterize their geographic distribution to determine which Canadians are particularly at risk. In this review, we summarize the history of emergence of LD in North America, our current knowledge of B. burgdorferi sensu stricto diversity, its intriguing origins in the ecology and evolution of the bacterium, and its importance for the epidemiology and clinical and laboratory diagnosis of LD. We propose methods for investigating associations between B. burgdorferi sensu stricto diversity, ecology, and pathogenicity and for developing predictive tools to guide public health interventions. We also highlight the emergence of B. burgdorferi sensu stricto in Canada as a unique opportunity for exploring the evolutionary aspects of tick-borne pathogen emergence.

  5. Investigating Alternatives to Broad-Scale Pesticide Spraying for Control of Lyme Disease Risk

    EPA Science Inventory

    More than 20,000 cases of Lyme disease are reported annually in the US. Here in the Northeast, the geographic range of the disease and infection rates continue to increase. Beginning this summer, scientists from EPA Region 1 (Robert Koethe, Bart Hoskins) and ORD (Jason Grear) w...

  6. Potential for Lyme disease in Maine: deer survey of distribution of Ixodes dammini, the tick vector.

    PubMed Central

    Smith, R P; Rand, P W; Lacombe, E H

    1990-01-01

    A survey of deer brought to tagging stations at 24 sites in Main revealed the presence of the deer tick, Ixodes dammini, on 5.1 percent of deer. Ticks were found almost exclusively on deer from southwest coastal sites in the state. The potential for endemic Lyme disease in coastal Maine merits further study. PMID:2305920

  7. Impact of the experimental removal of lizards on Lyme disease risk.

    PubMed

    Swei, Andrea; Ostfeld, Richard S; Lane, Robert S; Briggs, Cheryl J

    2011-10-07

    The distribution of vector meals in the host community is an important element of understanding and predicting vector-borne disease risk. Lizards (such as the western fence lizard; Sceloporus occidentalis) play a unique role in Lyme disease ecology in the far-western United States. Lizards rather than mammals serve as the blood meal hosts for a large fraction of larval and nymphal western black-legged ticks (Ixodes pacificus--the vector for Lyme disease in that region) but are not competent reservoirs for the pathogen, Borrelia burgdorferi. Prior studies have suggested that the net effect of lizards is to reduce risk of human exposure to Lyme disease, a hypothesis that we tested experimentally. Following experimental removal of lizards, we documented incomplete host switching by larval ticks (5.19%) from lizards to other hosts. Larval tick burdens increased on woodrats, a competent reservoir, but not on deer mice, a less competent pathogen reservoir. However, most larvae failed to find an alternate host. This resulted in significantly lower densities of nymphal ticks the following year. Unexpectedly, the removal of reservoir-incompetent lizards did not cause an increase in nymphal tick infection prevalence. The net result of lizard removal was a decrease in the density of infected nymphal ticks, and therefore a decreased risk to humans of Lyme disease. Our results indicate that an incompetent reservoir for a pathogen may, in fact, increase disease risk through the maintenance of higher vector density and therefore, higher density of infected vectors.

  8. Spatial and Temporal Distribution of Lyme Disease Infected Ticks in the Texas-Mexico Border Region

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lyme disease (LD) is the most prevalent arthropod-borne infection in the United States, with 33,097 cases of LD reported to the Centers for Disease Control and Prevention (CDC) in 2011. The disease is transmitted to a mammalian host by Ixodes ticks infected with Borrelia burgdorferi. Efforts to unde...

  9. Community Partnership Designed to Promote Lyme Disease Prevention and Engagement in Citizen Science †

    PubMed Central

    Seifert, Veronica A.; Wilson, Shane; Toivonen, Samantha; Clarke, Benjamin; Prunuske, Amy

    2016-01-01

    The goal of this project is to promote Lyme disease prevention and to cultivate an interest in science through a citizen-science project coordinated by researchers at a public university and teachers at rural high schools. The lesson plan is designed to increase student interest in pursuing a science career through participation in an authentic research experience, utilizing a topic that has implications on the health of the surrounding community. Students are introduced in the classroom to zoonotic diseases transmitted by the Ixodes tick, the health risks of Lyme disease, and disease prevention strategies. Students then participate in a research experience collecting field data and ticks from their community, which are used in university research. To measure changes in student knowledge and attitudes toward Lyme disease and science careers, students completed surveys related to the learning objectives associated with the experience. We found participation in the activity increased student confidence and ability to correctly differentiate a deer tick from a wood tick and to recognize the symptoms of Lyme disease. In addition, students reported increased interest in pursuing a science degree in college or graduate school. Authentic research experience related to a disease relevant to the local community is effective at enhancing high school student engagement in science. PMID:27047593

  10. Impacts of an Introduced Forest Pathogen on the Risk of Lyme Disease in California

    PubMed Central

    Briggs, Cheryl J.; Lane, Robert S.; Ostfeld, Richard S.

    2012-01-01

    Abstract Global changes such as deforestation, climate change, and invasive species have the potential to greatly alter zoonotic disease systems through impacts on biodiversity. This study examined the impact of the invasive pathogen that causes sudden oak death (SOD) on the ecology of Lyme disease in California. The Lyme disease bacterium, Borrelia burgdorferi, is maintained in the far western United States by a suite of animal reservoirs including the dusky-footed woodrat (Neotoma fuscipes) and deer mouse (Peromyscus maniculatus), and is transmitted by the western black-legged tick (Ixodes pacificus). Other vertebrates, such as the western fence lizard (Sceloporus occidentalis), are important tick hosts but are not reservoirs of the pathogen. Previous work found that higher levels of SOD are correlated with greater abundance of P. maniculatus and S. occidentalis and lower N. fuscipes abundance. Here we model the contribution of these tick hosts to Lyme disease risk and also evaluate the potential impact of SOD on infection prevalence of the tick vector. By empirically parameterizing a static model with field and laboratory data on tick hosts, we predict that SOD reduces an important index of disease risk, nymphal infection prevalence, leading to a reduction in Lyme disease risk in certain coastal woodlands. Direct observational analysis of the impact of SOD on nymphal infection prevalence supports these model results. This study underscores the important direct and indirect impacts of invasive plant pathogens on biodiversity, the transmission cycles of zoonotic diseases, and ultimately human health. PMID:22607076

  11. Lyme Disease: A Sourcebook for Teaching about a Major Environmental Problem.

    ERIC Educational Resources Information Center

    Anderson, Norman D.; Stubbs, Harriett S.

    This book and others in the Changes in the Environment Series were produced as part of the GLOBE-NET Project, a partnership of science teachers and research scientists working on various aspects of global change. This book contains up-to-date information about Lyme disease, activities for the classroom, and other resources useful in teaching about…

  12. Preliminary Bedrock Geologic Map of the Old Lyme Quadrangle, New London and Middlesex Counties, Connecticut

    USGS Publications Warehouse

    Walsh, Gregory J.; Scott, Robert B.; Aleinikoff, John N.; Armstrong, Thomas R.

    2006-01-01

    This report presents a preliminary map of the bedrock geology of the Old Lyme quadrangle, New London and Middlesex Counties, Connecticut. The map depicts contacts of bedrock geologic units, faults, outcrops, and structural geologic information. The map was published as part of a study of fractured bedrock aquifers and regional tectonics.

  13. A COMPARISON OF ANALYSIS UNITS FOR ASSOCIATING LYME DISEASE WITH FOREST-EDGE HABITAT

    EPA Science Inventory

    This study assessed the relationship between land-cover pattern and Lyme disease incidence rate when modeled under three designs for data aggregation. Incidence rates were calculated from passive surveillance data reported in 12 Maryland counties during 1996 – 2000. A design usin...

  14. Community Partnership Designed to Promote Lyme Disease Prevention and Engagement in Citizen Science.

    PubMed

    Seifert, Veronica A; Wilson, Shane; Toivonen, Samantha; Clarke, Benjamin; Prunuske, Amy

    2016-03-01

    The goal of this project is to promote Lyme disease prevention and to cultivate an interest in science through a citizen-science project coordinated by researchers at a public university and teachers at rural high schools. The lesson plan is designed to increase student interest in pursuing a science career through participation in an authentic research experience, utilizing a topic that has implications on the health of the surrounding community. Students are introduced in the classroom to zoonotic diseases transmitted by the Ixodes tick, the health risks of Lyme disease, and disease prevention strategies. Students then participate in a research experience collecting field data and ticks from their community, which are used in university research. To measure changes in student knowledge and attitudes toward Lyme disease and science careers, students completed surveys related to the learning objectives associated with the experience. We found participation in the activity increased student confidence and ability to correctly differentiate a deer tick from a wood tick and to recognize the symptoms of Lyme disease. In addition, students reported increased interest in pursuing a science degree in college or graduate school. Authentic research experience related to a disease relevant to the local community is effective at enhancing high school student engagement in science.

  15. Impact of the experimental removal of lizards on Lyme disease risk

    PubMed Central

    Swei, Andrea; Ostfeld, Richard S.; Lane, Robert S.; Briggs, Cheryl J.

    2011-01-01

    The distribution of vector meals in the host community is an important element of understanding and predicting vector-borne disease risk. Lizards (such as the western fence lizard; Sceloporus occidentalis) play a unique role in Lyme disease ecology in the far-western United States. Lizards rather than mammals serve as the blood meal hosts for a large fraction of larval and nymphal western black-legged ticks (Ixodes pacificus—the vector for Lyme disease in that region) but are not competent reservoirs for the pathogen, Borrelia burgdorferi. Prior studies have suggested that the net effect of lizards is to reduce risk of human exposure to Lyme disease, a hypothesis that we tested experimentally. Following experimental removal of lizards, we documented incomplete host switching by larval ticks (5.19%) from lizards to other hosts. Larval tick burdens increased on woodrats, a competent reservoir, but not on deer mice, a less competent pathogen reservoir. However, most larvae failed to find an alternate host. This resulted in significantly lower densities of nymphal ticks the following year. Unexpectedly, the removal of reservoir-incompetent lizards did not cause an increase in nymphal tick infection prevalence. The net result of lizard removal was a decrease in the density of infected nymphal ticks, and therefore a decreased risk to humans of Lyme disease. Our results indicate that an incompetent reservoir for a pathogen may, in fact, increase disease risk through the maintenance of higher vector density and therefore, higher density of infected vectors. PMID:21325326

  16. Role of Experience and Context in Learning To Diagnose Lyme Disease.

    ERIC Educational Resources Information Center

    Bakken, Lori L.

    2002-01-01

    Using grounded theory, the learning processes used by nine physicians to diagnose Lyme Disease were investigated. Repetition and counterexperiences served to frame the problem along a continuum of familiarity. Results suggest ways to prepare case studies that include variety, repetition, and counterexperiences to teach diagnosis. (Contains 28…

  17. Applying Educational Psychology and Instructional Technology to Health Care Issues: Combating Lyme Disease.

    ERIC Educational Resources Information Center

    Lawless, Kimberly A.; Brown, Scott W.; Cartter, Matthew

    1997-01-01

    Examines the effects of an instructional video on knowledge, attitudes, and behaviors of high school students concerning Lyme disease. Results indicate a positive and sustained increase of students' knowledge as a result of the short intervention but show less positive results for the long-term effect on students' attitudes and behaviors.…

  18. Borrelia burgdorferi elongation factor EF-Tu is an immunogenic protein during Lyme borreliosis.

    PubMed

    Carrasco, Sebastian E; Yang, Youyun; Troxell, Bryan; Yang, Xiuli; Pal, Utpal; Yang, X Frank

    2015-09-02

    Borrelia burgdorferi, the etiological agent of Lyme disease, does not produce lipopolysaccharide but expresses a large number of lipoproteins on its cell surface. These outer membrane lipoproteins are highly immunogenic and have been used for serodiagnosis of Lyme disease. Recent studies have shown that highly conserved cytosolic proteins such as enolase and elongation factor Tu (EF-Tu) unexpectedly localized on the surface of bacteria including B. burgdorferi, and surface-localized enolase has shown to contribute to the enzootic cycle of B. burgdorferi. In this study, we studied the immunogenicity, surface localization, and function of B. burgdorferi EF-Tu. We found that EF-Tu is highly immunogenic in mice, and EF-Tu antibodies were readily detected in Lyme disease patients. On the other hand, active immunization studies showed that EF-Tu antibodies did not protect mice from infection when challenged with B. burgdorferi via either needle inoculation or tick bites. Borrelial mouse-tick cycle studies showed that EF-Tu antibodies also did not block B. burgdorferi migration and survival in ticks. Consistent with these findings, we found that EF-Tu primarily localizes in the protoplasmic cylinder of spirochetes and is not on the surface of B. burgdorferi. Taken together, our studies suggest that B. burgdorferi EF-Tu is not surfaced exposed, but it is highly immunogenic and is a potential serodiagnostic marker for Lyme borreliosis.

  19. Repeated holdout Cross-Validation of Model to Estimate Risk of Lyme Disease by Landscape Attributes

    EPA Science Inventory

    We previously modeled Lyme disease (LD) risk at the landscape scale; here we evaluate the model's overall goodness-of-fit using holdout validation. Landscapes were characterized within road-bounded analysis units (AU). Observed LD cases (obsLD) were ascertained per AU. Data were ...

  20. Images in Health Surveillance: Tickborne Disease Vectors and Lyme Disease Clinical Diagnosis

    DTIC Science & Technology

    2012-05-01

    Rocky Mountain spotted fever (RMSF) ehrlichiosis, anaplasmosis...have vary- ing geographic distributions. In the U.S. tickborne diseases include Lyme disease, Rocky Mountain spotted fever (RMSF), ehrlichiosis...Tick vectors of Rocky Mountain Spotted Fever (RMSF) and other diseases Dermacentor variabilis, the American dog tick or wood tick, is found in

  1. Are Independent Probes Truly Independent?

    ERIC Educational Resources Information Center

    Camp, Gino; Pecher, Diane; Schmidt, Henk G.; Zeelenberg, Rene

    2009-01-01

    The independent cue technique has been developed to test traditional interference theories against inhibition theories of forgetting. In the present study, the authors tested the critical criterion for the independence of independent cues: Studied cues not presented during test (and unrelated to test cues) should not contribute to the retrieval…

  2. Consequences of Landscape Fragmentation on Lyme Disease Risk: A Cellular Automata Approach

    PubMed Central

    Li, Sen; Hartemink, Nienke; Speybroeck, Niko; Vanwambeke, Sophie O.

    2012-01-01

    The abundance of infected Ixodid ticks is an important component of human risk of Lyme disease, and various empirical studies have shown that this is associated, at least in part, to landscape fragmentation. In this study, we aimed at exploring how varying woodland fragmentation patterns affect the risk of Lyme disease, through infected tick abundance. A cellular automata model was developed, incorporating a heterogeneous landscape with three interactive components: an age-structured tick population, a classical disease transmission function, and hosts. A set of simplifying assumptions were adopted with respect to the study objective and field data limitations. In the model, the landscape influences both tick survival and host movement. The validation of the model was performed with an empirical study. Scenarios of various landscape configurations (focusing on woodland fragmentation) were simulated and compared. Lyme disease risk indices (density and infection prevalence of nymphs) differed considerably between scenarios: (i) the risk could be higher in highly fragmented woodlands, which is supported by a number of recently published empirical studies, and (ii) grassland could reduce the risk in adjacent woodland, which suggests landscape fragmentation studies of zoonotic diseases should not focus on the patch-level woodland patterns only, but also on landscape-level adjacent land cover patterns. Further analysis of the simulation results indicated strong correlations between Lyme disease risk indices and the density, shape and aggregation level of woodland patches. These findings highlight the strong effect of the spatial patterns of local host population and movement on the spatial dynamics of Lyme disease risks, which can be shaped by woodland fragmentation. In conclusion, using a cellular automata approach is beneficial for modelling complex zoonotic transmission systems as it can be combined with either real world landscapes for exploring direct spatial

  3. Consequences of landscape fragmentation on Lyme disease risk: a cellular automata approach.

    PubMed

    Li, Sen; Hartemink, Nienke; Speybroeck, Niko; Vanwambeke, Sophie O

    2012-01-01

    The abundance of infected Ixodid ticks is an important component of human risk of Lyme disease, and various empirical studies have shown that this is associated, at least in part, to landscape fragmentation. In this study, we aimed at exploring how varying woodland fragmentation patterns affect the risk of Lyme disease, through infected tick abundance. A cellular automata model was developed, incorporating a heterogeneous landscape with three interactive components: an age-structured tick population, a classical disease transmission function, and hosts. A set of simplifying assumptions were adopted with respect to the study objective and field data limitations. In the model, the landscape influences both tick survival and host movement. The validation of the model was performed with an empirical study. Scenarios of various landscape configurations (focusing on woodland fragmentation) were simulated and compared. Lyme disease risk indices (density and infection prevalence of nymphs) differed considerably between scenarios: (i) the risk could be higher in highly fragmented woodlands, which is supported by a number of recently published empirical studies, and (ii) grassland could reduce the risk in adjacent woodland, which suggests landscape fragmentation studies of zoonotic diseases should not focus on the patch-level woodland patterns only, but also on landscape-level adjacent land cover patterns. Further analysis of the simulation results indicated strong correlations between Lyme disease risk indices and the density, shape and aggregation level of woodland patches. These findings highlight the strong effect of the spatial patterns of local host population and movement on the spatial dynamics of Lyme disease risks, which can be shaped by woodland fragmentation. In conclusion, using a cellular automata approach is beneficial for modelling complex zoonotic transmission systems as it can be combined with either real world landscapes for exploring direct spatial

  4. Mitigation of Variability among 3D Echocardiography-Derived Regional Strain Values Acquired by Multiple Ultrasound Systems by Vendor Independent Analysis

    PubMed Central

    Streiff, Cole; Zhu, Meihua; Shimada, Eriko; Sahn, David J.; Ashraf, Muhammad

    2016-01-01

    Introduction This study compared the variability of 3D echo derived circumferential and longitudinal strain values computed from vendor-specific and vendor-independent analyses of images acquired using ultrasound systems from different vendors. Methods Ten freshly harvested porcine hearts were studied. Each heart was mounted on a custom designed phantom and driven to simulate normal cardiac motion. Cardiac rotation was digitally controlled and held constant at 5°, while pumped stroke volume (SV) ranged from 30-70ml. Full-volume image data was acquired using three different ultrasound systems from different vendors. The image data was analyzed for longitudinal and circumferential strains (LS, CS) using both vendor-specific and vendor-independent analysis packages. Results Good linear relationships were observed for each vendor-specific analysis package for both CS and LS at the mid-anterior segment, with correlation coefficients ranging from 0.82–0.91 (CS) and 0.86–0.89 (LS). Comparable linear regressions were observed for results determined by a vendor independent program (CS: R = 0.82–0.89; LS: R = 0.86–0.89). Variability between analysis packages was examined via a series of ANOVA tests. A statistical difference was found between vendor-specific analysis packages (p<0.001), while no such difference was observed between ultrasound systems when using the vendor-independent program (p>0.05). Conclusions Circumferential and longitudinal regional strain values differ when quantified by vendor-specific analysis packages; however, this variability is mitigated by use of a vendor-independent quantification method. These results suggest that echocardiograms acquired using different ultrasound systems could be meaningfully compared using vendor-independent software. PMID:27149685

  5. Longitudinal Transcriptome Analysis Reveals a Sustained Differential Gene Expression Signature in Patients Treated for Acute Lyme Disease

    PubMed Central

    Bouquet, Jerome; Soloski, Mark J.; Swei, Andrea; Cheadle, Chris; Federman, Scot; Billaud, Jean-Noel; Rebman, Alison W.; Kabre, Beniwende; Halpert, Richard; Boorgula, Meher

    2016-01-01

    ABSTRACT Lyme disease is a tick-borne illness caused by the bacterium Borrelia burgdorferi, and approximately 10 to 20% of patients report persistent symptoms lasting months to years despite appropriate treatment with antibiotics. To gain insights into the molecular basis of acute Lyme disease and the ensuing development of post-treatment symptoms, we conducted a longitudinal transcriptome study of 29 Lyme disease patients (and 13 matched controls) enrolled at the time of diagnosis and followed for up to 6 months. The differential gene expression signature of Lyme disease following the acute phase of infection persisted for at least 3 weeks and had fewer than 44% differentially expressed genes (DEGs) in common with other infectious or noninfectious syndromes. Early Lyme disease prior to antibiotic therapy was characterized by marked upregulation of Toll-like receptor signaling but lack of activation of the inflammatory T-cell apoptotic and B-cell developmental pathways seen in other acute infectious syndromes. Six months after completion of therapy, Lyme disease patients were found to have 31 to 60% of their pathways in common with three different immune-mediated chronic diseases. No differential gene expression signature was observed between Lyme disease patients with resolved illness to those with persistent symptoms at 6 months post-treatment. The identification of a sustained differential gene expression signature in Lyme disease suggests that a panel of selected human host-based biomarkers may address the need for sensitive clinical diagnostics during the “window period” of infection prior to the appearance of a detectable antibody response and may also inform the development of new therapeutic targets. PMID:26873097

  6. Munchausen's syndrome by proxy and Lyme disease: medical misogyny or diagnostic mystery?

    PubMed

    Sherr, Virginia T

    2005-01-01

    Chronic, tertiary Lyme disease, a vector-borne infection most accurately designated neuroborreliosis, is often misdiagnosed. Infectors of the human brain, Lyme borrelial spirochetes are neurotropic, similar to the spirochetes of syphilis. Symptoms of either disease may be stable and persistent, transient and inconsistent or severe yet fleeting. Characteristics may be incompatible with established knowledge of neurological dermatomes, appearing to conventional medical eyes as anatomically impossible, thus creating confusion for doctors, parents and child patients. Physicians unfamiliar with Lyme patients' shifting, seemingly vague, emotional, and/or bizarre-sounding complaints, frequently know little about late-stage spirochetal disease. Consequently, they may accuse mothers of fabricating their children's symptoms--the so-called Munchausen's by proxy (MBP) "diagnoses." Women, following ancient losses of feminine authority in provinces of religion, ethics, and healing - disciplines comprising known fields of early medicine, have been scapegoated throughout history. In the Middle Ages, women considered potentially weak-minded devil's apprentices became victims of witch-hunts throughout Europe and America. Millions of women were burned alive at the stake. Modern medicine's tendency to trivialize women's "offbeat" concerns and the fact that today's hurried physicians of both genders tend to seek easy panaceas, frequently result in the misogyny of mother-devaluation, especially by doctors who are spirochetally naïve. These factors, when involving cases of cryptic neuroborreliosis, may lead to accusations of MBP. Thousands of children, sick from complex diseases, have been forcibly removed from mothers who insist, contrary to customary evaluations, that their children are ill. The charges against these mothers relate to the idea they believe their children sick to satisfy warped internal agendas of their own. "MBP mothers" are then vilified, frequently jailed and

  7. Comparison of Five Diagnostic Modalities for Direct Detection of Borrelia burgdorferi in Patients with Early Lyme Disease

    PubMed Central

    Liveris, Dionysios; Schwartz, Ira; McKenna, Donna; Nowakowski, John; Nadelman, Robert; DeMarco, Joseph; Iyer, Radha; Bittker, Susan; Cooper, Denise; Holmgren, Diane; Wormser, Gary P.

    2012-01-01

    Lyme disease, the most commonly reported tick-borne infection in North America, is caused by infection with the spirochete Borrelia burgdorferi. Although an accurate clinical diagnosis can often be made based on the presence of erythema migrans, in research studies microbiologic or molecular microbiologic confirmation of the diagnosis may be required. In this study, we evaluated the sensitivity of five direct diagnostic methods (culture and nested PCR of a 2 mm skin biopsy specimen, nested PCR and quantitative PCR (qPCR) performed on the same 1 mL aliquot of plasma and a novel qPCR-blood culture method) in 66 untreated adult patients with erythema migrans. One or more these tests were positive in 93.9% of the patients. Culture was more sensitive than PCR for both skin and blood, but the difference was only statistically significant for blood samples (p< 0.005). Blood culture was significantly more likely to be positive in patients with multiple erythema migrans skin lesions compared to those with a single lesion (p=0.001). Positive test results among the 48 patients for whom all five assays were performed invariably included either a positive blood or skin culture. The results of this study demonstrate that direct detection methods such as PCR and culture are highly sensitive in untreated adult patients with erythema migrans. This enabled microbiologic or molecular microbiologic confirmation of the diagnosis of B. burgdorferi infection in all but four (6.1%) of the 66 patients evaluated. PMID:22571973

  8. Reviewing molecular adaptations of Lyme borreliosis spirochetes in the context of reproductive fitness in natural transmission cycles

    PubMed Central

    Tsao, Jean I.

    2009-01-01

    Lyme borreliosis (LB) is caused by a group of pathogenic spirochetes – most often Borrelia burgdorferi, B. afzelii, and B. garinii – that are vectored by hard ticks in the Ixodes ricinus-persulcatus complex, which feed on a variety of mammals, birds, and lizards. Although LB is one of the best-studied vector-borne zoonoses, the annual incidence in North America and Europe leads other vector-borne diseases and continues to increase. What factors make the LB system so successful, and how can researchers hope to reduce disease risk – either through vaccinating humans or reducing the risk of contacting infected ticks in nature? Discoveries of molecular interactions involved in the transmission of LB spirochetes have accelerated recently, revealing complex interactions among the spirochete-tick-vertebrate triad. These interactions involve multiple, and often redundant, pathways that reflect the evolution of general and specific mechanisms by which the spirochetes survive and reproduce. Previous reviews have focused on the molecular interactions or population biology of the system. Here molecular interactions among the LB spirochete, its vector, and vertebrate hosts are reviewed in the context of natural maintenance cycles, which represent the ecological and evolutionary contexts that shape these interactions. This holistic system approach may help researchers develop additional testable hypotheses about transmission processes, interpret laboratory results, and guide development of future LB control measures and management. PMID:19368764

  9. Analysis of the Genetic Phylogeny of Multifocal Prostate Cancer Identifies Multiple Independent Clonal Expansions in Neoplastic and Morphologically Normal Prostate Tissue

    PubMed Central

    Gundem, Gunes; Alexandrov, Ludmil B; Kremeyer, Barbara; Butler, Adam; Lynch, Andrew G; Camacho, Niedzica; Massie, Charlie E; Kay, Jonathan; Luxton, Hayley J; Edwards, Sandra; Kote-Jarai, ZSofia; Dennis, Nening; Merson, Sue; Leongamornlert, Daniel; Zamora, Jorge; Corbishley, Cathy; Thomas, Sarah; Nik-Zainal, Serena; O’Meara, Sarah; Matthews, Lucy; Clark, Jeremy; Hurst, Rachel; Mithen, Richard; Bristow, Robert G; Boutros, Paul C; Fraser, Michael; Cooke, Susanna; Raine, Keiran; Jones, David; Menzies, Andrew; Stebbings, Lucy; Hinton, Jon; Teague, Jon; McLaren, Stuart; Mudie, Laura; Hardy, Claire; Anderson, Elizabeth; Joseph, Olivia; Goody, Victoria; Robinson, Ben; Maddison, Mark; Gamble, Stephen; Greenman, Christopher; Berney, Dan; Hazell, Steven; Livni, Naomi; Fisher, Cyril; Ogden, Christopher; Kumar, Pardeep; Thompson, Alan; Woodhouse, Christopher; Nicol, David; Mayer, Erik; Dudderidge, Tim; Shah, Nimish C; Gnanapragasam, Vincent; Voet, Thierry; Campbell, Peter; Futreal, Andrew; Easton, Douglas; Stratton, Michael R

    2015-01-01

    Whole genome DNA sequencing was used to decrypt the phylogeny of multiple samples from distinct areas of cancer and morphologically normal tissue taken from the prostates of three men. Mutations were present at high levels in morphologically normal tissue distant from the cancer reflecting clonal expansions, and the underlying mutational processes at work in morphologically normal tissue were also at work in cancer. Our observations demonstrate the existence of on-going abnormal mutational processes, consistent with field-effects, underlying carcinogenesis. This mechanism gives rise to extensive branching evolution and cancer clone mixing as exemplified by the coexistence of multiple cancer lineages harboring distinct ERG fusions within a single cancer nodule. Subsets of mutations were shared either by morphologically normal and malignant tissue or between different ERG-lineages, indicating earlier or separate clonal cell expansions. Our observations inform on the origin of multifocal disease and have implications for prostate cancer therapy in individual cases. PMID:25730763

  10. Analysis of the genetic phylogeny of multifocal prostate cancer identifies multiple independent clonal expansions in neoplastic and morphologically normal prostate tissue.

    PubMed

    Cooper, Colin S; Eeles, Rosalind; Wedge, David C; Van Loo, Peter; Gundem, Gunes; Alexandrov, Ludmil B; Kremeyer, Barbara; Butler, Adam; Lynch, Andrew G; Camacho, Niedzica; Massie, Charlie E; Kay, Jonathan; Luxton, Hayley J; Edwards, Sandra; Kote-Jarai, Zsofia; Dennis, Nening; Merson, Sue; Leongamornlert, Daniel; Zamora, Jorge; Corbishley, Cathy; Thomas, Sarah; Nik-Zainal, Serena; Ramakrishna, Manasa; O'Meara, Sarah; Matthews, Lucy; Clark, Jeremy; Hurst, Rachel; Mithen, Richard; Bristow, Robert G; Boutros, Paul C; Fraser, Michael; Cooke, Susanna; Raine, Keiran; Jones, David; Menzies, Andrew; Stebbings, Lucy; Hinton, Jon; Teague, Jon; McLaren, Stuart; Mudie, Laura; Hardy, Claire; Anderson, Elizabeth; Joseph, Olivia; Goody, Victoria; Robinson, Ben; Maddison, Mark; Gamble, Stephen; Greenman, Christopher; Berney, Dan; Hazell, Steven; Livni, Naomi; Fisher, Cyril; Ogden, Christopher; Kumar, Pardeep; Thompson, Alan; Woodhouse, Christopher; Nicol, David; Mayer, Erik; Dudderidge, Tim; Shah, Nimish C; Gnanapragasam, Vincent; Voet, Thierry; Campbell, Peter; Futreal, Andrew; Easton, Douglas; Warren, Anne Y; Foster, Christopher S; Stratton, Michael R; Whitaker, Hayley C; McDermott, Ultan; Brewer, Daniel S; Neal, David E

    2015-04-01

    Genome-wide DNA sequencing was used to decrypt the phylogeny of multiple samples from distinct areas of cancer and morphologically normal tissue taken from the prostates of three men. Mutations were present at high levels in morphologically normal tissue distant from the cancer, reflecting clonal expansions, and the underlying mutational processes at work in morphologically normal tissue were also at work in cancer. Our observations demonstrate the existence of ongoing abnormal mutational processes, consistent with field effects, underlying carcinogenesis. This mechanism gives rise to extensive branching evolution and cancer clone mixing, as exemplified by the coexistence of multiple cancer lineages harboring distinct ERG fusions within a single cancer nodule. Subsets of mutations were shared either by morphologically normal and malignant tissues or between different ERG lineages, indicating earlier or separate clonal cell expansions. Our observations inform on the origin of multifocal disease and have implications for prostate cancer therapy in individual cases.

  11. Whole Genome Sequence and Comparative Genomics of the Novel Lyme Borreliosis Causing Pathogen, Borrelia mayonii

    PubMed Central

    Batra, Dhwani; Replogle, Adam; Rowe, Lori A.; Pritt, Bobbi S.; Petersen, Jeannine M.

    2016-01-01

    Borrelia mayonii, a Borrelia burgdorferi sensu lato (Bbsl) genospecies, was recently identified as a cause of Lyme borreliosis (LB) among patients from the upper midwestern United States. By microscopy and PCR, spirochete/genome loads in infected patients were estimated at 105 to 106 per milliliter of blood. Here, we present the full chromosome and plasmid sequences of two B. mayonii isolates, MN14-1420 and MN14-1539, cultured from blood of two of these patients. Whole genome sequencing and assembly was conducted using PacBio long read sequencing (Pacific Biosciences RSII instrument) followed by hierarchical genome-assembly process (HGAP). The B. mayonii genome is ~1.31 Mbp in size (26.9% average GC content) and is comprised of a linear chromosome, 8 linear and 7 circular plasmids. Consistent with its taxonomic designation as a new Bbsl genospecies, the B. mayonii linear chromosome shares only 93.83% average nucleotide identity with other genospecies. Both B. mayonii genomes contain plasmids similar to B. burgdorferi sensu stricto lp54, lp36, lp28-3, lp28-4, lp25, lp17, lp5, 5 cp32s, cp26, and cp9. The vls locus present on lp28-10 of B. mayonii MN14-1420 is remarkably long, being comprised of 24 silent vls cassettes. Genetic differences between the two B. mayonii genomes are limited and include 15 single nucleotide variations as well as 7 fewer silent vls cassettes and a lack of the lp5 plasmid in MN14-1539. Notably, 68 homologs to proteins present in B. burgdorferi sensu stricto appear to be lacking from the B. mayonii genomes. These include the complement inhibitor, CspZ (BB_H06), the fibronectin binding protein, BB_K32, as well as multiple lipoproteins and proteins of unknown function. This study shows the utility of long read sequencing for full genome assembly of Bbsl genomes, identifies putative genome regions of B. mayonii that may be linked to clinical manifestation or tissue tropism, and provides a valuable resource for pathogenicity, diagnostic and

  12. Salam's independence

    NASA Astrophysics Data System (ADS)

    Fraser, Gordon

    2009-01-01

    In his kind review of my biography of the Nobel laureate Abdus Salam (December 2008 pp45-46), John W Moffat wrongly claims that Salam had "independently thought of the idea of parity violation in weak interactions".

  13. GIS and Remote Sensing Use in the Exploration of Lyme Disease Epidemiology

    PubMed Central

    Ozdenerol, Esra

    2015-01-01

    Given the relatively recent recognition of Lyme disease (LD) by CDC in 1990 as a nationally notifiable infectious condition, the rise of reported human cases every year argues for a better understanding of its geographic scope. The aim of this inquiry was to explore research conducted on spatiotemporal patterns of Lyme disease in order to identify strategies for implementing vector and reservoir-targeted interventions. The focus of this review is on the use of GIS-based methods to study populations of the reservoir hosts, vectors and humans in addition to the spatiotemporal interactions between these populations. New GIS-based studies are monitoring occurrence at the macro-level, and helping pinpoint areas of occurrence at the micro-level, where spread within populations of reservoir hosts, clusters of infected ticks and tick to human transmission may be better understood. PMID:26633445

  14. Seroprevalence of Lyme disease in gray wolves from Minnesota and Wisconsin

    USGS Publications Warehouse

    Thieking, A.; Goyal, S.M.; Bey, R.F.; Loken, K.I.; Mech, L.D.; Thiel, R.P.; O'Connor, T.P.

    1992-01-01

    To determine the seroprevalence of Lyme disease in gray wolves (Canis lupus) from various counties of Minnesota and Wisconsin (USA), 589 serum samples were collected from 528 wolves from 1972 to 1989. An indirect fluorescent antibody (IFA) test was used to detect the presence of antibodies against Borrelia burgdorferi. Titers of greater than or equal to 1:100 were considered positive. Results were confirmed by testing a few selected sera by Western blotting. Of the 589 sera tested, 15 (3%) had IFA titers of greater than or equal to 1:100. Three of the positive samples were collected from Douglas County in Wisconsin and twelve were from Minnesota counties. This study indicates that wolves are exposed to B. burgdorferi and are susceptible to Lyme disease.

  15. Interactions of phagocytes with the Lyme disease spirochete: role of the Fc receptor

    SciTech Connect

    Benach, J.L.; Fleit, H.B.; Habicht, G.S.; Coleman, J.L.; Bosler, E.M.; Lane, B.P.

    1984-10-01

    The phagocytic capacity of murine and human mononuclear and polymorphonuclear phagocytes (including peripheral blood monocytes and neutrophils), rabbit and murine peritoneal exudate cells, and the murine macrophage cell line P388D1 against the Lyme disease spirochete was studied. All of these cells were capable of phagocytosing the spirochete; phagocytosis was measured by the uptake of radiolabeled spirochetes, the appearance of immunofluorescent bodies in phagocytic cells, and electron microscopy. Both opsonized and nonopsonized organisms were phagocytosed. The uptake of opsonized organisms by neutrophils was blocked by a monoclonal antibody specific for the Fc receptor and by immune complexes; these findings suggested that most phagocytosis is mediated by the Fc receptor. Similarly, the uptake of opsonized organisms by human monocytes was inhibited by human monomeric IgG1 and by immune complexes. These results illustrate the role of immune phagocytosis of spirochetes in host defense against Lyme disease.

  16. Reservoir targeted vaccine against Borrelia burgdorferi: a new strategy to prevent Lyme disease transmission.

    PubMed

    Richer, Luciana Meirelles; Brisson, Dustin; Melo, Rita; Ostfeld, Richard S; Zeidner, Nordin; Gomes-Solecki, Maria

    2014-06-15

    A high prevalence of infection with Borrelia burgdorferi in ixodid ticks is correlated with a high incidence of Lyme disease. The transmission of B. burgdorferi to humans can be disrupted by targeting 2 key elements in its enzootic cycle: the reservoir host and the tick vector. In a prospective 5-year field trial, we show that oral vaccination of wild white-footed mice resulted in outer surface protein A-specific seropositivity that led to reductions of 23% and 76% in the nymphal infection prevalence in a cumulative, time-dependent manner (2 and 5 years, respectively), whereas the proportion of infected ticks recovered from control plots varied randomly over time. Significant decreases in tick infection prevalence were observed within 3 years of vaccine deployment. Implementation of such a long-term public health measure could substantially reduce the risk of human exposure to Lyme disease.

  17. GIS and Remote Sensing Use in the Exploration of Lyme Disease Epidemiology.

    PubMed

    Ozdenerol, Esra

    2015-12-01

    Given the relatively recent recognition of Lyme disease (LD) by CDC in 1990 as a nationally notifiable infectious condition, the rise of reported human cases every year argues for a better understanding of its geographic scope. The aim of this inquiry was to explore research conducted on spatiotemporal patterns of Lyme disease in order to identify strategies for implementing vector and reservoir-targeted interventions. The focus of this review is on the use of GIS-based methods to study populations of the reservoir hosts, vectors and humans in addition to the spatiotemporal interactions between these populations. New GIS-based studies are monitoring occurrence at the macro-level, and helping pinpoint areas of occurrence at the micro-level, where spread within populations of reservoir hosts, clusters of infected ticks and tick to human transmission may be better understood.

  18. Immunochip analyses identify a novel risk locus for primary biliary cirrhosis at 13q14, multiple independent associations at four established risk loci and epistasis between 1p31 and 7q32 risk variants.

    PubMed

    Juran, Brian D; Hirschfield, Gideon M; Invernizzi, Pietro; Atkinson, Elizabeth J; Li, Yafang; Xie, Gang; Kosoy, Roman; Ransom, Michael; Sun, Ye; Bianchi, Ilaria; Schlicht, Erik M; Lleo, Ana; Coltescu, Catalina; Bernuzzi, Francesca; Podda, Mauro; Lammert, Craig; Shigeta, Russell; Chan, Landon L; Balschun, Tobias; Marconi, Maurizio; Cusi, Daniele; Heathcote, E Jenny; Mason, Andrew L; Myers, Robert P; Milkiewicz, Piotr; Odin, Joseph A; Luketic, Velimir A; Bacon, Bruce R; Bodenheimer, Henry C; Liakina, Valentina; Vincent, Catherine; Levy, Cynthia; Franke, Andre; Gregersen, Peter K; Bossa, Fabrizio; Gershwin, M Eric; deAndrade, Mariza; Amos, Christopher I; Lazaridis, Konstantinos N; Seldin, Michael F; Siminovitch, Katherine A

    2012-12-01

    To further characterize the genetic basis of primary biliary cirrhosis (PBC), we genotyped 2426 PBC patients and 5731 unaffected controls from three independent cohorts using a single nucleotide polymorphism (SNP) array (Immunochip) enriched for autoimmune disease risk loci. Meta-analysis of the genotype data sets identified a novel disease-associated locus near the TNFSF11 gene at 13q14, provided evidence for association at six additional immune-related loci not previously implicated in PBC and confirmed associations at 19 of 22 established risk loci. Results of conditional analyses also provided evidence for multiple independent association signals at four risk loci, with haplotype analyses suggesting independent SNP effects at the 2q32 and 16p13 loci, but complex haplotype driven effects at the 3q25 and 6p21 loci. By imputing classical HLA alleles from this data set, four class II alleles independently contributing to the association signal from this region were identified. Imputation of genotypes at the non-HLA loci also provided additional associations, but none with stronger effects than the genotyped variants. An epistatic interaction between the IL12RB2 risk locus at 1p31and the IRF5 risk locus at 7q32 was also identified and suggests a complementary effect of these loci in predisposing to disease. These data expand the repertoire of genes with potential roles in PBC pathogenesis that need to be explored by follow-up biological studies.

  19. Associations of HLA DR and DQ molecules with Lyme borreliosis in Latvian patients

    PubMed Central

    2012-01-01

    Background Many autoimmune diseases are associated with variants of HLA genes such as those encoding the MHC complex. This correlation is not absolute, but may help in understanding of the molecular mechanism of disease. The purpose of this study was to determine HLA-DR,-DQ alleles in Latvian patients with Lyme borreliosis and control (healthy) persons. Case patients and control subjects were similar in age, gender and ethnic heritage and differed only as regards the presence of Borrelia burgdorferi infection. The study included 25 patients with clinical stage – erythema migrans and 30 control (healthy) persons. HLA genotyping was performed by PCR with sequence-specific primers. Results The results show difference in HLA-DRB1 alleles distribution between patients and control subjects. The frequencies of HLA-DRB1 *04 (OR 11.24; p < 0.007) and HLA-DRB1 *17 (03) (OR 8.05; p < 0.033) were increased in the Lyme disease patients. And the frequency of allele DRB1*13 (OR 0.12; p < 0.017) was lower in Borreliosis patients and higher in control group. But, significant differences in frequencies of HLA-DQ alleles we did not detect. Conclusions HLA predisposition to Lyme borreliosis appears not to be limited to HLA molecules, but some HLA-DR alleles also have a significant influence, and, may have implications in our understanding of pathogenesis of this disease. In particular, HLA-DRB1*04 and DRB1 *17 (03) may contribute to the Lyme borreliosis development in Latvian population PMID:22892251

  20. Population genetic structure of the Lyme disease vector Ixodes scapularis at an apparent spatial expansion front.

    PubMed

    Kelly, Rebecca R; Gaines, David; Gilliam, Will F; Brinkerhoff, R Jory

    2014-10-01

    Modeling and empirical evidence suggests that Lyme disease is undergoing geographic expansion from principal foci in the midwestern and northeastern United States. Virginia is at the southern edge of the current expansion zone and has seen dramatic rise in human Lyme disease cases since 2007, potentially owing to a recent increase in vector abundance. Ixodes scapularis is known throughout the eastern US but behavioral or physiological variation between northern and southern lineages might lead northern-variant ticks to more frequently parasitize humans. We hypothesized that recent spatial and numerical increase in Lyme disease cases is associated with demographic and/or spatial expansion of I. scapularis and that signals of these phenomena would be detectable and discernable in population genetic signals. In summer and fall 2011, we collected nymphal I. scapularis by drag sampling and adult I. scapularis from deer carcasses at hunting check stations at nine sites arranged along an east-west transect through central Virginia. We analyzed 16S mtDNA sequences data from up to 24 I. scapularis individuals collected from each site and detected a total of 24 haplotypes containing 29 segregating sites. We found no evidence for population genetic structure among these sites but we did find strong signals of both demographic and spatial expansion throughout our study system. We found two haplotypes (one individual each) representing a lineage of ticks that is only found in the southeastern United States, with the remaining individuals representing a less genetically diverse clade that is typical of the northern United States, but that has also been detected in the American South. Taken together, these results lead us to conclude that I. scapularis populations in Virginia are expanding and that this expansion may account for recent observed increases in Lyme disease.

  1. Emergence of Ixodes scapularis and Borrelia burgdorferi, the Lyme disease vector and agent, in Ohio.

    PubMed

    Wang, Peng; Glowacki, Meaghan N; Hoet, Armando E; Needham, Glen R; Smith, Kathleen A; Gary, Richard E; Li, Xin

    2014-01-01

    Lyme disease, the most common vector-borne disease in the United States, is caused by a tick-borne infection with Borrelia burgdorferi. Currently, Ohio is considered by the Centers for Disease Control and Prevention (CDC) to be non-endemic for Lyme disease. The low incidence of Lyme disease in this state was largely attributed to the absence of the transmitting vector, Ixodes scapularis, commonly known as the blacklegged tick. However, a tick surveillance program established by Ohio Department of Health indicated that the number of I. scapularis in Ohio had increased sharply in recent years, from 0 - 5 ticks per year during 1983-2008 to 15 in 2009, 40 in 2010, and 184 in 2011. During the fall deer hunting season, examination of deer heads submitted to Ohio Department of Agriculture found 29 I. scapularis from 7 counties in 2010 and 1,830 from 25 counties in 2011. As of 2012, the tick had been found in 57 of the 88 counties of Ohio. In addition, all three active stages (larva, nymph, and adult) of I. scapularis were found in Tiverton Township of Coshocton County, demonstrating the presence of established tick populations at this central Ohio location. Of 530 nymphal or adult I. scapularis analyzed by quantitative polymerase chain reaction (qPCR), 32 (6.1%) tested positive for the B. burgdorferi flaB gene, ranging from 36 to 390,000 copies per tick. Antibodies to B. burgdorferi antigens were detected in 2 of 10 (20%) field-captured Peromyscus leucopus from Tiverton Township, and in 41 of 355 (11.5%) dogs residing in Ohio. Collectively, these data suggest that the enzootic life cycle of B. burgdorferi has become established in Ohio, which poses risk of Lyme disease to people and animals in the area.

  2. Psychiatric Comorbidity and Other Psychological Factors in Patients with “Chronic Lyme Disease”

    PubMed Central

    Hassett, Afton L.; Radvanski, Diane C.; Buyske, Steven; Savage, Shantal V.; Sigal, Leonard H.

    2009-01-01

    Background There is no evidence of current or previous B. burgdorferi infection in most patients evaluated at University-based Lyme disease referral centers. Instead, psychological factors likely exacerbate the persistent diffuse symptoms or “Chronic Multisymptom Illness” incorrectly ascribed to an ongoing chronic infection with B. burgdorferi. The objective of this study was to assess the medical and psychiatric status of such patients and compare these findings to those from patients without CMI. Methods 240 consecutive patients undergoing medical evaluation at an academic Lyme disease referral center in New Jersey were screened for clinical disorders (e.g. depression and anxiety) with diagnoses confirmed by structured clinical interviews. Personality disorders, catastrophizing, and negative and positive affect were also evaluated and all factors were compared between groups and to functional outcomes. Results 60.4% of our sample had symptoms that could not be explained by current Lyme disease or another medical condition other than CMI. After adjusting for age and gender, clinical disorders were more common in CMI than in the comparison group (p<.001, OR 3.54, 95% CI, 1.97 to 6.55), but personality disorders were not significantly more common. CMI patients had higher negative affect, lower positive affect and a greater tendency to catastrophize pain (p<.001) than did the comparison group. Except for personality disorders, all psychological factors were related to worse functioning. Our explanatory model based on these factors was confirmed. Conclusions Psychiatric comorbidity and other psychological factors are prominent in the presentation and outcome of some patients who inaccurately ascribe long-standing symptoms to “chronic Lyme disease.” PMID:19699380

  3. [The clinical picture and course of Lyme disease in children in the city of Krasnoyarsk].

    PubMed

    Bobrova, L V; Bazilevskaia, T N

    1999-01-01

    The paper describes the clinical picture and course of Lyme's disease (LD) in children from the city of Krasnoyarsk. The disease was ascertained to have a wide range of clinical manifestations: cutaneous changes, visceral abnormalities, involvement of the locomotor and nervous systems into the pathological process. The paper characterizes possible late consequences of the prior disease, which justifies the necessity of timely diagnosis and treatment of LD in children.

  4. Combined chemical (fluoranthene) and drought effects on Lumbricus rubellus demonstrate the applicability of the independent action model for multiple stressor assessment.

    PubMed

    Long, Sara M; Reichenberg, Fredrik; Lister, Lindsay J; Hankard, Peter K; Townsend, Joanna; Mayer, Philipp; Wright, Julian; Holmstrup, Martin; Svendsen, Claus; Spurgeon, David J

    2009-03-01

    The combined effect of a chemical (fluoranthene) and a nonchemical stress (reduced soil moisture content) to the widely distributed earthworm Lumbricus rubellus were investigated in a laboratory study. Neither fluoranthene (up to 500 microg/g) nor low soil moisture (15% below optimal) had a significant effect on the survival of the exposed worms, but a significant effect on reproduction (cocoon production rate) was found for both stressors (p < 0.001 in both cases). The response of cocoon production to each stressor could be well described by a logistic model; this suggested that the joint effects may be applicable to description using the independent action (IA) model that is widely used in pharmacology and chemical mixture risk assessment. Fitting of the IA model provided a good description of the combined stressor data (accounting for 53.7% of total variation) and was the most parsimonious model describing joint effect (i.e., the description of the data was not improved by addition of further parameters accounting for synergism or antagonism). Thus, the independent action of the two responses was further supported by measurement of internal fluoranthene exposure. The chemical activity of fluoranthene in worm tissue was correlated only with soil fluoranthene concentration and not with soil moisture content. Taken together these results suggest that the IA model can help interpret the joint effects of chemical and nonchemical stressors. Such analyses should, however, be done with caution since the literature data set suggests that there may be cases where interactions between stressors result in joint effects that differ significantly from IA predictions.

  5. Integrated assessment of behavioral and environmental risk factors for Lyme disease infection on Block Island, Rhode Island.

    PubMed

    Finch, Casey; Al-Damluji, Mohammed Salim; Krause, Peter J; Niccolai, Linda; Steeves, Tanner; O'Keefe, Corrine Folsom; Diuk-Wasser, Maria A

    2014-01-01

    Peridomestic exposure to Borrelia burgdorferi-infected Ixodes scapularis nymphs is considered the dominant means of infection with black-legged tick-borne pathogens in the eastern United States. Population level studies have detected a positive association between the density of infected nymphs and Lyme disease incidence. At a finer spatial scale within endemic communities, studies have focused on individual level risk behaviors, without accounting for differences in peridomestic nymphal density. This study simultaneously assessed the influence of peridomestic tick exposure risk and human behavior risk factors for Lyme disease infection on Block Island, Rhode Island. Tick exposure risk on Block Island properties was estimated using remotely sensed landscape metrics that strongly correlated with tick density at the individual property level. Behavioral risk factors and Lyme disease serology were assessed using a longitudinal serosurvey study. Significant factors associated with Lyme disease positive serology included one or more self-reported previous Lyme disease episodes, wearing protective clothing during outdoor activities, the average number of hours spent daily in tick habitat, the subject's age and the density of shrub edges on the subject's property. The best fit multivariate model included previous Lyme diagnoses and age. The strength of this association with previous Lyme disease suggests that the same sector of the population tends to be repeatedly infected. The second best multivariate model included a combination of environmental and behavioral factors, namely hours spent in vegetation, subject's age, shrub edge density (increase risk) and wearing protective clothing (decrease risk). Our findings highlight the importance of concurrent evaluation of both environmental and behavioral factors to design interventions to reduce the risk of tick-borne infections.

  6. Simple objective detection of human lyme disease infection using immuno-PCR and a single recombinant hybrid antigen.

    PubMed

    Halpern, Micah D; Molins, Claudia R; Schriefer, Martin; Jewett, Mollie W

    2014-08-01

    A serology-based tiered approach has, to date, provided the most effective means of laboratory confirmation of clinically suspected cases of Lyme disease, but it lacks sensitivity in the early stages of disease and is often dependent on subjectively scored immunoblots. We recently demonstrated the use of immuno-PCR (iPCR) for detecting Borrelia burgdorferi antibodies in patient serum samples that were positive for Lyme disease. To better understand the performance of the Lyme disease iPCR assay, the repeatability and variability of the background of the assay across samples from a healthy population (n = 36) were analyzed. Both of these parameters were found to have coefficients of variation of <3%. Using eight antigen-specific iPCR assays and positive call thresholds established for each assay, iPCR IgM and/or IgG diagnosis from Lyme disease patient serum samples (n = 12) demonstrated a strong correlation with that of 2-tier testing. Furthermore, a simplified iPCR approach using a single hybrid antigen and detecting only IgG antibodies confirmed the 2-tier diagnosis in the Lyme disease patient serum samples (n = 12). Validation of the hybrid antigen IgG iPCR assay using a blinded panel of Lyme disease and non-Lyme disease patient serum samples (n = 92) resulted in a sensitivity of 69% (95% confidence interval [CI], 50% to 84%), compared to that of the 2-tier analysis at 59% (95% CI, 41% to 76%), and a specificity of 98% (95% CI, 91% to 100%) compared to that of the 2-tier analysis at 97% (95% CI, 88% to 100%). A single-tier hybrid antigen iPCR assay has the potential to be an improved method for detecting host-generated antibodies against B. burgdorferi.

  7. Microfluidics-based point-of-care test for serodiagnosis of Lyme Disease

    PubMed Central

    Nayak, Samiksha; Sridhara, Archana; Melo, Rita; Richer, Luciana; Chee, Natalie H.; Kim, Jiyoon; Linder, Vincent; Steinmiller, David; Sia, Samuel K.; Gomes-Solecki, Maria

    2016-01-01

    Currently, diagnostic testing for Lyme disease is done by determination of the serologic responses to Borrelia burgdorferi antigens, with the exception of the early localized phase of disease where diagnosis must be done clinically. Here, we describe the use of microfluidics technology to develop a multiplexed rapid lab-on-a-chip point of care (POC) assay for the serologic diagnosis of human Lyme disease. Following ELISA screening of 12 candidate antigens, we tested 8 on a microfluidic diagnostic system, called mChip-Ld, using a set of 60 serological samples. The mChip-Ld test, which can be performed in 15 minutes at the point of care, showed promising performance for detection of antibodies to B. burgdorferi using the PPO triplex test (rP100 + PepVF + rOspC-K, AUC of 0.844) compared to a gold-standard reference of culture confirmed clinical samples. The performance is comparable to the commonly used C6 peptide by lab-based ELISA. In addition, the mChip-Ld test showed promising performance for early-stage diagnosis of the disease using the antigen OspC-K (sensitivity and specificity of 84% and 92%, respectively; AUC of 0.877). Overall, this study underscores the potential of using microfluidics to aid the diagnosis of Lyme disease at the point of care. PMID:27725740

  8. The lyme disease pathogen has no effect on the survival of its rodent reservoir host.

    PubMed

    Voordouw, Maarten J; Lachish, Shelly; Dolan, Marc C

    2015-01-01

    Zoonotic pathogens that cause devastating morbidity and mortality in humans may be relatively harmless in their natural reservoir hosts. The tick-borne bacterium Borrelia burgdorferi causes Lyme disease in humans but few studies have investigated whether this pathogen reduces the fitness of its reservoir hosts under natural conditions. We analyzed four years of capture-mark-recapture (CMR) data on a population of white-footed mice, Peromyscus leucopus, to test whether B. burgdorferi and its tick vector affect the survival of this important reservoir host. We used a multi-state CMR approach to model mouse survival and mouse infection rates as a function of a variety of ecologically relevant explanatory factors. We found no effect of B. burgdorferi infection or tick burden on the survival of P. leucopus. Our estimates of the probability of infection varied by an order of magnitude (0.051 to 0.535) and were consistent with our understanding of Lyme disease in the Northeastern United States. B. burgdorferi establishes a chronic avirulent infection in their rodent reservoir hosts because this pathogen depends on rodent mobility to achieve transmission to its sedentary tick vector. The estimates of B. burgdorferi infection risk will facilitate future theoretical studies on the epidemiology of Lyme disease.

  9. Superfund Record of Decision (EPA Region 5): New Lyme, Ashtabula County, Ohio, September 1985. Final report

    SciTech Connect

    Not Available

    1985-09-27

    The New Lyme Landfill is located near State Route 11 on Dodgeville Road in Ashtabula County, approximately 20 miles south of the City of Ashtabula, Ohio. The landfill occupies about 40 acres of a 100-acre tract. Operations began at the site in 1969, and were initially managed by two farmers. In 1971, the landfill was licensed by the State of Ohio and operations were taken over by a licensed landfill operator. According to documentation, the New Lyme Landfill received household, industrial, commercial, and institutional wastes and construction and demolition debris. However, numerous violations of the license occurred, including: open dumping; improper spreading and compacting of wastes; no State approval for disposal of certain industrial wastes; and excavation of trenches into the shale bedrock. In August 1978, the landfill was closed by the Ashtabula County Health Department. Documents indicate that wastes at the New Lyme Landfill site included: coal tar distillates, asbestos, coal tar, resins and resin tar, paint sludge, oils, paint lacquer thinner, peroxide, corrosive liquids, acetone, xylene, toluene, kerosene, naptha, benzene, linseed oil, mineral oil, fuel oil, chlorinated solvents, 2,4-D, and laboratory chemicals. The selected remedial action is included.

  10. Effects of climate on variability in Lyme disease incidence in the northeastern United States.

    PubMed

    Subak, Susan

    2003-03-15

    Numbers of reported Lyme disease cases have increased dramatically over the past decade in the northeastern United States, but the year-to-year variability is sizable (average standard deviation approximately 30% of the mean). An improved understanding of the causes of such variability would aid in prevention and control of the disease, which is transmitted by a spirochete carried in the "black-legged" tick, Ixodes scapularis. In this study, the variability in reported Lyme disease incidence between 1993 and 2001 in seven northeastern US states was analyzed as an outcome of weather variability. For all seven states analyzed, significant (p < 0.05) positive relations were found for the correlation of early summer disease incidence with the June moisture index (Palmer Hydrological Drought Index) in the region 2 years previously. The correlations may reflect enhanced nymph tick survival in wetter conditions. Few significant relations were found with same-year moisture index, which suggests that moisture has a greater effect on nymph tick survival following the insect's blood meal than before. In some states, significant correlations were observed related to warmer winter weather a year and a half prior to disease incidence, which may have been due to higher survival and activity levels of the white-footed mouse, the main host for Lyme disease-infected ticks.

  11. Cerebrospinal fluid T-regulatory cells recognize Borrelia burgdorferi NAPA in chronic Lyme borreliosis.

    PubMed

    Amedei, A; Codolo, G; Ozolins, D; Ballerini, C; Biagioli, T; Jaunalksne, I; Zilevica, A; D Elios, S; De Bernard, M; D' Elios, M M

    2013-01-01

    The NapA protein of B. burgdorferi is essential for the persistence of spirochetes in ticks. One of the most intriguing aspects of NapA is its potential to interfere with the host immune system. Here, we investigated the role of the acquired immune responses induced by NapA in the cerebrospinal fluids (CSF) of patients with chronic Lyme borreliosis. We evaluated the cytokine profile induced in microglia cells and CSF T cells following NapA stimulation. We report here that NapA induced a regulatory T (Treg) response in the CSF of patients with chronic Lyme borreliosis and it is able to expand this suppressive response by promoting the production of TGF-beta and IL-10 by microglia cells. Collectively, these data strongly support a central role of NapA in promoting both Treg response and immune suppression in the CSF of patients with chronic Lyme borreliosis and suggest that NapA and the Treg pathway may represent novel therapeutic targets for the prevention and treatment of the disease.

  12. Five-Antigen Fluorescent Bead-Based Assay for Diagnosis of Lyme Disease

    PubMed Central

    Hasenkampf, Nicole R.; Barnes, Mary B.; Didier, Elizabeth S.; Philipp, Mario T.; Tardo, Amanda C.

    2016-01-01

    The systematically difficult task of diagnosing Lyme disease can be simplified by sensitive and specific laboratory tests. The currently recommended two-tier test for serology is highly specific but falls short in sensitivity, especially in the early acute phase. We previously examined serially collected serum samples from Borrelia burgdorferi-infected rhesus macaques and defined a combination of antigens that could be utilized for detection of infection at all phases of disease in humans. The five B. burgdorferi antigens, consisting of OspC, OspA, DbpA, OppA2, and the C6 peptide, were combined into a fluorescent cytometric bead-based assay for the detection of B. burgdorferi antigen-specific IgG antibodies. Samples from Lyme disease patients and controls were used to determine the diagnostic value of this assay. Using this sample set, we found that our five-antigen multiplex IgG assay exhibited higher sensitivity (79.5%) than the enzyme immunoassay (EIA) (76.1%), the two-tier test (61.4%), and the C6 peptide enzyme-linked immunosorbent assay (ELISA) (77.2%) while maintaining specificity over 90%. When detection of IgM was added to the bead-based assay, the sensitivity improved to 91%, but at a cost of reduced specificity (78%). These results indicate that the rational combination of antigens in our multiplex assay may offer an improved serodiagnostic test for Lyme disease. PMID:26843487

  13. Development of a Public Health Assessment Tool to Prevent Lyme Disease: Tool Construction and Validation

    PubMed Central

    Garvin, Jennifer Hornung; Gordon, Thomas F; Haignere, Clara; DuCette, Joseph P

    2005-01-01

    This study involved the design and validation of a new Lyme disease risk assessment instrument. The study was funded in part by a research grant from the American Health Information Management Association (AHIMA) Foundation on Research and Education (FORE). The resulting instrument measured theoretical constructs such as attitudes, behaviors, beliefs, skills, and knowledge relative to Lyme disease. The survey assessment tool is described here, and the tool development process, the validation and reliability process, and results are presented. The assessment tool was created by using a standard instrument development process that first involved constructing possible items (questions) based on several health behavior theories and known health risk behaviors. These items were then further refined by using focus groups, a small pilot study, factor analysis, and a large-scale pilot study. Validity and reliability indices were established with a test-retest reliability coefficient of .66, and finally the tool was used among a population living in a Lyme-disease-endemic area. Cronbach's alpha coefficients of .737 for behavioral items, .573 for cognitive items, and .331 for environmental items were established. PMID:18066379

  14. Mitochondrial phylogeny shows multiple independent ecological transitions and northern dispersion despite of Pleistocene glaciations in meadow and steppe vipers (Vipera ursinii and Vipera renardi).

    PubMed

    Zinenko, Oleksandr; Stümpel, Nikolaus; Mazanaeva, Lyudmila; Bakiev, Andrey; Shiryaev, Konstantin; Pavlov, Aleksey; Kotenko, Tatiana; Kukushkin, Oleg; Chikin, Yury; Duisebayeva, Tatiana; Nilson, Göran; Orlov, Nikolai L; Tuniyev, Sako; Ananjeva, Natalia B; Murphy, Robert W; Joger, Ulrich

    2015-03-01

    The phylogeny and historical demography of small Eurasian vipers of the Vipera ursinii and V. renardi complexes were studied using mitochondrial DNA sequences analysed with Bayesian inference, Maximum Likelihood and Maximum Parsimony approaches, and mismatch distributions. Diversification in the group resulted from an initial dispersion in the later Pliocene - Pleistocene in two directions: north-westwards via the Balkans (V. ursinii complex) and north-eastwards from Asia Minor via the Caucasus (V. renardi complex). An independent, comparatively recent transition occurred from montane habitats to lowland grasslands in different mitochondrial lineages during the Late Pleistocene, when representatives of the both complexes had reached lowland steppes to the north. Effective population size showed clear signs of rapid growth in eastern V. renardi, triggered by colonization of vast lowland steppes, but in western V. ursinii complex grew during the Last Glaciation and experienced stabilization in Holocene. Expansion and population growth in lowland lineages of V. renardi was not strongly affected by Pleistocene climatic oscillations, when cold, dry conditions could have favoured species living in open grasslands. The high diversity of closely related haplotypes in the Caucasus and Tien-Shan could have resulted from repetitive expansion-constriction-isolation events in montane regions during Pleistocene climate fluctuations. The mitochondrial phylogeny pattern conflicts with the current taxonomy.

  15. A genome-wide association study of hepatitis B vaccine response in an Indonesian population reveals multiple independent risk variants in the HLA region.

    PubMed

    Png, Eileen; Thalamuthu, Anbupalam; Ong, Rick T H; Snippe, Harm; Boland, Greet J; Seielstad, Mark

    2011-10-01

    We performed a two-stage genome-wide association study (GWAS) of antibody titer in 3614 hepatitis B vaccine recipients from Indonesia's Riau Archipelago, leading to the identification of at least three independent signals within the human leukocyte antigen (HLA) complex. These appear to implicate HLA-DR [rs3135363; P= 6.53 × 10(-22); odds ratio (OR) = 1.53, 95% confidence interval (CI) = 1.35-1.74]; HLA-DP, previously associated with the risk of chronic hepatitis B infection (rs9277535; P= 2.91 × 10(-12); OR = 0.72, 95% CI = 0.63-0.81); and a gene rich HLA Class III interval (rs9267665; P = 1.24 × 10(-17); OR = 2.05, CI = 1.64-2.57). The substantial overlap of these variants and those identified by GWAS of chronic hepatitis B infection confirms vaccine response as a model for infection, while suggesting that the vaccine is least effective in those most at risk of lifelong infection, following exposure to the virus.

  16. Photocatalytic degradation of water contaminants in multiple photoreactors and evaluation of reaction kinetic constants independent of photon absorption, irradiance, reactor geometry, and hydrodynamics.

    PubMed

    Grčić, Ivana; Li Puma, Gianluca

    2013-12-03

    The literature on photocatalytic oxidation of water pollutants often reports reaction kinetic constants, which cannot be unraveled from photoreactor type and experimental conditions. This study addresses this challenging aspect by presenting a general and simple methodology for the evaluation of fundamental "intrinsic" reaction kinetic constants of photocatalytic degradation of water contaminants, which are independent of photoreactor type, catalyst concentration, irradiance levels, and hydrodynamics. The degradation of the model contaminant, oxalic acid (OA) on titanium dioxide (TiO2) aqueous suspensions, was monitored in two annular photoreactors (PR1 and PR2). The photoreactors with significantly different geometries were operated under different hydrodynamic regimes (turbulent batch mode and laminar flow-through recirculation mode), optical thicknesses, catalyst and OA concentrations, and photon irradiances. The local volumetric rate of photon absorption (LVRPA) was evaluated by the six-flux radiation absorption-scattering model (SFM). The SFM was further combined with a comprehensive kinetic model for the adsorption and photodecomposition of OA on TiO2 to determine local reaction rates and, after integration over the reactor volume, the intrinsic reaction kinetic constants. The model could determine the oxidation of OA in both PR1 and PR2 under a wide range of experimental conditions. This study demonstrates a more meaningful way for determining reaction kinetic constants of photocatalytic degradation of water contaminants.

  17. The Brd4 Extraterminal Domain Confers Transcription Activation Independent of pTEFb by Recruiting Multiple Proteins, Including NSD3 ▿ †

    PubMed Central

    Rahman, Shaila; Sowa, Mathew E.; Ottinger, Matthias; Smith, Jennifer A.; Shi, Yang; Harper, J. Wade; Howley, Peter M.

    2011-01-01

    Bromodomain protein 4 (Brd4) plays critical roles in development, cancer progression, and virus-host pathogenesis. To gain mechanistic insight into the various biological functions of Brd4, we performed a proteomic analysis to identify and characterize Brd4-associated cellular proteins. We found that the extraterminal (ET) domain, whose function has to date not been determined, interacts with NSD3, JMJD6, CHD4, GLTSCR1, and ATAD5. These ET-domain interactions were also conserved for Brd2 and Brd3, the other human BET proteins tested. We demonstrated that GLTSCR1, NSD3, and JMJD6 impart a pTEFb-independent transcriptional activation function on Brd4. NSD3 as well as JMJD6 is recruited to regulated genes in a Brd4-dependent manner. Moreover, we found that depletion of Brd4 or NSD3 reduces H3K36 methylation, demonstrating that the Brd4/NSD3 complex regulates this specific histone modification. Our results indicate that the Brd4 ET domain through the recruitment of the specific effectors regulates transcriptional activity. In particular, we show that one of these effectors, NSD3, regulates transcription by modifying the chromatin microenvironment at Brd4 target genes. Our study thus identifies the ET domain as a second important transcriptional regulatory domain for Brd4 in addition to the carboxyl-terminal domain (CTD) that interacts with pTEFb. PMID:21555454

  18. Independent Living.

    ERIC Educational Resources Information Center

    Nathanson, Jeanne H., Ed.

    1994-01-01

    This issue of "OSERS" addresses the subject of independent living of individuals with disabilities. The issue includes a message from Judith E. Heumann, the Assistant Secretary of the Office of Special Education and Rehabilitative Services (OSERS), and 10 papers. Papers have the following titles and authors: "Changes in the…

  19. Comparison of Algorithm-based Estimates of Occupational Diesel Exhaust Exposure to Those of Multiple Independent Raters in a Population-based Case–Control Study

    PubMed Central

    Friesen, Melissa C.

    2013-01-01

    Objectives: Algorithm-based exposure assessments based on patterns in questionnaire responses and professional judgment can readily apply transparent exposure decision rules to thousands of jobs quickly. However, we need to better understand how algorithms compare to a one-by-one job review by an exposure assessor. We compared algorithm-based estimates of diesel exhaust exposure to those of three independent raters within the New England Bladder Cancer Study, a population-based case–control study, and identified conditions under which disparities occurred in the assessments of the algorithm and the raters. Methods: Occupational diesel exhaust exposure was assessed previously using an algorithm and a single rater for all 14 983 jobs reported by 2631 study participants during personal interviews conducted from 2001 to 2004. Two additional raters independently assessed a random subset of 324 jobs that were selected based on strata defined by the cross-tabulations of the algorithm and the first rater’s probability assessments for each job, oversampling their disagreements. The algorithm and each rater assessed the probability, intensity and frequency of occupational diesel exhaust exposure, as well as a confidence rating for each metric. Agreement among the raters, their aggregate rating (average of the three raters’ ratings) and the algorithm were evaluated using proportion of agreement, kappa and weighted kappa (κw). Agreement analyses on the subset used inverse probability weighting to extrapolate the subset to estimate agreement for all jobs. Classification and Regression Tree (CART) models were used to identify patterns in questionnaire responses that predicted disparities in exposure status (i.e., unexposed versus exposed) between the first rater and the algorithm-based estimates. Results: For the probability, intensity and frequency exposure metrics, moderate to moderately high agreement was observed among raters (κw = 0.50–0.76) and between the

  20. The effectiveness of permethrin-treated deer stations for control of the Lyme disease vector Ixodes scapularis on Cape Cod and the islands: a five year experiment

    EPA Science Inventory

    The use of animal host-targeted pesticide application to control blacklegged ticks, which transmit the Lyme disease bacterium between wildlife hosts and humans, is receiving increased attention as an approach to Lyme disease risk management. Included among the attractive features...

  1. The effectiveness of permethrin-treated deer stations for control of the Lyme disease vector Ixodes scapularis on Cape Cod and the Islands

    EPA Science Inventory

    The use of animal host-targeted pesticide application to control blacklegged ticks, which transmit the Lyme disease bacterium between wildlife hosts and humans, is receiving increased attention as an approach to Lyme disease risk management. Included among the attractive feature...

  2. A genome-wide siRNA screen reveals multiple mTORC1 independent signaling pathways regulating autophagy under normal nutritional conditions

    PubMed Central

    Lipinski, Marta M.; Hoffman, Greg; Ng, Aylwin; Zhou, Wen; Py, Bénédicte F.; Hsu, Emily; Liu, Xuxin; Eisenberg, Jason; Liu, Jun; Blenis, John; Xavier, Ramnik J.; Yuan, Junying

    2010-01-01

    Summary Autophagy is a cellular catabolic mechanism that plays an essential function in protecting multicellular eukaryotes from neurodegeneration, cancer and other diseases. However, we still know very little about mechanisms regulating autophagy under normal homeostatic conditions when nutrients are not limiting. In a genome-wide human siRNA screen, we demonstrate that under normal nutrient conditions up regulation of autophagy requires the type III PI3 kinase, but not inhibition of mTORC1, the essential negative regulator of starvation-induced autophagy. We show that a group of growth factors and cytokines inhibit the type III PI3 kinase through multiple pathways, including the MAPK-ERK1/2, Stat3, Akt/Foxo3 and CXCR4/GPCR, which are all known to positively regulate cell growth and proliferation. Our study suggests that the type III PI3 kinase integrates diverse signals to regulate cellular levels of autophagy, and that autophagy and cell proliferation may represent two alternative cell fates that are regulated in a mutually exclusive manner. PMID:20627085

  3. The relationship between deer density, tick abundance, and human cases of Lyme disease in a residential community.

    PubMed

    Kilpatrick, Howard J; LaBonte, Andrew M; Stafford, Kirby C

    2014-07-01

    White-tailed deer (Odocoileus virginianus Zimmerman), serve as the primary host for the adult blacklegged tick (Ixodes scapularis Say), the vector for Lyme disease, human babesiosis, and human granulocytic anaplasmosis. Our objective was to evaluate the degree of association between deer density, tick abundance, and human cases of Lyme disease in one Connecticut community over a 13-yr period. We surveyed 90-98% of all permanent residents in the community six times from 1995 to 2008 to document resident's exposure to tick-related disease and frequency and abundance of deer observations. After hunts were initiated, number and frequency of deer observations in the community were greatly reduced as were resident-reported cases of Lyme disease. Number of resident-reported cases of Lyme disease per 100 households was strongly correlated to deer density in the community. Reducing deer density to 5.1 deer per square kilometer resulted in a 76% reduction in tick abundance, 70% reduction in the entomological risk index, and 80% reduction in resident-reported cases of Lyme disease in the community from before to after a hunt was initiated.

  4. Two Introductions of Lyme Disease into Connecticut: A Geospatial Analysis of Human Cases from 1984 to 2012.

    PubMed

    Xue, Ling; Scoglio, Caterina; McVey, D Scott; Boone, Rebecca; Cohnstaedt, Lee W

    2015-09-01

    Lyme disease has become the most prevalent vector-borne disease in the United States and results in morbidity in humans, especially children. We used historical case distributions to explain vector-borne disease introductions and subsequent geographic expansion in the absence of disease vector data. We used geographic information system analysis of publicly available Connecticut Department of Public Health case data from 1984, 1985, and 1991 to 2012 for the 169 towns in Connecticut to identify the yearly clusters of Lyme disease cases. Our analysis identified the spatial and temporal origins of two separate introductions of Lyme disease into Connecticut and identified the subsequent direction and rate of spread. We defined both epidemic clusters of cases using significant long-term spatial autocorrelation. The incidence-weighted geographic mean analysis indicates a northern trend of geographic expansion for both epidemic clusters. In eastern Connecticut, as the epidemic progressed, the yearly shift in the geographic mean (rate of epidemic expansion) decreased each year until spatial equilibrium was reached in 2007. The equilibrium indicates a transition from epidemic Lyme disease spread to stable endemic transmission, and we associate this with a reduction in incidence. In western Connecticut, the parabolic distribution of the yearly geographic mean indicates that following the establishment of Lyme disease (1988) the epidemic quickly expanded northward and established equilibrium in 2009.

  5. Lyme Disease Risk Influences Human Settlement in the Wildland–Urban Interface: Evidence from a Longitudinal Analysis of Counties in the Northeastern United States

    PubMed Central

    Larsen, Ashley E.; MacDonald, Andrew J.; Plantinga, Andrew J.

    2014-01-01

    The expansion of human settlement into wildland areas, including forests in the eastern United States, has resulted in fragmented forest habitat that has been shown to drive higher entomological risk for Lyme disease. We investigated an alternative pathway between fragmentation and Lyme disease, namely whether increased risk of Lyme disease results in a reduced propensity to settle in high-risk areas at the interface of developed and undeveloped lands. We used longitudinal data analyses at the county level to determine whether Lyme disease incidence (LDI) influences the proportion of the population residing in the wildland–urban interface in 12 high LDI states in the eastern United States. We found robust evidence that a higher LDI reduces the proportion of a county's population residing in the wildland–urban interface in high-LDI states. This study provides some of the first evidence of human behavioral responses to Lyme disease risk via settlement decisions. PMID:25048372

  6. Evidence assessments and guideline recommendations in Lyme disease: the clinical management of known tick bites, erythema migrans rashes and persistent disease

    PubMed Central

    Cameron, Daniel J; Johnson, Lorraine B; Maloney, Elizabeth L

    2014-01-01

    Evidence-based guidelines for the management of patients with Lyme disease were developed by the International Lyme and Associated Diseases Society (ILADS). The guidelines address three clinical questions – the usefulness of antibiotic prophylaxis for known tick bites, the effectiveness of erythema migrans treatment and the role of antibiotic retreatment in patients with persistent manifestations of Lyme disease. Healthcare providers who evaluate and manage patients with Lyme disease are the intended users of the new ILADS guidelines, which replace those issued in 2004 (Exp Rev Anti-infect Ther 2004;2:S1–13). These clinical practice guidelines are intended to assist clinicians by presenting evidence-based treatment recommendations, which follow the Grading of Recommendations Assessment, Development and Evaluation system. ILADS guidelines are not intended to be the sole source of guidance in managing Lyme disease and they should not be viewed as a substitute for clinical judgment nor used to establish treatment protocols. PMID:25077519

  7. Lyme disease risk influences human settlement in the wildland-urban interface: evidence from a longitudinal analysis of counties in the northeastern United States.

    PubMed

    Larsen, Ashley E; MacDonald, Andrew J; Plantinga, Andrew J

    2014-10-01

    The expansion of human settlement into wildland areas, including forests in the eastern United States, has resulted in fragmented forest habitat that has been shown to drive higher entomological risk for Lyme disease. We investigated an alternative pathway between fragmentation and Lyme disease, namely whether increased risk of Lyme disease results in a reduced propensity to settle in high-risk areas at the interface of developed and undeveloped lands. We used longitudinal data analyses at the county level to determine whether Lyme disease incidence (LDI) influences the proportion of the population residing in the wildland-urban interface in 12 high LDI states in the eastern United States. We found robust evidence that a higher LDI reduces the proportion of a county's population residing in the wildland-urban interface in high-LDI states. This study provides some of the first evidence of human behavioral responses to Lyme disease risk via settlement decisions.

  8. Evidence assessments and guideline recommendations in Lyme disease: the clinical management of known tick bites, erythema migrans rashes and persistent disease.

    PubMed

    Cameron, Daniel J; Johnson, Lorraine B; Maloney, Elizabeth L

    2014-09-01

    Evidence-based guidelines for the management of patients with Lyme disease were developed by the International Lyme and Associated Diseases Society (ILADS). The guidelines address three clinical questions - the usefulness of antibiotic prophylaxis for known tick bites, the effectiveness of erythema migrans treatment and the role of antibiotic retreatment in patients with persistent manifestations of Lyme disease. Healthcare providers who evaluate and manage patients with Lyme disease are the intended users of the new ILADS guidelines, which replace those issued in 2004 (Exp Rev Anti-infect Ther 2004;2:S1-13). These clinical practice guidelines are intended to assist clinicians by presenting evidence-based treatment recommendations, which follow the Grading of Recommendations Assessment, Development and Evaluation system. ILADS guidelines are not intended to be the sole source of guidance in managing Lyme disease and they should not be viewed as a substitute for clinical judgment nor used to establish treatment protocols.

  9. Understanding independence

    NASA Astrophysics Data System (ADS)

    Annan, James; Hargreaves, Julia

    2016-04-01

    In order to perform any Bayesian processing of a model ensemble, we need a prior over the ensemble members. In the case of multimodel ensembles such as CMIP, the historical approach of ``model democracy'' (i.e. equal weight for all models in the sample) is no longer credible (if it ever was) due to model duplication and inbreeding. The question of ``model independence'' is central to the question of prior weights. However, although this question has been repeatedly raised, it has not yet been satisfactorily addressed. Here I will discuss the issue of independence and present a theoretical foundation for understanding and analysing the ensemble in this context. I will also present some simple examples showing how these ideas may be applied and developed.

  10. Spinal Cord Stimulation for the Treatment of Upper and Lower Extremity Neuropathic Pain due to Lyme Disease.

    PubMed

    Mearini, Massimo; Podetta, Stefano; Catenacci, Emanuela; d'Auria, Patrizia; Cornali, Claudio; Mortini, Pietro

    2007-04-01

    Background.  Lyme disease is caused by Borrelia, a bacterium transmitted by the bite of a deer tick. A slow developing encephalopathy or an axonal polyneuropathy with distal paresthesia and spinal or radicular pain rarely occurs and can be hard to treat. Materials and Methods.  We report here the case of a 44-year-old woman with four-limb, intolerable, neuropathic pain as sequelae to Lyme disease, which was resistant to conservative measures and was treated successfully with concurrent, thoracic, and cervical percutaneous spinal cord stimulation (SCS). Results.  After 18 months of therapy and follow-up, this patient's analgesia, as a result of SCS, continues to be excellent, with almost complete subjective pain relief and cessation of adjuvant analgesic medication. Conclusions.  SCS may be efficacious for the treatment of neuropathic pain due to Lyme disease.

  11. Lyme borreliosis in southern United Kingdom and a case for a new syndrome, chronic arthropod-borne neuropathy.

    PubMed

    Dryden, M S; Saeed, K; Ogborn, S; Swales, P

    2015-02-01

    This series of serologically confirmed Lyme disease is the largest reported in the UK and represents 508 patients who presented to one hospital in the South of England between 1992 and 2012. The mean rate of borreliosis throughout this period was 9·8/100,000 population, much higher than the reported national rate of 1·7/100,000. The actual rate increased each year until 2009 when it levelled off. Patients clinically presented with rash (71%), neurological symptoms (16%, of whom half had VII cranial nerve palsies), arthropathy (8%), pyrexia (5%), cardiac abnormalities (1%) or other manifestations (<1%). Twenty percent of patients had additional non-specific symptoms of fatigue, myalgia, and cognitive changes. Serological diagnosis was with a two-tiered system of ELISA and immunoblot. There was a marked seasonal presentation in the summer months and in the first and sixth decades of life. A third of patients gave a clear history of a tick bite. The median interval between tick bite and clinical symptoms was 15 days [interquartile range (IQR) 9-28 days], with a further interval of 14 days to clinical diagnosis/treatment (IQR 2-31 days). Most cases were acquired locally and only 5% abroad. Patients responded to standard antibiotic therapy and recurrence or persistence was extremely rare. A second group of patients, not included in the clinical case series, were those who believed they had Lyme disease based on a probable tick bite but were seronegative by currently available validated tests and presented with subjective symptoms. This condition is often labelled chronic Lyme disease. These patients have a different disease from Lyme disease and therefore an alternative name, chronic arthropod-borne neuropathy (CAN), and case definition for this condition is proposed. We suggest that this chronic condition needs to be distinguished from Lyme disease, as calling the chronic illness 'Lyme disease' causes confusion to patients and physicians. We recommend research

  12. Single-tier testing with the C6 peptide ELISA kit compared with two-tier testing for Lyme disease.

    PubMed

    Wormser, Gary P; Schriefer, Martin; Aguero-Rosenfeld, Maria E; Levin, Andrew; Steere, Allen C; Nadelman, Robert B; Nowakowski, John; Marques, Adriana; Johnson, Barbara J B; Dumler, J Stephen

    2013-01-01

    For the diagnosis of Lyme disease, the 2-tier serologic testing protocol for Lyme disease has a number of shortcomings including low sensitivity in early disease; increased cost, time, and labor; and subjectivity in the interpretation of immunoblots. In this study, the diagnostic accuracy of a single-tier commercial C6 ELISA kit was compared with 2-tier testing. The results showed that the C6 ELISA was significantly more sensitive than 2-tier testing with sensitivities of 66.5% (95% confidence interval [CI] 61.7-71.1) and 35.2% (95% CI 30.6-40.1), respectively (P < 0.001) in 403 sera from patients with erythema migrans. The C6 ELISA had sensitivity statistically comparable to 2-tier testing in sera from Lyme disease patients with early neurologic manifestations (88.6% versus 77.3%, P = 0.13) or arthritis (98.3% versus 95.6%, P = 0.38). The specificities of C6 ELISA and 2-tier testing in over 2200 blood donors, patients with other conditions, and Lyme disease vaccine recipients were found to be 98.9% and 99.5%, respectively (P < 0.05, 95% CI surrounding the 0.6 percentage point difference of 0.04 to 1.15). In conclusion, using a reference standard of 2-tier testing, the C6 ELISA as a single-step serodiagnostic test provided increased sensitivity in early Lyme disease with comparable sensitivity in later manifestations of Lyme disease. The C6 ELISA had slightly decreased specificity. Future studies should evaluate the performance of the C6 ELISA compared with 2-tier testing in routine clinical practice.

  13. Different populations of blacklegged tick nymphs exhibit differences in questing behavior that have implications for human lyme disease risk

    USGS Publications Warehouse

    Arsnoe, Isis M.; Hickling, Graham J.; Ginsberg, Howard S.; McElreath, Richard; Tsao, Jean I.

    2015-01-01

    Animal behavior can have profound effects on pathogen transmission and disease incidence. We studied the questing (= host-seeking) behavior of blacklegged tick (Ixodes scapularis) nymphs, which are the primary vectors of Lyme disease in the eastern United States. Lyme disease is common in northern but not in southern regions, and prior ecological studies have found that standard methods used to collect host-seeking nymphs in northern regions are unsuccessful in the south. This led us to hypothesize that there are behavior differences between northern and southern nymphs that alter how readily they are collected, and how likely they are to transmit the etiological agent of Lyme disease to humans. To examine this question, we compared the questing behavior of I. scapularis nymphs originating from one northern (Lyme disease endemic) and two southern (non-endemic) US regions at field sites in Wisconsin, Rhode Island, Tennessee, and Florida. Laboratory-raised uninfected nymphs were monitored in circular 0.2 m2 arenas containing wooden dowels (mimicking stems of understory vegetation) for 10 (2011) and 19 (2012) weeks. The probability of observing nymphs questing on these stems (2011), and on stems, on top of leaf litter, and on arena walls (2012) was much greater for northern than for southern origin ticks in both years and at all field sites (19.5 times greater in 2011; 3.6-11.6 times greater in 2012). Our findings suggest that southern origin I. scapularis nymphs rarely emerge from the leaf litter, and consequently are unlikely to contact passing humans. We propose that this difference in questing behavior accounts for observed geographic differences in the efficacy of the standard sampling techniques used to collect questing nymphs. These findings also support our hypothesis that very low Lyme disease incidence in southern states is, in part, a consequence of the type of host-seeking behavior exhibited by southern populations of the key Lyme disease vector.

  14. Different Populations of Blacklegged Tick Nymphs Exhibit Differences in Questing Behavior That Have Implications for Human Lyme Disease Risk

    PubMed Central

    Arsnoe, Isis M.; Hickling, Graham J.; Ginsberg, Howard S.; McElreath, Richard; Tsao, Jean I.

    2015-01-01

    Animal behavior can have profound effects on pathogen transmission and disease incidence. We studied the questing (= host-seeking) behavior of blacklegged tick (Ixodes scapularis) nymphs, which are the primary vectors of Lyme disease in the eastern United States. Lyme disease is common in northern but not in southern regions, and prior ecological studies have found that standard methods used to collect host-seeking nymphs in northern regions are unsuccessful in the south. This led us to hypothesize that there are behavior differences between northern and southern nymphs that alter how readily they are collected, and how likely they are to transmit the etiological agent of Lyme disease to humans. To examine this question, we compared the questing behavior of I. scapularis nymphs originating from one northern (Lyme disease endemic) and two southern (non-endemic) US regions at field sites in Wisconsin, Rhode Island, Tennessee, and Florida. Laboratory-raised uninfected nymphs were monitored in circular 0.2 m2 arenas containing wooden dowels (mimicking stems of understory vegetation) for 10 (2011) and 19 (2012) weeks. The probability of observing nymphs questing on these stems (2011), and on stems, on top of leaf litter, and on arena walls (2012) was much greater for northern than for southern origin ticks in both years and at all field sites (19.5 times greater in 2011; 3.6–11.6 times greater in 2012). Our findings suggest that southern origin I. scapularis nymphs rarely emerge from the leaf litter, and consequently are unlikely to contact passing humans. We propose that this difference in questing behavior accounts for observed geographic differences in the efficacy of the standard sampling techniques used to collect questing nymphs. These findings also support our hypothesis that very low Lyme disease incidence in southern states is, in part, a consequence of the type of host-seeking behavior exhibited by southern populations of the key Lyme disease vector. PMID

  15. Different populations of blacklegged tick nymphs exhibit differences in questing behavior that have implications for human lyme disease risk.

    PubMed

    Arsnoe, Isis M; Hickling, Graham J; Ginsberg, Howard S; McElreath, Richard; Tsao, Jean I

    2015-01-01

    Animal behavior can have profound effects on pathogen transmission and disease incidence. We studied the questing (= host-seeking) behavior of blacklegged tick (Ixodes scapularis) nymphs, which are the primary vectors of Lyme disease in the eastern United States. Lyme disease is common in northern but not in southern regions, and prior ecological studies have found that standard methods used to collect host-seeking nymphs in northern regions are unsuccessful in the south. This led us to hypothesize that there are behavior differences between northern and southern nymphs that alter how readily they are collected, and how likely they are to transmit the etiological agent of Lyme disease to humans. To examine this question, we compared the questing behavior of I. scapularis nymphs originating from one northern (Lyme disease endemic) and two southern (non-endemic) US regions at field sites in Wisconsin, Rhode Island, Tennessee, and Florida. Laboratory-raised uninfected nymphs were monitored in circular 0.2 m2 arenas containing wooden dowels (mimicking stems of understory vegetation) for 10 (2011) and 19 (2012) weeks. The probability of observing nymphs questing on these stems (2011), and on stems, on top of leaf litter, and on arena walls (2012) was much greater for northern than for southern origin ticks in both years and at all field sites (19.5 times greater in 2011; 3.6-11.6 times greater in 2012). Our findings suggest that southern origin I. scapularis nymphs rarely emerge from the leaf litter, and consequently are unlikely to contact passing humans. We propose that this difference in questing behavior accounts for observed geographic differences in the efficacy of the standard sampling techniques used to collect questing nymphs. These findings also support our hypothesis that very low Lyme disease incidence in southern states is, in part, a consequence of the type of host-seeking behavior exhibited by southern populations of the key Lyme disease vector.

  16. The Western Progression of Lyme Disease: Infectious and Nonclonal Borrelia burgdorferi Sensu Lato Populations in Grand Forks County, North Dakota

    PubMed Central

    Stone, Brandee L.; Russart, Nathan M.; Gaultney, Robert A.; Floden, Angela M.; Vaughan, Jefferson A.

    2014-01-01

    Scant attention has been paid to Lyme disease, Borrelia burgdorferi, Ixodes scapularis, or reservoirs in eastern North Dakota despite the fact that it borders high-risk counties in Minnesota. Recent reports of B. burgdorferi and I. scapularis in North Dakota, however, prompted a more detailed examination. Spirochetes cultured from the hearts of five rodents trapped in Grand Forks County, ND, were identified as B. burgdorferi sensu lato through sequence analyses of the 16S rRNA gene, the 16S rRNA gene-ileT intergenic spacer region, flaB, ospA, ospC, and p66. OspC typing revealed the presence of groups A, B, E, F, L, and I. Two rodents were concurrently carrying multiple OspC types. Multilocus sequence typing suggested the eastern North Dakota strains are most closely related to those found in neighboring regions of the upper Midwest and Canada. BALB/c mice were infected with B. burgdorferi isolate M3 (OspC group B) by needle inoculation or tick bite. Tibiotarsal joints and ear pinnae were culture positive, and B. burgdorferi M3 was detected by quantitative PCR (qPCR) in the tibiotarsal joints, hearts, and ear pinnae of infected mice. Uninfected larval I. scapularis ticks were able to acquire B. burgdorferi M3 from infected mice; M3 was maintained in I. scapularis during the molt from larva to nymph; and further, M3 was transmitted from infected I. scapularis nymphs to naive mice, as evidenced by cultures and qPCR analyses. These results demonstrate that isolate M3 is capable of disseminated infection by both artificial and natural routes of infection. This study confirms the presence of unique (nonclonal) and infectious B. burgdorferi populations in eastern North Dakota. PMID:25304515

  17. The Western progression of lyme disease: infectious and Nonclonal Borrelia burgdorferi Sensu Lato populations in Grand Forks County, North Dakota.

    PubMed

    Stone, Brandee L; Russart, Nathan M; Gaultney, Robert A; Floden, Angela M; Vaughan, Jefferson A; Brissette, Catherine A

    2015-01-01

    Scant attention has been paid to Lyme disease, Borrelia burgdorferi, Ixodes scapularis, or reservoirs in eastern North Dakota despite the fact that it borders high-risk counties in Minnesota. Recent reports of B. burgdorferi and I. scapularis in North Dakota, however, prompted a more detailed examination. Spirochetes cultured from the hearts of five rodents trapped in Grand Forks County, ND, were identified as B. burgdorferi sensu lato through sequence analyses of the 16S rRNA gene, the 16S rRNA gene-ileT intergenic spacer region, flaB, ospA, ospC, and p66. OspC typing revealed the presence of groups A, B, E, F, L, and I. Two rodents were concurrently carrying multiple OspC types. Multilocus sequence typing suggested the eastern North Dakota strains are most closely related to those found in neighboring regions of the upper Midwest and Canada. BALB/c mice were infected with B. burgdorferi isolate M3 (OspC group B) by needle inoculation or tick bite. Tibiotarsal joints and ear pinnae were culture positive, and B. burgdorferi M3 was detected by quantitative PCR (qPCR) in the tibiotarsal joints, hearts, and ear pinnae of infected mice. Uninfected larval I. scapularis ticks were able to acquire B. burgdorferi M3 from infected mice; M3 was maintained in I. scapularis during the molt from larva to nymph; and further, M3 was transmitted from infected I. scapularis nymphs to naive mice, as evidenced by cultures and qPCR analyses. These results demonstrate that isolate M3 is capable of disseminated infection by both artificial and natural routes of infection. This study confirms the presence of unique (nonclonal) and infectious B. burgdorferi populations in eastern North Dakota.

  18. Evidence for Ixodes holocyclus (Acarina: Ixodidae) as a vector for human lyme Borreliosis infection in Australia.

    PubMed

    Mayne, P; Song, S; Shao, R; Burke, J; Wang, Y; Roberts, T

    2014-01-01

    Ixodes holocyclus (Acarina: Ixodidae) and Ixodes cornuatus (Acarina: Ixodidae) are two tick species found in the more densely populated areas of Australia and are known to be the cause of the neurotoxic disease tick paralysis in humans and mammals. Borreliosis otherwise known as Lyme disease is an emerging infectious disease in humans in Australia. Borrelia burgdorferi sensu stricto (Spirochaetales: Spirochaetaceae) and sensu lato are closely related spirochetal species that are the causative agents of Lyme disease in humans. Clinical transmission of this tick-borne disease can be identified in several but not all cases by a characteristic rash known as erythema migrans. However, there has been no study of the tick vectors of this infection in Australia. We used morphological and molecular techniques to identify unequivocally the ticks on the patients of this study to be I. holocyclus and then show the presence of B. burgdorferi sensu stricto infection in erythema migrans biopsies. I. holocyclus has not previously been associated with erythema migrans or Lyme disease. Two patients presented to the lead author's medical practice with erythema migrans in mid and late 2012. The morphology and cytochrome oxidase 1 and ITS2 genes of the two ticks were studied. The skin at the attachment site was sampled by central biopsy for both real time and endpoint Borrelia polymerase chain reaction (PCR) analysis and subsequent sequencing. Morphologically, the two ticks were either I. holocyclus or I. cornuatus. Molecular studies and nucleotide sequencing revealed that both ticks were I. holocyclus. Real time and endpoint PCR on the central tissue biopsy samples returned positive results for B. burgdorferi DNA. Our results are evidence for transmission of B. burgdorferi sensu stricto species to humans by the tick I. holocyclus in Australia. I. holocyclus is commonly associated with human tick bites on virtually the entire eastern coastline of Australia.

  19. Prevalence and spectrum of residual symptoms in Lyme neuroborreliosis after pharmacological treatment: a systematic review.

    PubMed

    Dersch, R; Sommer, H; Rauer, S; Meerpohl, J J

    2016-01-01

    Controversy exists about residual symptoms after pharmacological treatment of Lyme neuroborreliosis. Reports of disabling long-term sequels lead to concerns in patients and health care providers. We systematically reviewed the available evidence from studies reporting treatment of Lyme neuroborreliosis to assess the prevalence and spectrum of residual symptoms after treatment. A literature search was performed in three databases and three clinical trial registers to find eligible studies reporting on residual symptoms in patients after pharmacological treatment of LNB. Diagnosis must have been performed according to consensus-derived case definitions. No restrictions regarding study design or language were set. Symptom prevalence was pooled using a random-effects model. Forty-four eligible clinical trials and studies were found: 8 RCTs, 17 cohort studies, 2 case-control studies, and 17 case series. The follow-up period in the eligible studies ranged from 7 days to 20 years. The weighted mean proportion of residual symptoms was 28 % (95 % CI 23-34 %, n = 34 studies) for the latest reported time point. Prevalence of residual symptoms was statistically significantly higher in studies using the "possible" case definition (p = 0.0048). Cranial neuropathy, pain, paresis, cognitive disturbances, headache, and fatigue were statistically significantly lower in studies using the "probable/definite" case definition. LNB patients may experience residual symptoms after treatment with a prevalence of approximately 28 %. The prevalence and spectrum of residual symptoms differ according to the applied case definition. Symptoms like fatigue are not reported in studies using the "probable/definite" case definition. As the "possible" case definition is more unspecific, patients with other conditions may be included. Reports of debilitating fatigue and cognitive impairment after LNB, a "post-Lyme syndrome", could therefore be an artifact of unspecific case definitions in single

  20. Severity of chronic Lyme disease compared to other chronic conditions: a quality of life survey

    PubMed Central

    Johnson, Lorraine; Wilcox, Spencer; Mankoff, Jennifer

    2014-01-01

    Overview. The Centers for Disease Control and Prevention (CDC) health-related quality of life (HRQoL) indicators are widely used in the general population to determine the burden of disease, identify health needs, and direct public health policy. These indicators also allow the burden of illness to be compared across different diseases. Although Lyme disease has recently been acknowledged as a major health threat in the USA with more than 300,000 new cases per year, no comprehensive assessment of the health burden of this tickborne disease is available. This study assesses the HRQoL of patients with chronic Lyme disease (CLD) and compares the severity of CLD to other chronic conditions. Methods. Of 5,357 subjects who responded to an online survey, 3,090 were selected for the study. Respondents were characterized as having CLD if they were clinically diagnosed with Lyme disease and had persisting symptoms lasting more than 6 months following antibiotic treatment. HRQoL of CLD patients was assessed using the CDC 9-item metric. The HRQoL analysis for CLD was compared to published analyses for the general population and other chronic illnesses using standard statistical methods. Results. Compared to the general population and patients with other chronic diseases reviewed here, patients with CLD reported significantly lower health quality status, more bad mental and physical health days, a significant symptom disease burden, and greater activity limitations. They also reported impairment in their ability to work, increased utilization of healthcare services, and greater out of pocket medical costs. Conclusions. CLD patients have significantly impaired HRQoL and greater healthcare utilization compared to the general population and patients with other chronic diseases. The heavy burden of illness associated with CLD highlights the need for earlier diagnosis and innovative treatment approaches that may reduce the burden of illness and concomitant costs posed by this

  1. Borrelia sinica sp. nov., a lyme disease-related Borrelia species isolated in China.

    PubMed

    Masuzawa, T; Takada, N; Kudeken, M; Fukui, T; Yano, Y; Ishiguro, F; Kawamura, Y; Imai, Y; Ezaki, T

    2001-09-01

    A survey was performed for Lyme disease borrelia in the southern part of China, in Zhejiang, Sichuan and Anhui provinces, along the Yangtze River valley, in May of 1997 and 1998. Twenty isolates from Ixodes granulatus, Ixodes ovatus, Apodemus agrarius and Niviventer confucianus were obtained. These isolates were characterized by RFLP of the 5S-23S rDNA intergenic spacer, sequence analysis of the intergenic spacer, 16S rDNA and flagellin gene, DNA-DNA hybridization analysis, SDS-PAGE and Western blotting with mAbs. Six isolates from A. agrarius, five from I. granulatus collected in Zhejiang province and one from N. confucianus in Sichuan province were highly similar to strains 10MT and 5MT isolated in Korea and classified as Borrelia valaisiana. Four isolates from A. agrarius and I. granulatus collected in Zhejiang province generated unique RFLP patterns and phylogenetic analysis of the 16S rDNA and flagellin gene sequences suggested that the isolates should be classified as B. valaisiana. Furthermore, three isolates (CMN1a, CNM2, CMN3T) from N. confucianus captured in Sichuan province and one (CWO1) from I. ovatus in Anhui province showed lower 165 rDNA sequence similarity (less than 99.0%) to sequences of previously described Lyme disease-related Borrelia species. DNA-DNA hybridization results revealed that strains CMN3T and CMN1a were clearly distinct from all other known Lyme disease Borrelia species. Electron microscope observation showed the spirochaetes to be morphologically similar to those of Borrelia, but the cells contained only four periplasmic flagella inserted at each end of the spirochaetes. Based on these results, a new Borrelia species, Borrelia sinica sp. nov., is proposed. Strain CMN3T is the type strain of this new species.

  2. Design and Development of a Novel Vaccine for Protection against Lyme Borreliosis

    PubMed Central

    Comstedt, Pär; Hanner, Markus; Schüler, Wolfgang; Meinke, Andreas; Lundberg, Urban

    2014-01-01

    There is currently no Lyme borreliosis vaccine available for humans, although it has been shown that the disease can be prevented by immunization with an OspA-based vaccine (LYMErix). Outer surface protein A (OspA) is one of the dominant antigens expressed by the spirochetes when present in a tick. The Borrelia species causing Lyme borreliosis in Europe express different OspA serotypes on their surface, B. burgdorferi (serotype 1), B. afzelii (serotype 2), B. garinii (serotypes, 3, 5 and 6) and B. bavariensis (serotype 4), while only B. burgdorferi is present in the US. In order to target all these pathogenic Borrelia species, we have designed a multivalent OspA-based vaccine. The vaccine includes three proteins, each containing the C-terminal half of two OspA serotypes linked to form a heterodimer. In order to stabilize the C-terminal fragment and thus preserve important structural epitopes at physiological temperature, disulfide bonds were introduced. The immunogenicity was increased by introduction of a lipidation signal which ensures the addition of an N-terminal lipid moiety. Three immunizations with 3.0 µg adjuvanted vaccine protected mice from a challenge with spirochetes expressing either OspA serotype 1, 2 or 5. Mice were protected against both challenge with infected ticks and in vitro grown spirochetes. Immunological analyses (ELISA, surface binding and growth inhibition) indicated that the vaccine can provide protection against the majority of Borrelia species pathogenic for humans. This article presents the approach which allows for the generation of a hexavalent vaccine that can potentially protect against a broad range of globally distributed Borrelia species causing Lyme borreliosis. PMID:25409015

  3. Update of the Swiss guidelines on post-treatment Lyme disease syndrome.

    PubMed

    Nemeth, Johannes; Bernasconi, Enos; Heininger, Ulrich; Abbas, Mohamed; Nadal, David; Strahm, Carol; Erb, Stefan; Zimmerli, Stefan; Furrer, Hansjakob; Delaloye, Julie; Kuntzer, Thierry; Altpeter, Ekkehard; Sturzenegger, Mathias; Weber, Rainer; For The Swiss Society For Infectious Diseases And The Swiss Society For Neurology

    2016-01-01

    Lyme borreliosis is caused by Borrelia burgdorferi sensu lato infection, which responds well to antibiotic therapy in the overwhelming majority of cases. However, despite adequate antibiotic treatment some patients report persisting symptoms which are commonly summarised as post-treatment Lyme disease syndrome (PTLDS). In 2005, the Swiss Society of Infectious Diseases published a case definition for PTLDS. We aimed to review the scientific literature with a special emphasis on the last 10 years, questioning whether the definitions from 2005 are still valid in the light of current knowledge. Furthermore, we describe the clinical history of infection with Borrelia burgdorferi sensu lato, the estimated prevalence of PTLDS, the possible pathogenesis of PTLDS, and treatment options with an emphasis on clinical studies. In summary, we were unable to find a scientific reason for modification of the PTLDS definitions published in 2005. Thus, the diagnostic criteria remain unchanged, namely documented clinical and laboratory evidence of previous infection with B. burgdorferi, a completed course of appropriate antibiotic therapy, symptoms including fatigue, arthralgia, myalgia, cognitive dysfunction or radicular pain persisting for >6 months, a plausible timely association between documented B. burgdorferi infection and onset of symptoms (i.e., persistent or recurrent symptoms that began within 6 months of completion of a recommended antibiotic therapy for early or late Lyme borreliosis), and exclusion of other somatic or psychiatric causes of symptoms. The main therapeutic options remain cognitive behavioural therapy and low-impact aerobic exercise programmes. Growing and unequivocal evidence confirms that prolonged or repeated antibiotic therapy for PTLDS is not beneficial, but potentially harmful and therefore contraindicated. The Guidelines of the Swiss Society of Infectious Diseases offer an evidence based, diagnostic and therapeutic framework for physicians caring for

  4. Synthesis and antigenicity of BBGL-2 glycolipids of Borrelia burgdorferi, the causative agent of Lyme disease

    PubMed Central

    Pozsgay, Vince; Kubler-Kielb, Joanna; Coxon, Bruce; Marques, Adriana; Robbins, John B.; Schneerson, Rachel

    2011-01-01

    Borrelia burgdorferi is the etiological agent for Lyme disease (LD), the most common vector borne disease in the United States. There is no human vaccine against LD currently available. Our approach to a vaccine is based on its surface-exposed glycolipids. One group of these glycolipids termed BBGL-2 consists of 1,2-di-O-acyl-3-O-(α-D-galactopyranosyl)-sn-glycerol congeners having palmitic, oleic, stearic, linoleic, and myristic acids. In order to delineate the immunodominant region(s) of the BBGL-2 components, we embarked on a synthetic project to provide available structurally defined, homogeneous analogs of BBGL-2 that might help identify the best vaccine candidate. The antigenicity of the synthetic glycolipids was examined by dot-blot analysis using mice sera obtained by immunization with killed B. burgdorferi cells, with native BBGL-2 in complete Freund's adjuvant, as well as sera obtained from patients with Lyme disease. We found that the presence of two acyl groups in the glycerol moiety was essential for antigenicity. At least one of these groups must be an oleoyl moiety. Neither the anomeric configuration of the galactose nor the configuration of the glycerol at C-2 was a decisive factor. Based on these findings we designed an `unnatural' BBGL-2 analog having the structure 3-O-(β-D-galactopyranosyl)-1,2-di-O-oleoyl-DL-glycerol which is easier and less expensive to synthesize than the other BBGL-2 congeners prepared in this study. This substance proved to be antigenic and is considered a candidate vaccine for Lyme disease. PMID:21601180

  5. 'Independence' Panorama

    NASA Technical Reports Server (NTRS)

    2005-01-01

    [figure removed for brevity, see original site] Click on the image for 'Independence' Panorama (QTVR)

    This is the Spirit 'Independence' panorama, acquired on martian days, or sols, 536 to 543 (July 6 to 13, 2005), from a position in the 'Columbia Hills' near the summit of 'Husband Hill.' The summit of 'Husband Hill' is the peak near the right side of this panorama and is about 100 meters (328 feet) away from the rover and about 30 meters (98 feet) higher in elevation. The rocky outcrops downhill and on the left side of this mosaic include 'Larry's Lookout' and 'Cumberland Ridge,' which Spirit explored in April, May, and June of 2005.

    The panorama spans 360 degrees and consists of 108 individual images, each acquired with five filters of the rover's panoramic camera. The approximate true color of the mosaic was generated using the camera's 750-, 530-, and 480-nanometer filters. During the 8 martian days, or sols, that it took to acquire this image, the lighting varied considerably, partly because of imaging at different times of sol, and partly because of small sol-to-sol variations in the dustiness of the atmosphere. These slight changes produced some image seams and rock shadows. These seams have been eliminated from the sky portion of the mosaic to better simulate the vista a person standing on Mars would see. However, it is often not possible or practical to smooth out such seams for regions of rock, soil, rover tracks or solar panels. Such is the nature of acquiring and assembling large panoramas from the rovers.

  6. Persisting atypical and cystic forms of Borrelia burgdorferi and local inflammation in Lyme neuroborreliosis

    PubMed Central

    Miklossy, Judith; Kasas, Sandor; Zurn, Anne D; McCall, Sherman; Yu, Sheng; McGeer, Patrick L

    2008-01-01

    Background The long latent stage seen in syphilis, followed by chronic central nervous system infection and inflammation, can be explained by the persistence of atypical cystic and granular forms of Treponema pallidum. We investigated whether a similar situation may occur in Lyme neuroborreliosis. Method Atypical forms of Borrelia burgdorferi spirochetes were induced exposing cultures of Borrelia burgdorferi (strains B31 and ADB1) to such unfavorable conditions as osmotic and heat shock, and exposure to the binding agents Thioflavin S and Congo red. We also analyzed whether these forms may be induced in vitro, following infection of primary chicken and rat neurons, as well as rat and human astrocytes. We further analyzed whether atypical forms similar to those induced in vitro may also occur in vivo, in brains of three patients with Lyme neuroborreliosis. We used immunohistochemical methods to detect evidence of neuroinflammation in the form of reactive microglia and astrocytes. Results Under these conditions we observed atypical cystic, rolled and granular forms of these spirochetes. We characterized these abnormal forms by histochemical, immunohistochemical, dark field and atomic force microscopy (AFM) methods. The atypical and cystic forms found in the brains of three patients with neuropathologically confirmed Lyme neuroborreliosis were identical to those induced in vitro. We also observed nuclear fragmentation of the infected astrocytes using the TUNEL method. Abundant HLA-DR positive microglia and GFAP positive reactive astrocytes were present in the cerebral cortex. Conclusion The results indicate that atypical extra- and intracellular pleomorphic and cystic forms of Borrelia burgdorferi and local neuroinflammation occur in the brain in chronic Lyme neuroborreliosis. The persistence of these more resistant spirochete forms, and their intracellular location in neurons and glial cells, may explain the long latent stage and persistence of Borrelia infection

  7. Cimetidine as a novel adjunctive treatment for early stage Lyme disease.

    PubMed

    Shemenski, Justin

    2016-04-09

    Lyme disease, caused by the spirochete Borrelia burgdorferi (Bb), is the most common vector-borne illness in the United States. It is a complex disease which may affect the skin, joints, heart, eyes, and central nervous system. Prompt diagnosis and treatment is curative in most instances. However, a significant percentage of patients experience ongoing symptoms after treatment. Currently, there is much controversy regarding the diagnosis, pathophysiology, and treatment of Lyme disease. Pathogen persistence despite treatment lies at the heart of this debate. Many believe that the ongoing symptoms are due to factors such as autoimmunity or permanent damage that is incurred during the active infection. However, there is an emerging school of thought that states that ongoing symptoms are due to a persistent infection that is able to survive both the immune response and antibiotic therapy. Numerous studies have shown that Bb can indeed persist within the host despite treatment and several mechanisms have been proposed to explain Bb's persistence capabilities. These include: polymorphism, antigenic variance, biofilm formation, persister cells, and immunomodulation. There is evidence that Bb is able to alter cytokine profiles within the host which may allow the organism to survive the immune response. This immunomodulation follows a pattern of T-helper 1 (TH1) suppression in favor of T-helper 2 (TH2) processes. In contrast, it has been shown that the optimal immune response to Bb infection involves an early, robust TH1 response and a later conversion to TH2 dominance once the infection is controlled or cleared. It has been proposed that a reconstitution of proper immune-competency in the infected host may improve clinical outcomes in Lyme disease. Cimetidine (CIM) is an over-the-counter histamine-2 (H2) antagonist that is primarily used to lower acid secretions in the stomach. T-regulatory (Treg) cells also possess the H2 receptor, which has spurred interest in CIM as a

  8. Transformation of the Lyme disease spirochete Borrelia burgdorferi with heterologous DNA.

    PubMed

    Stevenson, B; Bono, J L; Elias, A; Tilly, K; Rosa, P

    1998-09-01

    Studies of the spirochete Borrelia burgdorferi have been hindered by the scarcity of genetic tools that can be used in these bacteria. For the first time, a method has been developed by which heterologous DNA (DNA without a naturally occurring B. burgdorferi homolog) can be introduced into and persistently maintained by B. burgdorferi. This technique uses integration of circular DNA into the bacterial genome via a single-crossover event. The ability to transform B. burgdorferi with heterologous DNA will now permit a wide range of experiments on the biology of these bacteria and their involvement in the many facets of Lyme disease.

  9. A Controlled Trial of a Novel Primary Prevention Program for Lyme Disease and Other Tick-Borne Illnesses

    ERIC Educational Resources Information Center

    Daltroy, Lawren H.; Phillips, Charlotte; Lew, Robert; Wright, Elizabeth; Shadick, Nancy A.; Liang, Matthew H.

    2007-01-01

    To evaluate a theory-based educational program to prevent Lyme disease and other tick-borne illnesses (TBI), a randomized controlled trial of an educational program was delivered to ferry passengers traveling to an endemic area in southeastern Massachusetts. Rates of TBI and precautionary and tick check behaviors were measured over three summers…

  10. The role of lizards in the ecology of Lyme disease in two endemic zones of the northeastern United States.

    PubMed

    Giery, Sean T; Ostfeld, Richard S

    2007-06-01

    We examined the role of lizards in the ecology of Lyme disease in New York and Maryland. We collected data on vector tick infestations, measured lizard "realized" reservoir competence for the Lyme disease spirochete Borrelia burgdorferi, and estimated lizard population density. These data were incorporated into a model that predicts a host's ability to influence the prevalence of B. burgdorferi in the tick population, a primary risk factor in the epidemiology of Lyme disease. Published data on other northeastern hosts were included in the model to provide a reference for interpreting the importance of lizards as hosts. The model results indicate that 5-lined skinks (Eumeces fasciatus) are dilution hosts, capable of reducing infection prevalence in the tick population by 10.7-51.5 percentage points, whereas eastern fence lizards (Sceloporus undulatus) are not dilution hosts in the areas studied. Owing to moderate burdens of larval ticks, relatively high population densities, and reservoir incompetence, E. fasciatus may play an important role in the ecology of Lyme disease by reducing vector infection prevalence and associated human risk of infection.

  11. Spatial Analysis of Environmental Factors Related to Lyme Disease in Alabama by Means of NASA Earth Observation Systems

    NASA Technical Reports Server (NTRS)

    Renneboog, Nathan; Capilouto, Emily G.; Firsing, Stephen L., III; Levy, Kyle; McAllister, Marilyn; Roa, Kathryn; Setia,Shveta; Xie, Lili; Burnett, Donna; Luvall, Jeffrey C.

    2009-01-01

    This slide presentation reviews the epidemiology of Lyme Disease that accounts for more than 95% or vector borne diseases in the United States. The history, symptoms and the life cycle of the tick, the transmitting agent of Lyme Disease, a map that shows the cases reported to the CDC between1990 and 2006 and the number of cases in Alabama by year from 1986 to 2007. A NASA project is described, the goals of which are to (1) Demonstrate the presence of the chain of infection of Lyme disease in Alabama (2) Identify areas with environmental factors that support tick population using NASA Earth Observation Systems data in selected areas of Alabama and (3) Increase community awareness of Lyme disease and recommend primary and secondary prevention strategies. The remote sensing methods included: Analyzed Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) and DigitalGlobe Quickbird satellite imagery from summer months and Performed image analyses in ER Mapper 7.1. Views from the ASTER and Quickbird land cover are shown, the Normalized Difference Vegetation Index (NDVI) algorithm was applied to all ASTER and Quickbird imagery. The use of the images to obtain the level of soil moisture is reviewed, and this analysis was used along with the NDVI, was used to identify the areas that support the tick population.

  12. Host Immune Evasion by Lyme and Relapsing Fever Borreliae: Findings to Lead Future Studies for Borrelia miyamotoi

    PubMed Central

    Stone, Brandee L.; Brissette, Catherine A.

    2017-01-01

    The emerging pathogen, Borrelia miyamotoi, is a relapsing fever spirochete vectored by the same species of Ixodes ticks that carry the causative agents of Lyme disease in the US, Europe, and Asia. Symptoms caused by infection with B. miyamotoi are similar to a relapsing fever infection. However, B. miyamotoi has adapted to different vectors and reservoirs, which could result in unique physiology, including immune evasion mechanisms. Lyme Borrelia utilize a combination of Ixodes-produced inhibitors and native proteins [i.e., factor H-binding proteins (FHBPs)/complement regulator-acquiring surface proteins, p43, BBK32, BGA66, BGA71, CD59-like protein] to inhibit complement, while some relapsing fever spirochetes use C4b-binding protein and likely Ornithodoros-produced inhibitors. To evade the humoral response, Borrelia utilize antigenic variation of either outer surface proteins (Osps) and the Vmp-like sequences (Vls) system (Lyme borreliae) or variable membrane proteins (Vmps, relapsing fever borreliae). B. miyamotoi possesses putative FHBPs and antigenic variation of Vmps has been demonstrated. This review summarizes and compares the common mechanisms utilized by Lyme and relapsing fever spirochetes, as well as the current state of understanding immune evasion by B. miyamotoi. PMID:28154563

  13. Evaluation of Borrelia burgdorferi BbHtrA Protease as a Vaccine Candidate for Lyme Borreliosis in Mice.

    PubMed

    Ullmann, Amy J; Russell, Theresa M; Dolan, Marc C; Williams, Martin; Hojgaard, Andrias; Weiner, Zachary P; Johnson, Barbara J B

    2015-01-01

    Borrelia burgdorferi synthesizes an HtrA protease (BbHtrA) which is a surface-exposed, conserved protein within Lyme disease spirochetes with activity toward CheX and BmpD of Borrelia spp, as well as aggrecan, fibronectin and proteoglycans found in skin, joints and neural tissues of vertebrates. An antibody response against BbHtrA is observed in Lyme disease patients and in experimentally infected laboratory mice and rabbits. Given the surface location of BbHtrA on B. burgdorferi and its ability to elicit an antibody response in infected hosts, we explored recombinant BbHtrA as a potential vaccine candidate in a mouse model of tick-transmitted Lyme disease. We immunized mice with two forms of BbHtrA: the proteolytically active native form and BbHtrA ablated of activity by a serine to alanine mutation at amino acid 226 (BbHtrA(S226A)). Although inoculation with either BbHtrA or BbHtrA(S226A) produced high-titer antibody responses in C3H/HeJ mice, neither antigen was successful in protecting mice from B. burgdorferi challenge. These results indicate that the search for novel vaccine candidates against Lyme borreliosis remains a challenge.

  14. IFNγ production in peripheral blood of early Lyme disease patients to hLFAαL (aa326-345)

    PubMed Central

    Gomes-Solecki, Maria JC; Wormser, Gary P; Dattwyler, Raymond J

    2002-01-01

    Background It has been proposed that outer surface protein A (OspA) of Borrelia burgdorferi sensu stricto contains a T helper 1 (Th1) cell epitope that could play a role in an autoimmune response to hLFA1. Methods We used two peptides, hLFAαL (aa326-345) and Borrelia burgdorferi OspAB31 (aa164-183), as stimulating antigens to measure Th1 proinflammatory IFNγ cytokine production in peripheral blood of Lyme disease patients presenting with EM without history of arthritis, as well as in peripheral blood of healthy individuals. Results IFNγ responses to hLFA1 peptide were observed in 11 of 19 Lyme disease patients and in 3 of 15 healthy controls. In contrast, only 2 of 19 of the Lyme disease patients and none of the controls responded to the homologous OspAB31 peptide. Conclusions IFNγ was produced in response to stimulation with peptide hLFAαL (aa326-345) in peripheral blood of 58% of patients with early Lyme disease without signs of arthritis, as well as in peripheral blood of 20% of healthy individuals, but not in response to stimulation with the homologous OspAB31 (aa164-183) peptide (p < 0.05). Our results suggest that reactivity to the hLFA1 peptide in peripheral blood may be the result of T cell degeneracy. PMID:12385648

  15. Landscape characterization of peridomestic risk for Lyme disease using satellite imagery

    NASA Technical Reports Server (NTRS)

    Dister, S. W.; Fish, D.; Bros, S. M.; Frank, D. H.; Wood, B. L.

    1997-01-01

    Remotely sensed characterizations of landscape composition were evaluated for Lyme disease exposure risk on 337 residential properties in two communities of suburban Westchester County, New York. Properties were categorized as no, low, or high risk based on seasonally adjusted densities of Ixodes scapularis nymphs, determined by drag sampling during June and July 1990. Spectral indices based on Landsat Thematic Mapper data provided relative measures of vegetation structure and moisture (wetness), as well as vegetation abundance (greenness). A geographic information system (GIS) was used to spatially quantify and relate the remotely sensed landscape variables to risk category. A comparison of the two communities showed that Chappaqua, which had more high-risk properties (P < 0.001), was significantly greener and wetter than Armonk (P < 0.001). Furthermore, within Chappaqua, high-risk properties were significantly greener and wetter than lower-risk properties in this community (P < 0.01). The high-risk properties appeared to contain a greater proportion of broadleaf trees, while lower-risk properties were interpreted as having a greater proportion of nonvegetative cover and/or open lawn. The ability to distinguish these fine scale differences among communities and individual properties illustrates the efficiency of a remote sensing/GIS-based approach for identifying peridomestic risk of Lyme disease over large geographic areas.

  16. Spatial stratification of various Lyme disease spirochetes in a Central European site.

    PubMed

    Richter, Dania; Schröder, Boris; Hartmann, Niklas K; Matuschka, Franz-Rainer

    2013-03-01

    To determine whether the genospecies composition of Lyme disease spirochetes is spatially stratified, we collected questing Ixodes ricinus ticks in neighboring plots where rodents, birds, and lizards were present as reservoir host and compared the prevalence of various genospecies. The overall prevalence of spirochetes in questing ticks varied across the study site. Borrelia lusitaniae appeared to infect adult ticks in one plot at the same frequency as did Borrelia afzelii in the other plots. The relative density of questing nymphal and adult ticks varied profoundly. Where lizards were exceedingly abundant, these vertebrates seemed to constitute the dominant host for nymphal ticks, contributing the majority of infected adult ticks. Because lizards support solely B. lusitaniae and appear to exclude other genospecies, their narrow genospecies association results in predominance of B. lusitaniae in sites where lizards are abundant, while limiting its spread to the host's habitat range. To the extent that Central European B. lusitaniae strains are nonpathogenic, the presence of numerous lizards should locally decrease risk of infection for people. Evaluation of regional risk of infection by Lyme disease spirochetes should take the spatial effect of hosts into consideration, which stratify the distribution of specifically infected ticks on a small scale.

  17. Genomic insights into the Ixodes scapularis tick vector of Lyme disease.

    PubMed

    Gulia-Nuss, Monika; Nuss, Andrew B; Meyer, Jason M; Sonenshine, Daniel E; Roe, R Michael; Waterhouse, Robert M; Sattelle, David B; de la Fuente, José; Ribeiro, Jose M; Megy, Karine; Thimmapuram, Jyothi; Miller, Jason R; Walenz, Brian P; Koren, Sergey; Hostetler, Jessica B; Thiagarajan, Mathangi; Joardar, Vinita S; Hannick, Linda I; Bidwell, Shelby; Hammond, Martin P; Young, Sarah; Zeng, Qiandong; Abrudan, Jenica L; Almeida, Francisca C; Ayllón, Nieves; Bhide, Ketaki; Bissinger, Brooke W; Bonzon-Kulichenko, Elena; Buckingham, Steven D; Caffrey, Daniel R; Caimano, Melissa J; Croset, Vincent; Driscoll, Timothy; Gilbert, Don; Gillespie, Joseph J; Giraldo-Calderón, Gloria I; Grabowski, Jeffrey M; Jiang, David; Khalil, Sayed M S; Kim, Donghun; Kocan, Katherine M; Koči, Juraj; Kuhn, Richard J; Kurtti, Timothy J; Lees, Kristin; Lang, Emma G; Kennedy, Ryan C; Kwon, Hyeogsun; Perera, Rushika; Qi, Yumin; Radolf, Justin D; Sakamoto, Joyce M; Sánchez-Gracia, Alejandro; Severo, Maiara S; Silverman, Neal; Šimo, Ladislav; Tojo, Marta; Tornador, Cristian; Van Zee, Janice P; Vázquez, Jesús; Vieira, Filipe G; Villar, Margarita; Wespiser, Adam R; Yang, Yunlong; Zhu, Jiwei; Arensburger, Peter; Pietrantonio, Patricia V; Barker, Stephen C; Shao, Renfu; Zdobnov, Evgeny M; Hauser, Frank; Grimmelikhuijzen, Cornelis J P; Park, Yoonseong; Rozas, Julio; Benton, Richard; Pedra, Joao H F; Nelson, David R; Unger, Maria F; Tubio, Jose M C; Tu, Zhijian; Robertson, Hugh M; Shumway, Martin; Sutton, Granger; Wortman, Jennifer R; Lawson, Daniel; Wikel, Stephen K; Nene, Vishvanath M; Fraser, Claire M; Collins, Frank H; Birren, Bruce; Nelson, Karen E; Caler, Elisabet; Hill, Catherine A

    2016-02-09

    Ticks transmit more pathogens to humans and animals than any other arthropod. We describe the 2.1 Gbp nuclear genome of the tick, Ixodes scapularis (Say), which vectors pathogens that cause Lyme disease, human granulocytic anaplasmosis, babesiosis and other diseases. The large genome reflects accumulation of repetitive DNA, new lineages of retro-transposons, and gene architecture patterns resembling ancient metazoans rather than pancrustaceans. Annotation of scaffolds representing ∼57% of the genome, reveals 20,486 protein-coding genes and expansions of gene families associated with tick-host interactions. We report insights from genome analyses into parasitic processes unique to ticks, including host 'questing', prolonged feeding, cuticle synthesis, blood meal concentration, novel methods of haemoglobin digestion, haem detoxification, vitellogenesis and prolonged off-host survival. We identify proteins associated with the agent of human granulocytic anaplasmosis, an emerging disease, and the encephalitis-causing Langat virus, and a population structure correlated to life-history traits and transmission of the Lyme disease agent.

  18. Frameworks for risk communication and disease management: the case of Lyme disease and countryside users

    PubMed Central

    Quine, Christopher P.; Barnett, Julie; Dobson, Andrew D. M.; Marcu, Afrodita; Marzano, Mariella; Moseley, Darren; O'Brien, Liz; Randolph, Sarah E.; Taylor, Jennifer L.; Uzzell, David

    2011-01-01

    Management of zoonotic disease is necessary if countryside users are to gain benefit rather than suffer harm from their activities, and to avoid disproportionate reaction to novel threats. We introduce a conceptual framework based on the pressure–state–response model with five broad responses to disease incidence. Influencing public behaviour is one response and requires risk communication based on an integration of knowledge about the disease with an understanding of how publics respond to precautionary advice. A second framework emphasizes how risk communication involves more than information provision and should address dimensions including points-of-intervention over time, place and audience. The frameworks are developed by reference to tick-borne Lyme borreliosis (also known as Lyme disease), for which informed precautionary behaviour is particularly relevant. Interventions to influence behaviour can be directed by knowledge of spatial and temporal variation of tick abundance, what constitutes risky behaviour, how people respond to information of varying content, and an understanding of the social practices related to countryside use. The frameworks clarify the response options and help identify who is responsible for risk communication. These aspects are not consistently understood, and may result in an underestimation of the role of land-based organizations in facilitating appropriate precautionary behaviour. PMID:21624921

  19. Frameworks for risk communication and disease management: the case of Lyme disease and countryside users.

    PubMed

    Quine, Christopher P; Barnett, Julie; Dobson, Andrew D M; Marcu, Afrodita; Marzano, Mariella; Moseley, Darren; O'Brien, Liz; Randolph, Sarah E; Taylor, Jennifer L; Uzzell, David

    2011-07-12

    Management of zoonotic disease is necessary if countryside users are to gain benefit rather than suffer harm from their activities, and to avoid disproportionate reaction to novel threats. We introduce a conceptual framework based on the pressure-state-response model with five broad responses to disease incidence. Influencing public behaviour is one response and requires risk communication based on an integration of knowledge about the disease with an understanding of how publics respond to precautionary advice. A second framework emphasizes how risk communication involves more than information provision and should address dimensions including points-of-intervention over time, place and audience. The frameworks are developed by reference to tick-borne Lyme borreliosis (also known as Lyme disease), for which informed precautionary behaviour is particularly relevant. Interventions to influence behaviour can be directed by knowledge of spatial and temporal variation of tick abundance, what constitutes risky behaviour, how people respond to information of varying content, and an understanding of the social practices related to countryside use. The frameworks clarify the response options and help identify who is responsible for risk communication. These aspects are not consistently understood, and may result in an underestimation of the role of land-based organizations in facilitating appropriate precautionary behaviour.

  20. Introduced Siberian chipmunks (Tamias sibiricus barberi) contribute more to lyme borreliosis risk than native reservoir rodents.

    PubMed

    Marsot, Maud; Chapuis, Jean-Louis; Gasqui, Patrick; Dozières, Anne; Masséglia, Sébastien; Pisanu, Benoit; Ferquel, Elisabeth; Vourc'h, Gwenaël

    2013-01-01

    The variation of the composition in species of host communities can modify the risk of disease transmission. In particular, the introduction of a new host species can increase health threats by adding a new reservoir and/or by amplifying the circulation of either exotic or native pathogens. Lyme borreliosis is a multi-host vector-borne disease caused by bacteria belonging to the Borrelia burgdorferi sensu lato complex. It is transmitted by the bite of hard ticks, especially Ixodes ricinus in Europe. Previous studies showed that the Siberian chipmunk, Tamias sibiricus barberi, an introduced ground squirrel in the Forest of Sénart (near Paris, France) was highly infested by I. ricinus, and consequently infected by B. burgdorferi sl. An index of the contribution of chipmunks to the density of infected questing nymphs on the vegetation (i.e., the acarological risk for humans) was compared to that of bank voles (Myodes glareolus) and of wood mice (Apodemus sylvaticus), two known native and sympatric competent reservoir hosts. Chipmunks produced nearly 8.5 times more infected questing nymphs than voles and mice. Furthermore, they contribute to a higher diversity of B. burgdorferi sl genospecies (B. afzelii, B. burgdorferi sensu stricto and B. garinii). The contribution of chipmunks varied between years and seasons, according to tick availability. As T. s. barberi must be a competent reservoir, it should amplify B. burgdorferi sl infection, hence increasing the risk of Lyme borreliosis in humans.

  1. Quality of life, fatigue, depression and cognitive impairment in Lyme neuroborreliosis.

    PubMed

    Dersch, Rick; Sarnes, Antonia A; Maul, Monika; Hottenrott, Tilman; Baumgartner, Annette; Rauer, Sebastian; Stich, Oliver

    2015-11-01

    The prognosis and impact of residual symptoms on quality of life in patients with Lyme neuroborreliosis (LNB) is subject to debate. The aim of this study was to assess quality of life, fatigue, depression, cognitive impairment and verbal learning in patients with definite LNB and healthy controls in a case-control study. We retrospectively identified all patients diagnosed with definite LNB between 2003 and 2014 in our tertiary care center. Healthy controls were recruited from the same area. Patients and healthy controls were assessed for quality of life [Short Form (36) with subscores for physical and mental components (PCS, MCS)], fatigue (fatigue severity scale), depression (Beck depression inventory), verbal memory and learning and cognitive impairment (mini-mental state examination). 53 patients with definite LNB could be identified, of which 30 partook in the follow-up assessment. Estimates for quality of life, fatigue, depression, verbal memory and cognitive impairment did not differ statistically significantly between 30 patients with LNB and 35 healthy controls. Patients with residual symptoms had lower scores for quality of life (PCS) compared to patients without residual symptoms. Our results do not support the hypothesis that a considerable proportion of patients with antibiotically treated LNB develop a 'post Lyme syndrome' consisting of debilitating fatigue or cognitive impairment or have severe limitations of quality of life. However, some patients experience residual symptoms of LNB.

  2. The cyclic-di-GMP signaling pathway in the Lyme disease spirochete, Borrelia burgdorferi

    PubMed Central

    Novak, Elizabeth A.; Sultan, Syed Z.; Motaleb, Md. A.

    2014-01-01

    In nature, the Lyme disease spirochete Borrelia burgdorferi cycles between the unrelated environments of the Ixodes tick vector and mammalian host. In order to survive transmission between hosts, B. burgdorferi must be able to not only detect changes in its environment, but also rapidly and appropriately respond to these changes. One manner in which this obligate parasite regulates and adapts to its changing environment is through cyclic-di-GMP (c-di-GMP) signaling. c-di-GMP has been shown to be instrumental in orchestrating the adaptation of B. burgdorferi to the tick environment. B. burgdorferi possesses only one set of c-di-GMP-metabolizing genes (one diguanylate cyclase and two distinct phosphodiesterases) and one c-di-GMP-binding PilZ-domain protein designated as PlzA. While studies in the realm of c-di-GMP signaling in B. burgdorferi have exploded in the last few years, there are still many more questions than answers. Elucidation of the importance of c-di-GMP signaling to B. burgdorferi may lead to the identification of mechanisms that are critical for the survival of B. burgdorferi in the tick phase of the enzootic cycle as well as potentially delineate a role (if any) c-di-GMP may play in the transmission and virulence of B. burgdorferi during the enzootic cycle, thereby enabling the development of effective drugs for the prevention and/or treatment of Lyme disease. PMID:24822172

  3. Genomic insights into the Ixodes scapularis tick vector of Lyme disease

    PubMed Central

    Gulia-Nuss, Monika; Nuss, Andrew B.; Meyer, Jason M.; Sonenshine, Daniel E.; Roe, R. Michael; Waterhouse, Robert M.; Sattelle, David B.; de la Fuente, José; Ribeiro, Jose M.; Megy, Karine; Thimmapuram, Jyothi; Miller, Jason R.; Walenz, Brian P.; Koren, Sergey; Hostetler, Jessica B.; Thiagarajan, Mathangi; Joardar, Vinita S.; Hannick, Linda I.; Bidwell, Shelby; Hammond, Martin P.; Young, Sarah; Zeng, Qiandong; Abrudan, Jenica L.; Almeida, Francisca C.; Ayllón, Nieves; Bhide, Ketaki; Bissinger, Brooke W.; Bonzon-Kulichenko, Elena; Buckingham, Steven D.; Caffrey, Daniel R.; Caimano, Melissa J.; Croset, Vincent; Driscoll, Timothy; Gilbert, Don; Gillespie, Joseph J.; Giraldo-Calderón, Gloria I.; Grabowski, Jeffrey M.; Jiang, David; Khalil, Sayed M. S.; Kim, Donghun; Kocan, Katherine M.; Koči, Juraj; Kuhn, Richard J.; Kurtti, Timothy J.; Lees, Kristin; Lang, Emma G.; Kennedy, Ryan C.; Kwon, Hyeogsun; Perera, Rushika; Qi, Yumin; Radolf, Justin D.; Sakamoto, Joyce M.; Sánchez-Gracia, Alejandro; Severo, Maiara S.; Silverman, Neal; Šimo, Ladislav; Tojo, Marta; Tornador, Cristian; Van Zee, Janice P.; Vázquez, Jesús; Vieira, Filipe G.; Villar, Margarita; Wespiser, Adam R.; Yang, Yunlong; Zhu, Jiwei; Arensburger, Peter; Pietrantonio, Patricia V.; Barker, Stephen C.; Shao, Renfu; Zdobnov, Evgeny M.; Hauser, Frank; Grimmelikhuijzen, Cornelis J. P.; Park, Yoonseong; Rozas, Julio; Benton, Richard; Pedra, Joao H. F.; Nelson, David R.; Unger, Maria F.; Tubio, Jose M. C.; Tu, Zhijian; Robertson, Hugh M.; Shumway, Martin; Sutton, Granger; Wortman, Jennifer R.; Lawson, Daniel; Wikel, Stephen K.; Nene, Vishvanath M.; Fraser, Claire M.; Collins, Frank H.; Birren, Bruce; Nelson, Karen E.; Caler, Elisabet; Hill, Catherine A.

    2016-01-01

    Ticks transmit more pathogens to humans and animals than any other arthropod. We describe the 2.1 Gbp nuclear genome of the tick, Ixodes scapularis (Say), which vectors pathogens that cause Lyme disease, human granulocytic anaplasmosis, babesiosis and other diseases. The large genome reflects accumulation of repetitive DNA, new lineages of retro-transposons, and gene architecture patterns resembling ancient metazoans rather than pancrustaceans. Annotation of scaffolds representing ∼57% of the genome, reveals 20,486 protein-coding genes and expansions of gene families associated with tick–host interactions. We report insights from genome analyses into parasitic processes unique to ticks, including host ‘questing', prolonged feeding, cuticle synthesis, blood meal concentration, novel methods of haemoglobin digestion, haem detoxification, vitellogenesis and prolonged off-host survival. We identify proteins associated with the agent of human granulocytic anaplasmosis, an emerging disease, and the encephalitis-causing Langat virus, and a population structure correlated to life-history traits and transmission of the Lyme disease agent. PMID:26856261

  4. Loss of Lyme disease spirochetes from Ixodes ricinus ticks feeding on European blackbirds.

    PubMed

    Matuschka, F R; Spielman, A

    1992-03-01

    To determine whether blackbirds (Turdus merula), the most abundant and most abundantly tick-infested ecotonal bird of Central Europe, may contribute to the transmission of the Lyme disease spirochete (Borrelia burgdorferi), we compared the infectivity to ticks of naturally as well as experimentally infected blackbirds and rodents. European blackbirds experience intense exposure to Ixodes ricinus ticks and to the pathogens that they transmit. In nature, subadult I. ricinus ticks found feeding on these birds generally contain no spirochetes, although infection is universal in those found on black-striped mice (Apodemus agrarius). Those found on yellow-necked mice (A. flavicollis) are less frequently infected. Ticks lose infection in the course of feeding on blackbirds and fail to infect them. Subadult I. ricinus ticks readily feed on blackbirds, black-striped mice, and jirds (Meriones unguiculatus), but engorge less fully on the bird than on the rodents. Although birds may burden human health by establishing new infestations of I. ricinus ticks, our observations indicate that particular birds may benefit health by locally diminishing transmission of the Lyme disease spirochete.

  5. Introduced Siberian Chipmunks (Tamias sibiricus barberi) Contribute More to Lyme Borreliosis Risk than Native Reservoir Rodents

    PubMed Central

    Marsot, Maud; Chapuis, Jean-Louis; Gasqui, Patrick; Dozières, Anne; Masséglia, Sébastien; Pisanu, Benoit; Ferquel, Elisabeth; Vourc’h, Gwenaël

    2013-01-01

    The variation of the composition in species of host communities can modify the risk of disease transmission. In particular, the introduction of a new host species can increase health threats by adding a new reservoir and/or by amplifying the circulation of either exotic or native pathogens. Lyme borreliosis is a multi-host vector-borne disease caused by bacteria belonging to the Borrelia burgdorferi sensu lato complex. It is transmitted by the bite of hard ticks, especially Ixodes ricinus in Europe. Previous studies showed that the Siberian chipmunk, Tamias sibiricus barberi, an introduced ground squirrel in the Forest of Sénart (near Paris, France) was highly infested by I. ricinus, and consequently infected by B. burgdorferi sl. An index of the contribution of chipmunks to the density of infected questing nymphs on the vegetation (i.e., the acarological risk for humans) was compared to that of bank voles (Myodes glareolus) and of wood mice (Apodemus sylvaticus), two known native and sympatric competent reservoir hosts. Chipmunks produced nearly 8.5 times more infected questing nymphs than voles and mice. Furthermore, they contribute to a higher diversity of B. burgdorferi sl genospecies (B. afzelii, B. burgdorferi sensu stricto and B. garinii). The contribution of chipmunks varied between years and seasons, according to tick availability. As T. s. barberi must be a competent reservoir, it should amplify B. burgdorferi sl infection, hence increasing the risk of Lyme borreliosis in humans. PMID:23383170

  6. Use of recombinant OspC from Borrelia burgdorferi for serodiagnosis of early Lyme disease.

    PubMed Central

    Padula, S J; Dias, F; Sampieri, A; Craven, R B; Ryan, R W

    1994-01-01

    Infection with Borrelia burgdorferi, the etiologic agent of Lyme disease, is associated with an early and dominant humoral response to the spirochete's 23-kDa outer surface protein C (OspC). We have cloned and expressed OspC as a fusion protein in Escherichia coli and have shown that patient serum samples react with it in an enzyme-linked immunosorbent assay (ELISA) (S. J. Padula, A. Sampieri, F. Dias, A. Szczepanski, and R. W. Ryan, Infect. Immun. 61:5097-5105, 1993). Now we have compared the detection of B. burgdorferi-specific immunoglobulin M antibodies in 74 individuals with culture-positive erythema migrans by a whole-cell ELISA, immunoblot, and the recombinant OspC (rOspC) ELISA. Seventy-six negative controls were also studied. With all of the tests, there was a statistically significant association between the duration of disease and the frequency of a positive result. With the rOspC ELISA, the predictive value of a positive test was 100% and the predictive value of a negative test was 74%. Similar results were obtained with the whole-cell ELISA and with the immunoblot using as the source of test antigen a strain of B. burgdorferi which expresses abundant levels of OspC. We conclude that the use of rOspC in an ELISA is a convenient, readily automated, and easily standardized test for the serodiagnosis of early Lyme disease. PMID:7929767

  7. Risk maps for range expansion of the Lyme disease vector, Ixodes scapularis, in Canada now and with climate change

    PubMed Central

    Ogden, Nicholas H; St-Onge, Laurie; Barker, Ian K; Brazeau, Stéphanie; Bigras-Poulin, Michel; Charron, Dominique F; Francis, Charles M; Heagy, Audrey; Lindsay, L Robbin; Maarouf, Abdel; Michel, Pascal; Milord, François; O'Callaghan, Christopher J; Trudel, Louise; Thompson, R Alex

    2008-01-01

    Background Lyme disease is the commonest vector-borne zoonosis in the temperate world, and an emerging infectious disease in Canada due to expansion of the geographic range of the tick vector Ixodes scapularis. Studies suggest that climate change will accelerate Lyme disease emergence by enhancing climatic suitability for I. scapularis. Risk maps will help to meet the public health challenge of Lyme disease by allowing targeting of surveillance and intervention activities. Results A risk map for possible Lyme endemicity was created using a simple risk algorithm for occurrence of I. scapularis populations. The algorithm was calculated for each census sub-division in central and eastern Canada from interpolated output of a temperature-driven simulation model of I. scapularis populations and an index of tick immigration. The latter was calculated from estimates of tick dispersion distances by migratory birds and recent knowledge of the current geographic range of endemic I. scapularis populations. The index of tick immigration closely predicted passive surveillance data on I. scapularis occurrence, and the risk algorithm was a significant predictor of the occurrence of I. scapularis populations in a prospective field study. Risk maps for I. scapularis occurrence in Canada under future projected climate (in the 2020s, 2050s and 2080s) were produced using temperature output from the Canadian Coupled Global Climate Model 2 with greenhouse gas emission scenario enforcing 'A2' of the Intergovernmental Panel on Climate Change. Conclusion We have prepared risk maps for the occurrence of I. scapularis in eastern and central Canada under current and future projected climate. Validation of the risk maps provides some confidence that they provide a useful first step in predicting the occurrence of I. scapularis populations, and directing public health objectives in minimizing risk from Lyme disease. Further field studies are needed, however, to continue validation and refinement

  8. Single-Tier Testing with the C6 Peptide ELISA Kit Compared with Two-Tier Testing for Lyme Disease

    PubMed Central

    Wormser, Gary P.; Schriefer, Martin; Aguero-Rosenfeld, Maria E.; Levin, Andrew; Steere, Allen C.; Nadelman, Robert B.; Nowakowski, John; Marques, Adriana; Johnson, Barbara J. B.; Dumler, J. Stephen

    2014-01-01

    Background The two-tier serologic testing protocol for Lyme disease has a number of shortcomings including low sensitivity in early disease; increased cost, time and labor; and subjectivity in the interpretation of immunoblots. Methods The diagnostic accuracy of a single-tier commercial C6 ELISA kit was compared with two-tier testing. Results The C6 ELISA was significantly more sensitive than two-tier testing with sensitivities of 66.5% (95% C.I.:61.7-71.1) and 35.2% (95%C.I.:30.6-40.1), respectively (p<0.001) in 403 sera from patients with erythema migrans. The C6 ELISA had sensitivity statistically comparable to two-tier testing in sera from Lyme disease patients with early neurological manifestations (88.6% vs. 77.3%, p=0.13) or arthritis (98.3% vs. 95.6%, p= 0.38). Te specificities of C6 ELISA and two-tier testing in over 2200 blood donors, patients with other conditions, and Lyme disease vaccine recipients were found to be 98.9% and 99.5%, respectively (p<0.05, 95% C.I. surrounding the 0.6 percentage point difference of 0.04 to 1.15). Conclusions Using a reference standard of two-tier testing, the C6 ELISA as a single step serodiagnostic test provided increased sensitivity in early Lyme disease with comparable sensitivity in later manifestations of Lyme disease. The C6 ELISA had slightly decreased specificity. Future studies should evaluate the performance of the C6 ELISA compared with two-tier testing in routine clinical practice. PMID:23062467

  9. Long-term Assessment of Post-Treatment Symptoms in Patients With Culture-Confirmed Early Lyme Disease

    PubMed Central

    Weitzner, Erica; McKenna, Donna; Nowakowski, John; Scavarda, Carol; Dornbush, Rhea; Bittker, Susan; Cooper, Denise; Nadelman, Robert B.; Visintainer, Paul; Schwartz, Ira; Wormser, Gary P.

    2015-01-01

    Background. Lyme disease patients with erythema migrans are said to have post-treatment Lyme disease symptoms (PTLDS) if there is persistence of subjective symptoms for at least 6 months following antibiotic treatment and resolution of the skin lesion. The purpose of this study was to characterize PTLDS in patients with culture-confirmed early Lyme disease followed for >10 years. Methods. Adult patients with erythema migrans with a positive skin or blood culture for Borrelia burgdorferi were enrolled in a prospective study beginning in 1991 and followed up at 6 months and annually thereafter to determine the long-term outcome of this infection. The genotype of the infecting strain of B. burgdorferi was evaluated in subjects with PTLDS. Results. One hundred twenty-eight subjects with culture-confirmed early Lyme disease, of whom 55% were male, were followed for a mean ± SD of 14.98 ± 2.71 years (median = 15 years; range = 11–20 years). Fourteen (10.9%) were regarded as having possible PTLDS, but only 6 (4.7%) had PTLDS documented at their last study visit. Nine (64.3%) had only a single symptom. None of the 6 with PTLDS at their last visit was considered to be functionally impaired by the symptom(s). PTLDS was not associated with a particular genotype of B. burgdorferi. Conclusions. PTLDS may persist for >10 years in some patients with culture-confirmed early Lyme disease. Such long-standing symptoms were not associated with functional impairment or a particular strain of B. burgdorferi. PMID:26385994

  10. Serum Leukocyte Immunoglobulin-Like Receptor A3 (LILRA3) Is Increased in Patients with Multiple Sclerosis and Is a Strong Independent Indicator of Disease Severity; 6.7kbp LILRA3 Gene Deletion Is Not Associated with Diseases Susceptibility.

    PubMed

    An, Hongyan; Lim, Chai; Guillemin, Gilles J; Vollmer-Conna, Ute; Rawlinson, William; Bryant, Katherine; Tedla, Nicodemus

    2016-01-01

    Leukocyte immunoglobulin-like receptor A3 (LILRA3) is a soluble immune regulatory molecule primarily expressed by monocytes and macrophages. A homozygous 6.7kbp LILRA3 gene deletion that removes the first seven of its eight exons is predicted to lead to lack of LILRA3 protein, although this has not been experimentally confirmed. Moreover, there are conflicting results with regards to the link between the LILRA3 homozygous genetic deletion and susceptibility to multiple sclerosis (MS) in different European populations. The aim of this study was to investigate whether LILRA3 gene deletion is associated with MS susceptibility in a North American cohort of European ancestry and assess if serum LILRA3 protein level is a marker of clinical subtype and/or disease severity in MS. A total of 456 patients with MS and 99 unrelated healthy controls were genotyped for the 6.7kbp LILRA3 gene deletion and levels of LILRA3 protein in sera determined by in-house sandwich ELISA. We showed that LILRA3 gene deletion was not associated with MS susceptibility and did not affect the age of disease onset, clinical subtype or disease severity. However, we discovered for the first time that homozygous LILRA3 gene deletion results in lack of production of LILRA3 protein. Importantly, LILRA3 protein level was significantly increased in sera of patients with MS when compared with control subjects, particularly in more severe type primary progressive MS. Multiple regression analysis showed that LILRA3 level in serum was one of the strongest independent markers of disease severity in MS, which potentially can be used as a diagnostic marker.

  11. Serum Leukocyte Immunoglobulin-Like Receptor A3 (LILRA3) Is Increased in Patients with Multiple Sclerosis and Is a Strong Independent Indicator of Disease Severity; 6.7kbp LILRA3 Gene Deletion Is Not Associated with Diseases Susceptibility

    PubMed Central

    An, Hongyan; Lim, Chai; Guillemin, Gilles J.; Vollmer-Conna, Ute; Rawlinson, William; Bryant, Katherine; Tedla, Nicodemus

    2016-01-01

    Leukocyte immunoglobulin-like receptor A3 (LILRA3) is a soluble immune regulatory molecule primarily expressed by monocytes and macrophages. A homozygous 6.7kbp LILRA3 gene deletion that removes the first seven of its eight exons is predicted to lead to lack of LILRA3 protein, although this has not been experimentally confirmed. Moreover, there are conflicting results with regards to the link between the LILRA3 homozygous genetic deletion and susceptibility to multiple sclerosis (MS) in different European populations. The aim of this study was to investigate whether LILRA3 gene deletion is associated with MS susceptibility in a North American cohort of European ancestry and assess if serum LILRA3 protein level is a marker of clinical subtype and/or disease severity in MS. A total of 456 patients with MS and 99 unrelated healthy controls were genotyped for the 6.7kbp LILRA3 gene deletion and levels of LILRA3 protein in sera determined by in-house sandwich ELISA. We showed that LILRA3 gene deletion was not associated with MS susceptibility and did not affect the age of disease onset, clinical subtype or disease severity. However, we discovered for the first time that homozygous LILRA3 gene deletion results in lack of production of LILRA3 protein. Importantly, LILRA3 protein level was significantly increased in sera of patients with MS when compared with control subjects, particularly in more severe type primary progressive MS. Multiple regression analysis showed that LILRA3 level in serum was one of the strongest independent markers of disease severity in MS, which potentially can be used as a diagnostic marker. PMID:26871720

  12. Landscape Risk Factors for Lyme Disease in the Eastern Broadleaf Forest Province of the Hudson River Valley and the Effect of Explanatory Data Classification Resolution

    EPA Science Inventory

    This study assessed how landcover classification affects associations between landscape characteristics and Lyme disease rate. Landscape variables were derived from the National Land Cover Database (NLCD), including native classes (e.g., deciduous forest, developed low intensity)...

  13. Using exploratory data analysis to identify and predict patterns of human Lyme disease case clustering within a multistate region, 2010-2014.

    PubMed

    Hendricks, Brian; Mark-Carew, Miguella

    2017-02-01

    Lyme disease is the most commonly reported vectorborne disease in the United States. The objective of our study was to identify patterns of Lyme disease reporting after multistate inclusion to mitigate potential border effects. County-level human Lyme disease surveillance data were obtained from Kentucky, Maryland, Ohio, Pennsylvania, Virginia, and West Virginia state health departments. Rate smoothing and Local Moran's I was performed to identify clusters of reporting activity and identify spatial outliers. A logistic generalized estimating equation was performed to identify significant associations in disease clustering over time. Resulting analyses identified statistically significant (P=0.05) clusters of high reporting activity and trends over time. High reporting activity aggregated near border counties in high incidence states, while low reporting aggregated near shared county borders in non-high incidence states. Findings highlight the need for exploratory surveillance approaches to describe the extent to which state level reporting affects accurate estimation of Lyme disease progression.

  14. Simultaneous expression of Borrelia OspA and OspC and IgM response in cerebrospinal fluid in early neurologic Lyme disease.

    PubMed Central

    Schutzer, S E; Coyle, P K; Krupp, L B; Deng, Z; Belman, A L; Dattwyler, R; Luft, B J

    1997-01-01

    Lyme disease is the major tick-borne disease, caused by Borrelia burgdorferi (Bb). Neurological involvement is common in all stages. In vivo expression of Bb antigens (Ags) and the immune response to them has not been well investigated in the cerebrospinal fluid (CSF). Upregulation of outer surface protein (Osp) C and concomitant downregulation of OspA before tick inoculation of the spirochete has been reported in skin and blood in animals. CSF OspA Ag in early disease suggests otherwise in CSF. Early Ag expression and IgM response in human CSF was investigated here. Paired CSF and serum was collected from 16 early, predominantly erythema migrans Lyme disease patients with neurologic problems, 13 late Lyme disease patients, and 19 other neurologic disease (OND) controls. Samples were examined for IgM reactivity to recombinant Bb-specific Osps using ELISA and immunoblot. Of 12 early Lyme disease patients with neurologic involvement with both CSF and serum IgM against OspC, 7 (58%) had IgM to OspA (n = 5) or OspB (n = 2) that was restricted to the CSF, not serum. Overall, 12 of 16 (75%) of these early Lyme disease patients with neurologic involvement had CSF and serum IgM against OspC. Only 3 of 13 (23%) late Lyme disease patients and none of 19 OND controls had CSF IgM directed against OspC. In conclusion, in CSF, OspC and OspA can be coexpressed, and IgM response to them occurs in early Lyme disease patients with neurologic involvement. This biologic finding may also provide a discriminating marker for CNS infection in Lyme disease. PMID:9259573

  15. Evaluation of Selected Borrelia burgdorferi lp54 Plasmid-Encoded Gene Products Expressed during Mammalian Infection as Antigens To Improve Serodiagnostic Testing for Early Lyme Disease.

    PubMed

    Weiner, Zachary P; Crew, Rebecca M; Brandt, Kevin S; Ullmann, Amy J; Schriefer, Martin E; Molins, Claudia R; Gilmore, Robert D

    2015-11-01

    Laboratory testing for the diagnosis of Lyme disease is performed primarily by serologic assays and is accurate for detection beyond the acute stage of the infection. Serodiagnostic assays to detect the early stages of infection, however, are limited in their sensitivity, and improvement is warranted. We analyzed a series of Borrelia burgdorferi proteins known to be induced within feeding ticks and/or during mammalian infection for their utility as serodiagnostic markers against a comprehensive panel of Lyme disease patient serum samples. The antigens were assayed for IgM and IgG reactivity in line immunoblots and separately by enzyme-linked immunosorbent assay (ELISA), with a focus on reactivity against early Lyme disease with erythema migrans (EM), early disseminated Lyme neuroborreliosis, and early Lyme carditis patient serum samples. By IgM immunoblotting, we found that recombinant proteins BBA65, BBA70, and BBA73 reacted with early Lyme EM samples at levels comparable to those of the OspC antigen used in the current IgM blotting criteria. Additionally, these proteins reacted with serum samples from patients with early neuroborreliosis and early carditis, suggesting value in detecting early stages of this disease progression. We also found serological reactivity against recombinant proteins BBA69 and BBA73 with early-Lyme-disease samples using IgG immunoblotting and ELISA. Significantly, some samples that had been scored negative by the Centers for Disease Control and Prevention-recommended 2-tiered testing algorithm demonstrated positive reactivity to one or more of the antigens by IgM/IgG immunoblot and ELISA. These results suggest that incorporating additional in vivo-expressed antigens into the current IgM/IgG immunoblotting tier in a recombinant protein platform assay may improve the performance of early-Lyme-disease serologic testing.

  16. Role of Osteopontin in Murine Lyme Arthritis and Host Defense against Borrelia burgdorferi

    PubMed Central

    Potter, Melissa R.; Rittling, Susan R.; Denhardt, David T.; Roper, Randall J.; Weis, John H.; Teuscher, Cory; Weis, Janis J.

    2002-01-01

    Several genetic loci in the mouse have been identified that regulate the severity of Lyme arthritis. The region of chromosome 5 including the osteopontin (OPN) gene (Opn) has been identified in intercross populations of C3H/HeN × C57BL/6 and C3H/HeJ × BALB/cAnN mice. OPN is of particular interest as it is involved in the maintenance and remodeling of tissue during inflammation, it regulates production of interleukin-10 (IL-10) and IL-12 (cytokines implicated in Lyme arthritis), it is necessary for host control of certain bacterial infections, and mice displaying different severities of Lyme arthritis possess different alleles of the OPN gene. Macrophages and splenocytes from OPN-deficient mice on mixed C57BL/6J-129S or inbred 129S backgrounds were stimulated with the Pam3Cys modified lipoprotein from Borrelia burgdorferi, OspA. OPN was not required for OspA-induced cytokine production; however, macrophages from 129S-Opn−/− mice displayed a reduced level of IL-10 production. OPN was also not required for resistance to severe arthritis, as B. burgdorferi-infected 129S-Opn−/− mice developed mild arthritis, as did their wild-type littermates. Arthritis was more severe in OPN-deficient mice on the mixed C57BL/6J-129S backgrounds than in inbred mice of either strain. This increase was most likely due to a gene(s) closely linked to Opn on chromosome 5 in conjunction with other randomly assorting genes. Deficiency in OPN did not influence the numbers of spirochetes in tissues from B. burgdorferi-infected mice, indicating OPN is not part of the host defense to this pathogen. Interestingly, there was no alteration in the B. burgdorferi-specific antibody isotypes in OPN-deficient mice, indicating that its effect on helper T-cell responses is not relevant to the host response to B. burgdorferi. PMID:11854223

  17. Gut Microbiota of the Tick Vector Ixodes scapularis Modulate Colonization of the Lyme Disease Spirochete

    PubMed Central

    Narasimhan, Sukanya; Rajeevan, Nallakkandi; Liu, Lei; Zhao, Yang O.; Heisig, Julia; Pan, Jingyi; Eppler-Epstein, Rebecca; DePonte, Kathleen; Fish, Durland; Fikrig, Erol

    2014-01-01

    SUMMARY Arthopods, such as Ixodes ticks, serve as vectors for many human pathogens. The arthropod gut presents a pivotal microbial entry point and determines pathogen colonization and survival. We show that the gut microbiota of Ixodes scapularis, a major vector of the Lyme disease spirochete Borrelia burgdorferi, influence spirochete colonization of ticks. Perturbing the gut microbiota of larval ticks reduced Borrelia colonization, with dysbiosed larvae displaying decreased expression of the transcription factor STAT. Diminished STAT expression corresponded to lower expression of peritrophin, a key glycoprotein scaffold of the glycan-rich mucus-like peritrophic matrix (PM) that separates the gut lumen from the epithelium. The integrity of the I. scapularis PM was essential for B. burgdorferi to efficiently colonize the gut epithelium. These data elucidate a functional link between the gut microbiota, STAT-signaling, and pathogen colonization in the context of the gut epithelial barrier of an arthropod vector. PMID:24439898

  18. Isolation and transmission of the Lyme disease spirochete from the southeastern United States.

    PubMed

    Oliver, J H; Chandler, F W; Luttrell, M P; James, A M; Stallknecht, D E; McGuire, B S; Hutcheson, H J; Cummins, G A; Lane, R S

    1993-08-01

    The isolation of the Lyme disease spirochete (Borrelia burgdorferi) from the southeastern United States is reported. Three isolates, two from cotton mice (Peromyscus gossypinus) and one from the black-legged tick (Ixodes scapularis), were recovered from Sapelo Island, Georgia, in July and September 1991. The spirochetes were characterized by indirect fluorescent antibody assay using a battery of five monoclonal antibodies, by sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS/PAGE) of whole cell lysates, and by the polymerase chain reaction (PCR) assay using primers for three DNA target sequences found in B. burgdorferi reference strain B-31. Transmission experiments indicate that the three Georgia isolates can infect experimentally inoculated hamsters and mice. Tick transmission of one of the isolates has been attempted so far; I. scapularis transmitted isolate SI-1 from hamsters to mice, but the lone-star tick, Amblyomma americanum, did not.

  19. [Complete atrioventricular block as the first clinical manifestation of a tick bite (Lyme disease)].

    PubMed

    Bacino, Luca; Gazzarata, Massimo; Siri, Giambattista; Cordone, Stefano; Bellotti, Paolo

    2011-03-01

    A 52-year-old male patient presented to the emergency department because of malaise and frequent dizziness. The ECG revealed high-grade atrioventricular block that required placement of a temporary pacemaker. There were no other abnormalities in physical and echocardiographic examination, and coronary angiography excluded the presence of coronary artery disease. IgM and IgG antibodies against Borrelia were positive, and antibiotic therapy with ceftriaxone at the dose of 2 g/die for 15 days resulted in rapid regression of atrioventricular block. Seven-day ECG recording immediately after discharge and 24h ECG monitoring at 40 days confirmed the total disappearance of atrioventricular block. This represents a case of atrioventricular block as the first manifestation of Borrelia infection (Lyme disease). A prompt diagnosis and antibiotic therapy usually result in complete resolution of atrioventricular block without the need for a permanent pacemaker.

  20. The NIH-3 immunodeficient mouse is a model for Lyme borreliosis myositis and carditis.

    PubMed Central

    Defosse, D. L.; Duray, P. H.; Johnson, R. C.

    1992-01-01

    Experimental infection of immunodeficient NIH-3 (N:NIH-bg-nu-xid) mice with Borrelia burgdorferi was found to result in multisystem histopathologic lesions. In addition to T-cell deficiency due to the nude mutation, these mice have an x-linked defect affecting the B-cell maturation and the beige mutation resulting in the absence of NK cells. NIH-3 mice were susceptible to progressive infection with B. burgdorferi resulting in pancarditis, synovitis, and skeletal interstitial myositis whereas controls remained normal. Cardiomyopathy was characterized by inflammatory mononuclear infiltration and fibrillar necrosis. Synovial hyperplasia and inflammation were seen in the tibiotarsal and ulna-carpal joints. Advanced myositis was observed in peripheral skeletal muscle. Gastrointestinal submucosa, heart, and skeletal muscle were heavily colonized with B. burgdorferi. This mouse is proposed as a model for Lyme borreliosis carditis, synovitis, and myositis. Images Figure 1 Figure 2 Figure 3 PMID:1632468

  1. Health assessment for New Lyme Landfill, Ashtabula, Ohio, Region 5. CERCLIS No. OHD980794614. Final report

    SciTech Connect

    Not Available

    1986-01-30

    The New Lyme Landfill is a 40-acre facility operated from 1969 until 1978 as a trench and fill landfill with majority of the waste coming from industrial and commercial sources. Leachate includes both leachate seeps at the surface of the landfill and water that is either stagnant or moving very slowly in or out of the trenches. Organic compounds detected consisted of VOCs and phenolic compounds. Concentrations of inorganic compounds were generally an order-of-magnitude or more in ground water. Chrysotile asbestos fibers were found in two leachate water samples. The primary potential exposure pathways for leachate are direct contact or inhalation of airborne asbestos fibers. Based on the nature of the contaminants and the hydrological conditions at the site, residential development of the area may not be suitable.

  2. Biodiversity and disease: a synthesis of ecological perspectives on Lyme disease transmission.

    USGS Publications Warehouse

    Wood, Chelsea L.; Lafferty, Kevin D.

    2013-01-01

    Recent reviews have argued that disease control is among the ecosystem services yielded by biodiversity. Lyme disease (LD) is commonly cited as the best example of the ‘diluting’ effect of biodiversity on disease transmission, but many studies document the opposite relationship, showing that human LD risk can increase with forestation. Here, we unify these divergent perspectives and find strong evidence for a positive link between biodiversity and LD at broad spatial scales (urban to suburban to rural) and equivocal evidence for a negative link between biodiversity and LD at varying levels of biodiversity within forests. This finding suggests that, across zoonotic disease agents, the biodiversity–disease relationship is scale dependent and complex.

  3. Remotely sensed vegetation moisture as explanatory variable of Lyme borreliosis incidence

    NASA Astrophysics Data System (ADS)

    Barrios, J. M.; Verstraeten, W. W.; Maes, P.; Clement, J.; Aerts, J. M.; Farifteh, J.; Lagrou, K.; Van Ranst, M.; Coppin, P.

    2012-08-01

    The strong correlation between environmental conditions and abundance and spatial spread of the tick Ixodes ricinus is widely documented. I. ricinus is in Europe the main vector of the bacterium Borrelia burgdorferi, the pathogen causing Lyme borreliosis (LB). Humidity in vegetated systems is a major factor in tick ecology and its effects might translate into disease incidence in humans. Time series of two remotely sensed indices with sensitivity to vegetation greenness and moisture were tested as explanatory variables of LB incidence. Wavelet-based multiresolution analysis allowed the examination of these signals at different temporal scales in study sites in Belgium, where increases in LB incidence were reported in recent years. The analysis showed the potential of the tested indices for disease monitoring, the usefulness of analyzing the signal in different time frames and the importance of local characteristics of the study area for the selection of the vegetation index.

  4. Reservoir competence of Microtus pennsylvanicus (Rodentia: Cricetidae) for the Lyme disease spirochete, Borrelia burgdorferi

    USGS Publications Warehouse

    Markowski, D.; Ginsberg, H.S.; Hyland, K.E.; Hu, R.

    1998-01-01

    The reservoir competence of the meadow vole, Microtus pennsylvanicus Ord, for the Lyme disease spirochete, Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner was established on Patience Island, RI. Meadow voles were collected from 5 locations throughout Rhode Island. At 4 of the field sites, M. pennsylvanicus represented only 4.0% (n = 141) of the animals captured. However, on Patience Island, M. pennsylvanicus was the sole small mammal collected (n = 48). Of the larval Ixodes scapularis Say obtained from the meadow voles on Patience Island, 62% (n = 78) was infected with B. burgdorferi. Meadow voles from all 5 locations were successfully infected with B. burgdorferi in the laboratory and were capable of passing the infection to xenodiagnostic I. scapularis larvae for 9 wk. We concluded that M. pennsylvanicus was physiologically capable of maintaining B. burgdorferi infection. However, in locations where Peromyscus leucopus (Rafinesque) is abundant, the role of M. pennsylvanicus as a primary reservoir for B. burgdorferi was reduced.

  5. The Lyme Disease Pathogen Borrelia burgdorferi Infects Murine Bone and Induces Trabecular Bone Loss

    PubMed Central

    Tang, Tian Tian; Zhang, Lucia; Bansal, Anil; Grynpas, Marc

    2016-01-01

    ABSTRACT Lyme disease is caused by members of the Borrelia burgdorferi sensu lato species complex. Arthritis is a well-known late-stage pathology of Lyme disease, but the effects of B. burgdorferi infection on bone at sites other than articular surfaces are largely unknown. In this study, we investigated whether B. burgdorferi infection affects bone health in mice. In mice inoculated with B. burgdorferi or vehicle (mock infection), we measured the presence of B. burgdorferi DNA in bones, bone mineral density (BMD), bone formation rates, biomechanical properties, cellular composition, and two- and three-dimensional features of bone microarchitecture. B. burgdorferi DNA was detected in bone. In the long bones, increasing B. burgdorferi DNA copy number correlated with reductions in areal and trabecular volumetric BMDs. Trabecular regions of femora exhibited significant, copy number-correlated microarchitectural disruption, but BMD, microarchitectural, and biomechanical properties of cortical bone were not affected. Bone loss in tibiae was not due to increased osteoclast numbers or bone-resorbing surface area, but it was associated with reduced osteoblast numbers, implying that bone loss in long bones was due to impaired bone building. Osteoid-producing and mineralization activities of existing osteoblasts were unaffected by infection. Therefore, deterioration of trabecular bone was not dependent on inhibition of osteoblast function but was more likely caused by blockade of osteoblastogenesis, reduced osteoblast survival, and/or induction of osteoblast death. Together, these data represent the first evidence that B. burgdorferi infection induces bone loss in mice and suggest that this phenotype results from inhibition of bone building rather than increased bone resorption. PMID:27956598

  6. Distribution and molecular analysis of Lyme disease spirochetes, Borrelia burgdorferi, isolated from ticks throughout California.

    PubMed

    Schwan, T G; Schrumpf, M E; Karstens, R H; Clover, J R; Wong, J; Daugherty, M; Struthers, M; Rosa, P A

    1993-12-01

    Previous studies describing the occurrence and molecular characteristics of Lyme disease spirochetes, Borrelia burgdorferi, from California have been restricted primarily to isolates obtained from the north coastal region of this large and ecologically diverse state. Our objective was to look for and examine B. burdorferi organisms isolated from Ixodes pacificus ticks collected from numerous regions spanning most parts of California where this tick is found. Thirty-one isolates of B. burgdorferi were examined from individual or pooled I. pacificus ticks collected from 25 counties throughout the state. One isolate was obtained from ticks collected at Wawona Campground in Yosemite National Park, documenting the occurrence of the Lyme disease spirochete in an area of intensive human recreational use. One isolate from an Ixodes neotomae tick from an additional county was also examined. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis, immunoblot analysis, agarose gel electrophoresis, Southern blot analysis, and the polymerase chain reaction were used to examine the molecular and genetic determinants of these uncloned, low-passage-number isolates. All of the isolates were identified as B. burgdorferi by their protein profiles and reactivities with monoclonal and polyclonal antibodies, and all the isolates were typed by the polymerase chain reaction as North American-type spirochetes (B. burgdorferi sensu stricto). Although products of the ospAB locus were identified in protein analyses in all of the isolates, several isolates contained deleted forms of this locus that would result in the expression of chimeric OspA-OspB proteins. The analysis of OspC demonstrated that this protein was widely conserved among the isolates but was also quite variable in its molecular mass and the amount of it that was expressed.

  7. Geographical and environmental factors driving the increase in the Lyme disease vector Ixodes scapularis

    PubMed Central

    Khatchikian, Camilo E.; Prusinski, Melissa; Stone, Melissa; Backenson, P. Bryon; Wang, Ing-Nang; Levy, Michael Z.; Brisson, Dustin

    2013-01-01

    The population densities of many organisms have changed dramatically in recent history. Increases in the population density of medically relevant organisms are of particular importance to public health as they are often correlated with the emergence of infectious diseases in human populations. Our aim is to delineate increases in density of a common disease vector in North America, the blacklegged tick, and to identify the environmental factors correlated with these population dynamics. Empirical data that capture the growth of a population are often necessary to identify environmental factors associated with these dynamics. We analyzed temporally- and spatially-structured field collected data in a geographical information systems framework to describe the population growth of blacklegged ticks (Ixodes scapularis) and to identify environmental and climatic factors correlated with these dynamics. The density of the ticks increased throughout the study’s temporal and spatial ranges. Tick density increases were positively correlated with mild temperatures, low precipitation, low forest cover, and high urbanization. Importantly, models that accounted for these environmental factors accurately forecast future tick densities across the region. Tick density increased annually along the south-to-north gradient. These trends parallel the increases in human incidences of diseases commonly vectored by I. scapularis. For example, I. scapularis densities are correlated with human Lyme disease incidence, albeit in a non-linear manner that disappears at low tick densities, potentially indicating that a threshold tick density is needed to support epidemiologically-relevant levels of the Lyme disease bacterium. Our results demonstrate a connection between the biogeography of this species and public health. PMID:24371541

  8. Diet-Induced Obesity Does Not Alter Tigecycline Treatment Efficacy in Murine Lyme Disease

    PubMed Central

    Pětrošová, Helena; Eshghi, Azad; Anjum, Zoha; Zlotnikov, Nataliya; Cameron, Caroline E.; Moriarty, Tara J.

    2017-01-01

    Obese individuals more frequently suffer from infections, as a result of increased susceptibility to a number of bacterial pathogens. Furthermore, obesity can alter antibiotic treatment efficacy due to changes in drug pharmacokinetics which can result in under-dosing. However, studies on the treatment of bacterial infections in the context of obesity are scarce. To address this research gap, we assessed efficacy of antibiotic treatment in diet-induced obese mice infected with the Lyme disease pathogen, Borrelia burgdorferi. Diet-induced obese C3H/HeN mice and normal-weight controls were infected with B. burgdorferi, and treated during the acute phase of infection with two doses of tigecycline, adjusted to the weights of diet-induced obese and normal-weight mice. Antibiotic treatment efficacy was assessed 1 month after the treatment by cultivating bacteria from tissues, measuring severity of Lyme carditis, and quantifying bacterial DNA clearance in ten tissues. In addition, B. burgdorferi-specific IgG production was monitored throughout the experiment. Tigecycline treatment was ineffective in reducing B. burgdorferi DNA copies in brain. However, diet-induced obesity did not affect antibiotic-dependent bacterial DNA clearance in any tissues, regardless of the tigecycline dose used for treatment. Production of B. burgdorferi-specific IgGs was delayed and attenuated in mock-treated diet-induced obese mice compared to mock-treated normal-weight animals, but did not differ among experimental groups following antibiotic treatment. No carditis or cultivatable B. burgdorferi were detected in any antibiotic-treated group. In conclusion, obesity was associated with attenuated and delayed humoral immune responses to B. burgdorferi, but did not affect efficacy of antibiotic treatment. PMID:28286500

  9. Lyme disease: Knowledge and practices of family practitioners in southern Quebec

    PubMed Central

    Ferrouillet, Cécile; Milord, François; Lambert, Louise; Vibien, Anne; Ravel, André

    2015-01-01

    BACKGROUND: Public health authorities in Quebec have responded to the progressive emergence of Lyme disease (LD) with surveillance activities and education for family physicians (FPs) who are key actors in both vigilance and case management. OBJECTIVES: To describe FPs’ clinical experience with LD, their degree of knowledge, and their practices in two areas, one with known infected tick populations (Montérégie) and one without (regions nearby Montérégie). METHODS: In the present descriptive cross-sectional study, FPs were recruited during educational sessions. They were asked to complete a questionnaire assessing their clinical experience with Lyme disease, their knowledge of signs and symptoms of LD, and their familiarity with accepted guidelines for diagnosing and treating LD in two clinical scenarios (tick bite and erythema migrans). RESULTS: A total of 201 FPs participated, mostly from Montérégie (n=151). Overall, results revealed a moderate lack of knowledge and suboptimal practices rather than systematically insufficient knowledge or inadequate practices. A majority of participants agreed to more education on LD. As expected, FPs from Montérégie had a higher clinical experience with tick bites (57% versus 25%), better knowledge of LD endemic areas in Canada and erythema migrans characteristics, and better management of erythema migrans (72% versus 50%). CONCLUSION: The present study documented the inappropriate intention to order serology tests for tick bites and the unjustified intention to use tick analysis for diagnostic purposes. Such practices should be discouraged because they are unnecessary and overuse collective laboratory and medical resources. In addition, public health authorities must pursue their education efforts regarding FPs to optimize case management. PMID:26236357

  10. Genome Stability of Lyme Disease Spirochetes: Comparative Genomics of Borrelia burgdorferi Plasmids

    SciTech Connect

    Casjens S. R.; Dunn J.; Mongodin, E. F.; Qiu, W.-G.; Luft, B. J.; Schutzer, S. E.; Gilcrease, E. B.; Huang, W. M.; Vujadinovic, M.; Aron, J. K.; Vargas, L. C.; Freeman, S.; Radune, D.; Weidman, J. F.; Dimitrov, G. I.; Khouri, H. M.; Sosa, J. E.; Halpin, R. A.; Fraser, C. M.

    2012-03-14

    Lyme disease is the most common tick-borne human illness in North America. In order to understand the molecular pathogenesis, natural diversity, population structure and epizootic spread of the North American Lyme agent, Borrelia burgdorferi sensu stricto, a much better understanding of the natural diversity of its genome will be required. Towards this end we present a comparative analysis of the nucleotide sequences of the numerous plasmids of B. burgdorferi isolates B31, N40, JD1 and 297. These strains were chosen because they include the three most commonly studied laboratory strains, and because they represent different major genetic lineages and so are informative regarding the genetic diversity and evolution of this organism. A unique feature of Borrelia genomes is that they carry a large number of linear and circular plasmids, and this work shows that strains N40, JD1, 297 and B31 carry related but non-identical sets of 16, 20, 19 and 21 plasmids, respectively, that comprise 33-40% of their genomes. We deduce that there are at least 28 plasmid compatibility types among the four strains. The B. burgdorferi {approx}900 Kbp linear chromosomes are evolutionarily exceptionally stable, except for a short {le}20 Kbp plasmid-like section at the right end. A few of the plasmids, including the linear lp54 and circular cp26, are also very stable. We show here that the other plasmids, especially the linear ones, are considerably more variable. Nearly all of the linear plasmids have undergone one or more substantial inter-plasmid rearrangements since their last common ancestor. In spite of these rearrangements and differences in plasmid contents, the overall gene complement of the different isolates has remained relatively constant.

  11. Susceptibility to Ticks and Lyme Disease Spirochetes Is Not Affected in Mice Coinfected with Nematodes

    PubMed Central

    Maaz, Denny; Rausch, Sebastian; Richter, Dania; Krücken, Jürgen; Kühl, Anja A.; Demeler, Janina; Blümke, Julia; Matuschka, Franz-Rainer; von Samson-Himmelstjerna, Georg

    2016-01-01

    Small rodents serve as reservoir hosts for tick-borne pathogens, such as the spirochetes causing Lyme disease. Whether natural coinfections with other macroparasites alter the success of tick feeding, antitick immunity, and the host's reservoir competence for tick-borne pathogens remains to be determined. In a parasitological survey of wild mice in Berlin, Germany, approximately 40% of Ixodes ricinus-infested animals simultaneously harbored a nematode of the genus Heligmosomoides. We therefore aimed to analyze the immunological impact of the nematode/tick coinfection as well as its effect on the tick-borne pathogen Borrelia afzelii. Hosts experimentally coinfected with Heligmosomoides polygyrus and larval/nymphal I. ricinus ticks developed substantially stronger systemic type 2 T helper cell (Th2) responses, on the basis of the levels of GATA-3 and interleukin-13 expression, than mice infected with a single pathogen. During repeated larval infestations, however, anti-tick Th2 reactivity and an observed partial immunity to tick feeding were unaffected by concurrent nematode infections. Importantly, the strong systemic Th2 immune response in coinfected mice did not affect susceptibility to tick-borne B. afzelii. An observed trend for decreased local and systemic Th1 reactivity against B. afzelii in coinfected mice did not result in a higher spirochete burden, nor did it facilitate bacterial dissemination or induce signs of immunopathology. Hence, this study indicates that strong systemic Th2 responses in nematode/tick-coinfected house mice do not affect the success of tick feeding and the control of the causative agent of Lyme disease. PMID:26883594

  12. Indications of Th1 and Th17 responses in cerebrospinal fluid from patients with Lyme neuroborreliosis: a large retrospective study

    PubMed Central

    2011-01-01

    Background Previous studies indicate that successful resolution of Lyme neuroborreliosis (NB) is associated with a strong T helper (Th) 1-type cytokine response in the cerebrospinal fluid (CSF) followed by a down-regulating Th2 response, whereas the role of the recently discovered Th17 cytokine response is unknown. Methods To investigate the relative contribution of different Th associated cytokine/chemokine responses, we used a multiple bead array to measure the levels of CXCL10 (Th1 marker), CCL22 (Th2 marker), IL-17 (Th17 marker) and CXCL8 (general inflammation marker), in serum and in CSF from untreated patients with confirmed NB (n = 133), and non-NB patients (n = 96), and related the findings to clinical data. Samples from patients with possible early NB (n = 15) and possible late NB (n = 19) were also analysed, as well as samples from an additional control group with orthopaedic patients (n = 17), where CSF was obtained at spinal anaesthesia. Results The most prominent differences across groups were found in the CSF. IL-17 was elevated in CSF in 49% of the patients with confirmed NB, but was not detectable in the other groups. Patients with confirmed NB and possible early NB had significantly higher CSF levels of CXCL10, CCL22 and CXCL8 compared to both the non-NB group and the control group (p < 0.0001 for all comparisons). Patients in the early NB group, showing a short duration of symptoms, had lower CCL22 levels in CSF than did the confirmed NB group (p < 0.0001). Furthermore, patients within the confirmed NB group showing a duration of symptoms <2 weeks, tended to have lower CCL22 levels in CSF than did those with longer symptom duration (p = 0.023). Cytokine/chemokine levels were not correlated with clinical parameters or to levels of anti-Borrelia-antibodies. Conclusion Our results support the notion that early NB is dominated by a Th1-type response, eventually accompanied by a Th2 response. Interestingly, IL-17 was increased exclusively in CSF from

  13. CXCL13 and neopterin concentrations in cerebrospinal fluid of patients with Lyme neuroborreliosis and other diseases that cause neuroinflammation

    PubMed Central

    2014-01-01

    Background Laboratory diagnosis of Lyme neuroborreliosis (LNB) is partly based on the detection of intrathecal Borrelia burgdorferi–specific antibody production (increased antibody index (AI)). However, AI can be negative in patients with early LNB and, conversely, can remain elevated for months after antibiotic treatment. Recent studies suggested that the chemokine CXCL13 in the cerebrospinal fluid (CSF) is a biomarker for active LNB. Also, CSF neopterin-level determination has been used to assess the degree of neuroinflammation in a wide variety of diseases. Methods CXCL13 concentrations were analyzed in CSF samples of 366 retrospectively identified individuals. The samples represented pretreatment LNB (38 patients), non-LNB comparison patients, tick-borne encephalitis, central nervous system (CNS) varicella zoster virus infection, CNS herpes simplex virus infection, CNS HHV6 infection, CNS enterovirus infection, and untreated neurosyphilis. The panel included also samples from patients with multiple sclerosis and other neuroinflammatory conditions. Of the LNB patients, 24 posttreatment CSF samples were available for CXCL13 analysis. Neopterin concentrations were determined in a subset of these samples. Results The CXCL13 concentrations in CSF samples of untreated LNB patients were significantly higher (median, 6,480 pg/ml) than the concentrations in the non-LNB group (median, <7.8 pg/ml), viral CNS infection samples (median, <7.8 pg/ml), or samples from patients with noninfectious neuroinflammatory conditions (median, <7.8 pg/ml). The use of cut-off 415 pg/ml led to a sensitivity of 100% and specificity of 99.7% for the diagnosis of LNB in these samples. CSF CXCL13 median concentrations declined significantly from 16,770 pg/ml before to 109 pg/ml after the treatment. CSF neopterin concentration was significantly higher among the untreated LNB patients than in the non-LNB group. The use of neopterin concentration 10.6 nM as the cut-off led to a

  14. Detection of Lyme Disease Bacterium, Borrelia burgdorferi sensu lato, in Blacklegged Ticks Collected in the Grand River Valley, Ontario, Canada

    PubMed Central

    Scott, John D.; Foley, Janet E.; Anderson, John F.; Clark, Kerry L.; Durden, Lance A.

    2017-01-01

    We document the presence of blacklegged ticks, Ixodes scapularis, in the Grand River valley, Centre Wellington, Ontario. Overall, 15 (36%) of 42 I. scapularis adults collected from 41 mammalian hosts (dogs, cats, humans) were positive for the Lyme disease bacterium, Borrelia burgdorferi sensu lato (s.l.). Using real-time PCR testing and DNA sequencing of the flagellin (fla) gene, we determined that Borrelia amplicons extracted from I. scapularis adults belonged to B. burgdorferi sensu stricto (s.s.), which is pathogenic to humans and certain domestic animals. Based on the distribution of I. scapularis adults within the river basin, it appears likely that migratory birds provide an annual influx of I. scapularis immatures during northward spring migration. Health-care providers need to be aware that local residents can present with Lyme disease symptoms anytime during the year. PMID:28260991

  15. Relevance of Chronic Lyme Disease to Family Medicine as a Complex Multidimensional Chronic Disease Construct: A Systematic Review

    PubMed Central

    Goderis, Geert

    2014-01-01

    Lyme disease has become a global public health problem and a prototype of an emerging infection. Both treatment-refractory infection and symptoms that are related to Borrelia burgdorferi infection remain subject to controversy. Because of the absence of solid evidence on prevalence, causes, diagnostic criteria, tools and treatment options, the role of autoimmunity to residual or persisting antigens, and the role of a toxin or other bacterial-associated products that are responsible for the symptoms and signs, chronic Lyme disease (CLD) remains a relatively poorly understood chronic disease construct. The role and performance of family medicine in the detection, integrative treatment, and follow-up of CLD are not well studied either. The purpose of this paper is to describe insights into the complexity of CLD as a multidimensional chronic disease construct and its relevance to family medicine by means of a systematic literature review. PMID:25506429

  16. Long-term assessment of health-related quality of life in patients with culture-confirmed early Lyme disease.

    PubMed

    Wormser, Gary P; Weitzner, Erica; McKenna, Donna; Nadelman, Robert B; Scavarda, Carol; Molla, Irida; Dornbush, Rhea; Visintainer, Paul; Nowakowski, John

    2015-07-15

    The health-related quality of life of 100 subjects with culture-confirmed early Lyme disease enrolled in a prospective study with annual follow-up visits was evaluated using the 36-Item Short Form General Health Survey version 2 (SF-36v2) questionnaire at 11-20 years after diagnosis. The mean summary scores of physical and mental health were similar to those of the general population.

  17. Collection and characterization of samples for establishment of a serum repository for lyme disease diagnostic test development and evaluation.

    PubMed

    Molins, Claudia R; Sexton, Christopher; Young, John W; Ashton, Laura V; Pappert, Ryan; Beard, Charles B; Schriefer, Martin E

    2014-10-01

    Serological assays and a two-tiered test algorithm are recommended for laboratory confirmation of Lyme disease. In the United States, the sensitivity of two-tiered testing using commercially available serology-based assays is dependent on the stage of infection and ranges from 30% in the early localized disease stage to near 100% in late-stage disease. Other variables, including subjectivity in reading Western blots, compliance with two-tiered recommendations, use of different first- and second-tier test combinations, and use of different test samples, all contribute to variation in two-tiered test performance. The availability and use of sample sets from well-characterized Lyme disease patients and controls are needed to better assess the performance of existing tests and for development of improved assays. To address this need, the Centers for Disease Control and Prevention and the National Institutes of Health prospectively collected sera from patients at all stages of Lyme disease, as well as healthy donors and patients with look-alike diseases. Patients and healthy controls were recruited using strict inclusion and exclusion criteria. Samples from all included patients were retrospectively characterized by two-tiered testing. The results from two-tiered testing corroborated the need for novel and improved diagnostics, particularly for laboratory diagnosis of earlier stages of infection. Furthermore, the two-tiered results provide a baseline with samples from well-characterized patients that can be used in comparing the sensitivity and specificity of novel diagnostics. Panels of sera and accompanying clinical and laboratory testing results are now available to Lyme disease serological test users and researchers developing novel tests.

  18. Lyme Disease

    MedlinePlus

    ... their instructions to help prevent bites. Use an insect repellent containing 20% to 30% DEET. Tick repellents ... I won't get sick?What tick or insect repellent should I use for my child?Which ...

  19. Lyme Disease

    MedlinePlus

    ... that's usually found in animals like mice and deer. Ixodes ticks (also called black-legged or deer ticks) are a kind of tick that feeds on mice, deer, and other animals that carry Borrelia burgdorferi . When ...

  20. Lyme Disease

    MedlinePlus

    ... was first isolated in 1982 by Willy Burgdorfer, Ph.D., a zoologist and microbiologist at the NIAID ... Letter Create a Resource Sharing Plan Use the PHS Assignment Request Form Research with Special Considerations Human ...