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Sample records for multiple independent lyme

  1. Phylogeography of Borrelia burgdorferi in the eastern United States reflects multiple independent Lyme disease emergence events

    PubMed Central

    Hoen, Anne Gatewood; Margos, Gabriele; Bent, Stephen J.; Diuk-Wasser, Maria A.; Barbour, Alan; Kurtenbach, Klaus; Fish, Durland

    2009-01-01

    Since its first description in coastal Connecticut in 1976, both the incidence of Lyme disease and the geographic extent of endemic areas in the US have increased dramatically. The rapid expansion of Lyme disease into its current distribution in the eastern half of the US has been due to the range expansion of the tick vector, Ixodes scapularis, upon which the causative agent, Borrelia burgdorferi is dependent for transmission to humans. In this study, we examined the phylogeographic population structure of B. burgdorferi throughout the range of I. scapularis-borne Lyme disease using multilocus sequence typing based on bacterial housekeeping genes. We show that B. burgdorferi populations from the Northeast and Midwest are genetically distinct, but phylogenetically related. Our findings provide strong evidence of prehistoric population size expansion and east-to-west radiation of descendent clones from founding sequence types in the Northeast. Estimates of the time scale of divergence of northeastern and midwestern populations suggest that B. burgdorferi was present in these regions of North America many thousands of years before European settlements. We conclude that B. burgdorferi populations have recently reemerged independently out of separate relict foci, where they have persisted since precolonial times. PMID:19706476

  2. [Lyme disease in patients with multiple sclerosis: clinical, diagnostic and therapeutic features].

    PubMed

    Baranova, N S; Spirin, N N; Fadeeva, O A; Shipova, E G; Stepanov, I O

    2012-01-01

    Lyme disease is one of the most frequent infections in the Russian Federation. In patients with multiple sclerosis, the Borrelia infection may act as a trigger in some cases and also worsens the clinical course of multiple sclerosis. One hundred patients with definite multiple sclerosis were examined including 19 patients with the combination of multiple sclerosis and Lyme disease. The difficulties of diagnosis, clinical features and treatment of Lyme disease in patients with multiple sclerosis are discussed.

  3. Empirical validation of the Horowitz Multiple Systemic Infectious Disease Syndrome Questionnaire for suspected Lyme disease.

    PubMed

    Citera, Maryalice; Freeman, Phyllis R; Horowitz, Richard I

    2017-01-01

    Lyme disease is spreading worldwide, with multiple Borrelia species causing a broad range of clinical symptoms that mimic other illnesses. A validated Lyme disease screening questionnaire would be clinically useful for both providers and patients. Three studies evaluated such a screening tool, namely the Horowitz Multiple Systemic Infectious Disease Syndrome (MSIDS) Questionnaire. The purpose was to see if the questionnaire could accurately distinguish between Lyme patients and healthy individuals. Study 1 examined the construct validity of the scale examining its factor structure and reliability of the questionnaire among 537 individuals being treated for Lyme disease. Study 2 involved an online sample of 999 participants, who self-identified as either healthy (N=217) or suffering from Lyme now (N=782) who completed the Horowitz MSIDS Questionnaire (HMQ) along with an outdoor activity survey. We examined convergent validity among components of the scale and evaluated discriminant validity with the Big Five personality characteristics. The third study compared a sample of 236 patients with confirmed Lyme disease with an online sample of 568 healthy individuals. Factor analysis results identified six underlying latent dimensions; four of these overlapped with critical symptoms identified by Horowitz - neuropathy, cognitive dysfunction, musculoskeletal pain, and fatigue. The HMQ showed acceptable levels of internal reliability using Cronbach's coefficient alpha and exhibited evidence of convergent and divergent validity. Components of the HMQ correlated more highly with each other than with unrelated traits. The results consistently demonstrated that the HMQ accurately differentiated those with Lyme disease from healthy individuals. Three migratory pain survey items (persistent muscular pain, arthritic pain, and nerve pain/paresthesias) robustly identified individuals with verified Lyme disease. The results support the use of the HMQ as a valid, efficient, and low

  4. Empirical validation of the Horowitz Multiple Systemic Infectious Disease Syndrome Questionnaire for suspected Lyme disease

    PubMed Central

    Citera, Maryalice; Freeman, Phyllis R; Horowitz, Richard I

    2017-01-01

    Purpose Lyme disease is spreading worldwide, with multiple Borrelia species causing a broad range of clinical symptoms that mimic other illnesses. A validated Lyme disease screening questionnaire would be clinically useful for both providers and patients. Three studies evaluated such a screening tool, namely the Horowitz Multiple Systemic Infectious Disease Syndrome (MSIDS) Questionnaire. The purpose was to see if the questionnaire could accurately distinguish between Lyme patients and healthy individuals. Methods Study 1 examined the construct validity of the scale examining its factor structure and reliability of the questionnaire among 537 individuals being treated for Lyme disease. Study 2 involved an online sample of 999 participants, who self-identified as either healthy (N=217) or suffering from Lyme now (N=782) who completed the Horowitz MSIDS Questionnaire (HMQ) along with an outdoor activity survey. We examined convergent validity among components of the scale and evaluated discriminant validity with the Big Five personality characteristics. The third study compared a sample of 236 patients with confirmed Lyme disease with an online sample of 568 healthy individuals. Results Factor analysis results identified six underlying latent dimensions; four of these overlapped with critical symptoms identified by Horowitz – neuropathy, cognitive dysfunction, musculoskeletal pain, and fatigue. The HMQ showed acceptable levels of internal reliability using Cronbach’s coefficient alpha and exhibited evidence of convergent and divergent validity. Components of the HMQ correlated more highly with each other than with unrelated traits. Discussion The results consistently demonstrated that the HMQ accurately differentiated those with Lyme disease from healthy individuals. Three migratory pain survey items (persistent muscular pain, arthritic pain, and nerve pain/paresthesias) robustly identified individuals with verified Lyme disease. The results support the use of

  5. [Lyme disease].

    PubMed

    Belaich, S

    1995-01-14

    The history of Lyme disease, a contagious condition caused by Borrelia burgdorferi transmitted to man by ticks offers infectiologists a formidable lesson on how medicine progresses. Clinical description started in Europe at the turn of the century with Pick's description of what was then labelled chronic atrophic acrodermatitis. Fifty years later Hauser noted the affection was transmitted by ticks. Independently, Afzelius, then Lipschutz, described erythema chronicum migrans and its relationship with tick bites. Neurological involvement was also described with the skin signs. These early dermatological descriptions suddenly came into the limelight in 1975 when an epidemia of arthritis occurred in children in Lyme, Connecticut, USA. Many of the affected children had erythema chronicum migrans. Based on these observations and an epidemiological analysis of the epidemia, Steele and co-workers defined "Lyme disease" as a rheumatological disorder commonly associated with erythema chronicum migrans and sometimes with multiple organ involvement. In 1982 Borgdorfer suggested that tick bites transmitted a Spirochaeta which was later authentified as the causal agent: Borrelia burgdorferi. Immunofluorescence and ELISA tests were rapidly developed for the diagnosis of infection by this germ which is very difficult to culture. Antibiotic curative treatment was immediately available and in 1991 a consensus conference established recommendations for treatment of isolated and disseminated forms. Antibiotic prophylaxis is not necessary but rapid extraction of the tick after the bite can prevent the disease as transmission from tick to man takes several hours. And medical progress continues. Work is now being conducted on evaluating the extent of late neurological manifestations, on developing polymerase chain reaction methods to identify B. burgdorferi infection in specific organs and on developing a vaccine.

  6. 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 ...

  7. 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

  8. 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

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

    PubMed

    Shroff, Geeta

    2016-12-13

    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.

  10. 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.

  11. 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

  12. Lyme disease.

    PubMed

    Murray, Thomas S; Shapiro, Eugene D

    2010-03-01

    Lyme disease, caused by the spirochete Borrelia burgdorferi, is the most common vector-borne disease in the United States. The clinical presentation varies depending on the stage of the illness: early disease includes erthyma migrans, early disseminated disease includes multiple erythema migrans, meningitis, cranial nerve palsies, and carditis; late disease is primarily arthritis. The symptoms and signs of infection resolve in most patients after treatment with appropriate antimicrobials for 2 to 4 weeks. Serologic testing should be used judiciously as it often results in misdiagnosis when performed on blood from patients with a low prior probability of disease and those with only nonspecific symptoms such as fatigue or arthralgia without objective signs of infection.

  13. Lyme Disease

    PubMed Central

    Murray, Thomas S.; Shapiro, Eugene D.

    2013-01-01

    Synopsis Lyme disease, caused by spirochete Borrelia burgdorferi, is the most common vector-borne disease in the United States. The clinical presentation varies depending on the stage of the illness: early disease includes erthyma migrans, early disseminated disease includes multiple erythema migrans, meningitis, cranial nerve palsies and carditis; late disease is primarily arthritis. The symptoms and signs of infection resolve in the vast majority of patients after appropriate treatment with antimicrobials for from 2-4 weeks. Serologic testing should be used judiciously as it often results in misdiagnosis when performed on blood from patients with a low prior probability of disease and those with non-specific symptoms such as fatigue or arthralgia without signs of infection. PMID:20513553

  14. Lyme disease

    MedlinePlus

    ... 3, or late disseminated, Lyme disease can cause long-term joint inflammation (Lyme arthritis) and heart rhythm problems. Brain and nervous system problems are also possible, and may include: Decreased concentration Memory disorders Nerve damage Numbness Pain Paralysis of the face ...

  15. [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.

  16. 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 ...

  17. Lyme Disease

    MedlinePlus

    ... causing the illnesses.Lyme disease is carried by black-legged ticks (sometimes called deer ticks). These ticks are typically about the size of a sesame seed. They live only in certain areas of the ...

  18. [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.

  19. 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

  20. 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.

  1. 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.

  2. 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…

  3. 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…

  4. 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.

  5. Chronic Lyme Disease and Co-infections: Differential Diagnosis

    PubMed Central

    Berghoff, Walter

    2012-01-01

    In Lyme disease concurrent infections frequently occur. The clinical and pathological impact of co-infections was first recognized in the 1990th, i.e. approximately ten years after the discovery of Lyme disease. Their pathological synergism can exacerbate Lyme disease or induce similar disease manifestations. Co-infecting agents can be transmitted together with Borrelia burgdorferi by tick bite resulting in multiple infections but a fraction of co-infections occur independently of tick bite. Clinically relevant co-infections are caused by Bartonella species, Yersinia enterocolitica, Chlamydophila pneumoniae, Chlamydia trachomatis, and Mycoplasma pneumoniae. In contrast to the USA, human granulocytic anaplasmosis (HGA) and babesiosis are not of major importance in Europe. Infections caused by these pathogens in patients not infected by Borrelia burgdorferi can result in clinical symptoms similar to those occurring in Lyme disease. This applies particularly to infections caused by Bartonella henselae, Yersinia enterocolitica, and Mycoplasma pneumoniae. Chlamydia trachomatis primarily causes polyarthritis. Chlamydophila pneumoniae not only causes arthritis but also affects the nervous system and the heart, which renders the differential diagnosis difficult. The diagnosis is even more complex when co-infections occur in association with Lyme disease. Treatment recommendations are based on individual expert opinions. In antibiotic therapy, the use of third generation cephalosporins should only be considered in cases of Lyme disease. The same applies to carbapenems, which however are used occasionally in infections caused by Yersinia enterocolitica. For the remaining infections predominantly tetracyclines and macrolides are used. Quinolones are for alternative treatment, particularly gemifloxacin. For Bartonella henselae, Chlamydia trachomatis, and Chlamydophila pneumoniae the combination with rifampicin is recommended. Erythromycin is the drug of choice for

  6. Chronic Lyme Disease and Co-infections: Differential Diagnosis.

    PubMed

    Berghoff, Walter

    2012-01-01

    In Lyme disease concurrent infections frequently occur. The clinical and pathological impact of co-infections was first recognized in the 1990th, i.e. approximately ten years after the discovery of Lyme disease. Their pathological synergism can exacerbate Lyme disease or induce similar disease manifestations. Co-infecting agents can be transmitted together with Borrelia burgdorferi by tick bite resulting in multiple infections but a fraction of co-infections occur independently of tick bite. Clinically relevant co-infections are caused by Bartonella species, Yersinia enterocolitica, Chlamydophila pneumoniae, Chlamydia trachomatis, and Mycoplasma pneumoniae. In contrast to the USA, human granulocytic anaplasmosis (HGA) and babesiosis are not of major importance in Europe. Infections caused by these pathogens in patients not infected by Borrelia burgdorferi can result in clinical symptoms similar to those occurring in Lyme disease. This applies particularly to infections caused by Bartonella henselae, Yersinia enterocolitica, and Mycoplasma pneumoniae. Chlamydia trachomatis primarily causes polyarthritis. Chlamydophila pneumoniae not only causes arthritis but also affects the nervous system and the heart, which renders the differential diagnosis difficult. The diagnosis is even more complex when co-infections occur in association with Lyme disease. Treatment recommendations are based on individual expert opinions. In antibiotic therapy, the use of third generation cephalosporins should only be considered in cases of Lyme disease. The same applies to carbapenems, which however are used occasionally in infections caused by Yersinia enterocolitica. For the remaining infections predominantly tetracyclines and macrolides are used. Quinolones are for alternative treatment, particularly gemifloxacin. For Bartonella henselae, Chlamydia trachomatis, and Chlamydophila pneumoniae the combination with rifampicin is recommended. Erythromycin is the drug of choice for

  7. [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.

  8. 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.

  9. 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.

  10. Lyme borreliosis

    PubMed Central

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

    2017-01-01

    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. PMID:27976670

  11. 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- ...

  12. 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.

  13. 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

  14. 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

  15. Lyme Disease Data

    MedlinePlus

    ... Lyme disease FAQ Health care providers Educational materials Data and Statistics Recommend on Facebook Tweet Share Compartir ... sixth most common Nationally Notifiable disease . Lyme Disease Data File To facilitate the public health and research ...

  16. 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 ...

  17. 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.

  18. 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 ...

  19. 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.

  20. Lyme disease.

    PubMed

    Goldings, E A; Jericho, J

    1986-08-01

    Although initially considered a localized epidemic form of arthritis. Lyme disease is now known to have protean manifestation (skin, joint, heart, nervous system) and worldwide distribution. It is caused by infection with the spirochaete Borrelia burgdorferi and is transmitted by a variety of hard ticks and, in some localities, fleas. Antigenic variation between isolates may determine the differences in clinical expression observed between cases in North America and Europe. The reservoir in the animal kingdom is primarily in deer and mice but house pets have also been implicated. The disease is easily treated with oral antibiotics (tetracycline or penicillin) at an early stage but requires parenteral penicillin and can become refractory to medication at late stages. Prompt diagnosis assures the best outcome. Whereas the classic rash, erythema chronicum migrans, is pathognomonic, diagnosis in its absence may rest on serological tests. Bacteriological isolation is seldom successful and is lengthy (Shrestha et al, 1985). Since cloning of the DNA for several of B. burgdorferi antigens has been accomplished, utilization of hybridization techniques may allow rapid detection of the presence of the organism and confirm difficult cases in the future.

  1. Neurological Complications of Lyme Disease

    MedlinePlus

    ... here Home » Disorders » All Disorders Neurological Complications of Lyme Disease Information Page Neurological Complications of Lyme Disease Information Page What research is being done? The ...

  2. 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.

  3. 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.

  4. 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.

  5. [Recurrent ischemic strokes revealing Lyme meningovascularitis].

    PubMed

    Sparsa, L; Blanc, F; Lauer, V; Cretin, B; Marescaux, C; Wolff, V

    2009-03-01

    Infectious vascularitis is an unusual cause of ischemic stroke (IS). We report a case of Lyme meningovascularitis complicated with multiple IS. A 64-year-old man, without any cardiovascular risk factor, was admitted for a right hemiparesia with a left thalamic hypodensity on the initial cerebral CT scan. No cause for this presumed IS could be identified. Later, the patient developed cognitive impairment and a bilateral cerebellar syndrome. Multiple infarcts and multiple intracranial stenosis were seen on cerebral MRI with magnetic resonance angiography (MRA). Cerebrospinal fluid tests showed meningitis and positive Lyme serology with an intrathecal specific anti-Borrelia antibody index. Antibiotic treatment was followed by good biological and partial clinicoradiological outcome. The diagnosis of Lyme neuroborreliosis should be entertained as a possible cause of IS in highly endemic zones.

  6. 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.

  7. Clinical predictors of Lyme disease among children with a peripheral facial palsy at an emergency department in a Lyme disease-endemic area.

    PubMed

    Nigrovic, Lise E; Thompson, Amy D; Fine, Andrew M; Kimia, Amir

    2008-11-01

    Although Lyme disease can cause peripheral facial palsy in Lyme disease-endemic areas, diagnostic predictors in children have not been described. Our goal was to determine clinical predictors of Lyme disease as the etiology of peripheral facial palsy in children presenting to an emergency department in a Lyme disease-endemic area. We reviewed all available electronic medical charts of children Lyme disease definition: presence of erythema migrans lesion or serologic evidence of infection with Borrelia burgdorferi. We performed binary logistic regression with bootstrapping validation to determine independent clinical predictors of Lyme disease. We identified 313 patients with peripheral facial palsy evaluated for Lyme disease. The mean age was 10.7 years, and 52% were male. Of these, 106 (34%) had Lyme disease facial palsy. After adjusting for year of study, the following were independently associated with Lyme disease facial palsy: onset of symptoms during peak Lyme disease season (June to October), absence of previous herpetic lesions, presence of fever, and history of headache. In the subset of patients without meningitis, both onset of symptoms during Lyme disease season and presence of headache remained significant independent predictors. Lyme disease is a frequent cause of facial palsy in children living in an endemic region. Serologic testing and empiric antibiotics should be strongly considered, especially when children present during peak Lyme disease season or with a headache.

  8. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. [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.

  10. Lyme Disease Transmission

    MedlinePlus

    ... is available on the Red Cross website . Although dogs and cats can get Lyme disease, there is ... include Lone star ticks ( Amblyomma americanum ), the American dog tick ( Dermacentor variabilis ), the Rocky Mountain wood tick ( ...

  11. Lyme disease antibody

    MedlinePlus

    ... Site Map FAQs Customer Support Health Topics Drugs & Supplements Videos & Tools Español You Are Here: Home → Medical Encyclopedia → Lyme disease blood test URL of this page: //medlineplus. ...

  12. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. 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.

  14. 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.

  15. 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.

  16. Final report of the Lyme disease review panel of the Infectious Diseases Society of America.

    PubMed

    Lantos, Paul M; Charini, William A; Medoff, Gerald; Moro, Manuel H; Mushatt, David M; Parsonnet, Jeffrey; Sanders, John W; Baker, Carol J

    2010-07-01

    In April 2008, the Infectious Diseases Society of America (IDSA) entered into an agreement with Connecticut Attorney General Richard Blumenthal to voluntarily undertake a special review of its 2006 Lyme disease guidelines. This agreement ended the Attorney General's investigation into the process by which the guidelines were developed. The IDSA agreed to convene an independent panel to conduct a one-time review of the guidelines. The Review Panel members, vetted by an ombudsman for potential conflicts of interest, reviewed the entirety of the 2006 guidelines, with particular attention to the recommendations devoted to post-Lyme disease syndromes. After multiple meetings, a public hearing, and extensive review of research and other information, the Review Panel concluded that the recommendations contained in the 2006 guidelines were medically and scientifically justified on the basis of all of the available evidence and that no changes to the guidelines were necessary.

  17. Delay Independent Criterion for Multiple Time-delay Systems

    NASA Astrophysics Data System (ADS)

    Chang, C. J.; Liu, K. F. R.; Yeh, K.; Chen, C. W.; Chung, P. Y.

    Based on the fuzzy Lyapunov method, this work addresses the stability conditions for nonlinear systems with multiple time delays to ensure the stability of building structure control systems. The delay independent conditions are derived via the traditional Lyapunov and fuzzy Lyapunov methods for multiple time-delay systems as approximated by the Tagagi-Sugeno (T-S) fuzzy model. The fuzzy Lyapunov function is defined as a fuzzy blending of quadratic Lyapunov functions. A parallel distributed compensation (PDC) scheme is utilized to construct a global fuzzy logic control (FLC) by blending all linear local state feedback controllers in the controller design procedure. Furthermore, the H infinity performance and robustness of the design for modeling errors also need to be considered in the stability conditions.

  18. Lyme Disease and the Orthopaedic Implications of Lyme Arthritis

    PubMed Central

    Smith, Brian G.; Cruz, Aristides I.; Milewski, Matthew D.; Shapiro, Eugene D.

    2013-01-01

    Lyme disease is the most common tick-borne disease in the United States and Europe. Increased awareness of the clinical manifestations of the disease is needed to improve detection and treatment. In the acute and late stages, Lyme disease may be difficult to distinguish from other disease processes. The epidemiology and pathophysiology of Lyme disease are directly related to the Borrelia burgdorferi spirochete and its effects on the integumentary, neurologic, cardiac, and musculoskeletal systems. Lyme arthritis is a common clinical manifestation of Lyme disease and should be considered in the evaluation of patients with monoarticular or pauciarticular joint complaints in a geographic area in which Lyme disease is endemic. Management of Lyme arthritis involves eradication of the spirochete with antibiotics. Generally, the prognosis is excellent. Arthroscopic synovectomy is reserved for refractory cases that do not respond to antibiotics. PMID:21292932

  19. Admissions file review: applying the multiple independent sampling (MIS) methodology.

    PubMed

    Hanson, Mark D; Kulasegaram, Kulamakan Mahan; Coombs, Deborah L; Herold, Jodi

    2012-10-01

    Although multiple independent sampling (MIS) has been adapted for admissions interviews, its application for assessing written materials in the admissions file has been limited. Currently, admissions file review at the University of Toronto medical school involves one rater per file to enable holistic assessment, which may introduce a halo effect-that is, impressions of one component influencing the evaluation of other components. The authors examined whether MIS file review, through which multiple raters evaluate specific file components independently, may reduce this effect. The authors selected a stratified random sample of 300 applicant files from the 2010-2011 admissions cycle for rescoring by MIS. They divided each of the 300 applicant files into their four components (academic transcript, autobiographical sketch, personal statement, reference letters) and rebundled them into packages of 38 same-component items (purposely creating some overlap among packages to assess inter-rater reliability). The authors distributed each package to 1 of 36 raters; thus, each rater evaluated only one of four components across many applicants. The authors compared the inter-component reliability and factor analysis of MIS with that of holistic scoring. Ratings were returned for all applicants. Inter-component reliability (Cronbach alpha) was 0.69 for holistic scoring and 0.29 for MIS. Factor analysis showed all components loading heavily onto one factor in the holistic approach and onto three factors in the MIS method. Using MIS to assess the admissions file may reduce the halo effect and should be considered when evaluating applicants' written submissions.

  20. 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.

  1. Musculoskeletal manifestations of Lyme disease.

    PubMed

    Bitar, Imad; Lally, Edward V

    2008-07-01

    Musculoskeletal symptoms in Lyme disease are very common at all stages of the disease. Lyme arthritis, whether intermittent or chronic, is a hallmark of late Lyme disease. This may cause severe joint pain and swelling especially confined to one or a few joints, most notably the knee. Antibiotic therapy is very effective in treating Lyme arthritis in the majority of cases. However, a small proportion of individuals will develop persistent chronic arthritis which is likely mediated through immunologic mechanisms. In these patients treatment strategies should include anti-inflammatory medications and possibly immunosuppressive treatments. Arthroscopic synovectomy ma ybe very helpful in some of these patients. Post Lyme disease syndrome and Lyme myositis are two other sequelae that are associated with Lyme disease.

  2. 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. © 2016 Royal Australasian College of Physicians.

  3. 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 ...

  4. Beware of Ticks … & Lyme Disease

    MedlinePlus

    ... for ticks after outdoor activities. Lyme Disease in Dogs and Other Pets Household pets can get Lyme ... FDA’s Center for Veterinary Medicine (CVM) say that dogs with Lyme disease occasionally develop serious kidney disease ...

  5. Effect of independent multiple reading of mammograms on detection performance

    NASA Astrophysics Data System (ADS)

    Karssemeijer, Nico; Otten, Johannes D.; Roelofs, Antonius A. J.; van Woudenberg, Sander; Hendriks, Jan H. C. L.

    2004-05-01

    The goal of this study was to assess the effect of independent combination of multiple readers in mammography on detection performance, using different rules to combine localized observer responses. A group of 12 radiologists each read a series of 192 screening mammograms, including 96 prior mammograms of breast cancer cases in which a visible sign of abnormality could be identifed in retrospect. The other 96 cases were normal. In total the 12 readers annotated 1890 findings. LROC analysis was used to measure performance. The mean sensitivity in a false positive interval from 2 to 8% was 31.4% for single reading (range: 14.4% - 46.9%). The best rule for combination of observer scores was taking the average of all radiologists, using a zero score for radiologists who did not annotate the finding. With this strategy the average performance of 2 readers combined, in the interval selected, went up to 42.2%. When the interpretations of more readers were independently combined the mean sensitivity further increased, up to a level of 64.8% for the combination of all 12 readers. Using the mean score of only those readers who reported a finding turned out to be a poor strategy, yielding results that were similar or worse than single reading.

  6. Chronic Lyme Disease

    MedlinePlus

    ... PTLDS was not supported by the evidence. Another study supported by the National Institute of Neurological Disorders and Stroke again showed that long-term antibiotic use for Lyme disease is not an effective strategy for cognitive improvement ( Neurology 70(13):992-1003, ...

  7. 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.

  8. Carrier allocation combined with independent component analysis for multiple-input-multiple-output visible light communication

    NASA Astrophysics Data System (ADS)

    Jiang, Fangqing; Deng, Honggui; Yang, Fang; Zhu, Kaicheng; Zhu, Congxu

    2014-02-01

    We present a scheme based on precoding carrier allocation and independent component analysis (ICA) for indoor multiple-input-multiple-output (MIMO) visible light communication (VLC). In order to improve the reliability of the ICA algorithm for the mixed signal separation, at the sending end, frequency doubled-carriers are employed to module the parallel data which ensure that the modulated signals are independent of each other. The ICA algorithm is applied to separate the mixed signal at the receiving end directly without the requirement of the channel information. Simulation results show that this indoor MIMO VLC scheme can achieve excellent performance. When the signal-to-noise ratio is equal to 14 dB, the bit error ratio (BER) reaches the level of 10-5. So, the communication performance is superior to that of the commonly used schemes based on the channel estimation.

  9. 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.

  10. 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

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

    PubMed

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

    2016-06-30

    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 distinct cases in mammals (Tasmanian devils and dogs), but these are generally considered to be rare exceptions in nature. The discovery of transmissible cancer in soft-shell clams (Mya arenaria) suggested that this phenomenon might be more widespread. Here we analyse disseminated neoplasia in mussels (Mytilus trossulus), cockles (Cerastoderma edule), and golden carpet shell clams (Polititapes aureus) and find 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; however, unexpectedly, cancer cells in P. aureus are all derived from Venerupis corrugata, a different species living in the same geographical 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 are found spreading within the species of origin, cross-species transmission of cancer cells can occur.

  12. 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

  13. [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.

  14. Multiple Independent Oscillatory Networks in the Degenerating Retina.

    PubMed

    Euler, Thomas; Schubert, Timm

    2015-01-01

    During neuronal degenerative diseases, microcircuits undergo severe structural alterations, leading to remodeling of synaptic connectivity. This can be particularly well observed in the retina, where photoreceptor degeneration triggers rewiring of connections in the retina's first synaptic layer (e.g., Strettoi et al., 2003; Haq et al., 2014), while the synaptic organization of inner retinal circuits appears to be little affected (O'Brien et al., 2014; Figures 1A,B). Remodeling of (outer) retinal circuits and diminishing light-driven activity due to the loss of functional photoreceptors lead to spontaneous activity that can be observed at different retinal levels (Figure 1C), including the retinal ganglion cells, which display rhythmic spiking activity in the degenerative retina (Margolis et al., 2008; Stasheff, 2008; Menzler and Zeck, 2011; Stasheff et al., 2011). Two networks have been suggested to drive the oscillatory activity in the degenerating retina: a network of remnant cone photoreceptors, rod bipolar cells (RBCs) and horizontal cells in the outer retina (Haq et al., 2014), and the AII amacrine cell-cone bipolar cell network in the inner retina (Borowska et al., 2011). Notably, spontaneous rhythmic activity in the inner retinal network can be triggered in the absence of synaptic remodeling in the outer retina, for example, in the healthy retina after photo-bleaching (Menzler et al., 2014). In addition, the two networks show remarkable differences in their dominant oscillation frequency range as well as in the types and numbers of involved cells (Menzler and Zeck, 2011; Haq et al., 2014). Taken together this suggests that the two networks are self-sustained and can be active independently from each other. However, it is not known if and how they modulate each other. In this mini review, we will discuss: (i) commonalities and differences between these two oscillatory networks as well as possible interaction pathways; (ii) how multiple self

  15. 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,…

  16. 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,…

  17. Isolation of Borrelia burgdorferi sensu lato from blood of adult patients with borrelial lymphocytoma, Lyme neuroborreliosis, Lyme arthritis and acrodermatitis chronica atrophicans.

    PubMed

    Maraspin, V; Ogrinc, K; Ružić-Sabljić, E; Lotrič-Furlan, S; Strle, F

    2011-02-01

    Reports on patients with European Lyme borreliosis in whom borreliae were isolated from the blood are rare and nearly exclusively limited to those with solitary or multiple erythema migrans. Here we report on patients with other manifestations of Lyme borreliosis in whom borreliae were isolated from their blood. This is a retrospective review of the medical files of patients diagnosed with borrelial lymphocytoma, Lyme neuroborreliosis, Lyme arthritis and acrodermatitis chronica atrophicans at the Department of Infectious Diseases of the UMC Ljubljana, Slovenia, for whom a borrelia blood culture was ordered. The clinical features of patients whose blood culture tested positive for Borrelia burgdorferi sensu lato were reviewed, and the association between the proportion of patients with a positive blood culture and various clinical manifestations was examined. Borrelia burgdorferi sensu lato was isolated from the blood of 1/53 (1.9%) patients with borrelial lymphocytoma, 6/176 (3.4%) patients with Lyme neuroborreliosis, 1/13 (7.7%) patients with Lyme arthritis, and 3/200 (1.5%) patients with acrodermatitis chronica atrophicans. The time interval from the onset of symptoms attributed to Lyme borreliosis and the blood culture ranged from 1 day to >2 years (median 3.5 weeks). At the time of the blood culture, erythema migrans was present in 4/11 (36.4%) borrelia blood culture-positive patients, i.e. in the patient with borrelial lymphocytoma, the patient with Lyme arthritis and the 2/6 patients with Lyme neuroborreliosis. Only two of these 11 (18.2%) patients had fever at the time of the blood culture. In European patients with Lyme borreliosis, borreliae can be cultured from the blood not only early in the course of the disease but also occasionally later during disease progression.

  18. How multiple causes combine: independence constraints on causal inference.

    PubMed

    Liljeholm, Mimi

    2015-01-01

    According to the causal power view, two core constraints-that causes occur independently (i.e., no confounding) and influence their effects independently-serve as boundary conditions for causal induction. This study investigated how violations of these constraints modulate uncertainty about the existence and strength of a causal relationship. Participants were presented with pairs of candidate causes that were either confounded or not, and that either interacted or exerted their influences independently. Consistent with the causal power view, uncertainty about the existence and strength of causal relationships was greater when causes were confounded or interacted than when unconfounded and acting independently. An elemental Bayesian causal model captured differences in uncertainty due to confounding but not those due to an interaction. Implications of distinct sources of uncertainty for the selection of contingency information and causal generalization are discussed.

  19. 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.

  20. 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.

  1. 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. 2016 BMJ Publishing Group Ltd.

  2. 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. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Lyme disease: the next decade

    PubMed Central

    Stricker, Raphael B; Johnson, Lorraine

    2011-01-01

    Although Lyme disease remains a controversial illness, recent events have created an unprecedented opportunity to make progress against this serious tick-borne infection. Evidence presented during the legally mandated review of the restrictive Lyme guidelines of the Infectious Diseases Society of America (IDSA) has confirmed the potential for persistent infection with the Lyme spirochete, Borrelia burgdorferi, as well as the complicating role of tick-borne coinfections such as Babesia, Anaplasma, Ehrlichia, and Bartonella species associated with failure of short-course antibiotic therapy. Furthermore, renewed interest in the role of cell wall-deficient (CWD) forms in chronic bacterial infection and progress in understanding the molecular mechanisms of biofilms has focused attention on these processes in chronic Lyme disease. Recognition of the importance of CWD forms and biofilms in persistent B. burgdorferi infection should stimulate pharmaceutical research into new antimicrobial agents that target these mechanisms of chronic infection with the Lyme spirochete. Concurrent clinical implementation of proteomic screening offers a chance to correct significant deficiencies in Lyme testing. Advances in these areas have the potential to revolutionize the diagnosis and treatment of Lyme disease in the coming decade. PMID:21694904

  4. Chronic Lyme Disease: An appraisal

    PubMed Central

    Marques, Adriana

    2008-01-01

    Synopsis “Chronic Lyme disease” is a confusing term that has been used to describe very different patient populations. Studies have shown that most patients diagnosed with “chronic Lyme disease” either have no objective evidence of previous or current infection with B. burgdorferi or are patients that should be classified as having post-Lyme disease syndrome, which is defined as continuing or relapsing non-specific symptoms (such as fatigue, musculoskeletal pain, and cognitive complaints) in a patient previously treated for Lyme disease. Despite extensive study, there is currently no clear evidence that post-Lyme disease syndrome is due to persistent infection with B. burgdorferi. Four randomized placebo-controlled studies have shown that antibiotic therapy offers no sustained benefit to patients with post-Lyme disease syndrome. These studies also showed a substantial placebo effect and a significant risk of treatment-related adverse events. Further research to elucidate the mechanisms underlying persistent symptoms after Lyme disease and controlled trials of new approaches to the treatment and management of these patients are needed. PMID:18452806

  5. 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.

  6. Lyme Disease Diagnosis: Serology.

    PubMed

    Schriefer, Martin E

    2015-12-01

    Serology is the mainstay of confirmation of Lyme borreliosis; direct detection has limited application. Because standardized 2-tier testing (STTT) has been commonly used since the mid 1990s, standardization and performance have improved. STTT detection of early, localized infection is poor; that of late disease is good. The best indicator of stage 1 infection, erythema migrans, is presented in the majority of US cases and should prompt treatment without testing. Clinical and epidemiologic correlates should be carefully assessed before ordering STTT. STTT has great value in confirming extracutaneous infection. Recent developments promise to improve performance, particularly in early disease detection. Published by Elsevier Inc.

  7. Acute lyme infection presenting with amyopathic dermatomyositis and rapidly fatal interstitial pulmonary fibrosis: a case report.

    PubMed

    Nguyen, Hien; Le, Connie; Nguyen, Hanh

    2010-06-21

    Dermatomyositis has been described in the setting of lyme infection in only nine previous case reports. Although lyme disease is known to induce typical clinical findings that are observed in various collagen vascular diseases, to our knowledge, we believe that our case is the first presentation of acute lyme disease associated with amyopathic dermatomyositis, which was then followed by severe and fatal interstitial pulmonary fibrosis only two months later. We present a case of a 64-year-old African-American man with multiple medical problems who was diagnosed with acute lyme infection after presenting with the pathognomonic rash and confirmatory serology. In spite of appropriate antimicrobial therapy for lyme infection, he developed unexpected amyopathic dermatomyositis and then interstitial lung disease. This case illustrates a potential for lyme disease to produce clinical syndromes that may be indistinguishable from primary connective tissue diseases. An atypical and sequential presentation (dermatomyositis and interstitial lung disease) of a common disease (lyme infection) is discussed. This case illustrates that in patients who are diagnosed with lyme infection who subsequently develop atypical muscular, respiratory or other systemic complaints, the possibility of severe rheumatological and pulmonary complications should be considered.

  8. 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.

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

    PubMed Central

    Kugeler, Kiersten J.; Perea, Anna E.; Pastula, Daniel M.; Mead, Paul S.

    2015-01-01

    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. PMID:26488307

  10. 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

  11. 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

  12. Diagnosing and managing Lyme disease.

    PubMed

    Ziegler, Rachel M; Didas, Colleen M; Smith, Jami S

    2013-11-01

    All primary care providers should be familiar with the symptoms, diagnostic criteria, and treatments for Lyme disease. This tick-borne illness is increasing in incidence and geographic spread in the United States.

  13. European Lyme borreliosis clinical spectrum.

    PubMed

    Cimmino, M; Granström, M; Gray, J S; Guy, E C; O'Connell, S; Stanek, G

    1998-03-01

    At a series of meetings, involving 27 clinicians from 11 countries, case definitions for the diagnosis of Lyme borreliosis in Europe were agreed and are presented here, with appropriate serological criteria, as a diagnostic guide. In a separate study questionnaires directed to clinicians were used to collect information on clinical aspects and risk factors of Lyme borreliosis. Data on the number of Lyme borreliosis patients seen by physicians indicated a low prevalence of the disease in western Europe and a relatively high prevalence in eastern Europe. The most commonly encountered symptom was erythema migrans, followed by neurological manifestations. Cardiac problems were rare. Tick bite was strongly associated with Lyme borreliosis, but the only other significantly associated risk factor was the pastime of gardening.

  14. 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

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. On revenue maximization for selling multiple independently distributed items

    PubMed Central

    Li, Xinye; Yao, Andrew Chi-Chih

    2013-01-01

    Consider the revenue-maximizing problem in which a single seller wants to sell k different items to a single buyer, who has independently distributed values for the items with additive valuation. The case was completely resolved by Myerson’s classical work in 1981, whereas for larger k the problem has been the subject of much research efforts ever since. Recently, Hart and Nisan analyzed two simple mechanisms: selling the items separately, or selling them as a single bundle. They showed that selling separately guarantees at least a fraction of the optimal revenue; and for identically distributed items, bundling yields at least a fraction of the optimal revenue. In this paper, we prove that selling separately guarantees at least fraction of the optimal revenue, whereas for identically distributed items, bundling yields at least a constant fraction of the optimal revenue. These bounds are tight (up to a constant factor), settling the open questions raised by Hart and Nisan. The results are valid for arbitrary probability distributions without restrictions. Our results also have implications on other interesting issues, such as monotonicity and randomization of selling mechanisms. PMID:23798394

  20. On revenue maximization for selling multiple independently distributed items.

    PubMed

    Li, Xinye; Yao, Andrew Chi-Chih

    2013-07-09

    Consider the revenue-maximizing problem in which a single seller wants to sell k different items to a single buyer, who has independently distributed values for the items with additive valuation. The k = 1 case was completely resolved by Myerson's classical work in 1981, whereas for larger k the problem has been the subject of much research efforts ever since. Recently, Hart and Nisan analyzed two simple mechanisms: selling the items separately, or selling them as a single bundle. They showed that selling separately guarantees at least a c/log2 k fraction of the optimal revenue; and for identically distributed items, bundling yields at least a c/log k fraction of the optimal revenue. In this paper, we prove that selling separately guarantees at least c/log k fraction of the optimal revenue, whereas for identically distributed items, bundling yields at least a constant fraction of the optimal revenue. These bounds are tight (up to a constant factor), settling the open questions raised by Hart and Nisan. The results are valid for arbitrary probability distributions without restrictions. Our results also have implications on other interesting issues, such as monotonicity and randomization of selling mechanisms.

  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. Borrelia burgdorferi-specific IgA in Lyme Disease.

    PubMed

    D'Arco, Christina; Dattwyler, Raymond J; Arnaboldi, Paul M

    2017-05-01

    The laboratory diagnosis of Lyme disease is currently dependent on the detection of IgM and IgG antibodies against Borrelia burgdorferi, the causative agent of the disease. The significance of serum IgA against B. burgdorferi remains unclear. The production of intrathecal IgA has been noted in patients with the late Lyme disease manifestation, neuroborreliosis, but production of antigen-specific IgA during early disease has not been evaluated. In the current study, we assessed serum IgA binding to the B. burgdorferi peptide antigens, C6, the target of the FDA-cleared C6 EIA, and FlaB(211-223)-modVlsE(275-291), a peptide containing a Borrelia flagellin epitope linked to a modified VlsE sequence, in patients with early and late Lyme disease. Specific IgA was detected in 59 of 152 serum samples (38.8%) from early Lyme disease patients. Approximately 50% of early Lyme disease patients who were seropositive for peptide-specific IgM and/or IgG were also seropositive for peptide-specific IgA. In a subpopulation of patients, high peptide-specific IgA could be correlated with disseminated disease, defined as multiple erythema migrans lesions, and neurological disease complications. These results suggest that there may be an association between elevated levels of antigen-specific IgA and particular disease manifestations in some patients with early Lyme disease. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Sulforaphane inhibits multiple inflammasomes through an Nrf2-independent mechanism.

    PubMed

    Greaney, Allison J; Maier, Nolan K; Leppla, Stephen H; Moayeri, Mahtab

    2016-01-01

    The inflammasomes are intracellular complexes that have an important role in cytosolic innate immune sensing and pathogen defense. Inflammasome sensors detect a diversity of intracellular microbial ligands and endogenous danger signals and activate caspase-1, thus initiating maturation and release of the proinflammatory cytokines interleukin-1β and interleukin-18. These events, although crucial to the innate immune response, have also been linked to the pathology of several inflammatory and autoimmune disorders. The natural isothiocyanate sulforaphane, present in broccoli sprouts and available as a dietary supplement, has gained attention for its antioxidant, anti-inflammatory, and chemopreventive properties. We discovered that sulforaphane inhibits caspase-1 autoproteolytic activation and interleukin-1β maturation and secretion downstream of the nucleotide-binding oligomerization domain-like receptor leucine-rich repeat proteins NLRP1 and NLRP3, NLR family apoptosis inhibitory protein 5/NLR family caspase-1 recruitment domain-containing protein 4 (NAIP5/NLRC4), and absent in melanoma 2 (AIM2) inflammasome receptors. Sulforaphane does not inhibit the inflammasome by direct modification of active caspase-1 and its mechanism is not dependent on protein degradation by the proteasome or de novo protein synthesis. Furthermore, sulforaphane-mediated inhibition of the inflammasomes is independent of the transcription factor nuclear factor erythroid-derived 2-like factor 2 (Nrf2) and the antioxidant response-element pathway, to which many of the antioxidant and anti-inflammatory effects of sulforaphane have been attributed. Sulforaphane was also found to inhibit cell recruitment to the peritoneum and interleukin-1β secretion in an in vivo peritonitis model of acute gout and to reverse NLRP1-mediated murine resistance to Bacillus anthracis spore infection. These findings demonstrate that sulforaphane inhibits the inflammasomes through a novel mechanism and contributes to

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. Cutaneous Lyme borreliosis: Guideline of the German Dermatology Society

    PubMed Central

    Hofmann, Heidelore; Fingerle, Volker; Hunfeld, Klaus-Peter; Huppertz, Hans-Iko; Krause, Andreas; Rauer, Sebastian; Ruf, Bernhard

    2017-01-01

    This guideline of the German Dermatology Society primarily focuses on the diagnosis and treatment of cutaneous manifestations of Lyme borreliosis. It has received consensus from 22 German medical societies and 2 German patient organisations. It is the first part of an AWMF (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e.V.) interdisciplinary guideline: “Lyme Borreliosis – Diagnosis and Treatment, development stage S3”. The guideline is directed at physicians in private practices and clinics who treat Lyme borreliosis. Objectives of this guideline are recommendations for confirming a clinical diagnosis, recommendations for a stage-related laboratory diagnosis (serological detection of IgM and IgG Borrelia antibodies using the 2-tiered ELISA/immunoblot process, sensible use of molecular diagnostic and culture procedures) and recommendations for the treatment of the localised, early-stage infection (erythema migrans, erythema chronicum migrans, and borrelial lymphocytoma), the disseminated early-stage infection (multiple erythemata migrantia, flu-like symptoms) and treatment of the late-stage infection (acrodermatitis chronica atrophicans with and without neurological manifestations). In addition, an information sheet for patients containing recommendations for the prevention of Lyme borreliosis is attached to the guideline. PMID:28943834

  9. [Lyme disease with hepatitis and corticosteroids: a case report].

    PubMed

    Muslmani, M; Gilson, M; Sudre, A; Juvin, R; Gaudin, P

    2012-06-01

    Abnormalities of liver function tests have been occasionally described in large series of Lyme disease, but only one case of hepatitis directly related to infection have been described in literature. A 78-year-old-man, with a past medical history of polymyalgia rheumatica (PMR) who had discontinued corticosteroids two years before, presented a transient acute fever and liver cholestasis and cytolysis after an exposure to tick bites. A few days later, cervical pain occurred and corticosteroids were resumed as a PMR relapse was suspected. Hematogenous dissemination with acute meningoradiculitis and multiple erythema migrans led to conclude to a stage 2 Lyme disease. Although hepatitis complicating the course of Lyme disease has been described in literature, the marked inflammation in our patient led us to investigate the possibility of a co-infection. Also, we discuss the responsibility of corticosteroids in clinical worsening of Lyme disease if they are prescribed without concomitant antibiotics. Copyright © 2012 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  10. Conspicuous impacts of inconspicuous hosts on the Lyme disease epidemic

    PubMed Central

    Brisson, Dustin; Dykhuizen, Daniel E; Ostfeld, Richard S

    2007-01-01

    Emerging zoonotic pathogens are a constant threat to human health throughout the world. Control strategies to protect public health regularly fail, due in part to the tendency to focus on a single host species assumed to be the primary reservoir for a pathogen. Here, we present evidence that a diverse set of species can play an important role in determining disease risk to humans using Lyme disease as a model. Host-targeted public health strategies to control the Lyme disease epidemic in North America have focused on interrupting Borrelia burgdorferi sensu stricto (ss) transmission between blacklegged ticks and the putative dominant reservoir species, white-footed mice. However, B. burgdorferi ss infects more than a dozen vertebrate species, any of which could transmit the pathogen to feeding ticks and increase the density of infected ticks and Lyme disease risk. Using genetic and ecological data, we demonstrate that mice are neither the primary host for ticks nor the primary reservoir for B. burgdorferi ss, feeding 10% of all ticks and 25% of B. burgdorferi-infected ticks. Inconspicuous shrews feed 35% of all ticks and 55% of infected ticks. Because several important host species influence Lyme disease risk, interventions directed at a multiple host species will be required to control this epidemic. PMID:18029304

  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. 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...

  13. 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)

  14. 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...

  15. 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)

  16. [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. © 2016 MEDPRESS.

  17. Independence.

    ERIC Educational Resources Information Center

    Stephenson, Margaret E.

    2000-01-01

    Discusses the four planes of development and the periods of creation and crystallization within each plane. Identifies the type of independence that should be achieved by the end of the first two planes of development. Maintains that it is through individual work on the environment that one achieves independence. (KB)

  18. Clinical and geographic characteristics of Lyme disease in New York.

    PubMed

    Benach, J L; Coleman, J L

    1987-02-01

    The clinical and geographic characteristics of 679 patients who met the clinical definition of Lyme disease and who had antibody titers of greater than or equal to 1: 128 to Borrelia burgdorferi for a two year period, 1983-1984, are described. Males outnumbered females 60% to 40% for the two year period and nearly half of all cases were children and young adults nineteen years old or younger. Forty percent of the patients reported single or multiple tick bites prior to the onset of illness and tick bites were clustered in the summer months. Skin lesions (ECM) were reported in 63% of all the patients. Joint involvement as the only manifestation of Lyme disease was reported in 21% and 22% of all the patients in 1983 and 1984 respectively. A 2: 1 ratio of males to females was noted on this subgroup and 63% of these were 19 years old or less. Onset of joint manifestations were most frequent in the last three months of the year. Neurological manifestations were noted in 20% of the patients with facial palsy being the most frequent. Twenty nine patients had neurological disorders as the only manifestation of Lyme disease. Cardiovascular symptoms were reported in 26 patients (4%). The secondary manifestations of Lyme disease were of summer and early fall onset. Lyme disease in New York is restricted to suburbs north of New York City in Westchester County, and in suburbs to the east of New York City in Suffolk County, Long Island. Incidence for the two year period can range from 0.01 cases per 1000 in some communities to 28 cases per 1000 in highly endemic areas.

  19. 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.

  20. Hypersensitivity to Ticks and Lyme Disease Risk

    PubMed Central

    Burke, Georgine; Wikel, Stephen K.; Spielman, Andrew; Telford, Sam R.; McKay, Kathleen

    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 >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. PMID:15705320

  1. Dispelling the chronic Lyme disease myth.

    PubMed

    Kemperman, Melissa M; Bakken, Johan S; Kravitz, Gary R

    2008-07-01

    Lyme disease is a tick-borne illness endemic to Minnesota that can have potentially severe complications. As the incidence of Lyme disease continues to increase, it is important for physicians in Minnesota to become familiar with its clinical aspects, including the concept of "chronic Lyme disease." Chronic Lyme disease is a misnomer that is often applied to patients with nonspecific presentations who may or may not have a history of infection with Borrelia burgdorferi, the agent that causes Lyme disease. When a patient does present with persistent nonspecific symptoms attributed to chronic Lyme disease, clinicians should ascertain the presence of objective manifestations, obtain laboratory results, and get a history of tick exposure. If active infection with B. burgdorferi is unlikely, they should avoid prescribing empiric antibiotic therapy and instead thoroughly evaluate the patient for other possible causes of the complaints and recommend appropriate care.

  2. 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.

  3. 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.

  4. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. 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. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. 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.

  7. Lyme disease presenting with persistent headache.

    PubMed

    Moses, James M; Riseberg, Robyn S; Mansbach, Jonathan M

    2003-12-01

    Increased intracranial pressure in patients with Lyme disease is an uncommon but reported finding. We discuss 2 patients from Lyme endemic areas who initially presented with headache, nausea, and vomiting and were eventually found to have increased intracranial pressure, a mild cerebrospinal fluid pleocytosis, and positive Lyme titers. It has been shown that increased intracranial pressure in association with neuroborreliosis can lead to blindness. In endemic areas, it is important for practitioners to consider Lyme disease when patients present with persistent headache, especially in those who have evidence of increased intracranial pressure.

  8. 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…

  9. 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.

  10. 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.

  11. 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…

  12. Treatment complications in children with lyme meningitis.

    PubMed

    Thompson, Amy D; Cohn, Keri A; Shah, Samir S; Lyons, Todd; Welsh, Elizabeth J; Hines, Elizabeth M; Nigrovic, Lise E

    2012-10-01

    The rate and type of treatment complications in children treated for Lyme meningitis have not been described. We performed a retrospective cohort study of children with Lyme meningitis who presented to 1 of 3 emergency departments located in Lyme disease endemic areas between 1997 and 2010. We defined a case of Lyme meningitis as a child with cerebrospinal fluid pleocytosis and either positive Lyme serology or an erythema migrans rash. We identified prescribed treatment and reasons for all return visits. Our primary outcome was the presence of any treatment complication within 30 days of diagnosis. We identified 157 patients with Lyme meningitis with a median age of 10 years (interquartile range: 7-13 years). Of the 149 children with Lyme meningitis and available follow-up records, 39 (26%) had 1 or more complications, and 21 (14%) required a change in prescribed antibiotic therapy. The median time for developing the first complication was 11 days (interquartile range: 9-14 days). Ten percent of the patients had an adverse drug reaction. Of the 144 children who had a peripherally inserted central catheter placed, 25 (17%) had at least 1 peripherally inserted central catheter-associated complication: 14 (10%) had a mechanical problem, 11 (8%) had an infectious complication and 1 (1%) had a venous thromboembolism. As current Lyme meningitis treatment regimens have substantial associated morbidity, future research should investigate the efficacy of alternate regimens.

  13. 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…

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. Seroprevalence of Babesia microti in Individuals with Lyme Disease.

    PubMed

    Curcio, Sabino R; Tria, Laurel P; Gucwa, Azad L

    2016-12-01

    Babesiosis is an emerging tick-borne disease (TBD) caused by Babesia microti, an intracellular parasite of red blood cells. Currently, it is the highest ranked pathogen transmitted by blood transfusion. Most healthy individuals infected with B. microti are asymptomatic, but may be at risk for chronic infection. Similar to Lyme disease transmitted by Borrelia burgdorferi, B. microti is spread by Ixodes scapularis ticks. The rate of coinfection with these TBDs in humans is unclear as most studies have focused their prevalence in ticks or rodent reservoirs. In this study, we aimed to determine the seroprevalence of B. microti infection in individuals who tested positive for Lyme disease. Serum samples obtained from 130 subjects in New York were tested by immunofluorescence assay (IFA) for the presence of IgM and IgG antibodies against B. microti. Overall, 26.9% of the serum samples tested were positive for IgM and IgG antibodies against B. microti, suggesting exposure to TBD. Individuals who tested positive for Lyme disease as determined by two-tiered serological testing and the presence of both IgM and IgG antibodies directed against B. burgdorferi, were significantly increased for antibodies directed against B. microti (28.6%; p < 0.05), suggesting the possibility of coinfection with both TBDs. In contrast, the Lyme disease-negative control group had only 6.7% of samples seropositive for B. microti. These findings suggest the need for more extensive studies investigating infection rates with multiple TBDs in areas where they are endemic and further support for the need to implement an FDA-approved screening test for blood products to help prevent transfusion-transmitted babesiosis.

  20. 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

  1. 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.

  2. [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.

  3. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. 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.

  5. [Prognostic factors for inability to walk independently in patients with multiple system atrophy].

    PubMed

    Wang, Z W; Wu, X H; Qiu, F; Liu, J G; Yao, W; Jiang, M; Wang, S S; Chen, Z G; Qi, X K

    2017-02-01

    Objective: To explore the prognostic factors for inability to walk independently in patients with multiple system atrophy (MSA). Methods: A total of 123 patients with clinically confirmed MSA admitted to Navy General Hospital and Dongfang Hospital affiliated to the Second Clinical Medical College of Beijing University of Chinese Medicine, from February 2013 to February 2016, were retrospectively reviewed. Clinical data and all records were collected and all subjects were followed up by a telephone call in February 2016. The second milestone of activities of daily living scale (ADL), defined as inability to walk independently, was taken as the primary outcome. Eight possible prognostic factors were investigated and the survival analysis was performed with Cox proportional hazards model regression. Results: Of all the MSA patients, 74 subjects were men and 49 were women with a sex radio of 1.51∶1(M∶F). Seventy cases were diagnosed with MSA-cerebellar type (MSA-C) and 53 with MSA-Parkinson type (MSA-P) (C∶P=1.32∶1). Mean age at the onset of first symptom was (53±8) years old. All patients had severe autonomic nervous dysfunction. At the last follow-up, 56 cases (45.5%) were unable to walk independently. The median survival time from the onset of MSA to inability to walk independently was 73 months. The age of onset ≥ 55 years (HR=1.969, 95%CI 1.095-3.542, P=0.024) and the interval time from disease onset to combined motor and autonomic involvement≤3 years (HR=2.308, 95%CI 1.158-4.600, P=0.017) were independent prognostic factors for inability to walk independently, while gender, MSA clinical subtypes, initial symptoms, alcohol intake, smoking and toxic exposure were not indicators for independent walking (P>0.05). Conclusions: The prognostic factors for inability to walk independently in patients with MSA are the age of onset ≥55 years and the interval time from disease onset to combined motor and autonomic involvement≤3 years. Although factors

  6. 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.

  7. Predictive Factors for Differentiating Between Septic Arthritis and Lyme Disease of the Knee in Children.

    PubMed

    Baldwin, Keith D; Brusalis, Christopher M; Nduaguba, Afamefuna M; Sankar, Wudbhav N

    2016-05-04

    Differentiating between septic arthritis and Lyme disease of the knee in endemic areas can be challenging and has major implications for patient management. The purpose of this study was to identify a prediction rule to differentiate septic arthritis from Lyme disease in children presenting with knee pain and effusion. We retrospectively reviewed the records of patients younger than 18 years of age with knee effusions who underwent arthrocentesis at our institution from 2005 to 2013. Patients with either septic arthritis (positive joint fluid culture or synovial white blood-cell count of >60,000 white blood cells/mm(3) with negative Lyme titer) or Lyme disease (positive Lyme immunoglobulin G on Western blot analysis) were included. To avoid misclassification bias, undiagnosed knee effusions and joints with both a positive culture and positive Lyme titers were excluded. Historical, clinical, and laboratory data were compared between groups to identify variables for comparison. Binary logistic regression analysis was used to identify independent predictive variables. One hundred and eighty-nine patients were studied: 23 with culture-positive septic arthritis, 26 with culture-negative septic arthritis, and 140 with Lyme disease. Multivariate binary logistic regression identified pain with short arc motion, history of fever reported by the patient or a family member, C-reactive protein of >4 mg/L, and age younger than 2 years as independent predictive factors for septic arthritis. A simpler model was developed that showed that the risk of septic arthritis with none of these factors was 2%, with 1 of these factors was 18%, with 2 of these factors was 45%, with 3 of these factors was 84%, or with all 4 of these factors was 100%. Although septic arthritis of the knee and Lyme monoarthritis share common features that can make them difficult to distinguish clinically, the presence of pain with short arc motion, C-reactive protein of >4.0 mg/L, patient-reported history of

  8. Treatment Trials for Post-Lyme Disease Symptoms Revisited

    PubMed Central

    Klempner, Mark S.; Baker, Phillip J.; Shapiro, Eugene D.; Marques, Adriana; Dattwyler, Raymond J.; Halperin, John J.; Wormser, Gary P.

    2014-01-01

    The authors of four National Institutes of Health (NIH)-sponsored antibiotic treatment trials of patients with persistent unexplained symptoms despite previous antibiotic treatment of Lyme disease determined that retreatment provides little if any benefit and carries significant risk. Recently, two groups have provided an independent reassessment of these trials and concluded that prolonged courses of antibiotics are likely to be helpful. We have carefully considered the points raised by these groups, along with our own critical review of the treatment trials. Based on this analysis, the conclusion that there is a meaningful clinical benefit to be gained from retreatment of such patients with parenteral antibiotic therapy cannot be justified. PMID:23764268

  9. 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

  10. From Lyme Disease to Art and Advocacy

    MedlinePlus

    ... to those with Lyme disease is to keep learning, questioning, and sharing information. "Get all the information ... tweezers. If you are unable to remove the mouth easily with clean tweezers, leave it alone and ...

  11. 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.

  12. [Stage-oriented treatment of Lyme borreliosis].

    PubMed

    Fingerle, V; Wilske, B

    2006-06-22

    Every manifestation of Lyme borreliosis needs to be treated with antibiotics. The type of antibiotic applied and duration of treatment will depend on the stage and severity of the disease. Erythema migrans, Borrelia lymphocytoma, Lyme arthritis and acrodermatitis chronica atrophicans are primarily treated orally. If neurological symptoms, severe Lyme carditis or eye manifestations are present, intravenous treatment is initially recommended. For oral therapy, doxycycline, amoxicillin, cefuroxime and, if intolerance is shown, azithromycin, are available. For intravenous treatment ceftriaxone, cefotaxime or penicillin G is employed. The overall prognosis for treated Lyme borreliosis is good. However, in particular when manifestations with substantial organic injury have persisted, incomplete healing must be expected. With the exception of erythema migrans, every manifestation should be subjected to a careful diagnostic work-up prior to the start of treatment, because premature antibiotic administration is not only associated with an elevated risk for the patient, but can also mask important diagnostic signs.

  13. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. 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. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  15. 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

  16. Lyme disease in Poland in 2012.

    PubMed

    Paradowska-Stankiewicz, Iwona; Chrześcijańska, Irena

    2014-01-01

    In Poland registration of all cases of Lyme disease is conducted by the Epidemiological Unit of National Institute of Public Health - National Institute of Hygiene. Most cases of Lyme disease occur in the North- East region of Poland; however, it is important to note that the disease is no longer solely a problem of this region of Poland. The aim of this work is to assess the epidemiological situation of Lyme disease in Poland in 2012 as compared to the situation in the previous years. Assessment of the epidemiological situation of Lyme disease in Poland was made on the basis of an analysis of individual notifications of suspected Lyme disease submitted to NIZP-NIH by the Provincial Sanitary- Epidemiological Stations; as well as data from "Infectious diseases and poisoning in Poland in 2012" bulletin, and "Vaccinations in Poland in 2012" bulletin (MP Czarkowski and Co, Warsaw 2013, NIPH-NIH, NCI). In 2012 there were 8 782 registered cases of Lyme disease and it is 4.3% higher than in the previous year. The overall incidence in the country amounted to 23.8 per 100 000 people. The highest incidence rate was recorded in Podlaskie province - 75.5 per 100 000 people. 2 063 people were hospitalized due to Lyme disease. In 2012 incidence rate of Lyme disease was gradually dropping down. The registered number of cases was reduced by 4.1% in comparison to the previous year. There is still a fairly low percentage of cases detected with diagnostic test called Western blot method.

  17. 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.

  18. Suicide and Lyme and associated diseases

    PubMed Central

    Bransfield, Robert C

    2017-01-01

    Purpose The aim of this paper is to investigate the association between suicide and Lyme and associated diseases (LAD). No journal article has previously performed a comprehensive assessment of this subject. Introduction Multiple case reports and other references demonstrate a causal association between suicidal risk and LAD. Suicide risk is greater in outdoor workers and veterans, both with greater LAD exposure. Multiple studies demonstrate many infections and the associated proinflammatory cytokines, inflammatory-mediated metabolic changes, and quinolinic acid and glutamate changes alter neural circuits which increase suicidality. A similar pathophysiology occurs in LAD. Method A retrospective chart review and epidemiological calculations were performed. Results LAD contributed to suicidality, and sometimes homicidality, in individuals who were not suicidal before infection. A higher level of risk to self and others is associated with multiple symptoms developing after acquiring LAD, in particular, explosive anger, intrusive images, sudden mood swings, paranoia, dissociative episodes, hallucinations, disinhibition, panic disorder, rapid cycling bipolar, depersonalization, social anxiety disorder, substance abuse, hypervigilance, generalized anxiety disorder, genital–urinary symptoms, chronic pain, anhedonia, depression, low frustration tolerance, and posttraumatic stress disorder. Negative attitudes about LAD from family, friends, doctors, and the health care system may also contribute to suicide risk. By indirect calculations, it is estimated there are possibly over 1,200 LAD suicides in the US per year. Conclusion Suicidality seen in LAD contributes to causing a significant number of previously unexplained suicides and is associated with immune-mediated and metabolic changes resulting in psychiatric and other symptoms which are possibly intensified by negative attitudes about LAD from others. Some LAD suicides are associated with being overwhelmed by multiple

  19. Lyme disease and post-treatment Lyme disease syndrome: the neglected disease in our own backyard.

    PubMed

    Crowder, L A; Yedlin, V A; Weinstein, E R; Kortte, K B; Aucott, J N

    2014-09-01

    A survey was developed to assess experience and opinions about Lyme disease and post-treatment Lyme disease syndrome (PTLDS) among faculties in public health. No previous surveys of public health faculties have been found in the literature. This is a cross sectional study of public health school faculty members designed to measure knowledge and experience with Lyme disease and PTLDS using an internet survey instrument. Participants were recruited using all the publicly available e-mail addresses of faculty members in all the 50 accredited Schools of Public Health in the United States. A 15% response rate was seen for the survey. 50% of respondents were from Lyme endemic states. Less than 5% of faculty members consider themselves expert in Lyme or PTLDS. Many faculty members had known someone with Lyme disease or PTLDS, but few had been diagnosed themselves. Most believe that PTLDS can be severe and chronic, is not easy to treat, and does not resolve on its own, but were uncertain about its aetiology. Most respondents also felt that the incidence of Lyme disease will increase and that more education is needed. The need for further understanding and communication presents an opportunity for public health research and education in Lyme disease and the sequelae of PTLDS. Copyright © 2014 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  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. 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

  2. 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

  3. Longitudinal Transcriptome Analysis Reveals a Sustained Differential Gene Expression Signature in Patients Treated for Acute Lyme Disease.

    PubMed

    Bouquet, Jerome; Soloski, Mark J; Swei, Andrea; Cheadle, Chris; Federman, Scot; Billaud, Jean-Noel; Rebman, Alison W; Kabre, Beniwende; Halpert, Richard; Boorgula, Meher; Aucott, John N; Chiu, Charles Y

    2016-02-12

    development of post-treatment symptoms, we conducted the first longitudinal gene expression (transcriptome) study of patients enrolled at the time of diagnosis and followed up for up to 6 months after treatment. Importantly, we found that the gene expression signature of early Lyme disease is distinct from that of other acute infectious diseases and persists for at least 3 weeks following infection. This study also uncovered multiple previously undescribed pathways and genes that may be useful in the future as human host biomarkers for diagnosis and that constitute potential targets for the development of new therapies. Copyright © 2016 Bouquet et al.

  4. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Common misconceptions about Lyme disease.

    PubMed

    Halperin, John J; Baker, Phillip; Wormser, Gary P

    2013-03-01

    Lyme disease, infection with Borrelia burgdorferi, is a focally endemic tick-transmitted zoonosis. During the 3 decades since the responsible spirochete was identified, a series of misconceptions and misunderstandings have become widely prevalent, leading to frequent misdiagnosis and inappropriate treatment. Persistent misconceptions concern the reliability of available diagnostic tools, the signs and symptoms of nervous system involvement, the appropriate choice and duration of antimicrobial therapy, the curability of the infection, and the cause of symptoms that may persist in some patients after treatment. Concern about disparate perspectives led the Institute of Medicine to review the subject. In this article we review the principal misconceptions, discussing their origins and the best currently available scientific evidence related to each one. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Lyme borreliosis and cranial neuropathy.

    PubMed

    Kindstrand, E

    1995-10-01

    In a 2-year study of 37 consecutive adult patients with isolated cranial nerve affection of primarily unknown origin, seen at a neurological clinic, borrelia infection was identified as the cause in six cases. Four patients had a peripheral facial palsy and two had a sixth nerve palsy. The patients with borreliosis had headaches or other pain considerably more often than patients with other or unknown aetiology. All six patients had accompanying symptoms and/or signs; in five cases these were obvious, and pointed to a borrelia infection. This study indicates that a careful history to elicit other symptoms of Lyme borreliosis will usually identify the cranial nerve affections with borrelial aetiology in adult patients. To verify the diagnosis, both serum and CSF analysis should be performed. Routine testing for borrelia serology in all patients with cranial neuropathy is generally not indicated.

  7. Vaccination of horses with Lyme vaccines for dogs induces short-lasting antibody responses.

    PubMed

    Guarino, Cassandra; Asbie, Sanda; Rohde, Jennifer; Glaser, Amy; Wagner, Bettina

    2017-07-24

    Borrelia burgdorferi can induce Lyme disease. Approved Lyme vaccines for horses are currently not available. In an effort to protect horses, veterinarians are using Lyme vaccines licensed for dogs. However, data to assess the response of horses to, or determine the efficacy of this off-label vaccine use are missing. Here, antibodies against outer surface protein A (OspA), OspC, and OspF were quantified in diagnostic serum submissions from horses with a history of vaccination with canine Lyme vaccines. The results suggested that many horses respond with low and often short-lasting antibody responses. Subsequently, four experimental vaccination trials were performed. First, we investigated antibody responses to three canine vaccines in B. burgdorferi-naïve horses. One killed bacterin vaccine induced antibodies against OspC. OspA antibodies were low for all three vaccines and lasted less than 16weeks. The second trial tested the impact of the vaccine dose using the OspA/OspC inducing bacterin vaccine in horses. A 2mL dose produced higher OspA and OspC antibody values than a 1mL dose. However, the antibody response again quickly declined, independent of dose. Third, the horses were vaccinated with 2 doses of a recombinant OspA vaccine. Previous vaccination and/or environmental exposure enhanced the magnitude and longevity of the OspA antibody response to about 20weeks. Last, the influence of intramuscular versus subcutaneous vaccine administration was investigated for the recombinant OspA vaccine. OspA antibody responses were not influenced by injection route. The current work highlights that commercial Lyme vaccines for dogs induce only transient antibody responses in horses which can also be of low magnitude. Protection from infection with B. burgdorferi should not be automatically assumed after vaccinating horses with Lyme vaccines for dogs. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  8. 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.

  9. The increasing risk of Lyme disease in Canada

    PubMed Central

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

    2015-01-01

    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. PMID:26130829

  10. 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…

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. Independent colonization of multiple urban centres by a formerly forest specialist bird species

    PubMed Central

    Evans, Karl L.; Gaston, Kevin J.; Frantz, Alain C.; Simeoni, Michelle; Sharp, Stuart P.; McGowan, Andrew; Dawson, Deborah A.; Walasz, Kazimierz; Partecke, Jesko; Burke, Terry; Hatchwell, Ben J.

    2009-01-01

    Urban areas are expanding rapidly, but a few native species have successfully colonized them. The processes underlying such colonization events are poorly understood. Using the blackbird Turdus merula, a former forest specialist that is now one of the most common urban birds in its range, we provide the first assessment of two contrasting urban colonization models. First, that urbanization occurred independently. Second, that following initial urbanization, urban-adapted individuals colonized other urban areas in a leapfrog manner. Previous analyses of spatial patterns in the timing of blackbird urbanization, and experimental introductions of urban and rural blackbirds to uncolonized cities, suggest that the leapfrog model is likely to apply. We found that, across the western Palaearctic, urban blackbird populations contain less genetic diversity than rural ones, urban populations are more strongly differentiated from each other than from rural populations and assignment tests support a rural source population for most urban individuals. In combination, these results provide much stronger support for the independent urbanization model than the leapfrog one. If the former model predominates, colonization of multiple urban centres will be particularly difficult when urbanization requires genetic adaptations, having implications for urban species diversity. PMID:19364751

  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. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. How Does Independent Practice of Multiple-Criteria Text Influence the Reading Performance and Development of Second Graders?

    ERIC Educational Resources Information Center

    Cheatham, Jennifer P.; Allor, Jill H.; Roberts, J. Kyle

    2014-01-01

    This study examined the impact of independent practice of multiple-criteria text that targeted high-frequency words, decodability, and meaningfulness. Second-grade students, including at-risk students, were randomly assigned within classroom to a treatment group that read multiple-criteria text ("n" = 34), or contrast group that read…

  5. Lyme disease in Poland in 2014

    PubMed

    Paradowska-Stankiewicz, Iwona; Chrześcijańska, Irena

    Lyme disease is the most common tick-borne disease, caused by spirochetes of the Borrelia genus transmitted by ticks of the Ixodes genus. Infection caused by Borrelia burgdorferi occur throughout Poland and therefore, according also to ECDC description, the whole country should be considered as an endemic area. The aim of this study was to assess the epidemiological situation of Lyme disease in Poland in 2014 in comparison to the previous years. The descriptive analysis was based on data retrieved from routine mandatory surveillance system and published in the annual bulletin “Infectious diseases and poisonings in Poland in 2014” (MP Czarkowski et al., Warsaw 2015, NIZP-PZH, GIS). The number of cases of Lyme disease in recent years is steadily increasing. In total, 13.870 cases of Lyme disease registered in Poland in 2014, i.e. 8% more cases than in the previous year. The overall incidence in the country was 36.0 per 100,000 population. The highest incidence rate was recorded in Podlaskie voivodeship – 106.8 per 100,000. In 2014, 2.236 people were hospitalized due to Lyme disease. In 2014, the growth rate of incidence decreased significantly. 8% more cases were registered compared with the previous year. There is still a need for bringing awareness of the need for diagnostic laboratory testing according to recommendations.

  6. [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.

  7. 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.

  8. 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.

  9. 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.

  10. Knowledge on Lyme disease among foresters.

    PubMed

    Kurnatowski, Piotr; Warpechowska, Małgorzata; Kurnatowska, Anna J

    2011-03-01

    The first aim was an attempt to evaluate the level of knowledge on Lyme disease among people whose profession involves working in the forest; the second--recognition of the health problems that should be included in health education programmes concerning Lyme disease in this group of professionals. The study was performed on 159 subjects. Only 15% know the etiological factor of disease, 98%--the main cause of infection, and route of pathogen transmission. Propagation of knowledge on Lyme disease, particularly among risk group people, is not satisfactory. Little knowledge on tick risk among secondary school students indicate the necessity for cooperation between teachers, epidemiologists, and health service providers in order to propagate the knowledge on parasites, symptoms, spread and methods of prevention.

  11. 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

  12. 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

  13. 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.

  14. [Lyme-Arthritis--a case report].

    PubMed

    von Ameln-Mayerhofer, Andreas

    2016-05-01

    Lyme disease is a serious infectious disease which, if untreated, does not recover and leads to further complications that might be severe. This exemplary case report describes a possible secondary Borrelia infection. It underlines that early antibiotic therapy in the correct dosage is essential. Furthermore, problems are discussed that might occur in context of the decision process concerning the best antibiotic substance and the optimal application route. Last but not least, possible problems associated with the discharge from hospital are discussed. In conclusion, early diagnosis together with an on-time optimal antibiotic therapy are fundamental in the clinical management of Lyme disease.

  15. Prevalence of Lyme disease infection in Oklahoma.

    PubMed Central

    Lawrence, C. H.; Botchlet, R.; Silberg, S. L.; Flournoy, D. J.; Guthrie, P. J.

    1992-01-01

    Even though Lyme disease probably existed in Oklahoma prior to 1975 when the disease was first reported in Connecticut and even though ecological conditions favor a high prevalence, an unexpectedly low rate was evidenced in both a serological survey and the number of cases reported to the Oklahoma State Department of Health. Lyme disease does not appear to pose a significant public health threat in Oklahoma at the present time; however, the the presence of all the necessary factors for transmission and the rapidly increasing number of cases reported in nearby areas merits continued surveillance in this state. The need for consistent case definition is discussed. PMID:1404480

  16. 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

  17. 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

  18. 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.

  19. 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.

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

    PubMed Central

    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

    2016-01-01

    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. PMID:27466198

  1. Serum calcium is an independent prognostic factor of overall survival in Mexican patients with multiple myeloma.

    PubMed

    Maillet, Daniela; Montiel-Cervantes, Laura; Padilla-González, Ysabel; Sánchez-Cortés, Evelia; Xolotl-Castillo, Moisés; Vela-Ojed, Jorge; Reyes-Maldonado, Elba

    2012-01-01

    To evaluate the impact of different prognostic factors that has been suggested to be useful in predicting the survival of patients with multiple myeloma (MM). A longitudinal prospective study was conducted on 24 adult Mexican patients diagnosed with primary MM. The levels of expression of CD38, CD138 and cyclin D1 were analyzed in plasma cells (PCs) from patients and mononuclear cells from healthy donors. Serum levels of lactate dehydrogenase, creatinine, calcium, beta2 microglobulin and interleukin-6 (IL-6) as well as hemoglobin and platelet count were taken into consideration. RESULTS; CD138 and cyclin D1 levels in absolute numbers were significantly overexpressed in malignant PCs. A positive correlation was noted between cyclin D1 and CD38 expression levels in malignant PCs. IL-6 and serum calcium were also positively correlated in MM patients. Cyclin D1 overexpression was not associated with better overall survival (OS). Normal calcium levels were associated with better overall survival (OS). Serum calcium was the only variable correlating with better OS in Cox regression analysis. Serum calcium is an independent prognostic factor of OS in a population of Mexican patients with MM.

  2. 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.

  3. Adaptive radiation in extremophilic Dorvilleidae (Annelida): diversification of a single colonizer or multiple independent lineages?

    PubMed

    Thornhill, Daniel J; Struck, Torsten H; Ebbe, Brigitte; Lee, Raymond W; Mendoza, Guillermo F; Levin, Lisa A; Halanych, Kenneth M

    2012-08-01

    Metazoan inhabitants of extreme environments typically evolved from forms found in less extreme habitats. Understanding the prevalence with which animals move into and ultimately thrive in extreme environments is critical to elucidating how complex life adapts to extreme conditions. Methane seep sediments along the Oregon and California margins have low oxygen and very high hydrogen sulfide levels, rendering them inhospitable to many life forms. Nonetheless, several closely related lineages of dorvilleid annelids, including members of Ophryotrocha, Parougia, and Exallopus, thrive at these sites in association with bacterial mats and vesicomyid clam beds. These organisms are ideal for examining adaptive radiations in extreme environments. Did dorvilleid annelids invade these extreme environments once and then diversify? Alternatively, did multiple independent lineages adapt to seep conditions? To address these questions, we examined the evolutionary history of methane-seep dorvilleids using 16S and Cyt b genes in an ecological context. Our results indicate that dorvilleids invaded these extreme habitats at least four times, implying preadaptation to life at seeps. Additionally, we recovered considerably more dorvilleid diversity than is currently recognized. A total of 3 major clades (designated "Ophryotrocha," "Mixed Genera" and "Parougia") and 12 terminal lineages or species were encountered. Two of these lineages represented a known species, Parougia oregonensis, whereas the remaining 10 lineages were newly discovered species. Certain lineages exhibited affinity to geography, habitat, sediment depth, and/or diet, suggesting that dorvilleids at methane seeps radiated via specialization and resource partitioning.

  4. Adaptive radiation in extremophilic Dorvilleidae (Annelida): diversification of a single colonizer or multiple independent lineages?

    PubMed Central

    Thornhill, Daniel J; Struck, Torsten H; Ebbe, Brigitte; Lee, Raymond W; Mendoza, Guillermo F; Levin, Lisa A; Halanych, Kenneth M

    2012-01-01

    Metazoan inhabitants of extreme environments typically evolved from forms found in less extreme habitats. Understanding the prevalence with which animals move into and ultimately thrive in extreme environments is critical to elucidating how complex life adapts to extreme conditions. Methane seep sediments along the Oregon and California margins have low oxygen and very high hydrogen sulfide levels, rendering them inhospitable to many life forms. Nonetheless, several closely related lineages of dorvilleid annelids, including members of Ophryotrocha, Parougia, and Exallopus, thrive at these sites in association with bacterial mats and vesicomyid clam beds. These organisms are ideal for examining adaptive radiations in extreme environments. Did dorvilleid annelids invade these extreme environments once and then diversify? Alternatively, did multiple independent lineages adapt to seep conditions? To address these questions, we examined the evolutionary history of methane-seep dorvilleids using 16S and Cyt b genes in an ecological context. Our results indicate that dorvilleids invaded these extreme habitats at least four times, implying preadaptation to life at seeps. Additionally, we recovered considerably more dorvilleid diversity than is currently recognized. A total of 3 major clades (designated “Ophryotrocha,” “Mixed Genera” and “Parougia”) and 12 terminal lineages or species were encountered. Two of these lineages represented a known species, Parougia oregonensis, whereas the remaining 10 lineages were newly discovered species. Certain lineages exhibited affinity to geography, habitat, sediment depth, and/or diet, suggesting that dorvilleids at methane seeps radiated via specialization and resource partitioning. PMID:22957196

  5. A two-layer multiple-time-scale turbulence model and grid independence study

    NASA Technical Reports Server (NTRS)

    Kim, S.-W.; Chen, C.-P.

    1989-01-01

    A two-layer multiple-time-scale turbulence model is presented. The near-wall model is based on the classical Kolmogorov-Prandtl turbulence hypothesis and the semi-empirical logarithmic law of the wall. In the two-layer model presented, the computational domain of the conservation of mass equation and the mean momentum equation penetrated up to the wall, where no slip boundary condition has been prescribed; and the near wall boundary of the turbulence equations has been located at the fully turbulent region, yet very close to the wall, where the standard wall function method has been applied. Thus, the conservation of mass constraint can be satisfied more rigorously in the two-layer model than in the standard wall function method. In most of the two-layer turbulence models, the number of grid points to be used inside the near-wall layer posed the issue of computational efficiency. The present finite element computational results showed that the grid independent solutions were obtained with as small as two grid points, i.e., one quadratic element, inside the near wall layer. Comparison of the computational results obtained by using the two-layer model and those obtained by using the wall function method is also presented.

  6. 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.

  7. 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.

  8. 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)

  9. 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…

  10. [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.

  11. 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.

  12. 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.

  13. 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)

  14. 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…

  15. Lyme disease: an infectious and postinfectious syndrome.

    PubMed

    Asch, E S; Bujak, D I; Weiss, M; Peterson, M G; Weinstein, A

    1994-03-01

    To determine chronic morbidity and the variables that influence recovery in patients who had been treated for Lyme disease. Retrospective evaluation of 215 patients from Westchester County, NY, who fulfilled Centers for Disease Control case definition for Lyme disease, were anti-Borrelia antibody positive and were diagnosed and treated at least one year before our examination. Erythema migrans had occurred in 70% of patients, neurological involvement in 29%, objective cardiac problems in 6%, arthralgia in 78% and arthritis in 41%. Patients were seen at a mean of 3.2 years after initial treatment. A history of relapse with major organ involvement had occurred in 28% and a history of reinfection in 18%. Anti-Borrelia antibodies, initially present in all patients, were still positive in 32%. At followup, 82 (38%) patients were asymptomatic and clinically active Lyme disease was found in 19 (9%). Persistent symptoms of arthralgia, arthritis, cardiac or neurologic involvement with or without fatigue were present in 114 (53%) patients. Persistent symptoms correlated with a history of major organ involvement or relapse but not the continued presence of anti-Borrelial antibodies. Thirty-five of the 114 (31%) patients with persistent symptoms had predominantly arthralgia and fatigue. Antibiotic treatment within 4 weeks of disease onset was more likely to result in complete recovery. Children did not significantly differ from adults in disease manifestations or in the frequency of relapse, reinfection or complete recovery. Despite recognition and treatment, Lyme disease is associated with significant infectious and postinfectious sequelae.

  16. 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

  17. 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.

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

    PubMed

    Williams, Rachel; Rohr, Aaron M; Wang, Wen-Tung; Choi, In-Young; Lee, Phil; Berman, Nancy E J; Lynch, Sharon G; LeVine, Steven M

    2011-06-23

    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. 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. 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. The findings indicate that iron deposition around vessels can occur independently of inflammation providing evidence against the hypothesis that iron

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

    PubMed

    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; Moriarty, Tara J

    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.

  20. 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

  1. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Pediatric Lyme Arthritis of the Hip: The Great Imitator?

    PubMed

    Cruz, Aristides I; Aversano, Francis J; Seeley, Mark A; Sankar, Wudbhav N; Baldwin, Keith D

    Lyme arthritis (LA) of the hip can present similarly to septic arthritis (SA) and transient synovitis (TS). The primary purpose of this study was to determine clinical and laboratory parameters differentiating LA of the hip from SA or TS among children who had undergone hip aspiration during the evaluation of hip pain. This was a retrospective review of all patients who underwent hip aspiration for the evaluation of hip pain at a tertiary care children's hospital in a Lyme endemic area. Clinical and laboratory data were reviewed and comparative analyses were performed between those diagnosed with LA, SA, and TS. Independent samples t test, ANOVA, and χ test were used to compare clinical and laboratory variables as appropriate. Multivariable logistic regression was used to elucidate independent predictors of LA. Statistical significance was set at P<0.05. Ninety-three hip aspirations (93 patients) were included in the final analysis. Seventeen patients were diagnosed with LA, 40 with SA, and 36 with TS. Multivariable logistic regression revealed febrile history (OR=16.3; 95% CI, 2.35-113.0) and increased peripheral white blood cell (WBC) count (OR=1.26; 95% CI, 1.01-1.58) to be significantly associated with increased odds of being diagnosed with SA versus LA. Increased erythrocyte sedimentation rate (ESR) was significantly associated with increased odds of being diagnosed with LA versus TS (OR=1.06; 95% CI, 1.02-1.10), whereas febrile history (OR=0.06; 95% CI, 0.01-0.49) and increased peripheral WBC count (OR=0.8; 95% CI, 0.65-0.98) were associated with decreased odds of LA. Children presenting in a Lyme endemic area with an isolated hip effusion are more likely to have LA versus SA if they have no history of fever and a decreased peripheral WBC count. Compared with TS, patients with LA are more likely to have an elevated ESR. This study adds to existing knowledge because there are few investigations examining isolated LA of the hip. Level III-retrospective case

  3. Design of Experiments with Multiple Independent Variables: A Resource Management Perspective on Complete and Reduced Factorial Designs

    ERIC Educational Resources Information Center

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

    2009-01-01

    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.…

  4. 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…

  5. System and Method for Detecting Unauthorized Device Access by Comparing Multiple Independent Spatial-Time Data Sets from Other Devices

    NASA Technical Reports Server (NTRS)

    Krage, Frederick J. (Inventor); Westmeyer, Paul A. (Inventor); Wertenberg, Russell F. (Inventor); Riegel, Jack F. (Inventor)

    2017-01-01

    An authentication procedure utilizes multiple independent sources of data to determine whether usage of a device, such as a desktop computer, is authorized. When a comparison indicates an anomaly from the base-line usage data, the system, provides a notice that access of the first device is not authorized.

  6. Diagnosis, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: A Review.

    PubMed

    Sanchez, Edgar; Vannier, Edouard; Wormser, Gary P; Hu, Linden T

    2016-04-26

    Lyme disease, human granulocytic anaplasmosis (HGA), and babesiosis are emerging tick-borne infections. To provide an update on diagnosis, treatment, and prevention of tick-borne infections. Search of PubMed and Scopus for articles on diagnosis, treatment, and prevention of tick-borne infections published in English from January 2005 through December 2015. The search yielded 3550 articles for diagnosis and treatment and 752 articles for prevention. Of these articles, 361 were reviewed in depth. Evidence supports the use of US Food and Drug Administration-approved serologic tests, such as an enzyme immunoassay (EIA), followed by Western blot testing, to diagnose extracutaneous manifestations of Lyme disease. Microscopy and polymerase chain reaction assay of blood specimens are used to diagnose active HGA and babesiosis. The efficacy of oral doxycycline, amoxicillin, and cefuroxime axetil for treating Lyme disease has been established in multiple trials. Ceftriaxone is recommended when parenteral antibiotic therapy is recommended. Multiple trials have shown efficacy for a 10-day course of oral doxycycline for treatment of erythema migrans and for a 14-day course for treatment of early neurologic Lyme disease in ambulatory patients. Evidence indicates that a 10-day course of oral doxycycline is effective for HGA and that a 7- to 10-day course of azithromycin plus atovaquone is effective for mild babesiosis. Based on multiple case reports, a 7- to 10-day course of clindamycin plus quinine is often used to treat severe babesiosis. A recent study supports a minimum of 6 weeks of antibiotics for highly immunocompromised patients with babesiosis, with no parasites detected on blood smear for at least the final 2 weeks of treatment. Evidence is evolving regarding the diagnosis, treatment, and prevention of Lyme disease, HGA, and babesiosis. Recent evidence supports treating patients with erythema migrans for no longer than 10 days when doxycycline is used and prescription

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. [Prevalence of Lyme disease among forestry workers].

    PubMed

    Kocbach, Piotr Paweł; Kocbach, Bartłomiej Piotr

    2014-01-01

    The aim of the study is to assess the incidence of Lyme disease, established diagnosis based on medical history and clinical symptoms, serology, duration of exposure in the workplace and occupational disease certification among forestry workers in selected districts of the Warmia and Mazury region. The study consisted of annual screening of 332 employees in 6 forest districts under the supervision of the Health Center Medica in Ostróda. Serological tests were performed in all serum samples and IgG and IgM antibodies were determined by ELISA test. Positive results were confirmed by Western-blot test. Diagnosis was made based on medical history and clinical symptoms. Results were presented by the division of selected forest districts, gender, duration of exposure in the workplace and genospecies of spirochete Borrelia responsible for the disease development. Lyme disease incidence was found in all selected forest districts. Positive results in Western-blot test were determined in 120 people (63.1% of all the surveyed). However, after taking a detailed medical history of the patients Lyme disease was diagnosed in 91 people which makes 27.4% of all the examined. Among patients with diagnosed disease, IgG antibodies were found in 76 people, IgM in 25 people, while both IgM and IgG in 10 people. There was also variation in the involvement of genospecies generating the disease; spirochete B. afzeli--46% for IgG antibodies, whereas spirochete B. burgdorferi--50% of all cases for IgM antibodies. At the same time the relationship between the extended duration of occupational exposure to tick bites and the increased incidence of Lyme disease was confirmed, indicating the group of workers employed for at least 25 years. Forestry districts of the Warmia and Mazury region, creates extremely dangerous occupational conditions because of exposure to tick bites. At the same time the duration of employment significantly increases the risk of Lyme. The analysis of serological tests

  13. Meta-analysis of gene-environment interaction exploiting gene-environment independence across multiple case-control studies.

    PubMed

    Estes, Jason P; Rice, John D; Li, Shi; Stringham, Heather M; Boehnke, Michael; Mukherjee, Bhramar

    2017-10-30

    Multiple papers have studied the use of gene-environment (G-E) independence to enhance power for testing gene-environment interaction in case-control studies. However, studies that evaluate the role of G-E independence in a meta-analysis framework are limited. In this paper, we extend the single-study empirical Bayes type shrinkage estimators proposed by Mukherjee and Chatterjee (2008) to a meta-analysis setting that adjusts for uncertainty regarding the assumption of G-E independence across studies. We use the retrospective likelihood framework to derive an adaptive combination of estimators obtained under the constrained model (assuming G-E independence) and unconstrained model (without assumptions of G-E independence) with weights determined by measures of G-E association derived from multiple studies. Our simulation studies indicate that this newly proposed estimator has improved average performance across different simulation scenarios than the standard alternative of using inverse variance (covariance) weighted estimators that combines study-specific constrained, unconstrained, or empirical Bayes estimators. The results are illustrated by meta-analyzing 6 different studies of type 2 diabetes investigating interactions between genetic markers on the obesity related FTO gene and environmental factors body mass index and age. Copyright © 2017 John Wiley & Sons, Ltd.

  14. 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.

  15. [Facial paresis in children; consider Lyme disease].

    PubMed

    Dorresteijn, E M; Kouwenberg, J M

    2001-05-26

    Three girls, aged 3, 7 and 13 years, developed acute peripheral facial palsy. The first patient was initially diagnosed as having Bell's palsy. The third patient had negative serology at first assessment, on the basis of which the diagnosis of Lyme disease was temporarily rejected. Ultimately, all three appeared to have neuroborreliosis. They were treated with intravenous ceftriaxone and recovered well. Facial palsy in childhood is frequently caused by Lyme borreliosis and infection with Borrelia burgdorferi should therefore be investigated, even if there are no signs of a tick bite or erythema migrans. Diagnosis is made by serology, followed by immunoblotting to confirm a positive result. In case of strong suspicion based on the patient's history or physical examination or a positive serology, lumbar puncture should be carried out. Antibiotic treatment facilitates recovery and prevents complications.

  16. 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

  17. Lyme neuroborreliosis: infection, immunity, and inflammation.

    PubMed

    Pachner, Andrew R; Steiner, Israel

    2007-06-01

    Lyme neuroborreliosis (LNB), the neurological manifestation of systemic infection with the complex spirochaete Borrelia burgdorferi, can pose a challenge for practising neurologists. This Review is a summary of clinical presentation, diagnosis, and therapy, as well as of recent advances in our understanding of LNB. Many new insights have been gained through work in experimental models of the disease. An appreciation of the genetic heterogeneity of the causative pathogen has helped clinicians in their understanding of the diverse presentations of LNB.

  18. Lyme disease. Recognising and treating erythema migrans.

    PubMed

    2015-10-01

    Lyme disease is a tick-borne bacterial infection caused by Borrelia spirochetes. The first stage of infection involves a characteristic skin lesion, erythema migrans. Erythema migrans is a ring-shaped skin lesion, centred on the bite, which expands outwards. It usually appears within two weeks after a bite from an infected tick. If left untreated, the infection sometimes extends or progresses over a period of months or years, leading to potentially severe neurological, articular, cutaneous and cardiac complications. How is erythema migrans associated with Lyme disease recognised and managed? We conducted a systematic review of the literature using the standard Prescrire methodology. This review does not address the complications of Lyme disease. Diagnosis of erythema migrans is based on clinical findings in a patient with a possible or confirmed recent tick bite. Serological tests are not useful at this stage of the infection. Antibiotics shown to be active in vitro also proved effective in non-comparative trials. In randomised trials, amoxicillin, doxycycline, cefuroxime and ceftriaxone had similar efficacy, clearing signs and symptoms in about 90% of patients, with a relapse rate of less than 5% at 6 months. Azithromycin, clarithromycin, erythromycin, three macrolide antibiotics, appear to have lower efficacy. Doxycycline should not be used to treat pregnant or breast-feeding women, or children under 8 years old, due to a risk of tooth and bone disorders in children. In practice, a diagnosis of erythema migrans should be borne in mind when a patient presents with recent history of a possible or confirmed tick bite and skin lesions suggestive of erythema migrans. Oral amoxicillin or doxycycline will prevent progression of the infection to the potentially severe, later stages of Lyme disease. Routine antibiotic prophylaxis is not justified after a tick bite, even in an endemic area, as the risk of infection is low. It is best to monitor the skin around the bite and

  19. 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.

  20. 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.

  1. γδ T Cells and dendritic cells in refractory Lyme arthritis.

    PubMed

    Divan, Ali; Budd, Ralph C; Tobin, Richard P; Newell-Rogers, M Karen

    2015-04-01

    Lyme disease is a multisystem infection transmitted by tick vectors with an incidence of up to 300,000 individuals/yr in the United States. The primary treatments are oral or i.v. antibiotics. Despite treatment, some individuals do not recover and have prolonged symptoms affecting multiple organs, including the nervous system and connective tissues. Inflammatory arthritis is a common symptom associated with Lyme pathology. In the past decades, γδ T cells have emerged as candidates that contribute to the transition from innate to adaptive responses. These cells are also differentially regulated within the synovia of patients affected by RLA. Here, we review and discuss potential cellular mechanisms involving γδ T cells and DCs in RLA. TLR signaling and antigen processing and presentation will be the key concepts that we review in aid of understanding the impact of γδ T cells in RLA. © Society for Leukocyte Biology.

  2. γδ T Cells and dendritic cells in refractory Lyme arthritis

    PubMed Central

    Divan, Ali; Budd, Ralph C.; Tobin, Richard P.; Newell-Rogers, M. Karen

    2015-01-01

    Lyme disease is a multisystem infection transmitted by tick vectors with an incidence of up to 300,000 individuals/yr in the United States. The primary treatments are oral or i.v. antibiotics. Despite treatment, some individuals do not recover and have prolonged symptoms affecting multiple organs, including the nervous system and connective tissues. Inflammatory arthritis is a common symptom associated with Lyme pathology. In the past decades, γδ T cells have emerged as candidates that contribute to the transition from innate to adaptive responses. These cells are also differentially regulated within the synovia of patients affected by RLA. Here, we review and discuss potential cellular mechanisms involving γδ T cells and DCs in RLA. TLR signaling and antigen processing and presentation will be the key concepts that we review in aid of understanding the impact of γδ T cells in RLA. PMID:25605869

  3. Articular manifestations in patients with Lyme disease.

    PubMed

    Vázquez-López, María Esther; Díez-Morrondo, Carolina; Sánchez-Andrade, Amalia; Pego-Reigosa, Robustiano; Díaz, Pablo; Castro-Gago, Manuel

    To determine the percentage of Lyme patients with articular manifestations in NW Spain and to know their evolution and response to treatment. A retrospective study (2006-2013) was performed using medical histories of confirmed cases of Lyme disease showing articular manifestations. Clinical and laboratory characteristics, together with the treatment and evolution of the patients, were analysed. Seventeen out of 108 LD confirmed patients (15.7%) showed articular manifestations. Regarding those 17 patients, 64.7%, 29.4% and 5.9% presented arthritis, arthralgia and bursitis, respectively. The knee was the most affected joint. Articular manifestations were often associated to neurological, dermatological and cardiac pathologies. Otherwise, most patients were in Stage III. The 11.8% of the cases progressed to a recurrent chronic arthritis despite the administration of an appropriate treatment. Lyme disease patients showing articular manifestations should be included in the diagnosis of articular affections in areas of high risk of hard tick bite, in order to establish a suitable and early treatment and to avoid sequels. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  4. 5. Diagnosis and Treatment of Lyme Arthritis

    PubMed Central

    Arvikar, Sheila L.; Steere, Allen C.

    2015-01-01

    SYNOPSIS In the United States, Lyme arthritis is the most common feature of late stage infection with the tick-borne spirochete, Borrelia burgdorferi, usually beginning months after the initial tick bite. However, in some patients, including most of those seen today, the earlier phases of the infection are asymptomatic and arthritis is the presenting manifestation of the disease. Patients with Lyme arthritis have intermittent or persistent attacks of joint swelling and pain in one or a few large joints, especially the knee, usually over a period of several years, without prominent systemic manifestations. Serologic testing is the mainstay of diagnosis. Synovial fluid PCR testing for B. burgdorferi DNA is often positive prior to treatment, but it is not a reliable marker of spirochetal eradication after antibiotic therapy. Responses to oral or intravenous antibiotic treatment are generally excellent, although a small percentage of patients have persistent synovitis after 2-3 months of oral and IV antibiotics, which usually then responds to anti-inflammatory therapies, disease modifying anti-rheumatic drugs (DMARDs), or synovectomy. This chapter reviews the clinical manifestations, diagnosis, and management of Lyme arthritis. PMID:25999223

  5. 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. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. 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.

  7. 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...

  8. "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…

  9. "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…

  10. 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.

  11. 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...

  12. 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…

  13. 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...

  14. 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…

  15. Rapid attentional selection processes operate independently and in parallel for multiple targets.

    PubMed

    Grubert, Anna; Eimer, Martin

    2016-12-01

    The question whether multiple objects are selected serially or in parallel remains contentious. Previous studies employed the N2pc component as a marker of attentional selection to show that multiple selection processes can be activated concurrently. The present study demonstrates that the concurrent selection of multiple targets reflects genuinely parallel processing that is unaffected by whether or when an additional selection process is elicited simultaneously for another target. Experiment 1 showed that N2pc components triggered during the selection of a colour-defined target were not modulated by the presence versus absence of a second target that appeared in close temporal proximity. Experiment 2 revealed that the same rapid parallel selection processes were elicited regardless of whether two targets appeared simultaneously or in two successive displays. Results show that rapid attentional selection processes within the first 200ms after stimulus onset can be triggered in parallel for multiple objects in the visual field. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Field Independence-Dependence, Multiple and Linear Imagery in a Visual Location Task.

    ERIC Educational Resources Information Center

    Moore, David M.

    This study examined the effects and interaction of multiple and linear visual presentation modes and cognitive style on performance in a visual location task. Subjects were 132 undergraduate college students (40 males, 92 females) in professional education courses. The Group Embedded Figures Test (GEFT, Wilkin et al., 1971) was used to identify…

  17. Brave New Worlds: The Expanding Universe of Lyme Disease.

    PubMed

    Stone, Brandee L; Tourand, Yvonne; Brissette, Catherine A

    2017-09-01

    Projections around the globe suggest an increase in tick-vectored disease incidence and distribution, and the potential for emergence of novel tick-borne pathogens. Lyme disease is the most common reported tick-borne illness in the Unites States and is prevalent throughout much of central Europe. In recent years, the worldwide burden of Lyme disease has increased and extended into regions and countries where the disease was not previously reported. In this review, we discuss the trends for increasing Lyme disease, and examine the factors driving Lyme disease expansion, including the effect of climate change on the spread of vector Ixodid ticks and reservoir hosts; and the impacts of increased awareness on disease reporting and diagnosis. To understand the growing threat of Lyme disease, we need to study the interplay between vector, reservoir, and pathogen. In addition, we need to understand the contributions of climate conditions to changes in disease risk.

  18. A case revealing the natural history of untreated Lyme disease.

    PubMed

    Schoen, Robert T

    2011-03-01

    A 71-year-old woman presented to a rheumatologist with what she believed to be a 2-year history of Lyme disease, progressing from erythema migrans to Lyme arthritis. History, physical examination and serologic testing confirmed the diagnosis of Lyme disease. Lyme disease. The patient refused antibiotic therapy during the first 2 years of her illness. During the next 2 years, she consulted a rheumatologist, but declined antibiotic therapy. She continued to have recurrent episodes of arthritis, following which she was successfully treated with doxycycline, given initially for 2 weeks, with a second, 4-week cycle administered 2 months later. This case illustrates the natural history of untreated Lyme disease, which is rarely observed in most patients since diagnosis almost always leads to successful antibiotic treatment. Furthermore, this case also demonstrates that infection with Borrelia burgdorferi can persist for years in untreated patients; however, antibiotic therapy is still likely to be effective, despite long-term infection.

  19. Recurrent Rearrangements of Human Amylase Genes Create Multiple Independent CNV Series.

    PubMed

    Shwan, Nzar A A; Louzada, Sandra; Yang, Fengtang; Armour, John A L

    2017-05-01

    The human amylase gene cluster includes the human salivary (AMY1) and pancreatic amylase genes (AMY2A and AMY2B), and is a highly variable and dynamic region of the genome. Copy number variation (CNV) of AMY1 has been implicated in human dietary adaptation, and in population association with obesity, but neither of these findings has been independently replicated. Despite these functional implications, the structural genomic basis of CNV has only been defined in detail very recently. In this work, we use high-resolution analysis of copy number, and analysis of segregation in trios, to define new, independent allelic series of amylase CNVs in sub-Saharan Africans, including a series of higher-order expansions of a unit consisting of one copy each of AMY1, AMY2A, and AMY2B. We use fiber-FISH (fluorescence in situ hybridization) to define unexpected complexity in the accompanying rearrangements. These findings demonstrate recurrent involvement of the amylase gene region in genomic instability, involving at least five independent rearrangements of the pancreatic amylase genes (AMY2A and AMY2B). Structural features shared by fundamentally distinct lineages strongly suggest that the common ancestral state for the human amylase cluster contained more than one, and probably three, copies of AMY1. © 2017 WILEY PERIODICALS, INC.

  20. 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.

  1. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. 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.

  3. Multiple single unit recording in the cortex of monkeys using independently moveable microelectrodes.

    PubMed

    Baker, S N; Philbin, N; Spinks, R; Pinches, E M; Wolpert, D M; MacManus, D G; Pauluis, Q; Lemon, R N

    1999-12-15

    Simultaneous recording from multiple single neurones presents many technical difficulties. However, obtaining such data has many advantages, which make it highly worthwhile to overcome the technical problems. This report describes methods which we have developed to permit recordings in awake behaving monkeys using the 'Eckhorn' 16 electrode microdrive. Structural magnetic resonance images are collected to guide electrode placement. Head fixation is achieved using a specially designed headpiece, modified for the multiple electrode approach, and access to the cortex is provided via a novel recording chamber. Growth of scar tissue over the exposed dura mater is reduced using an anti-mitotic compound. Control of the microdrive is achieved by a computerised system which permits several experimenters to move different electrodes simultaneously, considerably reducing the load on an individual operator. Neurones are identified as pyramidal tract neurones by antidromic stimulation through chronically implanted electrodes; stimulus control is integrated into the computerised system. Finally, analysis of multiple single unit recordings requires accurate methods to correct for non-stationarity in unit firing. A novel technique for such correction is discussed.

  4. Thyroid hormone controls multiple independent programs required for limb development in Xenopus laevis metamorphosis.

    PubMed

    Brown, Donald D; Cai, Liquan; Das, Biswajit; Marsh-Armstrong, Nicholas; Schreiber, Alexander M; Juste, Rejeanne

    2005-08-30

    Thyroid hormone (TH) is required for limb development in Xenopus laevis. Specific cell types in the growing limb were targeted for expression of a dominant negative form of the TH receptor by sperm-mediated transgenesis. Limb muscle development, the innervation of muscle from the spinal cord, and cartilage growth can be inhibited without affecting patterning of the limb or differentiation of other cell types. Remodeling of the skin occurs late in metamorphosis after the limb has formed. The coordination of these independent programs is affected in part by the control that TH exerts over DNA replication in all cell types of the limb.

  5. 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.

  6. 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.

  7. Evaluation of the C6 Lyme Enzyme Immunoassay for the Diagnosis of Lyme Disease in Children and Adolescents.

    PubMed

    Lipsett, Susan C; Branda, John A; McAdam, Alexander J; Vernacchio, Louis; Gordon, Caroline D; Gordon, Catherine R; Nigrovic, Lise E

    2016-10-01

    The commercially-available C6 Lyme enzyme immunoassay (EIA) has been approved to replace the standard whole-cell sonicate EIA as a first-tier test for the diagnosis of Lyme disease and has been suggested as a stand-alone diagnostic. However, the C6 EIA has not been extensively studied in pediatric patients undergoing evaluation for Lyme disease. We collected discarded serum samples from children and adolescents (aged ≤21 years) undergoing conventional 2-tiered testing for Lyme disease at a single hospital-based clinical laboratory located in an area endemic for Lyme disease. We performed a C6 EIA on all collected specimens, followed by a supplemental immunoblot if the C6 EIA result was positive but the whole-cell sonicate EIA result was negative. We defined a case of Lyme disease as either a clinician-diagnosed erythema migrans lesion or a positive standard 2-tiered serologic result in a patient with symptoms compatible with Lyme disease. We then compared the performance of the C6 EIA alone and as a first-tier test followed by immunoblot, with that of standard 2-tiered serology for the diagnosis of Lyme disease. Of the 944 specimens collected, 114 (12%) were from patients with Lyme disease. The C6 EIA alone had sensitivity similar to that of standard 2-tiered testing (79.8% vs 81.6% for standard 2-tiered testing; P = .71) with slightly lower specificity (94.2% vs 98.8% 2; P < .002). Addition of a supplemental immunoblot improved the specificity of the C6 EIA to 98.6%. For children and adolescents undergoing evaluation for Lyme disease, the C6 EIA could guide initial clinical decision making, although a supplemental immunoblot should still be performed. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  8. 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.

  9. Multiple Vital-Sign-Based Infection Screening Outperforms Thermography Independent of the Classification Algorithm.

    PubMed

    Yao, Yu; Sun, Guanghao; Matsui, Takemi; Hakozaki, Yukiya; van Waasen, Stefan; Schiek, Michael

    2016-05-01

    Thermography-based infection screening at international airports plays an important role in the prevention of pandemics. However, studies show that thermography suffers from low sensitivity and specificity. To achieve higher screening accuracy, we developed a screening system based on the acquisition of multiple vital-signs. This multimodal approach increases accuracy, but introduces the need for sophisticated classification methods. This paper presents a comprehensive analysis of the multimodal approach to infection screening from a machine learning perspective. We conduct an empirical study applying six classification algorithms to measurements from the multimodal screening system and comparing their performance among each other, as well as to the performance of thermography. In addition, we provide an information theoretic view on the use of multiple vital-signs for infection screening. The classification methods are tested using the same clinical data, which has been analyzed in our previous study using linear discriminant analysis. A total of 92 subjects were recruited for influenza screening using the system, consisting of 57 inpatients diagnosed to have seasonal influenza and 35 healthy controls. Our study revealed that the multimodal screening system reduces the misclassification rate by more than 50% compared to thermography. At the same time, none of the multimodal classifiers needed more than 6 ms for classification, which is negligible for practical purposes. Among the tested classifiers k-nearest neighbors, support vector machine and quadratic discriminant analysis achieved the highest cross-validated sensitivity score of 93%. Multimodal infection screening might be able to address the shortcomings of thermography.

  10. Multiple independent lineages of HIV-1 persist in breast milk and plasma

    PubMed Central

    GRAY, Rebecca R.; SALEMI, Marco; LOWE, Amanda; NAKAMURA, Kyle J.; DECKER, William D.; SINKALA, Moses; KANKASA, Chipepo; MULLIGAN, Connie J.; THEA, Don; KUHN, Louise; ALDROVANDI, Grace; GOODENOW, Maureen M.

    2010-01-01

    Design The origin and evolution of HIV-1 in breast milk is unclear, despite the continuing significance of this tissue as a transmitting compartment. To elucidate the evolutionary trajectory of viral populations in a transient mucosal compartment, longitudinal sequences of the envelope gp120 region from plasma and breast milk spanning the first year after delivery were analyzed in six women infected by HIV-1 subtype C. Methods Multiple phylogenetic algorithms were used to elucidate the evolutionary history and spatial structure of virus populations between tissues. Results Overall persistent mixing of viral sequences between plasma and breast milk indicated that breast milk is not a distinct genetic viral compartment. Unexpectedly, longitudinal phylogenies showed multiple lineages defined by long branches that included virus from both the breast milk and the plasma. Plasma was unlikely the anatomical origin of the most recent common ancestor (MRCA) in at least three of the subjects, while in other women, the temporal origin of the MRCA of the viral populations following delivery occurred well before the onset of breast milk production. Conclusions These findings suggest that during pregnancy/lactation, a viral variant distinct from the plasma virus initially seeds the breast milk, followed by subsequent gene flow between the plasma and breast milk tissues. This study indicates the potential for reactivation or re-introduction of distinct lineages during major immunological disruptions during the course of natural infection. PMID:21173592

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Multiple regions within 8q24 independently affect risk for prostate cancer

    PubMed Central

    Haiman, Christopher A; Patterson, Nick; Freedman, Matthew L; Myers, Simon R; Pike, Malcolm C; Waliszewska, Alicja; Neubauer, Julie; Tandon, Arti; Schirmer, Christine; McDonald, Gavin J; Greenway, Steven C; Stram, Daniel O; Marchand, Loic Le; Kolonel, Laurence N; Frasco, Melissa; Wong, David; Pooler, Loreall C; Ardlie, Kristin; Oakley-Girvan, Ingrid; Whittemore, Alice S; Cooney, Kathleen A; John, Esther M; Ingles, Sue A; Altshuler, David; Henderson, Brian E; Reich, David

    2008-01-01

    After the recent discovery that common genetic variation in 8q24 influences inherited risk of prostate cancer, we genotyped 2,973 SNPs in up to 7,518 men with and without prostate cancer from five populations. We identified seven risk variants, five of them previously undescribed, spanning 430 kb and each independently predicting risk for prostate cancer (P = 7.9 × 10−19 for the strongest association, and P < 1.5 × 10−4 for five of the variants, after controlling for each of the others). The variants define common genotypes that span a more than fivefold range of susceptibility to cancer in some populations. None of the prostate cancer risk variants aligns to a known gene or alters the coding sequence of an encoded protein. PMID:17401364

  16. 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

  17. Association Analysis of the Extended MHC Region in Celiac Disease Implicates Multiple Independent Susceptibility Loci

    PubMed Central

    Ahn, Richard; Ding, Yuan Chun; Murray, Joseph; Fasano, Alessio; Green, Peter H. R.; Neuhausen, Susan L.; Garner, Chad

    2012-01-01

    Celiac disease is a common autoimmune disease caused by sensitivity to the dietary protein gluten. Forty loci have been implicated in the disease. All disease loci have been characterized as low-penetrance, with the exception of the high-risk genotypes in the HLA-DQA1 and HLA-DQB1 genes, which are necessary but not sufficient to cause the disease. The very strong effects from the known HLA loci and the genetically complex nature of the major histocompatibility complex (MHC) have precluded a thorough investigation of the region. The purpose of this study was to test the hypothesis that additional celiac disease loci exist within the extended MHC (xMHC). A set of 1898 SNPs was analyzed for association across the 7.6 Mb xMHC region in 1668 confirmed celiac disease cases and 517 unaffected controls. Conditional recursive partitioning was used to create an informative indicator of the known HLA-DQA1 and HLA-DQB1 high-risk genotypes that was included in the association analysis to account for their effects. A linkage disequilibrium-based grouping procedure was utilized to estimate the number of independent celiac disease loci present in the xMHC after accounting for the known effects. There was significant statistical evidence for four new independent celiac disease loci within the classic MHC region. This study is the first comprehensive association analysis of the xMHC in celiac disease that specifically accounts for the known HLA disease genotypes and the genetic complexity of the region. PMID:22615847

  18. 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

  19. Mimicry of lyme arthritis by synovial hemangioma.

    PubMed

    Hospach, Toni; Langendörfer, M; Kalle, T V; Tewald, F; Wirth, T; Dannecker, G E

    2011-12-01

    To report on the differential diagnosis of lyme arthritis and synovial hemangioma due to similar clinical and radiological signs and symptoms. A 15-year-old boy presented at the age of 9 with recurrent rather painless swelling of the right knee. Altogether four episodes lasting for 1-2 weeks each occurred over a period of 18 months before medical advice was sought. Physical examination revealed only a slightly limited range of motion. Living in an endemic area of borreliosis, he reported a tick bite 6 months prior to onset of his symptoms with erythema migrans and was treated for 10 days with amoxicillin. Serology revealed two positive unspecific bands in IgG immunoblot (p41 and 66) with slight positivity for ELISA. Ultrasound revealed synovial thickening and increased fluid. Despite the weak positive serology a diagnosis of lyme arthritis could not be excluded and intravenous antibiotic treatment with ceftriaxone was started. After two further relapses antiinflammatory therapy including intraarticular steroids were introduced with no long lasting effect. A chronical disease developed with alternate periods of swelling and almost complete remission. Ultrasound as well as MRI demonstrated ongoing signs of synovitis, therefore after further progression, a diagnostic arthroscopy was performed showing an inconspicuous knee joint. A second MRI showed focal suprapatellar enhancement and was followed by open arthrotomy revealing a histopathological proven synovial cavernous juxtaarticular hemangioma. To our knowledge, the differential diagnosis of lyme arthritis and synovial hemangioma has not yet been reported despite obvious clinical similarities. In conclusion, in children and adolescents synovial hemangioma has to be considered in differential diagnosis of recurrent knee swelling. Early diagnosis is important to prevent prolonged suffering from chronic joint swelling with probable joint damages, unnecessary treatment procedures and as well school and sports

  20. 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.

  1. 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

  2. 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

  3. Update on persistent symptoms associated with Lyme disease.

    PubMed

    Oliveira, Carlos R; Shapiro, Eugene D

    2015-02-01

    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. 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. 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.

  4. Geographic Expansion of Lyme Disease in Michigan, 2000-2014.

    PubMed

    Lantos, Paul M; Tsao, Jean; Nigrovic, Lise E; Auwaerter, Paul G; Fowler, Vance G; Ruffin, Felicia; Foster, Erik; Hickling, Graham

    2017-01-01

    Most Lyme disease cases in the Midwestern United States are reported in Minnesota and Wisconsin. In recent years, however, a widening geographic extent of Lyme disease has been noted with evidence of expansion eastwards into Michigan and neighboring states with historically low incidence rates. We collected confirmed and probable cases of Lyme disease from 2000 through 2014 from the Michigan Department of Health and Human Services, entering them in a geographic information system. We performed spatial focal cluster analyses to characterize Lyme disease expansion. We compared the distribution of human cases with recent Ixodes scapularis tick distribution studies. Lyme disease cases in both the Upper and Lower Peninsulas of Michigan expanded more than 5-fold over the study period. Although increases were seen throughout the Upper Peninsula, the Lower Peninsula particularly expanded along the Indiana border north along the eastern shore of Lake Michigan. Human cases corresponded to a simultaneous expansion in established I scapularis tick populations. The geographic distribution of Lyme disease cases significantly expanded in Michigan between 2000 and 2014, particularly northward along the Lake Michigan shore. If such dynamic trends continue, Michigan-and possibly neighboring areas of Indiana, Ohio, and Ontario, Canada-can expect a continued increase in Lyme disease cases.

  5. Not All Erythema Migrans Lesions Are Lyme Disease.

    PubMed

    Goddard, Jerome

    2017-02-01

    Lyme disease is the number one arthropod-transmitted disease in the US, and one of the diagnostic criteria for the illness is development of an erythematous bull's-eye rash around a tick bite that may expand over time, hence the term erythema migrans. However, there are other erythema migrans-like rashes, such as those from a condition known as southern tick-associated rash illness. This article describes a patient with an erythema migrans-like lesion similar to that associated with Lyme disease, resulting from a bite by a nymphal-stage lone star tick, Amblyomma americanum. A tick removed from the center of an erythema migrans-like lesion in a patient was identified to species and then submitted to the Centers for Disease Control and Prevention for testing for the agent of Lyme disease, Borrelia burgdorferi. The patient was evaluated by an internist 7 weeks later. After another 3 weeks, the patient's blood was tested serologically for Lyme disease by American Esoteric Laboratories, Memphis, Tenn. Both the tick and human blood sample from this patient were negative for evidence of Lyme disease. Clinically, other than the erythema migrans-like lesion, the patient displayed no signs or symptoms consistent with Lyme disease. This case presents clinical, serological, and molecular evidence that erythema migrans lesions may occur after tick bites in patients and that these lesions may not be due to infection with the agent of Lyme disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. 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.

  7. 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

  8. 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

  9. 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

  10. A Comparison of Mangrove Canopy Height Using Multiple Independent Measurements from Land, Air, and Space

    NASA Technical Reports Server (NTRS)

    Lagomasino, David; Fatoyinbo, Temilola; Lee, SeungKuk; Feliciano, Emanuelle; Trettin, Carl; Simard, Marc

    2016-01-01

    Canopy height is one of the strongest predictors of biomass and carbon in forested ecosystems. Additionally, mangrove ecosystems represent one of the most concentrated carbon reservoirs that are rapidly degrading as a result of deforestation, development, and hydrologic manipulation. Therefore, the accuracy of Canopy Height Models (CHM) over mangrove forest can provide crucial information for monitoring and verification protocols. We compared four CHMs derived from independent remotely sensed imagery and identified potential errors and bias between measurement types. CHMs were derived from three spaceborne datasets; Very-High Resolution (VHR) stereophotogrammetry, TerraSAR-X add-on for Digital Elevation Measurement (DEM), and Shuttle Radar Topography Mission (TanDEM-X), and lidar data which was acquired from an airborne platform. Each dataset exhibited different error characteristics that were related to spatial resolution, sensitivities of the sensors, and reference frames. Canopies over 10 meters were accurately predicted by all CHMs while the distributions of canopy height were best predicted by the VHR CHM. Depending on the guidelines and strategies needed for monitoring and verification activities, coarse resolution CHMs could be used to track canopy height at regional and global scales with finer resolution imagery used to validate and monitor critical areas undergoing rapid changes.

  11. 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

  12. 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. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. Tempo and mode of performance evolution across multiple independent origins of adhesive toe pads in lizards.

    PubMed

    Hagey, Travis J; Uyeda, Josef C; Crandell, Kristen E; Cheney, Jorn A; Autumn, Kellar; Harmon, Luke J

    2017-07-26

    Understanding macroevolutionary dynamics of trait evolution is an important endeavor in evolutionary biology. Ecological opportunity can liberate a trait as it diversifies through trait space, while genetic and selective constraints can limit diversification. While many studies have examined the dynamics of morphological traits, diverse morphological traits may yield the same or similar performance and as performance is often more proximately the target of selection, examining only morphology may give an incomplete understanding of evolutionary dynamics. Here, we ask whether convergent evolution of pad-bearing lizards has followed similar evolutionary dynamics, or whether independent origins are accompanied by unique constraints and selective pressures over macroevolutionary time. We hypothesized that geckos and anoles each have unique evolutionary tempos and modes. Using performance data from 59 species, we modified Brownian motion (BM) and Ornstein-Uhlenbeck (OU) models to account for repeated origins estimated using Bayesian ancestral state reconstructions. We discovered that adhesive performance in geckos evolved in a fashion consistent with Brownian motion with a trend, whereas anoles evolved in bounded performance space consistent with more constrained evolution (an Ornstein-Uhlenbeck model). Our results suggest that convergent phenotypes can have quite distinctive evolutionary patterns, likely as a result of idiosyncratic constraints or ecological opportunities. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

  19. 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

  20. 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

  1. Deer, predators, and the emergence of Lyme disease

    PubMed Central

    Levi, Taal; Kilpatrick, A. Marm; Mangel, Marc; Wilmers, Christopher C.

    2012-01-01

    Lyme disease is the most prevalent vector-borne disease in North America, and both the annual incidence and geographic range are increasing. The emergence of Lyme disease has been attributed to a century-long recovery of deer, an important reproductive host for adult ticks. However, a growing body of evidence suggests that Lyme disease risk may now be more dynamically linked to fluctuations in the abundance of small-mammal hosts that are thought to infect the majority of ticks. The continuing and rapid increase in Lyme disease over the past two decades, long after the recolonization of deer, suggests that other factors, including changes in the ecology of small-mammal hosts may be responsible for the continuing emergence of Lyme disease. We present a theoretical model that illustrates how reductions in small-mammal predators can sharply increase Lyme disease risk. We then show that increases in Lyme disease in the northeastern and midwestern United States over the past three decades are frequently uncorrelated with deer abundance and instead coincide with a range-wide decline of a key small-mammal predator, the red fox, likely due to expansion of coyote populations. Further, across four states we find poor spatial correlation between deer abundance and Lyme disease incidence, but coyote abundance and fox rarity effectively predict the spatial distribution of Lyme disease in New York. These results suggest that changes in predator communities may have cascading impacts that facilitate the emergence of zoonotic diseases, the vast majority of which rely on hosts that occupy low trophic levels. PMID:22711825

  2. Concerted versus independent evolution and the search for multiple refugia: comparative phylogeography of four forest beetles.

    PubMed

    Marske, Katharine A; Leschen, Richard A B; Buckley, Thomas R

    2012-06-01

    Phylogeographic structure and its underlying causes are not necessarily shared among community members, with important implications for using individual organisms as indicators for ecosystem evolution, such as the identification of forest refugia. We used mitochondrial DNA (cox1), Bayesian coalescent ancestral state reconstruction (implemented in BEAST), and ecological niche models (ENMs) to construct geospatial histories for four codistributed New Zealand forest beetles (Leiodidae, Nitidulidae, Staphylinidae, and Zopheridae) to examine the extent to which they have tracked environmental changes together through time. Hindcast ENMs identified potential forest refugia during the Last Glacial Maximum, whereas ancestral state reconstruction identified key geographic connections for each species, facilitating direct comparison of dispersal patterns supported by the data and the time frame in which they occurred. Well-supported geographic state transitions for each species were mostly between neighboring regions, favoring a historical scenario of stepping stone colonization of newly suitable habitat rather than long distance dispersal. No geographic state transitions were shared by all four species, but three shared multiple projected South Island refugia and recent dispersal from the southernmost refugium. In contrast, strongly supported dispersal patterns in the refugia-rich northern South Island suggest more individualistic responses to environmental change in these ecologically similar forest species. © 2012 The Author(s). Evolution © 2012 The Society for the Study of Evolution.

  3. Increased statistical power with combined independent randomization tests used with multiple-baseline design.

    PubMed

    Tyrrell, Pascal N; Corey, Paul N; Feldman, Brian M; Silverman, Earl D

    2013-06-01

    Physicians often assess the effectiveness of treatments on a small number of patients. Multiple-baseline designs (MBDs), based on the Wampold-Worsham (WW) method of randomization and applied to four subjects, have relatively low power. Our objective was to propose another approach with greater power that does not suffer from the time requirements of the WW method applied to a greater number of subjects. The power of a design that involves the combination of two four-subject MBDs was estimated using computer simulation and compared with the four- and eight-subject designs. The effect of a delayed linear response to treatment on the power of the test was also investigated. Power was found to be adequate (>80%) for a standardized mean difference (SMD) greater than 0.8. The effect size associated with 80% power from combined tests was smaller than that of the single four-subject MBD (SMD=1.3) and comparable with the eight-subject MBD (SMD=0.6). A delayed linear response to the treatment resulted in important reductions in power (20-35%). By combining two four-subject MBD tests, an investigator can detect better effect sizes (SMD=0.8) and be able to complete a comparatively timelier and feasible study. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. 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.

  5. 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

  6. High consumption of coffee is associated with decreased multiple sclerosis risk; results from two independent studies.

    PubMed

    Hedström, A K; Mowry, E M; Gianfrancesco, M A; Shao, X; Schaefer, C A; Shen, L; Olsson, T; Barcellos, L F; Alfredsson, L

    2016-05-01

    Previous studies on consumption of caffeine and risk of multiple sclerosis (MS) have yielded inconclusive results. We aimed to investigate whether consumption of coffee is associated with risk of MS. Using two population-representative case-control studies (a Swedish study comprising 1620 cases and 2788 controls, and a US study comprising 1159 cases and 1172 controls), participants with different habits of coffee consumption based on retrospective data collection were compared regarding risk of MS, by calculating ORs with 95% CIs. Logistic regression models were adjusted for a broad range of potential confounding factors. Compared with those who reported no coffee consumption, the risk of MS was substantially reduced among those who reported a high consumption of coffee exceeding 900 mL daily (OR 0.70 (95% CI 0.49 to 0.99) in the Swedish study, and OR 0.69 (95% CI 0.50 to 0.96) in the US study). Lower odds of MS with increasing consumption of coffee were observed, regardless of whether coffee consumption at disease onset or 5 or 10 years prior to disease onset was considered. In accordance with studies in animal models of MS, high consumption of coffee may decrease the risk of developing MS. Caffeine, one component of coffee, has neuroprotective properties, and has been shown to suppress the production of proinflammatory cytokines, which may be mechanisms underlying the observed association. However, further investigations are needed to determine whether exposure to caffeine underlies the observed association and, if so, to evaluate its mechanisms of action. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  7. High consumption of coffee is associated with decreased multiple sclerosis risk; results from two independent studies

    PubMed Central

    Hedström, A K; Mowry, E M; Gianfrancesco, M A; Shao, X; Schaefer, C A; Shen, L; Olsson, T; Barcellos, L F; Alfredsson, L

    2016-01-01

    Objective Previous studies on consumption of caffeine and risk of multiple sclerosis (MS) have yielded inconclusive results. We aimed to investigate whether consumption of coffee is associated with risk of MS. Methods Using two population-representative case–control studies (a Swedish study comprising 1620 cases and 2788 controls, and a US study comprising 1159 cases and 1172 controls), participants with different habits of coffee consumption based on retrospective data collection were compared regarding risk of MS, by calculating ORs with 95% CIs. Logistic regression models were adjusted for a broad range of potential confounding factors. Results Compared with those who reported no coffee consumption, the risk of MS was substantially reduced among those who reported a high consumption of coffee exceeding 900 mL daily (OR 0.70 (95% CI 0.49 to 0.99) in the Swedish study, and OR 0.69 (95% CI 0.50 to 0.96) in the US study). Lower odds of MS with increasing consumption of coffee were observed, regardless of whether coffee consumption at disease onset or 5 or 10 years prior to disease onset was considered. Conclusions In accordance with studies in animal models of MS, high consumption of coffee may decrease the risk of developing MS. Caffeine, one component of coffee, has neuroprotective properties, and has been shown to suppress the production of proinflammatory cytokines, which may be mechanisms underlying the observed association. However, further investigations are needed to determine whether exposure to caffeine underlies the observed association and, if so, to evaluate its mechanisms of action. PMID:26940586

  8. 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

  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. Multiple independent insertions of 5S rRNA genes in the spliced-leader gene family of trypanosome species.

    PubMed

    Beauparlant, Marc A; Drouin, Guy

    2014-02-01

    Analyses of the 5S rRNA genes found in the spliced-leader (SL) gene repeat units of numerous trypanosome species suggest that such linkages were not inherited from a common ancestor, but were the result of independent 5S rRNA gene insertions. In trypanosomes, 5S rRNA genes are found either in the tandemly repeated units coding for SL genes or in independent tandemly repeated units. Given that trypanosome species where 5S rRNA genes are within the tandemly repeated units coding for SL genes are phylogenetically related, one might hypothesize that this arrangement is the result of an ancestral insertion of 5S rRNA genes into the tandemly repeated SL gene family of trypanosomes. Here, we use the types of 5S rRNA genes found associated with SL genes, the flanking regions of the inserted 5S rRNA genes and the position of these insertions to show that most of the 5S rRNA genes found within SL gene repeat units of trypanosome species were not acquired from a common ancestor but are the results of independent insertions. These multiple 5S rRNA genes insertion events in trypanosomes are likely the result of frequent founder events in different hosts and/or geographical locations in species having short generation times.

  12. Post-treatment Lyme disease syndrome symptomatology and the impact on life functioning: is there something here?

    PubMed

    Aucott, John N; Rebman, Alison W; Crowder, Lauren A; Kortte, Kathleen B

    2013-02-01

    A subset of patients treated for Lyme disease report persistent or recurrent symptoms of unknown etiology named post-treatment Lyme disease syndrome (PTLDS). This study aims to describe a cohort of participants with early, untreated Lyme disease, and characterize post-treatment symptomatology and functional impact of PTLDS over time. Sixty-three participants with erythema migrans and systemic symptoms were enrolled in a prospective cohort study. Participants underwent physical exams and clinical assessments, and completed the SF-36 (daily life functioning) and the Beck Depression Inventory, Second Edition (BDI-II) (depression), at each of five visits over a period of 6 months. Signs of Lyme disease disappeared post-treatment; however, new-onset patient-reported symptoms increased or plateaued over time. At 6 months, 36% of patients reported new-onset fatigue, 20% widespread pain, and 45% neurocognitive difficulties. However, less than 10% reported greater than “minimal” depression across the entire period. Those with PTLDS (36%) did not differ significantly from those without with respect to demographics, pre-treatment SF-36, and BDI-II scores. Statistically significant differences were found over time on the Role Physical, Vitality, Social Functioning, Role Emotional, and Mental Health subscales (with a trend toward significance for the remaining three subscales of Physical Functioning, Bodily Pain, and General Health) of the SF-36 between those with an eventual PTLDS diagnosis and those without when measured at 6 months. Unlike clinical signs of Lyme disease, new-onset symptoms are reported by a subset of participants without evidence of depressive symptomatology. Patients who developed PTLDS had significantly lower life functioning compared to those without PTLDS. We propose future avenues for researching infection-triggered symptoms resulting from multiple mechanisms.

  13. [Incidence of skin manifestations of Lyme disease in Croatia].

    PubMed

    Kansky, A; Balić-Winter, A; Bolanca-Bumber, S; Skerlev, M

    1992-01-01

    In the study, the most relevant historical data concerning Lyme-borreliosis are shortly reviewed. The most frequent skin manifestations, i.e. erythema cronicum migrans (ECM), lymphocytoma cutis (LCC) and acrodermatitis chronica atrophicans (ACA) are described. The clinical course of Lyme disease and the chronologic review of the most significant data on the disease are given. The frequency of skin manifestations of Lyme-borreliosis in various areas of Croatia from 1988 to 1989 based on the reports of dermatologists throughout Croatia is presented. According to our results, it can be concluded that skin manifestations of Lyme-borreliosis are much more frequent in the central and western parts of Croatia than elsewhere. The authors hope that the use of a fluorescent method for detecting antibodies to Borrelia burgdorferi since 1989 in the Serologic Laboratory of the Department of Dermatology, Salata, Zagreb will lead to more precise results about this disorder in the future.

  14. 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. Copyright 2015 by the American Academy of Orthopaedic Surgeons.

  15. Lyme disease: sudden hearing loss as the sole presentation.

    PubMed

    Espiney Amaro, C; Montalvão, P; Huins, C; Saraiva, J

    2015-02-01

    Lyme disease is an uncommon tick-borne multisystemic infection caused by Borrelia burgdorferi. The most common clinical manifestation is erythema migrans. In this report, a very unusual presentation of this condition is described, in which sudden onset sensorineural hearing loss was the sole presenting symptom. Case report and review of English-language literature. A patient presented with sensorineural hearing loss, with no other symptoms or signs. Acute Lyme infection was detected by laboratory tests. Magnetic resonance imaging showed signs of labyrinthitis of the same inner ear. After hyperbaric oxygen and systemic antibiotic treatment, the patient showed total hearing recovery, and magnetic resonance imaging showed complete resolution of the labyrinthitis. To our knowledge, this is the first reported case of Lyme disease presenting only with sensorineural hearing loss. Borreliosis should be considered as an aetiological factor in sensorineural hearing loss. Adequate treatment may provide total recovery and prevent more severe forms of Lyme disease.

  16. Close to Home: A History of Yale and Lyme Disease

    PubMed Central

    Elbaum-Garfinkle, Shana

    2011-01-01

    Yale scientists played a pivotal role in the discovery of Lyme disease and are credited as the first to recognize, name, characterize, and treat the affliction. Today, Lyme disease is the most commonly reported vector-borne illness in the United States, affecting approximately 20,000 people each year, with the incidence having doubled in the past 10 years [1]. Lyme disease is the result of a bacterial infection transmitted to humans through the bite of an infected deer tick, which typically results in a skin rash at the site of attack. While most cases, when caught early, are easily treated by antibiotic therapy, delayed treatment can lead to serious systemic side effects involving the joints, heart, and central nervous system. Here we review Yale’s role in the discovery and initial characterization of Lyme disease and how those early discoveries are crucial to our current understanding of the disease. PMID:21698040

  17. 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.

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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.

  9. Bilateral Facial Diplegia: A Rare Presenting Symptom of Lyme

    PubMed Central

    Perry, Matthew

    2017-01-01

    Lyme disease is a common disease that is faced by the physician but also acts a mimicker of many other disease processes. Facial palsies, especially bilateral, are a relatively rare presenting symptom of Lyme disease and may warrant further investigation. A thorough history and physical examination coupled with precision testing may aid the physician when faced with a patient with the diagnostic dilemma of facial diplegia. PMID:28409041

  10. 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.

  11. Lyme Carditis Buried Beneath ST-Segment Elevations

    PubMed Central

    Umpierrez De Reguero, Adrian

    2017-01-01

    Lyme disease is caused by the spirochete Borrelia burgdorferi and is carried to human hosts by infected ticks. There are nearly 30,000 cases of Lyme disease reported to the CDC each year, with 3-4% of those cases reporting Lyme carditis. The most common manifestation of Lyme carditis is partial heart block following bacterial-induced inflammation of the conducting nodes. Here we report a 45-year-old gentleman that presented to the hospital with intense nonradiating chest pressure and tightness. Lab studies were remarkable for elevated troponins. EKG demonstrated normal sinus rhythm with mild ST elevations. Three weeks prior to hospital presentation, patient had gone hunting near Madison. One week prior to admission, he noticed an erythematous lesion on his right shoulder. Because of his constellation of history, arthralgias, and carditis, he was started on ceftriaxone to treat probable Lyme disease. This case illustrates the importance of thorough history taking and extensive physical examination when assessing a case of possible acute myocardial infarction. Because Lyme carditis is reversible, recognition of this syndrome in young patients, whether in the form of AV block, myocarditis, or acute myocardial ischemia, is critical to the initiation of appropriate antibiotics in order to prevent permanent heart block, or even death. PMID:28713599

  12. 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.

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

    PubMed Central

    Kaaijk, Patricia; Luytjes, Willem

    2016-01-01

    Abstract 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. PMID:26337648

  14. 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.

  15. Testing the Independence of Multiple Personality Factors in Relation to Health Among Community-Dwelling Older Men.

    PubMed

    Smagula, Stephen F; Faulkner, Kimberly; Scheier, Michael F; Tindle, Hilary A; Cauley, Jane A

    2016-06-01

    We assessed associations between specific personality factors and health, and tested whether specific personality factors were related to health outcomes independent of each other. We performed cross-sectional analyses of personality and health among a sample of community-dwelling older men (n = 613, M age = 81.4, SD = 5.04 years) living in Pittsburgh, Pennsylvania. Personality factors (dispositional optimism, conscientiousness, and goal adjustment) were crudely related to both physical and mental health, but adjusting for other personality factors completely attenuated several of these associations. Conscientiousness remained uniquely related to every physical and mental health outcome. Optimism remained uniquely related to all health outcomes, except physical activity (which was more highly related to conscientiousness and goal adjustment). Associations between goal adjustment and probable depression appeared to be explained by conscientiousness and optimism. Correlations among multiple aspects of personality may mask unique associations of specific personality aspects with successful aging. © The Author(s) 2015.

  16. Two adults with multiple disabilities use a computer-aided telephone system to make phone calls independently.

    PubMed

    Lancioni, Giulio E; O'Reilly, Mark F; Singh, Nirbhay N; Sigafoos, Jeff; Oliva, Doretta; Alberti, Gloria; Lang, Russell

    2011-01-01

    This study extended the assessment of a newly developed computer-aided telephone system with two participants (adults) who presented with blindness or severe visual impairment and motor or motor and intellectual disabilities. For each participant, the study was carried out according to an ABAB design, in which the A represented baseline phases and the B represented intervention phases, during which the special telephone system was available. The system involved among others a net-book computer provided with specific software, a global system for mobile communication modem, and a microswitch. Both participants learned to use the system very rapidly and managed to make phone calls independently to a variety of partners such as family members, friends and staff personnel. The results were discussed in terms of the technology under investigation (its advantages, drawbacks, and need of improvement) and the social-communication impact it can make for persons with multiple disabilities. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. 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.

  18. Independent sources of condition dependency and multiple pathways determine a composite trait: lessons from carotenoid-based plumage colouration.

    PubMed

    Romero-Diaz, C; Richner, H; Granado-Lorencio, F; Tschirren, B; Fitze, P S

    2013-03-01

    Many colour ornaments are composite traits consisting of at least four components, which themselves may be more complex, determined by independent evolutionary pathways, and potentially being under different environmental control. To date, little evidence exists that several different components of colour elaboration are condition dependent and no direct evidence exists that different ornamental components are affected by different sources of variation. For example, in carotenoid-based plumage colouration, one of the best-known condition-dependent ornaments, colour elaboration stems from both condition-dependent pigment concentration and structural components. Some environmental flexibility of these components has been suggested, but specifically which and how they are affected remains unknown. Here, we tested whether multiple colour components may be condition dependent, by using a comprehensive 3 × 2 experimental design, in which we carotenoid supplemented and immune challenged great tit nestlings (Parus major) and quantified effects on different components of colouration. Plumage colouration was affected by an interaction between carotenoid availability and immune challenge. Path analyses showed that carotenoid supplementation increased plumage saturation via feather carotenoid concentration and via mechanisms unrelated to carotenoid deposition, while immune challenge affected feather length, but not carotenoid concentration. Thus, independent condition-dependent pathways, affected by different sources of variation, determine colour elaboration. This provides opportunities for the evolution of multiple signals within components of ornamental traits. This finding indicates that the selective forces shaping the evolution of different components of a composite trait and the trait's signal content may be more complex than believed so far, and that holistic approaches are required for drawing comprehensive evolutionary conclusions.

  19. 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.

  20. 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.

  1. Prognostic Validation of SKY92 and Its Combination With ISS in an Independent Cohort of Patients With Multiple Myeloma.

    PubMed

    van Beers, Erik H; van Vliet, Martin H; Kuiper, Rowan; de Best, Leonie; Anderson, Kenneth C; Chari, Ajai; Jagannath, Sundar; Jakubowiak, Andrzej; Kumar, Shaji K; Levy, Joan B; Auclair, Daniel; Lonial, Sagar; Reece, Donna; Richardson, Paul; Siegel, David S; Stewart, A Keith; Trudel, Suzanne; Vij, Ravi; Zimmerman, Todd M; Fonseca, Rafael

    2017-09-01

    High risk and low risk multiple myeloma patients follow a very different clinical course as reflected in their PFS and OS. To be clinically useful, methodologies used to identify high and low risk disease must be validated in representative independent clinical data and available so that patients can be managed appropriately. A recent analysis has indicated that SKY92 combined with the International Staging System (ISS) identifies patients with different risk disease with high sensitivity. Here we computed the performance of eight gene expression based classifiers SKY92, UAMS70, UAMS80, IFM15, Proliferation Index, Centrosome Index, Cancer Testis Antigen and HM19 as well as the combination of SKY92/ISS in an independent cohort of 91 newly diagnosed MM patients. The classifiers identified between 9%-21% of patients as high risk, with hazard ratios (HRs) between 1.9 and 8.2. Among the eight signatures, SKY92 identified the largest proportion of patients (21%) also with the highest HR (8.2). Our analysis also validated the combination SKY92/ISS for identification of three classes; low risk (42%), intermediate risk (37%) and high risk (21%). Between low risk and high risk classes the HR is >10. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. 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.

  3. [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.

  4. 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.

  5. 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.

  6. 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

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

    PubMed Central

    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

    2017-01-01

    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. PMID:28234347

  8. 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.

  9. Proliferation is a central independent prognostic factor and target for personalized and risk-adapted treatment in multiple myeloma

    PubMed Central

    Hose, Dirk; Rème, Thierry; Hielscher, Thomas; Moreaux, Jérôme; Messner, Tobias; Seckinger, Anja; Benner, Axel; Shaughnessy, John D.; Barlogie, Bart; Zhou, Yiming; Hillengass, Jens; Bertsch, Uta; Neben, Kai; Möhler, Thomas; Rossi, Jean François; Jauch, Anna; Klein, Bernard; Goldschmidt, Hartmut

    2011-01-01

    Background Proliferation of malignant plasma cells is a strong adverse prognostic factor in multiple myeloma and simultaneously targetable by available (e.g. tubulin polymerase inhibitors) and upcoming (e.g. aurora kinase inhibitors) compounds. Design and Methods We assessed proliferation using gene expression-based indices in 757 samples including independent cohorts of 298 and 345 samples of CD138-purified myeloma cells from previously untreated patients undergoing high-dose chemotherapy, together with clinical prognostic factors, chromosomal aberrations, and gene expression-based high-risk scores. Results In the two cohorts, 43.3% and 39.4% of the myeloma cell samples showed a proliferation index above the median plus three standard deviations of normal bone marrow plasma cells. Malignant plasma cells of patients in advanced stages or those harboring disease progression-associated gain of 1q21 or deletion of 13q14.3 showed significantly higher proliferation indices; patients with gain of chromosome 9, 15 or 19 (hyperdiploid samples) had significantly lower proliferation indices. Proliferation correlated with the presence of chromosomal aberrations in metaphase cytogenetics. It was significantly predictive for event-free and overall survival in both cohorts, allowed highly predictive risk stratification (e.g. event-free survival 12.7 versus 26.2 versus 40.6 months, P<0.001) of patients, and was largely independent of clinical prognostic factors, e.g. serum β2-microglobulin, International Staging System stage, associated high-risk chromosomal aberrations, e.g. translocation t(4;14), and gene expression-based high-risk scores. Conclusions Proliferation assessed by gene expression profiling, being independent of serum-β2-microglobulin, International Staging System stage, t(4;14), and gene expression-based risk scores, is a central prognostic factor in multiple myeloma. Surrogating a biological targetable variable, gene expression-based assessment of proliferation

  10. Fractal Characteristics of May-Grünwald-Giemsa Stained Chromatin Are Independent Prognostic Factors for Survival in Multiple Myeloma

    PubMed Central

    Ferro, Daniela P.; Falconi, Monica A.; Adam, Randall L.; Ortega, Manoela M.; Lima, Carmen P.; de Souza, Carmino A.; Lorand-Metze, Irene; Metze, Konradin

    2011-01-01

    Background The use of computerized image analysis for the study of nuclear texture features has provided important prognostic information for several neoplasias. Recently fractal characteristics of the chromatin structure in routinely stained smears have shown to be independent prognostic factors in acute leukemia. In the present study we investigated the influence of the fractal dimension (FD) of chromatin on survival of patients with multiple myeloma. Methodology We analyzed 67 newly diagnosed patients from our Institution treated in the Brazilian Multiple Myeloma Study Group. Diagnostic work-up consisted of peripheral blood counts, bone marrow cytology, bone radiograms, serum biochemistry and cytogenetics. The International Staging System (ISS) was used. In every patient, at least 40 digital nuclear images from diagnostic May-Grünwald-Giemsa stained bone marrow smears were acquired and transformed into pseudo-3D images. FD was determined by the Minkowski-Bouligand method extended to three dimensions. Goodness-of-fit of FD was estimated by the R2 values in the log-log plots. The influence of diagnostic features on overall survival was analyzed in Cox regressions. Patients that underwent autologous bone marrow transplantation were censored at the day of transplantation. Principal Findings Median age was 56 years. According to ISS, 14% of the patients were stage I, 39% were stage II and 47% were stage III. Additional features of a bad prognosis were observed in 46% of the cases. When stratifying for ISS, both FD and its goodness-of-fit were significant prognostic factors in univariate analyses. Patients with higher FD values or lower goodness-of-fit showed a worse outcome. In the multivariate Cox-regression, FD, R2, and ISS stage entered the final model, which showed to be stable in a bootstrap resampling study. Conclusions Fractal characteristics of the chromatin texture in routine cytological preparations revealed relevant prognostic information in patients with

  11. Borrelia burgdorferi aggrecanase activity: more evidence for persistent infection in Lyme disease

    PubMed Central

    Stricker, Raphael B.; Johnson, Lorraine

    2013-01-01

    Lyme disease is the most common tickborne illness in the world today. A recent study describes for the first time an enzyme produced by the spirochetal agent of Lyme disease, Borrelia burgdorferi, that cleaves aggrecan, a proteoglycan found in joints and connective tissue. Discovery of the spirochetal aggrecanase raises many questions about the pathogenesis of Lyme arthritis and lends support to the concept of persistent B. burgdorferi infection in patients with chronic Lyme disease symptoms. PMID:23967405

  12. 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.

  13. 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,...

  14. 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.

  15. 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.

  16. 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

  17. Unorthodox alternative therapies marketed to treat Lyme disease.

    PubMed

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

    2015-06-15

    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. 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. 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. 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. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Role of psychiatric comorbidity in chronic Lyme disease.

    PubMed

    Hassett, Afton L; Radvanski, Diane C; Buyske, Steven; Savage, Shantal V; Gara, Michael; Escobar, Javier I; Sigal, Leonard H

    2008-12-15

    To evaluate the prevalence and role of psychiatric comorbidity and other psychological factors in patients with chronic Lyme disease (CLD). We assessed 159 patients drawn from a cohort of 240 patients evaluated at an academic Lyme disease referral center. Patients were screened for common axis I psychiatric disorders (e.g., depressive and anxiety disorders); structured clinical interviews confirmed diagnoses. Axis II personality disorders, functional status, and traits like negative and positive affect and pain catastrophizing were also evaluated. A physician blind to psychiatric assessment results performed a medical evaluation. Two groups of CLD patients (those with post-Lyme disease syndrome and those with medically unexplained symptoms attributed to Lyme disease but without Borrelia burgdorferi infection) were compared with 2 groups of patients without CLD (patients recovered from Lyme disease and those with an identifiable medical condition explaining symptoms attributed to Lyme disease). After adjusting for age and sex, axis I psychiatric disorders were more common in CLD patients than in comparison patients (P = 0.02, odds ratio 2.64, 95% confidence interval 1.30-5.35), but personality disorders were not. Patients with CLD had higher negative affect, lower positive affect, and a greater tendency to catastrophize pain (P < 0.001) than comparison patients. All psychological factors except personality disorders were related to level of functioning. A predictive model based on these psychological variables was confirmed. Fibromyalgia was diagnosed in 46.8% of CLD patients. Psychiatric comorbidity and other psychological factors distinguished CLD patients from other patients commonly seen in Lyme disease referral centers, and were related to poor functional outcomes.

  19. 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

  20. Serum prealbumin: an independent marker of short-term energy intake in the presence of multiple-organ disease involvement.

    PubMed

    Caccialanza, Riccardo; Palladini, Giovanni; Klersy, Catherine; Cereda, Emanuele; Bonardi, Chiara; Quarleri, Lara; Vadacca, Giovanbattista; Albertini, Riccardo; Merlini, Giampaolo

    2013-03-01

    Serum prealbumin has a prognostic value in several diseases, but its serum levels can be influenced by different factors. However, a multivariable analysis to test the independent effect of each has not yet, to our knowledge, been performed. The aim of this cross-sectional study was to investigate the association between prealbumin and several factors possibly affecting its serum levels to test the potential of using prealbumin as an indicator of nutritional status and short-term energy intake in patients newly diagnosed with immunoglobulin light-chain amyloidosis. Multivariable general linear regression models of non-collinear variables were fitted to assess the association of demographic (sex, age), nutritional (short-term energy intake, unintentional weight loss, body mass index), and clinical (cardiac and liver involvement, kidney function, C-reactive protein) parameters with serum prealbumin levels in 187 patients newly diagnosed with immunoglobulin light-chain amyloidosis. Serum prealbumin levels were associated with C-reactive protein and short-term energy intake (P < 0.001 for both). A significant association was also detected with age (P = 0.023), serum creatinine (P = 0.017), liver involvement (P = 0.002), and peripheral edema (P = 0.032). In a prespecified subgroup analysis (n = 140) in patients with normal C-reactive protein level (<0.5 mg/dL), all other associations were confirmed. A significant relation was also observed with sex (P = 0.022) and body mass index (P = 0.041). Serum prealbumin is associated with short-term energy intake independently of the presence of multiple-organ involvement and inflammation. Its serum levels should be always interpreted in light of its influencing factors, among which inflammation and liver and kidney functions appear predominant. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. 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.

  2. Clinical trials validate the severity of persistent Lyme disease symptoms.

    PubMed

    Cameron, Daniel J

    2009-02-01

    Persistent Lyme Disease Symptoms (PLDS) have included fatigue, headaches, poor concentration and memory, lightheadedness, joint pain, and mood disturbances. Evidence-based guidelines committees disagree over the severity of PLDS. The 2004 International Lyme and Associated Diseases Society (ILADS) concluded that PLDS are severe. The 2006 Infectious Disease Society of America (IDSA) guidelines committee concluded that PLDS are nothing more than the "aches and pains of daily living" and an ad hoc International Lyme group concluded that PLDS are "symptoms common in persons who have never had Lyme disease." Clinical trials validate the severity of persistent Lyme disease symptoms. There are 22 standardized instruments used to measure the severity of PLDS among the four published National Institutes of Health (NIH) sponsored double-blind randomized placebo-controlled trials (RCTs). VALIDATING THE HYPOTHESIS: All four NIH sponsored RCTs validate the severity of PLDS. PLDS are as severe as symptoms seen in other serious chronic illnesses, and result in a quality of life lower than for the general population as determined by 22 standardized measures of QOL, including fatigue, pain, role function, psychopathology, and cognition. None of the four RCTs support the IDSA hypothesis that PLDS are nothing more than "the aches and pains of daily living" nor the ad hoc International Lyme group conclusion that PLDS are "symptoms common in persons who have never had Lyme disease." If the QOL of life for these patients is as poor as for patients with other serious chronic diseases, their symptoms need to be addressed by their doctors. Studies differ as to the precise cause of PLDS, the most effective treatments, and whether a cure is possible. But the fact that there is disagreement is not a license for physicians to ignore or turn away patients complaining of PLDS, or to dismiss their symptoms as purely psychosomatic. For physicians, the goal or purpose of treating PLDS should be the

  3. Multistrain Infections with Lyme Borreliosis Pathogens in the Tick Vector.

    PubMed

    Durand, Jonas; Herrmann, Coralie; Genné, Dolores; Sarr, Anouk; Gern, Lise; Voordouw, Maarten J

    2017-02-01

    Mixed or multiple-strain infections are common in vector-borne diseases and have important implications for the epidemiology of these pathogens. Previous studies have mainly focused on interactions between pathogen strains in the vertebrate host, but little is known about what happens in the arthropod vector. Borrelia afzelii and Borrelia garinii are two species of spirochete bacteria that cause Lyme borreliosis in Europe and that share a tick vector, Ixodes ricinus Each of these two tick-borne pathogens consists of multiple strains that are often differentiated using the highly polymorphic ospC gene. For each Borrelia species, we studied the frequencies and abundances of the ospC strains in a wild population of I. ricinus ticks that had been sampled from the same field site over a period of 3 years. We used quantitative PCR (qPCR) and 454 sequencing to estimate the spirochete load and the strain diversity within each tick. For B. afzelii, there was a negative relationship between the two most common ospC strains, suggesting the presence of competitive interactions in the vertebrate host and possibly the tick vector. The flat relationship between total spirochete abundance and strain richness in the nymphal tick indicates that the mean abundance per strain decreases as the number of strains in the tick increases. Strains with the highest spirochete load in the nymphal tick were the most common strains in the tick population. The spirochete abundance in the nymphal tick appears to be an important life history trait that explains why some strains are more common than others in nature.

  4. 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.

  5. 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. © 2015 Blackwell Verlag GmbH.

  6. Risk factors for lyme disease in Chester County, Pennsylvania.

    PubMed Central

    Smith, G.; Wileyto, E. P.; Hopkins, R. B.; Cherry, B. R.; Maher, J. P.

    2001-01-01

    OBJECTIVE: To identify factors associated with increased or decreased risk of infection for Lyme disease in Chester County, Pennyslvania. METHODS: The authors designed an unmatched case-control study involving 294 incident cases reported to the Chester County Health Department in 1998 and 449 controls selected by random digit dialing. All case and control participants were interviewed by telephone. RESULTS: Age is a risk factor for Lyme disease for groups aged 10-19 years old and 50 years or older. Sex was not a risk factor. Incidence of Lyme disease in a rural setting was three times the incidence in an urban setting. Increased risk also was associated with living in single family homes, homes with yards or attached land, woods on the land, signs of tick hosts seen on the land, and homes within 100 feet of woodland. Gardening for more than four hours per week was also a risk factor, but most other outdoor activities were not. Twice as many participants took protective measures against tick bites before outdoor employment than those who merely ventured into the yard or land associated with the home. Only checking for ticks during outdoor activity and the use of repellents prior to outdoor activities outside the yard were unequivocally associated with a reduced risk of Lyme disease. CONCLUSIONS: It is important to increase public awareness about the risk of acquiring Lyme disease from ticks in the immediate environment of the home. PMID:11889282

  7. Chronic Lyme disease: misconceptions and challenges for patient management

    PubMed Central

    Halperin, John J

    2015-01-01

    Lyme disease, infection with the tick-borne spirochete Borrelia burgdorferi, causes both specific and nonspecific symptoms. In untreated chronic infection, specific manifestations such as a relapsing large-joint oligoarthritis can persist for years, yet subside with appropriate antimicrobial therapy. Nervous system involvement occurs in 10%–15% of untreated patients and typically involves lymphocytic meningitis, cranial neuritis, and/or mononeuritis multiplex; in some rare cases, patients have parenchymal inflammation in the brain or spinal cord. Nervous system infection is similarly highly responsive to antimicrobial therapy, including oral doxycycline. Nonspecific symptoms such as fatigue, perceived cognitive slowing, headache, and others occur in patients with Lyme disease and are indistinguishable from comparable symptoms occurring in innumerable other inflammatory states. There is no evidence that these nonspecific symptoms reflect nervous system infection or damage, or that they are in any way specific to or diagnostic of this or other tick-borne infections. When these symptoms occur in patients with Lyme disease, they typically also subside after antimicrobial treatment, although this may take time. Chronic fatigue states have been reported to occur following any number of infections, including Lyme disease. The mechanism underlying this association is unclear, although there is no evidence in any of these infections that these chronic posttreatment symptoms are attributable to ongoing infection with B. burgdorferi or any other identified organism. Available appropriately controlled studies indicate that additional or prolonged courses of antimicrobial therapy do not benefit patients with a chronic fatigue-like state after appropriately treated Lyme disease. PMID:26028977

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

    PubMed Central

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

    2013-01-01

    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. PMID:24334460

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. Design of Experiments with Multiple Independent Variables: A Resource Management Perspective on Complete and Reduced Factorial Designs

    PubMed Central

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

    2009-01-01

    An investigator who plans to conduct experiments 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 four design options are compared: complete factorial, individual experiments, single factor, and fractional factorial designs. 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. PMID:19719358

  15. 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

  16. 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.

  17. Independently controllable multiple Fano resonances in side-coupled MDM structure and its applications for sensing and wavelength demultiplexing

    NASA Astrophysics Data System (ADS)

    Yang, Jianhua; Song, Xiaokang; Yang, Song; Cui, Luna; Yu, Li

    2017-08-01

    Tunable single and multiple Fano resonances are investigated theoretically and numerically in a plasmonic structure, which consists of a cavity (or cavities) side-coupled with a defective metal-dielectric-metal (MDM) waveguide. The results show the Fano resonances originate from the interference between discrete states and a continuum state. These Fano resonances can be independently tuned by adjusting the corresponding cavity parameters. This structure can be utilized to achieve ultrasensitive plasmonic sensor yields with a sensitivity of 1400 nm/RIU. The highest figure of merit (FOM) ~1.75  ×  104 is obtained by optimizing structure. Furthermore, compact and high wavelength resolution plasmonic 1  ×  2 and 1  ×  3 wavelength demultiplexers based on Fano resonances are designed and investigated. This compact and flexible structure has significant applications for sensing, switching, wavelength selecting, as well as constructing highly integrated optical circuits and complex waveguide networks.

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

    PubMed

    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; Lee, Young Kyung

    2016-11-01

    We comprehensively profiled cytogenetic abnormalities in multiple myeloma (MM) and analyzed the relationship between cytogenetic abnormalities of undetermined prognostic significance and established prognostic factors. The karyotype of 333 newly diagnosed MM cases was analyzed in association with established prognostic factors. Survival analysis was also performed. 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. 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.

  19. Cross-species chromosome painting tracks the independent origin of multiple sex chromosomes in two cofamiliar Erythrinidae fishes.

    PubMed

    Cioffi, Marcelo B; Sánchez, Antonio; Marchal, Juan A; Kosyakova, Nadezda; Liehr, Thomas; Trifonov, Vladimir; Bertollo, Luiz Ac

    2011-06-30

    The Erythrinidae fish family is characterized by a large variation with respect to diploid chromosome numbers and sex-determining systems among its species, including two multiple X1X2Y sex systems in Hoplias malabaricus and Erythrinus erythrinus. At first, the occurrence of a same sex chromosome system within a family suggests that the sex chromosomes are correlated and originated from ancestral XY chromosomes that were either homomorphic or at an early stage of differentiation. To identify the origin and evolution of these X1X2Y sex chromosomes, we performed reciprocal cross-species FISH experiments with two sex-chromosome-specific probes designed from microdissected X1 and Y chromosomes of H. malabaricus and E. erythrinus, respectively. Our results yield valuable information regarding the origin and evolution of these sex chromosome systems. Our data indicate that these sex chromosomes evolved independently in these two closed related Erythrinidae species. Different autosomes were first converted into a poorly differentiated XY sex pair in each species, and additional chromosomal rearrangements produced both X1X2Y sex systems that are currently present. Our data provide new insights into the origin and evolution of sex chromosomes, which increases our knowledge about fish sex chromosome evolution.

  20. 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.

  1. 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

  2. Cycloheximide Can Induce Bax/Bak Dependent Myeloid Cell Death Independently of Multiple BH3-Only Proteins

    PubMed Central

    Goodall, Katharine J.; Finch-Edmondson, Megan L.; van Vuuren, Joanne; Yeoh, George C.; Gentle, Ian E.; Vince, James E.; Ekert, Paul G.; Vaux, David L.; Callus, Bernard A.

    2016-01-01

    Apoptosis mediated by Bax or Bak is usually thought to be triggered by BH3-only members of the Bcl-2 protein family. BH3-only proteins can directly bind to and activate Bax or Bak, or indirectly activate them by binding to anti-apoptotic Bcl-2 family members, thereby relieving their inhibition of Bax and Bak. Here we describe a third way of activation of Bax/Bak dependent apoptosis that does not require triggering by multiple BH3-only proteins. In factor dependent myeloid (FDM) cell lines, cycloheximide induced apoptosis by a Bax/Bak dependent mechanism, because Bax-/-Bak-/- lines were profoundly resistant, whereas FDM lines lacking one or more genes for BH3-only proteins remained highly sensitive. Addition of cycloheximide led to the rapid loss of Mcl-1 but did not affect the expression of other Bcl-2 family proteins. In support of these findings, similar results were observed by treating FDM cells with the CDK inhibitor, roscovitine. Roscovitine reduced Mcl-1 abundance and caused Bax/Bak dependent cell death, yet FDM lines lacking one or more genes for BH3-only proteins remained highly sensitive. Therefore Bax/Bak dependent apoptosis can be regulated by the abundance of anti-apoptotic Bcl-2 family members such as Mcl-1, independently of several known BH3-only proteins. PMID:27806040

  3. Cycloheximide Can Induce Bax/Bak Dependent Myeloid Cell Death Independently of Multiple BH3-Only Proteins.

    PubMed

    Goodall, Katharine J; Finch-Edmondson, Megan L; van Vuuren, Joanne; Yeoh, George C; Gentle, Ian E; Vince, James E; Ekert, Paul G; Vaux, David L; Callus, Bernard A

    2016-01-01

    Apoptosis mediated by Bax or Bak is usually thought to be triggered by BH3-only members of the Bcl-2 protein family. BH3-only proteins can directly bind to and activate Bax or Bak, or indirectly activate them by binding to anti-apoptotic Bcl-2 family members, thereby relieving their inhibition of Bax and Bak. Here we describe a third way of activation of Bax/Bak dependent apoptosis that does not require triggering by multiple BH3-only proteins. In factor dependent myeloid (FDM) cell lines, cycloheximide induced apoptosis by a Bax/Bak dependent mechanism, because Bax-/-Bak-/- lines were profoundly resistant, whereas FDM lines lacking one or more genes for BH3-only proteins remained highly sensitive. Addition of cycloheximide led to the rapid loss of Mcl-1 but did not affect the expression of other Bcl-2 family proteins. In support of these findings, similar results were observed by treating FDM cells with the CDK inhibitor, roscovitine. Roscovitine reduced Mcl-1 abundance and caused Bax/Bak dependent cell death, yet FDM lines lacking one or more genes for BH3-only proteins remained highly sensitive. Therefore Bax/Bak dependent apoptosis can be regulated by the abundance of anti-apoptotic Bcl-2 family members such as Mcl-1, independently of several known BH3-only proteins.

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

    NASA Astrophysics Data System (ADS)

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

    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.

  5. 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.

  6. The amber theory of Lyme arthritis: initial description and clinical implications.

    PubMed

    Wormser, Gary P; Nadelman, Robert B; Schwartz, Ira

    2012-06-01

    Lyme arthritis differs in many respects from other bacterial causes of arthritis. Based on an observation made for a patient with Lyme arthritis, we propose that the pathogenesis of joint swelling in Lyme arthritis is due to the introduction into the joint space of non-viable spirochetes or more likely spirochetal debris enmeshed in a host-derived fibrinous or collagenous matrix. This "amber" hypothesis can account for the clinical and laboratory features of Lyme arthritis and is amenable to experimental validation. Validation would directly impact the clinical management of patients with Lyme arthritis.

  7. 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].

  8. 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.

  9. 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

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

    PubMed Central

    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. PMID:23407755

  11. 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.

  12. [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. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  13. 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.

  14. 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.

  15. Spatial and Temporal Emergence Pattern of Lyme Disease in Virginia

    PubMed Central

    Li, Jie; Kolivras, Korine N.; Hong, Yili; Duan, Yuanyuan; Seukep, Sara E.; Prisley, Stephen P.; Campbell, James B.; Gaines, David N.

    2014-01-01

    The emergence of infectious diseases over the past several decades has highlighted the need to better understand epidemics and prepare for the spread of diseases into new areas. As these diseases expand their geographic range, cases are recorded at different geographic locations over time, making the analysis and prediction of this expansion complicated. In this study, we analyze spatial patterns of the disease using a statistical smoothing analysis based on areal (census tract level) count data of Lyme disease cases in Virginia from 1998 to 2011. We also use space and space–time scan statistics to reveal the presence of clusters in the spatial and spatiotemporal distribution of Lyme disease. Our results confirm and quantify the continued emergence of Lyme disease to the south and west in states along the eastern coast of the United States. The results also highlight areas where education and surveillance needs are highest. PMID:25331806

  16. Lyme neuroborreliosis presenting as Alice in Wonderland syndrome.

    PubMed

    Binalsheikh, Ibrahim M; Griesemer, David; Wang, Sonya; Alvarez-Altalef, Rebeca

    2012-03-01

    We describe a 7-year-old boy with Alice in Wonderland syndrome associated with Lyme disease. He presented with metamorphopsia and auditory hallucinations in the absence of previous tick bites or other signs of Lyme disease. The boy never developed clinical seizures, and electroencephalograms during these spells indicated no epileptic activity. There was no history of migraine. Cranial magnetic resonance imaging produced normal results. Lyme serology tested positive in both serum and cerebrospinal fluid. He was treated with intravenous ceftriaxone for 3 weeks, with complete resolution of signs. This case report is the first, to our knowledge, of neuroborreliosis presenting as Alice in Wonderland syndrome with complete resolution of findings after intravenous antibiotic treatment. Published by Elsevier Inc.

  17. 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.

  18. 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

  19. 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.

  20. [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.

  1. Isolated trochlear palsy secondary to Lyme neuroborreliosis.

    PubMed

    Bababeygy, Simon R; Quiros, Peter A

    2011-12-01

    The objective of the study is to report the first case of isolated trochlear palsy secondary to Lyme neuroborreliosis in an adult. A 22-year-old male presented with history of flu-like illness and headache, accompanied by vertical binocular diplopia, worse on downgaze and better in upgaze and right head tilt. Physical examination revealed trochlear palsy on the left side with a compensatory head tilt to the opposite side. A subsequent workup for trochlear palsy was conducted, including hematological and cerebral spinal fluid serum studies, and magnetic resonance imaging of the brain. Immunoglobulin (Ig)M and IgG antibodies against Borrelia burgdorferi were positive in serum and cerebral spinal fluid (CSF). Symptoms of double vision completely resolved after 3 weeks of antibiotic treatment with intravenous ceftriaxone. CSF studies, in addition to clinical symptoms of vertical double vision and a positive Parks 3-step test, are a good diagnostic tool for B. burgdorferi. Resolution of symptoms was noted after a complete course of intravenous ceftriaxone.

  2. 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.

  3. Celebrity over science? An analysis of Lyme disease video content on YouTube.

    PubMed

    Yiannakoulias, N; Tooby, R; Sturrock, S L

    2017-10-01

    Lyme disease has been a subject of medical controversy for several decades. In this study we looked at the availability and type of content represented in a (n = 700) selection of YouTube videos on the subject of Lyme disease. We classified video content into a small number of content areas, and studied the relationship between these content areas and 1) video views and 2) video likeability. We found very little content uploaded by government or academic institutions; the vast majority of content was uploaded by independent users. The most viewed videos tend to contain celebrity content and personal stories; videos with prevention information tend to be of less interest, and videos with science and medical information tend to be less liked. Our results suggest that important public health information on YouTube is very likely to be ignored unless it is made more appealing to modern consumers of online video content. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. White-tailed deer (Odocoileus virginianus) as a potential sentinel for human Lyme disease in Indiana.

    PubMed

    Raizman, E A; Holland, J D; Shukle, J T

    2013-05-01

    We assessed the potential of white-tailed deer (WTD) (Odocoileus virginianus) to be a sentinel for human cases of Lyme disease (LD) in Indiana using location data from a 3-year survey of approximately 3400 hunted deer with associated tick Ixodes scapularis and Borrelia burgdorferi (Bb) data. Data on human LD cases at the county level were obtained from the Indiana Department of Health. All data were assigned to county centroids to match the resolution of the LD data before creating optimized trend surfaces for LD incidence, hunted deer count, Ixodes scapularis and Bb prevalence. To determine whether LD was spatially associated with the areas of high densities of deer, deer with Ixodes scapularis and deer with ticks infected with Bb, we used spatial analysis with distance indices (SADIE). The SADIE analysis found significant spatial association between LD and the distribution of three organismal predictor variables, that is, WTD, Ixodes ticks and Bb. Lyme disease incident rate varied between 0.08 cases per 10,000 habitants (Johnson county) and 5.9 cases per 10,000 habitants (Warren county). In conclusion, WTD can be used as an accurate and cost-effective sentinel for human LD. This method will permit public health workers to identify potentially endemic areas independently of human case reports. © 2012 Blackwell Verlag GmbH.

  5. Distribution of Twelve Linear Extrachromosomal DNAs in Natural Isolates of Lyme Disease Spirochetes

    PubMed Central

    Palmer, Nanette; Fraser, Claire; Casjens, Sherwood

    2000-01-01

    We have analyzed a panel of independent North American isolates of the Lyme disease agent spirochete, Borrelia burgdorferi (sensu stricto), for the presence of linear plasmids with sequence similarities to the 12 linear plasmids present in the B. burgdorferi type strain, isolate B31. The frequency of similarities to probes from each of the 12 B31 plasmids varied from 13 to 100% in the strain panel examined, and these similarities usually reside on plasmids similar in size to the cognate B31 plasmid. Sequences similar to 5 of the 12 B31 plasmids were found in all of the isolates examined, and >66% of the panel members hybridized to probes from 4 other plasmids. Sequences similar to most of the B. burgdorferi B31 plasmid-derived DNA probes used were also found on linear plasmids in the related Eurasian Lyme agents Borrelia garinii and Borrelia afzelii; however, some of these plasmids had uniform but substantially different sizes from their B. burgdorferi counterparts. PMID:10762248

  6. Integrins αvβ3 and α5β1 Mediate Attachment of Lyme Disease Spirochetes to Human Cells

    PubMed Central

    Coburn, Jenifer; Magoun, Loranne; Bodary, Sarah C.; Leong, John M.

    1998-01-01

    Borrelia burgdorferi (sensu lato), the agent of Lyme disease, is able to cause chronic, multisystemic infections in human and animal hosts. Attachment of the spirochete to host cells is likely to be important for the colonization of diverse tissues. The platelet-specific integrin αIIbβ3 was previously identified as a receptor for all three species of Lyme disease spirochetes (B. burgdorferi sensu stricto, B. garinii, and B. afzelii). Here we show that B. burgdorferi also recognizes the widely expressed integrins αvβ3 and α5β1, known as the vitronectin and fibronectin receptors, respectively. Three representatives of each species of Lyme disease spirochete were tested for the ability to bind to purified αvβ3 and α5β1. All of the strains tested bound to at least one integrin. Binding to one integrin was not always predictive of binding to other integrins, and several different integrin preference profiles were identified. Attachment of the infectious B. burgdorferi strain N40 to purified αvβ3 and α5β1 was inhibited by RGD peptides and the appropriate receptor-specific antibodies. Binding to αvβ3 was also shown by using a transfected cell line that expresses this receptor but not αIIbβ3. Attachment of B. burgdorferi N40 to human erythroleukemia cells and to human saphenous vein endothelial cells was mediated by both α5β1 and αvβ3. Our results show that multiple integrins mediate attachment of Lyme disease spirochetes to host cells. PMID:9573074

  7. Country, sex, EDSS change and therapy choice independently predict treatment discontinuation in multiple sclerosis and clinically isolated syndrome.

    PubMed

    Meyniel, Claire; Spelman, Timothy; 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

    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). 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. 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. In this multivariable survival analysis, female sex, country of residence, EDSS change and IMD choice independently predicted time to first IMD cessation.

  8. 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.

  9. Dietary specialization drives multiple independent losses and gains in the bitter taste gene repertoire of Laurasiatherian Mammals.

    PubMed

    Liu, Zhijin; Liu, Guangjian; Hailer, Frank; Orozco-terWengel, Pablo; Tan, Xinxin; Tian, Jundong; Yan, Zhongze; Zhang, Baowei; Li, Ming

    2016-01-01

    Bitter taste perception is essential for species with selective food intake, enabling them to avoid unpalatable or toxic items. Previous studies noted a marked variation in the number of TAS2R genes among various vertebrate species, but the underlying causes are not well understood. Laurasiatherian mammals have highly diversified dietary niche, showing repeated evolution of specialized feeding preferences in multiple lineages and offering a unique chance to investigate how various feeding niches are associated with copy number variation for bitter taste receptor genes. Here we investigated the evolutionary trajectories of TAS2Rs and their implications on bitter taste perception in whole-genome assemblies of 41 Laurasiatherian species. The number of intact TAS2Rs copies varied considerably, ranging from 0 to 52. As an extreme example of a narrow dietary niche, the Chinese pangolin possessed the lowest number of intact TAS2Rs (n = 2) among studied terrestrial vertebrates. Marine mammals (cetacea and pinnipedia), which swallow prey whole, presented a reduced copy number of TAS2Rs (n = 0-5). In contrast, independent insectivorous lineages, such as the shrew and insectivorous bats possessed a higher TAS2R diversity (n = 52 and n = 20-32, respectively), exceeding that in herbivores (n = 9-22) and omnivores (n = 18-22). Besides herbivores, insectivores in Laurasiatheria tend to have more functional TAS2Rs in comparison to carnivores and omnivores. Furthermore, animals swallowing food whole (cetacean, pinnipedia and pangolin) have lost most functional TAS2Rs. These findings provide the most comprehensive view of the bitter taste gene repertoire in Laurasiatherian mammals to date, casting new light on the relationship between losses and gains of TAS2Rs and dietary specialization in mammals.

  10. 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

  11. 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

  12. [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.

  13. 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. PMID:28405553

  14. Epidemic Spread of Lyme Borreliosis, Northeastern United States

    PubMed Central

    Kurtenbach, Klaus; Diuk-Wasser, Maria; Brei, Brandon; Fish, Durland

    2006-01-01

    We examined the degree of host specialization of different strains of Borrelia burgdorferi, the tickborne pathogen that causes Lyme borreliosis in the northeastern United States. We first assessed the genetic population structures of B. burgdorferi in ticks obtained from different mammalian host species and in questing ticks sampled in a woodland ecosystem in Connecticut. By comparing the patterns found in our study with data from another cross-sectional study, we demonstrate that B. burgdorferi is a generalist microparasite and conclude that efficient cross-species transmission of B. burgdorferi is a key feature that has allowed the rapid spread of Lyme borreliosis across the northeastern United States. PMID:16704808

  15. Comparison of males versus females with culture-confirmed early Lyme disease at presentation and at 11-20 years after diagnosis.

    PubMed

    Weitzner, Erica; Visintainer, Paul; Wormser, Gary P

    2016-08-01

    Lyme disease is the most common vector-borne infection in the United States with 300,000 estimated cases per year. The purpose of this study was to compare the presenting clinical features and long-term outcome of males versus females with culture-confirmed early Lyme disease. 174 males and 109 females with culture-confirmed erythema migrans were entered into a prospective study with follow-up visits scheduled at six months, 12 months and annually thereafter for up to 20 years. Males and females with early Lyme disease had a similar likelihood of having multiple erythema migrans skin lesions and had a similar number of additional subjective symptoms, such as fatigue, at study entry. Among the 71 males and 57 females able to be followed up for 11-20 years, there were no significant differences in baseline symptoms, rate of seroreactivity to Borrelia burgdorferi, or in frequency of post-treatment symptoms. Females, however, were significantly more likely than males to return for follow-up visits (P = 0.0003). Males and females with culture-confirmed early Lyme disease had similar clinical features, rates of seropositivity, and long-term outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Heart rate as an independent risk factor in patients with multiple organ dysfunction: a prospective, observational study.

    PubMed

    Hoke, Robert S; Müller-Werdan, Ursula; Lautenschläger, Christine; Werdan, Karl; Ebelt, Henning

    2012-02-01

    To study the association between baseline heart rate and outcome in patients with multiple organ dysfunction (MODS) as well as the course of heart rate over the first 4 days during MODS. Prospective observational study in 89 patients with MODS, defined as an APACHE-II score ≥20. Baseline heart rate (HR(0)) was determined over a 60-minute period at the time of MODS diagnosis. 28-day all-cause mortality was the primary endpoint of the study, a fall of the APACHE-II score by 4 points or more from day 0 to day 4 constituted the secondary endpoint. Hazard ratios for heart rate of 90 beats per minute (bpm) or greater relative to less than 90 bpm were calculated using Cox proportional hazards model and adjusted for confounding variables. Median baseline heart rate was 83 bpm in survivors and 92 bpm in non-survivors (p = 0.048). 28-day mortality was 32 and 61% in patients with HR(0) < 90 bpm and HR(0) ≥ 90 bpm, respectively. The adjusted hazard ratio for 28-day mortality was 2.30 (95% confidence interval 1.21-4.36, p = 0.001) for HR(0) ≥ 90 bpm relative to HR(0) < 90 bpm. No correlation was found between baseline heart rate and the secondary endpoint. From day 0 to day 4, heart rate remained elevated in all patients, as well as in survivors and non-survivors. A heart rate ≥90 bpm at the time of MODS diagnosis is an independent risk factor for increased 28-day mortality. As in patients with cardiovascular conditions such as coronary heart disease or chronic heart failure, heart rate might constitute a target for heart rate-lowering therapy in the narrow initial treatment window of MODS.

  17. 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

  18. 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 ...

  19. Laboratory evaluation in the diagnosis of Lyme disease.

    PubMed

    Tugwell, P; Dennis, D T; Weinstein, A; Wells, G; Shea, B; Nichol, G; Hayward, R; Lightfoot, R; Baker, P; Steere, A C

    1997-12-15

    To provide a qualitative evaluation of the predictive value of the laboratory diagnosis of Lyme disease and to use the resultant data to formulate guidelines for clinical diagnosis. A MEDLINE search of English-language articles or articles with English-language abstracts published from 1982 to 1996. Sensitivity, specificity, and likelihood ratios were calculated, and a random-effects model was used to combine the proportions from the eligible studies. Prespecified criteria were used to determine which studies were eligible for analysis. Laboratory testing in general is not clinically useful if the pretest probability of Lyme disease is less than 0.20 or greater than 0.80. When the pretest probability is 0.20 to 0.80, sequential testing with enzyme-linked immunosorbent assay and Western blot is the most accurate method for ruling in or ruling out the possibility of Lyme disease. Laboratory testing is recommended only in patients whose pretest probability of Lyme disease is 0.20 to 0.80. If the pretest probability is less than 0.20, testing will result in more false-positive results than true-positive results; a negative test result in this situation effectively rules out the disease.

  20. 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.

  1. 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

  2. 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...

  3. Management of tick bites and lyme disease during pregnancy.

    PubMed

    Smith, Graeme N; Gemmill, Ian; Moore, Kieran M

    2012-11-01

    Lyme disease results from the bite of a black-legged tick, populations of which have now become established in parts of Nova Scotia, southeastern Quebec, southern Ontario from the Thousand Islands through the geographic regions on the north shore of Lake Ontario and Lake Erie, southeastern Manitoba, and British Columbia's Lower Mainland, Fraser Valley, and Vancouver Island. It takes more than 24 hours of attachment to transfer the spirochete Borrelia burgdorferi to the bitten animal or human. The diagnosis of Lyme disease is primarily clinical, with early Lyme disease characterized by a skin lesion (erythema migrans, a bull's-eye rash), which expands out from the site of the tick bite, and is often accompanied by influenza-like symptoms, arthralgia, myalgia, and fever. These signs and symptoms can present anywhere from three to 30 days after the tick bite. The management of pregnant women with a tick bite or suspected Lyme disease should be similar to that of non-pregnant adults, except that doxycyline, the first line antibiotic of choice, should not be used in pregnant women because of risk of permanent tooth discolouration and possible impact on bone formation in the fetus. An algorithm for the management of tick bites in pregnancy is presented. Clinical, serological, and epidemiological studies have all failed to demonstrate a causal association between infection with B. burgdorferi and any adverse pregnancy outcomes regardless of whether maternal exposure occurs before conception or during pregnancy itself.

  4. The phenomenon of 'chronic Lyme'; an observational study.

    PubMed

    Ljøstad, U; Mygland, Å

    2012-08-01

    To chart clinical, laboratory, and psychometric profiles in patients who attribute their complaints to chronic Lyme disease. We assessed the patients by clinical examination, laboratory tests, and questionnaires measuring fatigue, depression, anxiety, health-related quality of life, hypochondriasis, and illness perceptions. We found no evidence of ongoing Borrelia burgdorferi (Bb) infection in any of the 29 included patients using current diagnostic guidelines and an extended array of tests. Eight (28%) had other well-defined illnesses. Twenty-one (72%) had symptoms of unknown cause, of those six met the suggested criteria for post-Lyme disease syndrome. Fourteen (48%) had presence of anti-Bb antibodies. The patients had more fatigue and poorer health-related quality of life as compared to normative data, but were not more depressed, anxious, or hypochondriacal. Their beliefs about the illness were characterized by negative expectations. Our patients, who all attributed their symptoms to chronic Lyme disease, were heterogeneous. None had evidences of persistent Bb infection, but whether current diagnostic criteria are functional in patients with longstanding complaints is controversial. Other well-defined illnesses or sequelae from earlier Lyme disease were probable as main explanatory factor in some cases. The patients were not more depressed, anxious, or hypochondriacal than the normal population, but they had poorer health-related quality of life, more fatigue, and negative expectations about their illness. © 2012 The Author(s). European Journal of Neurology © 2012 EFNS.

  5. Long term treatment of chronic Lyme arthritis with benzathine penicillin.

    PubMed Central

    Cimmino, M A; Accardo, S

    1992-01-01

    The cases are reported of two patients with chronic Lyme arthritis resistant to the recommended antibiotic regimens who were cured by long term treatment with benzathine penicillin. It is suggested that the sustained therapeutic levels of penicillin were effective either by the inhibition of germ replication or by lysis of the spirochaetes when they were leaving their sanctuaries. PMID:1417107

  6. 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...

  7. 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.

  8. [Lyme borreliosis--guidelines of treatment and expectations of patients].

    PubMed

    Zajkowska, Joanna

    2008-01-01

    Clinical and patophysiological aspects of Lyme borreliosis influencing effectives of treatments are introduced. European recommendations--results of EUCALB export group (regarding European multistrains specificity), AAN-American Academy Neurology as well ILADS Working Group based on experience from North America supported of some important studies connected with duration of therapy are described. Expectations of patients are introduced.

  9. 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.

  10. 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

  11. Patterns of Lyme disease diagnosis and treatment by family physicians in a southeastern state.

    PubMed

    Boltri, John M; Hash, Robert B; Vogel, Robert L

    2002-12-01

    This study examined how often physicians in Georgia diagnose and treat Lyme disease as well as the criteria they use to reach a diagnosis of Lyme disease. A survey was sent to 1,331 family physicians in Georgia concerning how many cases of Lyme disease the physicians diagnosed, and the criteria used to make the diagnosis, during the preceding 12 months. Of 710 responses, 167 physicians treated 316 cases of Lyme disease without a firm diagnosis. In addition, 125 physicians diagnosed 262 cases of Lyme disease, 130 without serologic testing and 132 with serologic testing. Family Physicians in Georgia diagnose Lyme disease at a rate 40 times greater than the surveillance case rate reported in Georgia.

  12. 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.

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

    PubMed Central

    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. PMID:27672336

  14. Lyme borreliosis and peripheral facial palsy.

    PubMed

    Lotric-Furlan, S; Cimperman, J; Maraspin, V; Ruzić-Sabljić, E; Logar, M; Jurca, T; Strle, F

    1999-12-10

    From 1994 to 1996, 114 consecutive patients older than 15 years who presented at the Department of Infectious Diseases, University Medical Centre, Ljubljana, fulfilled the criteria for inclusion into this study on the borrelial aetiology of peripheral facial palsy (PFP). The study was restricted to patients without a conceivable explanation for their PFP, erythema migrans or history of erythema migrans, clinical signs/symptoms of frank meningitis or any other neurological manifestation in addition to PFP. In 22 (19.3%) of these 114 patients borrelial infection was confirmed by one of the following: in 3 (13.6%) by the isolation of Borrelia burgdorferi sensu lato from cerebrospinal fluid (CSF), in 11 (50%) by the presence of intrathecal antibody production, and in 8 (36.4%) by seroconversion to borrelial antigens. Additional 20 (17.5%) patients interpreted as having had a probable borrelial infection, had positive (> or = 1:256) IFA IgM and/or IgG borrelial serum antibody titres, and in 9 (7.9%) patients borderline borrelial antibody titres (1:128) were found (interpreted as a possible infection). In 63 (55.3%) patients the serological tests remained negative. Lymphocytic pleocytosis was found at the first visit in 12/22 (54.5%) patients with confirmed borrelial infection, in 3/20 (15%) with probable infection, in 1/9 (11.1%) with possible infection, and in 10/63 (15.9%) patients with symptoms of unknown aetiology. Patients with confirmed borrelial infection had abnormal CSF findings significantly more often than did patients with symptoms of unknown aetiology (p = 0.0139 for lymphocytic pleocytosis and/or elevated CSF protein levels, and p = 0.0010 for lymphocytic pleocytosis). Local and systemic signs/-symptoms were also more common in patients with confirmed borrelial infection than in those with an symptoms of unknown aetiology (p = 0.0258). In Slovenia which is a highly endemic region for Lyme borreliosis, borrelial infection is a frequent cause of PFP in adult

  15. An Unexpected Case of Lyme Disease in a Soldier Serving in Northern Iraq

    DTIC Science & Technology

    2010-05-01

    MILITARY MEDICINE, 175,5:367,2010 An Unexpected Case of Lyme Disease in a Soldier Serving in Northern Iraq CPT Jeremy B. Fisher, SP USA *; CPT...Christopher E. Curtis, MC USAt 188143 ABSTRACT Lyme disease is a tick-transmitted disease caused by the spirochete Borrelia burgdorferi. Cases have been...Turkey.3-S We report an unexpected case of Lyme disease from Iraq. CASE REPORT A 28-year-old active duty Army male, on a deployment to northern Iraq

  16. 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. © 2014 Wiley Periodicals, Inc.

  17. Management of Lyme Disease in European Children: a Review for Practical Purpose.

    PubMed

    D'Alessandro, Matteo; Loy, Anna; Castagnola, Elio

    2017-08-01

    Lyme disease is a tick-borne zoonosis transmitted through a bite of a tick carrying a spirochete belonging to Borrelia species. In the last 20 years, the reported incidence of Lyme disease is increased by three times in Europe. Clinically, the illness develops through a primary stage with a typical skin rash (erythema marginatum), then a secondary stage with possible neurologic or cardiac involvement. The last stage (chronic Lyme disease) is mainly represented by arthritis or late neurological complications but nowadays is rarely seen due to precocious antibiotic use. The diagnosis of Lyme disease is essentially based on history in agreement with tick exposure (living/recent traveling in endemic area or tick bite) and clinical findings compatible with the disease. At present, no laboratory diagnostic tool available can neither establish nor exclude the diagnosis of Lyme disease. The management of Lyme disease should comprise a prophylactic administration of antibiotic in selected population (patients exposed to a tick bite in endemic regions) in which the typical signs of Lyme disease are not yet appeared; conversely, patients with current signs of Lyme disease should undergo a standard therapeutic course. First-line therapy should be oral tetracycline or oral penicillin/cephalosporin (in pediatric populations, beta-lactamic drugs are preferred). In severe courses, intravenous route should be preferred. The aim of this review is to provide an updated guide to the management of pediatric Lyme patients, from prophylaxis to first- and second-line therapy in European setting.

  18. 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

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

    PubMed

    Fogel, Joshua; Kusz, Martin

    2016-01-01

    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. 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. 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). 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.

  20. [Prediction of potential geographic distribution of Lyme disease in Qinghai province with Maximum Entropy model].

    PubMed

    Zhang, Lin; Hou, Xuexia; Liu, Huixin; Liu, Wei; Wan, Kanglin; Hao, Qin

    2016-01-01

    To predict the potential geographic distribution of Lyme disease in Qinghai by using Maximum Entropy model (MaxEnt). The sero-diagnosis data of Lyme disease in 6 counties (Huzhu, Zeku, Tongde, Datong, Qilian and Xunhua) and the environmental and anthropogenic data including altitude, human footprint, normalized difference vegetation index (NDVI) and temperature in Qinghai province since 1990 were collected. By using the data of Huzhu Zeku and Tongde, the prediction of potential distribution of Lyme disease in Qinghai was conducted with MaxEnt. The prediction results were compared with the human sero-prevalence of Lyme disease in Datong, Qilian and Xunhua counties in Qinghai. Three hot spots of Lyme disease were predicted in Qinghai, which were all in the east forest areas. Furthermore, the NDVI showed the most important role in the model prediction, followed by human footprint. Datong, Qilian and Xunhua counties were all in eastern Qinghai. Xunhua was in hot spot areaⅡ, Datong was close to the north of hot spot area Ⅲ, while Qilian with lowest sero-prevalence of Lyme disease was not in the hot spot areas. The data were well modeled in MaxEnt (Area Under Curve=0.980). The actual distribution of Lyme disease in Qinghai was in consistent with the results of the model prediction. MaxEnt could be used in predicting the potential distribution patterns of Lyme disease. The distribution of vegetation and the range and intensity of human activity might be related with Lyme disease distribution.

  1. 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.

  2. Three sudden cardiac deaths associated with Lyme carditis - United States, November 2012-July 2013.

    PubMed

    2013-12-13

    Lyme disease is a multisystem illness caused by Borrelia burgdorferi, a spirochete transmitted by certain species of Ixodes ticks. Approximately 30,000 confirmed and probable cases of Lyme disease were reported in the United States in 2012, primarily from high-incidence states in the Northeast (Connecticut, Delaware, Maine, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, and Vermont) and upper Midwest (Minnesota and Wisconsin). Common manifestations include cutaneous, neurologic, and rheumatologic signs and symptoms. Symptomatic infection of the heart is rare in recognized Lyme disease cases and usually resolves promptly with appropriate antibiotic therapy. Nonetheless, cardiac involvement occasionally can cause life-threatening cardiac conduction abnormalities. During November 2012-July 2013, one woman and two men (ranging in age from 26 to 38 years) from high-incidence Lyme disease states experienced sudden cardiac death and, on postmortem examination, were found to have evidence of Lyme carditis. The three deaths were investigated by the Connecticut Department of Public Health, Massachusetts Department of Public Health, New Hampshire Department of Public Health, New York State Department of Health, and CDC. Donated corneas from two decedents had been transplanted to three recipients before the diagnosis of Lyme disease was established, but no evidence of disease transmission was found. Although death from Lyme carditis is rare, it should be considered in cases of sudden cardiac death in patients from high-incidence Lyme disease regions. Reducing exposure to ticks is the best method for preventing Lyme disease and other tickborne infections.

  3. 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.

  4. 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.

  5. 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

  6. 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

  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. A Verbal-Instruction System to Help Persons with Multiple Disabilities Perform Complex Food- and Drink-Preparation Tasks Independently

    ERIC Educational Resources Information Center

    Lancioni, Giulio E.; Singh, Nirbhay N.; O'Reilly, Mark F.; Sigafoos, Jeff; Oliva, Doretta; Smaldone, Angela; La Martire, Maria L.; Alberti, Gloria; Scigliuzzo, Francesca

    2011-01-01

    In a recent single-case study, we showed that a new verbal-instruction system, ensuring the automatic presentation of step instructions, was beneficial for promoting the task performance of a woman with multiple disabilities (including blindness). The present study was aimed at replicating and extending the aforementioned investigation with three…

  9. Generalization of the model-independent Laurent-Pietarinen single-channel pole-extraction formalism to multiple channels

    NASA Astrophysics Data System (ADS)

    Švarc, Alfred; Hadžimehmedović, Mirza; Osmanović, Hedim; Stahov, Jugoslav; Tiator, Lothar; Workman, Ron L.

    2016-04-01

    A method to extract resonance pole information from single-channel partial-wave amplitudes based on a Laurent (Mittag-Leffler) expansion and conformal mapping techniques has recently been developed. This method has been applied to a number of reactions and provides a model-independent extraction procedure which is particularly useful in cases where a set of amplitudes is available only at discrete energies. This method has been generalized and applied to the case of a multi-channel fit, where several sets of amplitudes are analyzed simultaneously. The importance of unitarity constraints is discussed. The final result provides a powerful, model-independent tool for analyzing partial-wave amplitudes of coupled or connected channels based entirely on the concepts of analyticity and unitarity.

  10. 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

  11. Clinical association: Lyme disease and Guillain-Barre syndrome.

    PubMed

    Patel, Kinner; Shah, Siddharth; Subedi, Dinesh

    2017-07-08

    Guillain-Barre Syndrome (GBS) is a life-threatening condition in which patients may present to the Emergency Department in respiratory distress leading to death. The early identification and treatment of such a condition is paramount in preventing mortality. While there are many infections associated with GBS, the association with Lyme disease is uncommon. Through our case we aim to highlight Borrelia burgdorferi as an important antecedent infection associated with the development of GBS. In this case we report a 31-year-old male who was diagnosed with Lyme disease and GBS with relevant clinical presentation including progressive numbness and weakness in bilateral hands and feet for the past 1week along with areflexia. Initiation of medical therapy with intravenous immunoglobulin and parenteral ceftriaxone resulted in resolution of his symptoms. The treatment of both diseases early can help prevent further central nervous complications leading to high morbidity and mortality. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. 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.

  13. The HUMTICK study: protocol for a prospective cohort study on post-treatment Lyme disease syndrome and the disease and cost burden of Lyme borreliosis in Belgium.

    PubMed

    Geebelen, Laurence; Lernout, Tinne; Kabamba-Mukadi, Benoît; Saegeman, Veroniek; Sprong, Hein; Van Gucht, Steven; Beutels, Philippe; Speybroeck, Niko; Tersago, Katrien

    2017-01-01

    In Belgium, different routine surveillance systems are in place to follow-up Lyme borreliosis trends. However, accurate data on the disease and monetary burden for the different clinical manifestations are lacking. Despite recommended antibiotic treatment, a proportion of Lyme patients report persisting aspecific symptoms for six months or more (e.g. fatigue, widespread musculoskeletal pain, cognitive difficulties), a syndrome now named "post-treatment Lyme disease syndrome" (PTLDS). Controversy exists on the cause, incidence and severity of PTLDS. This study aims to estimate the incidence of PTLDS in patients with Lyme borreliosis and to quantify the disease burden and economic costs associated with the different clinical manifestations of Lyme borreliosis in Belgium. The project is a prospective cohort study in which about 600 patients with an erythema migrans and 100 patients with disseminated Lyme borreliosis will be followed up. Questionnaires, including the SF-36 vitality and pain subscale, the Cognitive Failure Questionnaire and the EQ-5D-5L, will be used to collect information on acute and persisting symptoms and the impact on quality of life. Symptom frequency and severity will be compared with self-reported pre-Lyme health status, a control group and existing Belgian population norms. Additionally, information on the associated costs and possible risk factors for the development of PTLDS will be collected. A study of the health burden will allow evaluation of the relative importance of Lyme borreliosis in Belgium and information on the economic cost will help to formulate cost-effective measures. There are only few prospective studies conducted estimating the incidence of PTLDS and even though discussion exists about the prevalence of subjective symptoms in the general population, a control group of non-Lyme borreliosis participants has often not been included.

  14. Poor Positive Predictive Value of Lyme Disease Serologic Testing in an Area of Low Disease Incidence.

    PubMed

    Lantos, Paul M; Branda, John A; Boggan, Joel C; Chudgar, Saumil M; Wilson, Elizabeth A; Ruffin, Felicia; Fowler, Vance; Auwaerter, Paul G; Nigrovic, Lise E

    2015-11-01

    Lyme disease is diagnosed by 2-tiered serologic testing in patients with a compatible clinical illness, but the significance of positive test results in low-prevalence regions has not been investigated. We reviewed the medical records of patients who tested positive for Lyme disease with standardized 2-tiered serologic testing between 2005 and 2010 at a single hospital system in a region with little endemic Lyme disease. Based on clinical findings, we calculated the positive predictive value of Lyme disease serology. Next, we reviewed the outcome of serologic testing in patients with select clinical syndromes compatible with disseminated Lyme disease (arthritis, cranial neuropathy, or meningitis). During the 6-year study period 4723 patients were tested for Lyme disease, but only 76 (1.6%) had positive results by established laboratory criteria. Among 70 seropositive patients whose medical records were available for review, 12 (17%; 95% confidence interval, 9%-28%) were found to have Lyme disease (6 with documented travel to endemic regions). During the same time period, 297 patients with a clinical illness compatible with disseminated Lyme disease underwent 2-tiered serologic testing. Six of them (2%; 95% confidence interval, 0.7%-4.3%) were seropositive, 3 with documented travel and 1 who had an alternative diagnosis that explained the clinical findings. In this low-prevalence cohort, fewer than 20% of positive Lyme disease tests are obtained from patients with clinically likely Lyme disease. Positive Lyme disease test results may have little diagnostic value in this setting. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. Poor Positive Predictive Value of Lyme Disease Serologic Testing in an Area of Low Disease Incidence

    PubMed Central

    Lantos, Paul M.; Branda, John A.; Boggan, Joel C.; Chudgar, Saumil M.; Wilson, Elizabeth A.; Ruffin, Felicia; Fowler, Vance; Auwaerter, Paul G.; Nigrovic, Lise E.

    2015-01-01

    Background. Lyme disease is diagnosed by 2-tiered serologic testing in patients with a compatible clinical illness, but the significance of positive test results in low-prevalence regions has not been investigated. Methods. We reviewed the medical records of patients who tested positive for Lyme disease with standardized 2-tiered serologic testing between 2005 and 2010 at a single hospital system in a region with little endemic Lyme disease. Based on clinical findings, we calculated the positive predictive value of Lyme disease serology. Next, we reviewed the outcome of serologic testing in patients with select clinical syndromes compatible with disseminated Lyme disease (arthritis, cranial neuropathy, or meningitis). Results. During the 6-year study period 4723 patients were tested for Lyme disease, but only 76 (1.6%) had positive results by established laboratory criteria. Among 70 seropositive patients whose medical records were available for review, 12 (17%; 95% confidence interval, 9%–28%) were found to have Lyme disease (6 with documented travel to endemic regions). During the same time period, 297 patients with a clinical illness compatible with disseminated Lyme disease underwent 2-tiered serologic testing. Six of them (2%; 95% confidence interval, 0.7%–4.3%) were seropositive, 3 with documented travel and 1 who had an alternative diagnosis that explained the clinical findings. Conclusions. In this low-prevalence cohort, fewer than 20% of positive Lyme disease tests are obtained from patients with clinically likely Lyme disease. Positive Lyme disease test results may have little diagnostic value in this setting. PMID:26195017

  16. Synovial fluid findings in children with knee monoarthritis in lyme disease endemic areas.

    PubMed

    Deanehan, Julia K; Nigrovic, Peter A; Milewski, Matthew D; Tan Tanny, Sharman P; Kimia, Amir A; Smith, Brian G; Nigrovic, Lise E

    2014-01-01

    Although Lyme and septic arthritis of the knee may have similar clinical presentations, septic arthritis requires prompt identification and treatment to avoid joint destruction. We sought to determine whether synovial fluid cell counts alone can discriminate between Lyme, septic, and other inflammatory arthritis. We conducted a retrospective cohort study of children aged 1 to 18 years with knee monoarthritis who presented to 1 of 2 pediatric emergency departments located in Lyme endemic areas. We included children who had both a synovial fluid culture and an evaluation for Lyme disease. Septic arthritis was defined as a positive synovial fluid culture or synovial fluid pleocytosis (white blood cell [WBC] ≥40,000 cells/μL) with a positive blood culture. Lyme arthritis was defined as positive Lyme serology without a positive bacterial culture. All other children were considered to have other inflammatory arthritis. We compared the synovial fluid counts by arthritis type. We identified 384 children with knee monoarthritis, of whom 19 (5%) had septic arthritis, 257 (67%) had Lyme arthritis and 108 (28%) had other inflammatory arthritis. Children with other inflammatory arthritis had lower synovial WBC and absolute neutrophil count, as well as percent neutrophils, than those with either Lyme or septic arthritis. There were no significant differences in the synovial fluid WBC, absolute neutrophil count, and percent neutrophils for children with Lyme and septic arthritis. In Lyme endemic areas, synovial fluid results alone do not differentiate septic from Lyme arthritis. Therefore, other clinical or laboratory indicators are needed to direct the care of patients with knee monoarthritis.

  17. Interferon-γ-induced protein 10 in Lyme disease.

    PubMed

    Fallahi, P; Elia, G; Bonatti, A

    2017-01-01

    Lyme disease is an infectious disease caused by bacteria of the Borrelia type, that affects about 300,000 people a year in the USA and 65,000 people a year in Europe. Borrelia infection, and Lyme disease, following occupational exposure has been frequently reported in USA, Europe and Asia. The manifestations of Lyme disease include erythema migrans (EM), arthritis, neuroborrelliosis (NB), and others. Cytokines and chemokines primarily orchestrate leukocyte recruitment to the areas of Borrelia infection, and they are critical mediators of immune and inflammatory responses, in particular of the induction of interferon (IFN)-γ and IFN-γ dependent chemokines. In EM high levels of T helper (Th) 1 cells chemoattranctants [monokine induced by IFN-γ (MIG), IFN-γ-induced protein 10 (IP- 10), and IFN-inducible T cell alpha chemoattractant (I-TAC)] have been shown. Synovial tissues and fluids of patients with Lyme Arthritis (LA) (overall with antibiotic-refractory LA) contained exceptionally high levels of Th1 chemoattractants and cytokines, particularly MIG and IFN-γ. In NB concentrations of IP-10 and I-TAC in the cerebrospinal fluid (CSF) were significantly higher, suggesting that IP-10 and I-TAC create a chemokine gradient between the CSF and serum and recruite C-X-C chemokine receptor 3-expressing memory CD4+ T-cells into the CSF of these patients. A positive association between the disseminating capacity of B. burgdorferi and early type I IFN induction has also been shown. These results suggest that IFN-γ dependent chemokines are important biomarkers to monitor the progression and diffusion of the disease in patients with Borrelia infection; further larger studies are needed.

  18. [Epidemiological characteristics of Lyme-like disease in children].

    PubMed

    Passos, Saulo Duarte; Gazeta, Rosa Estela; Latorre, Maria do Rosario; Durigon, Edison Luis; Gauditano, Giancarla; Yoshinari, Natalino H

    2009-01-01

    To determine the prevalence, age distribution, seasonality and clinical characteristics of Lyme-simile disease in Brazilians less than 15 years of age. METHODS. From July, 1998 to November, 2000, a cross-sectional study was conducted in 333 patients with skin rash and fever. Paired blood samples were collected for identification of the pathogens. Only 193 samples which were negative for other pathogens (Parvovirus B19 Human, Herpesvirus 6 Human, Measles, Rubella, Dengue, Scarlet fever and Enterovirus), were tested for borreliosis by Enzyme-Linked Immunosorbent Assay and Western-blotting. Other clinical, socioeconomic, demographic and climatic variables were studied. Prevalence of the disease was 6.2%(12/193). Of the variables studied, there was predominance in: <6 years old (83.2%); females (66.7%); being from the city of Franco da Rocha (58.3 %); and a summer/fall seasonality. The duration of care was 4 days. Signs and symptoms with statistical significance were itching; absence of lip notch and ocular pain; irritability and good clinical condition. Other clinical data presented were: pruritus (90%), irritability (80%) and fever (38 masculineC) (58.3%) with a duration of 1 to 3 days. Erythema was maculo-papular (40%), urticaria-like (25%) and scarlatiniform (16.7%), occurring predominately on the trunk (60%). There were no primary clinical evidences of Lyme-simile disease in the patients under study. The sensitivity and specificity of the clinical diagnosis as opposed to the laboratory diagnosis was zero. There was no initial clinical suspicion of the disease in the 10 cases studied and followed up for two years that showed no evidence of cardiologic or neurological complications. This is the first study of Lyme-simile in Brazilian children. Prevalence of Lyme-simile disease was low, and it was not remembered at the initial diagnosis of those with skin rash. However, practical knowledge is necessary, demanding increased medical attention.

  19. 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

  20. CSF B - lymphocyte chemoattractant (CXCL13) in the early diagnosis of acute Lyme neuroborreliosis.

    PubMed

    Ljøstad, U; Mygland, Å

    2008-05-01

    Recent studies have suggested a diagnostic role of the B-lymphocyte attracting chemokine (CXCL13) in the cerebrospinal fluid (CSF) in Lyme neuroborreliosis (LNB). Our aim was to evaluate diagnostic accuracy of CSF CXCL13 in a cohort of 59 consecutive patients referred to hospital for suspected LNB. Thirty-seven patients were classified as definite LNB and used as the reference standard. Seven were classified as probable, and seven as possible LNB. Eight patients did not fulfil case definitions and were used as controls.At presentation, CSF CXCL13 was elevated in all patients with definite LNB, as compared to a positive CSF B. burgdorferi (Bb) antibody index (AI) in 33 of 37. Pre-treatment sensitivity of elevated CSF CXCL13 and positive CSF Bb AI was 100 % (95 % CI = 91-100) and 78 % (95 % CI = 75-96) respectively (p = 0.053).Among the eight control patients, CSF CXCL13 was normal in five and only slightly elevated in three, and Bb AI was negative in five. Specificity of CSF CXCL13 and Bb AI was similar 63 % (95 % CI = 31-86) (p = 1.0).CSF CXCL13 was elevated in 6/7 patients with probable LNB and 3/7 patients with possible LNB. Bb AI was negative in all these 14 patients.An additional control group consisted of 31 patients with multiple sclerosis (MS), 11 with non-inflammatory neurological diseases, and ten with verified non-Lyme meningitis and high CSF cell count. CSF CXCL13 was slightly elevated in 15 MS patients, and in nine meningitis patients. Mean CSF CXCL13 was higher in definite LNB (3524 ng/g CSF protein) than in MS (27 ng/g) and non-Lyme meningitis (23 ng/g) (p < 0.001).Four months post-treatment CSF CXCL13 was normalized in 82 % of patients with definite LNB, as compared to a negative Bb AI in 10 % (p < 0.001).CSF CXCL13 may be a useful supplement in early diagnosis of acute LNB.

  1. CSF B--lymphocyte chemoattractant (CXCL13) in the early diagnosis of acute Lyme neuroborreliosis.

    PubMed

    Ljøstad, Unn; Mygland, Ase

    2008-05-01

    Recent studies have suggested a diagnostic role of the B-lymphocyte attracting chemokine (CXCL13) in the cerebrospinal fluid (CSF) in Lyme neuroborreliosis (LNB). Our aim was to evaluate diagnostic accuracy of CSF CXCL13 in a cohort of 59 consecutive patients referred to hospital for suspected LNB. Thirty-seven patients were classified as definite LNB and used as the reference standard. Seven were classified as probable, and seven as possible LNB. Eight patients did not fulfil case definitions and were used as controls. At presentation, CSF CXCL13 was elevated in all patients with definite LNB, as compared to a positive CSF B. burgdorferi (Bb) antibody index (AI) in 33 of 37. Pre-treatment sensitivity of elevated CSF [corrected] Bb Al [corrected] was 100 % (95 % CI = 91-100) and 89 % [corrected] (95 % CI = 75-96) respectively (p = 0.053). Among the eight control patients, CSF CXCL13 was normal in five and only slightly elevated in three, and Bb AI was negative in five. Specificity of CSF CXCL13 and Bb AI was similar 63 % (95 % CI = 31-86) (p = 1.0).CSF CXCL13 was elevated in 6/7 patients with probable LNB and 3/7 patients with possible LNB. Bb AI was negative in all these 14 patients. An additional control group consisted of 31 patients with multiple sclerosis (MS), 11 with non-inflammatory neurological diseases, and ten with verified non-Lyme meningitis and high CSF cell count. CSF CXCL13 was slightly elevated in 15 MS patients, and in nine meningitis patients. Mean CSF CXCL13 was higher in definite LNB (3524 ng/g CSF protein) than in MS (27 ng/g) and non-Lyme meningitis (23 ng/g) (p < 0.001). Four months post-treatment CSF CXCL13 was normalized in 82 % of patients with definite LNB, as compared to a negative Bb AI in 10 % (p < 0.001).CSF CXCL13 may be a useful supplement in early diagnosis of acute LNB.

  2. Acute Lyme Neuroborreliosis With Transient Hemiparesis and Aphasia.

    PubMed

    Sokolov, Arseny A; Lienhard, Reto; Du Pasquier, Renaud; Erard, Véronique

    2015-07-01

    Nervous system involvement in Lyme disease often mimics other conditions and thus represents a diagnostic challenge, especially in an emergency department setting. We report a case of a female teenager presenting with sudden-onset aphasia and transient right-sided faciobrachial hemiplegia, along with headache and agitation. Ischemia, vasculitis, or another structural lesion was excluded by brain imaging. Toxicologic evaluation results were negative. Cerebral perfusion computed tomography and electroencephalography showed left parietotemporal brain dysfunction. Lumbar puncture result, although atypical, suggested bacterial infection and intravenous ceftriaxone was initiated. Finally, microbiological cerebrospinal fluid analysis revealed Lyme neuroborreliosis, showing specific intrathecal antibody production and high level of C-X-C motif chemokine 13. The patient rapidly recovered. To our knowledge, this report for the first time illustrates that acute-onset language and motor symptoms may be directly related to Lyme neuroborreliosis. Neuroborreliosis may mimic other acute neurologic events such as stroke and should be taken into diagnostic consideration even in the absence of classic symptoms and evolution. Copyright © 2015 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

  3. Stroke as an Unusual First Presentation of Lyme Disease.

    PubMed

    Almoussa, Mohamad; Goertzen, Angelika; Fauser, Barbara; Zimmermann, Christoph W

    2015-01-01

    Introduction. Lyme neuroborreliosis is a nervous system infection caused by spirochete Borrelia burgdorferi with diverse neurological complications. Stroke due to cerebral vasculitis is a rare consequence of neuroborreliosis and has been described in just a few case reports. Case Presentation. Here, we report the case of a 43-year-old patient who presented with discrete left-sided hemiparesis and amnestic cognitive impairment. Brain magnetic resonance imaging showed a thalamic infarct, and serological and cerebrospinal fluid (CSF) tests confirmed the diagnosis of active neuroborreliosis. The antibiotic treatment with intravenous ceftriaxone for three weeks led to an improvement of the symptoms and remarkable regression of radiological findings, but not to full recovery of the amnestic cognitive disorder. Conclusion. Lyme neuroborreliosis should be suspected in patients with cerebrovascular events without obvious risk factors, especially those living in endemic areas such as northern Europe or those who have been exposed to ticks and those with clinical or radiological findings suggesting Lyme neuroborreliosis, in order to establish the diagnosis and start a proper antibiotic therapy.

  4. 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.

  5. 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

  6. 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

  7. Keratin 6 Expression Correlates to Areas of Squamous Differentiation in Multiple Independent Isolates of As+3-Induced Bladder Cancer

    PubMed Central

    Cao, Ling; Zhou, Xu Dong; Sens, Mary Ann; Garrett, Scott H.; Zheng, Yun; Dunlevy, Jane R.; Sens, Donald A.; Somji, Seema

    2011-01-01

    This laboratory has shown that arsenite (As+3) exposure can cause the malignant transformation of the UROtsa human urothelial cell line. This single isolate formed subcutaneous tumors with a histology similar to human urothelial cell carcinoma. The tumors also displayed areas of squamous differentiation of the urothelial cells, an infrequent, but known component of human bladder cancer. In the present study, five additional independent isolates of As+3 -transformed urothelial cells were isolated and each were shown to produce subcutaneous urothelial cell tumors with a characteristic histology very similar to those described in the initial report. That there were underlying phenotypic differences in the 6 independent isolates was demonstrated when they were assessed for their ability to form tumors within the peritoneal cavity. It was shown that two isolates could form hundreds of small peritoneal tumor nodules, one isolate a moderate number of tumor nodules, and three isolates no or only one tumor nodule. The peritoneal tumors were also characterized for their degree of squamous differentiation of the urothelial cells and, while areas of squamous differentiation could be found, such differentiation was substantially reduced compared to subcutaneous tumors. Immunostaining for keratin 6 was tested as a potential marker for malignant urothelial cells that had undergone squamous differentiation. Keratin 6 was shown to consistently stain only cells having some evidence of squamous differentiation. Keratin 16 was shown to follow the staining pattern of keratin 6. The isolates and tumor heterotransplants were all examined for keratin 6, 16 and 17 mRNA and protein expression. PMID:20186695

  8. 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.

  9. 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 Central

    Lathan, Corinna E.; Bleiberg, Joseph; Tsao, Jack W.

    2014-01-01

    Abstract 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. PMID:25003552

  10. 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

  11. Murine Borrelia arthritis is highly dependent on ASC and caspase-1, but independent of NLRP3.

    PubMed

    Oosting, Marije; Buffen, Kathrin; Malireddi, Subbarao R K; Sturm, Patrick; Verschueren, Ineke; Koenders, Marije I; van de Veerdonk, Frank L; van der Meer, Jos W M; Netea, Mihai G; Kanneganti, Thirumala-Devi; Joosten, Leo A B

    2012-11-13

    The protein platform called the NOD-like-receptor -family member (NLRP)-3 inflammasome needs to be activated to process intracellular caspase-1. Active caspase-1 is able to cleave pro-Interleukin (IL)-1β, resulting in bioactive IL-1β. IL-1β is a potent proinflammatory cytokine, and thought to play a key role in the pathogenesis of Lyme arthritis, a common manifestation of Borrelia burgdorferi infection. The precise pathways through which B. burgdorferi recognition leads to inflammasome activation and processing of IL-1β in Lyme arthritis has not been elucidated. In the present study, we investigated the contribution of several pattern recognition receptors and inflammasome components in a novel murine model of Lyme arthritis. Lyme arthritis was elicited by live B. burgdorferi, injected intra-articularly in knee joints of mice. To identify the relevant pathway components, the model was applied to wild-type, NLRP3-/-, ASC-/-, caspase-1-/-, NOD1-/-, NOD2-/-, and RICK-/- mice. As a control, TLR2-/-, Myd88-/- and IL-1R-/- mice were used. Peritoneal macrophages and bone marrow-derived macrophages were used for in vitro cytokine production and inflammasome activation studies. Joint inflammation was analyzed in synovial specimens and whole knee joints. Mann-Whitney U tests were used to detect statistical differences. We demonstrate that ASC/caspase-1-driven IL-1β is crucial for induction of B. burgdorferi-induced murine Lyme arthritis. In addition, we show that B. burgdorferi-induced murine Lyme arthritis is less dependent on NOD1/NOD2/RICK pathways while the TLR2-MyD88 pathway is crucial. Murine Lyme arthritis is strongly dependent on IL-1 production, and B. burgdorferi induces inflammasome-mediated caspase-1 activation. Next to that, murine Lyme arthritis is ASC- and caspase-1-dependent, but NLRP3, NOD1, NOD2, and RICK independent. Also, caspase-1 activation by B. burgdorferi is dependent on TLR2 and MyD88. Based on present results indicating that IL-1 is one of the

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

    PubMed Central

    Jones, Stephen G.; Dunn, John R.; Schaffner, William; Jones, Timothy F.

    2015-01-01

    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. PMID:26291336

  13. 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,…

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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,…

  20. Incidence and cumulative frequency of endemic Lyme disease in a community.

    PubMed

    Hanrahan, J P; Benach, J L; Coleman, J L; Bosler, E M; Morse, D L; Cameron, D J; Edelman, R; Kaslow, R A

    1984-10-01

    We conducted an epidemiological study of the cumulative frequency and incidence of Lyme disease in a summer community on Fire Island, New York, an area endemic for the disease. Fifteen (7.5%) of 200 persons studied in the community in 1982 reported a history of Lyme disease. An indirect immunofluorescent antibody assay showed that seventeen (9.7%) of 176 persons had serological evidence of exposure to the Lyme spirochete, including six of the 15 persons with a history of Lyme disease. Seven (0.7%-1.2%) of 600-1,000 persons in the community developed clinical symptoms and serological evidence of Lyme disease during the summer season, including two (1%) of the 200 persons in the study group. Four (3.1%) of 129 persons who had sera collected before and after the summer season demonstrated fourfold or greater rises in IgG antibody titers to the Lyme spirochete, including 2 (1.6%) persons without symptoms of Lyme disease. We conclude that the incidence of Lyme disease can be appreciably higher in endemic areas than previously recognized and that subclinical or inapparent seroconversion may occur after infection.

  1. 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.

  2. Prospective study of serologic tests for lyme disease.

    PubMed

    Steere, Allen C; McHugh, Gail; Damle, Nitin; Sikand, Vijay K

    2008-07-15

    Tests to determine serum antibody levels-the 2-tier sonicate immunoglobulin M (IgM) and immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) and Western blot method or the IgG of the variable major protein-like sequence-expressed (VlsE) sixth invariant region (C6) peptide ELISA method-are the major tests available for support of the diagnosis of Lyme disease. However, these tests have not been assessed prospectively. We used these tests prospectively to determine serologic responses in 134 patients with various manifestations of Lyme disease, 89 patients with other illnesses (with or without a history of Lyme disease), and 136 healthy subjects from areas of endemicity and areas in which the infection was not endemic. With 2-tier tests and the C6 peptide ELISA, only approximately one-third of 76 patients with erythema migrans had results that were positive for IgM or IgG seroreactivity with Borrelia burgdorferi in acute-phase samples. During convalescence, 3-4 weeks later, almost two-thirds of patients had seroreactivity with the spirochete B. burgdorferi. The frequencies of seroreactivity were significantly greater among patients with spirochetal dissemination than they were among those who lacked evidence of disseminated disease. Of the 44 patients with Lyme disease who had neurologic, heart, or joint involvement, all had positive C6 peptide ELISA results, 42 had IgG responses with 2-tier tests, and 2 patients with facial palsy had only IgM responses. However, among the control groups, the IgG Western blot was slightly more specific than the C6 peptide ELISA. The differences between the 2 test systems (2-tier testing and C6 peptide ELISA) with respect to sensitivity and specificity were not statistically significant. Except in patients with erythema migrans, both test systems were sensitive for support of the diagnosis of Lyme disease. However, with current methods, 2-tier testing was associated with slightly better specificity.

  3. A non-independent energy-based multiple sequence alignment improves prediction of transcription factor binding sites.

    PubMed

    Salama, Rafik A; Stekel, Dov J

    2013-11-01

    Multiple sequence alignments (MSAs) are usually scored under the assumption that the sequences being aligned have evolved by common descent. Consequently, the differences between sequences reflect the impact of insertions, deletions and mutations. However, non-coding DNA binding sequences, such as transcription factor binding sites (TFBSs), are frequently not related by common descent, and so the existing alignment scoring methods are not well suited for aligning such sequences. We present a novel multiple MSA methodology that scores TFBS DNA sequences by including the interdependence of neighboring bases. We introduced two variants supported by different underlying null hypotheses, one statistically and the other thermodynamically generated. We assessed the alignments through their performance in TFBS prediction; both methods show considerable improvements when compared with standard MSA algorithms. Moreover, the thermodynamically generated null hypothesis outperforms the statistical one due to improved stability in the base stacking free energy of the alignment. The thermodynamically generated null hypothesis method can be downloaded from http://sourceforge.net/projects/msa-edna/. dov.stekel@nottingham.ac.uk. Supplementary data are available at Bioinformatics online.

  4. 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

  5. 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

  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. Stratifying empiric risk of schizophrenia among first degree relatives using multiple predictors in two independent Indian samples.

    PubMed

    Bhatia, Triptish; Gettig, Elizabeth A; Gottesman, Irving I; Berliner, Jonathan; Mishra, N N; Nimgaonkar, Vishwajit L; Deshpande, Smita N

    2016-12-01

    Schizophrenia (SZ) has an estimated heritability of 64-88%, with the higher values based on twin studies. Conventionally, family history of psychosis is the best individual-level predictor of risk, but reliable risk estimates are unavailable for Indian populations. Genetic, environmental, and epigenetic factors are equally important and should be considered when predicting risk in 'at risk' individuals. To estimate risk based on an Indian schizophrenia participant's family history combined with selected demographic factors. To incorporate variables in addition to family history, and to stratify risk, we constructed a regression equation that included demographic variables in addition to family history. The equation was tested in two independent Indian samples: (i) an initial sample of SZ participants (N=128) with one sibling or offspring; (ii) a second, independent sample consisting of multiply affected families (N=138 families, with two or more sibs/offspring affected with SZ). The overall estimated risk was 4.31±0.27 (mean±standard deviation). There were 19 (14.8%) individuals in the high risk group, 75 (58.6%) in the moderate risk and 34 (26.6%) in the above average risk (in Sample A). In the validation sample, risks were distributed as: high (45%), moderate (38%) and above average (17%). Consistent risk estimates were obtained from both samples using the regression equation. Familial risk can be combined with demographic factors to estimate risk for SZ in India. If replicated, the proposed stratification of risk may be easier and more realistic for family members. Copyright © 2016. Published by Elsevier B.V.

  8. Probable late lyme disease: a variant manifestation of untreated Borrelia burgdorferi infection

    PubMed Central

    2012-01-01

    Background Lyme disease, a bacterial infection with the tick-borne spirochete Borrelia burgdorferi, can cause early and late manifestations. The category of probable Lyme disease was recently added to the CDC surveillance case definition to describe patients with serologic evidence of exposure and physician-diagnosed disease in the absence of objective signs. We present a retrospective case series of 13 untreated patients with persistent symptoms of greater than 12 weeks duration who meet these criteria and suggest a label of ‘probable late Lyme disease’ for this presentation. Methods The sample for this analysis draws from a retrospective chart review of consecutive, adult patients presenting between August 2002 and August 2007 to the author (JA), an infectious disease specialist. Patients were included in the analysis if their current illness had lasted greater than or equal to 12 weeks duration at the time of evaluation. Results Probable late Lyme patients with positive IgG serology but no history of previous physician-documented Lyme disease or appropriate Lyme treatment were found to represent 6% of our heterogeneous sample presenting with ≥ 12 weeks of symptom duration. Patients experienced a range of symptoms including fatigue, widespread pain, and cognitive complaints. Approximately one-third of this subset reported a patient-observed rash at illness onset, with a similar proportion having been exposed to non-recommended antibiotics or glucocorticosteroid treatment for their initial disease. A clinically significant response to antibiotics treatment was noted in the majority of patients with probable late Lyme disease, although post-treatment symptom recurrence was common. Conclusions We suggest that patients with probable late Lyme disease share features with both confirmed late Lyme disease and post-treatment Lyme disease syndrome. Physicians should consider the recent inclusion of probable Lyme disease in the CDC Lyme disease surveillance

  9. Lyme Disease Manifestations in the Foot and Ankle: A Retrospective Case Series.

    PubMed

    Miller, Jason R; Dunn, Karl W; Braccia, Domenick; Ciliberti, Louis J; Becker, Dina K; Hollinger, Joshua K; Brand, Shelley M

    Lyme disease is the result of Borrelia burgdorferi bacterial infection after exposure from a tick bite. A pathognomonic finding in early-stage Lyme disease is an expanding, red macular ring known as erythema migrans. Lyme arthritis is a late-stage manifestation of this disease, affecting the large, weightbearing joints with intermittent pain and swelling. The existing data on Lyme disease and subsequent arthritis have reported manifestations in the lower extremity, primarily in the knee and ankle and less commonly the small joints of the foot. We present a retrospective case series of 11 cases of painful arthritis in the foot and ankle with confirmatory Lyme disease testing. Copyright © 2015 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  10. Clinical evidence for rapid transmission of Lyme disease following a tickbite.

    PubMed

    Hynote, Eleanor D; Mervine, Phyllis C; Stricker, Raphael B

    2012-02-01

    Lyme disease transmission to humans by Ixodes ticks is thought to require at least 36-48 h of tick attachment. We describe 3 cases in which transmission of Borrelia burgdorferi, the spirochetal agent of Lyme disease, appears to have occurred in less than 24 h based on the degree of tick engorgement, clinical signs of acute infection, and immunologic evidence of acute Lyme disease. Health care providers and individuals exposed to ticks should be aware that transmission of Lyme disease may occur more rapidly than animal models suggest. A diagnosis of Lyme disease should not be ruled out based on a short tick attachment time in a subject with clinical evidence of B. burgdorferi infection. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Lyme disease following a dog bite--was there a tick?

    PubMed

    Owen, David

    2011-08-17

    Lyme disease is the most common tick borne infection in temperate zones and the reported incidence of the condition is increasing. Erythema migrans is one of the few clinical signs of Lyme disease and is usually indicative of recently acquired infection. A case is presented of Lyme disease with erythema migrans which followed shortly after a dog bite. The author is not aware of any previously reported similar case. The author considers that the development of Lyme disease in the case was most likely due to a coincidental tick bite which was not noticed by the patient but an alternative possibility is that the disease was activated from a latent form. Patients with Lyme disease may not give a history of tick bite and clinicians should be aware of this.

  12. Clinical characteristics, treatment and outcome of children with Lyme arthritis in Nova Scotia

    PubMed Central

    Glaude, Pier Diane; Huber, Adam M; Mailman, Timothy; Ramsey, Suzanne; Lang, Bianca; Stringer, Elizabeth

    2015-01-01

    BACKGROUND: Lyme disease is an emerging problem in Nova Scotia. Lyme arthritis is a late manifestation of Lyme disease. OBJECTIVE: To describe the demographic characteristics, referral patterns and clinical course of children diagnosed with Lyme arthritis in a tertiary care pediatric rheumatology clinic in Nova Scotia. METHODS: In the present retrospective chart review, subjects diagnosed with Lyme arthritis between 2006 and 2013 were identified through the clinic database. Demographic variables, referral patterns, clinical presentation and information regarding treatment course and outcome were collected. RESULTS: Seventeen patients were identified; 76% presented in 2012 and 2013. In 37.5% of cases, the referring physician suspected Lyme disease. Most patients presented with one or more painful and/or swollen joints; 94% had knee involvement. Only three of 17 patients had a history of erythema migrans and four of 17 recalled a tick bite. Five patients had a history of neurological manifestations consistent with Lyme disease, although, none had a diagnosis made at the time. Arthritis usually resolved after treatment with standard antibiotics; however, at last follow-up, two patients had antibiotic refractory Lyme arthritis, with one having joint damage despite aggressive arthritis treatment. CONCLUSION: A significant increase in cases of Lyme arthritis has recently been recognized in a pediatric rheumatology clinic in Nova Scotia. A history of a tick bite or erythema migrans were not sensitive markers of Lyme arthritis, and this diagnosis was often not considered by the referring physician. Educational initiatives should be undertaken to increase local awareness of this treatable cause of arthritis in children. PMID:26526378

  13. Multiple branches of the meiotic recombination pathway contribute independently to homolog pairing and stable juxtaposition during meiosis in budding yeast

    PubMed Central

    Peoples-Holst, Tamara L.; Burgess, Sean M.

    2005-01-01

    A unique aspect of meiosis is the segregation of homologous chromosomes at the meiosis I division. Homologs are physically connected prior to segregation by crossing over between nonsister chromatids. Crossovers arise from the repair of induced double-strand breaks (DSBs). In many organisms, more DSBs are formed than crossovers in a given nucleus. It has been previously suggested that repair of DSBs to noncrossover recombination products aids homolog alignment. Here we explore how two modes of the meiotic recombination pathway (crossover and noncrossover) and meiotic telomere reorganization contribute to the pairing and close juxtaposition of homologous chromosomes in budding yeast. We found that intermediates in the DSB repair pathway leading to both crossover and noncrossover recombination products contribute independently to close, stable homolog juxtaposition (CSHJ), a measurable state of homolog pairing. Analysis of the ndj1Δ mutant indicates that the effect of meiotic telomere reorganization on CSHJ is exerted through recombination intermediates at interstitial chromosomal loci, perhaps through the noncrossover branch of the DSB repair pathway. We suggest that transient, early DSB-initiated interactions, including those that give rise to noncrossovers, are important for homolog recognition and juxtaposition. PMID:15805472

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  19. TonEBP stimulates multiple cellular pathways for adaptation to hypertonic stress: organic osmolyte-dependent and -independent pathways

    PubMed Central

    Lee, Sang Do; Choi, Soo Youn; Lim, Sun Woo; Lamitina, S. Todd; Ho, Steffan N.; Go, William Y.

    2011-01-01

    TonEBP (tonicity-responsive enhancer binding protein) is a transcription factor that promotes cellular accumulation of organic osmolytes in the hypertonic renal medulla by stimulating expression of its target genes. Genetically modified animals with deficient TonEBP activity in the kidney suffer from severe medullary atrophy in association with cell death, demonstrating that TonEBP is essential for the survival of the renal medullary cells. Using both TonEBP knockout cells and RNA interference of TonEBP, we found that TonEBP promoted cellular adaptation to hypertonic stress. Microarray analyses revealed that the genetic response to hypertonicity was dominated by TonEBP in that expression of totally different sets of genes was increased by hypertonicity in those cells with TonEBP vs. those without TonEBP activity. Of over 100 potentially new TonEBP-regulated genes, we selected seven for further analyses and found that their expressions were all dependent on TonEBP. RNA interference experiments showed that some of these genes, asporin, insulin-like growth factor-binding protein-5 and -7, and an extracellular lysophospholipase D, plus heat shock protein 70, a known TonEBP target gene, contributed to the adaptation to hypertonicity without promoting organic osmolyte accumulation. We conclude that TonEBP stimulates multiple cellular pathways for adaptation to hypertonic stress in addition to organic osmolyte accumulation. PMID:21209002

  20. TonEBP stimulates multiple cellular pathways for adaptation to hypertonic stress: organic osmolyte-dependent and -independent pathways.

    PubMed

    Lee, Sang Do; Choi, Soo Youn; Lim, Sun Woo; Lamitina, S Todd; Ho, Steffan N; Go, William Y; Kwon, H Moo

    2011-03-01

    TonEBP (tonicity-responsive enhancer binding protein) is a transcription factor that promotes cellular accumulation of organic osmolytes in the hypertonic renal medulla by stimulating expression of its target genes. Genetically modified animals with deficient TonEBP activity in the kidney suffer from severe medullary atrophy in association with cell death, demonstrating that TonEBP is essential for the survival of the renal medullary cells. Using both TonEBP knockout cells and RNA interference of TonEBP, we found that TonEBP promoted cellular adaptation to hypertonic stress. Microarray analyses revealed that the genetic response to hypertonicity was dominated by TonEBP in that expression of totally different sets of genes was increased by hypertonicity in those cells with TonEBP vs. those without TonEBP activity. Of over 100 potentially new TonEBP-regulated genes, we selected seven for further analyses and found that their expressions were all dependent on TonEBP. RNA interference experiments showed that some of these genes, asporin, insulin-like growth factor-binding protein-5 and -7, and an extracellular lysophospholipase D, plus heat shock protein 70, a known TonEBP target gene, contributed to the adaptation to hypertonicity without promoting organic osmolyte accumulation. We conclude that TonEBP stimulates multiple cellular pathways for adaptation to hypertonic stress in addition to organic osmolyte accumulation.