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Sample records for disease spirochete adhering

  1. Real-Time High Resolution 3D Imaging of the Lyme Disease Spirochete Adhering to and Escaping from the Vasculature of a Living Host

    PubMed Central

    Colarusso, Pina; Bankhead, Troy; Kubes, Paul; Chaconas, George

    2008-01-01

    Pathogenic spirochetes are bacteria that cause a number of emerging and re-emerging diseases worldwide, including syphilis, leptospirosis, relapsing fever, and Lyme borreliosis. They navigate efficiently through dense extracellular matrix and cross the blood–brain barrier by unknown mechanisms. Due to their slender morphology, spirochetes are difficult to visualize by standard light microscopy, impeding studies of their behavior in situ. We engineered a fluorescent infectious strain of Borrelia burgdorferi, the Lyme disease pathogen, which expressed green fluorescent protein (GFP). Real-time 3D and 4D quantitative analysis of fluorescent spirochete dissemination from the microvasculature of living mice at high resolution revealed that dissemination was a multi-stage process that included transient tethering-type associations, short-term dragging interactions, and stationary adhesion. Stationary adhesions and extravasating spirochetes were most commonly observed at endothelial junctions, and translational motility of spirochetes appeared to play an integral role in transendothelial migration. To our knowledge, this is the first report of high resolution 3D and 4D visualization of dissemination of a bacterial pathogen in a living mammalian host, and provides the first direct insight into spirochete dissemination in vivo. PMID:18566656

  2. Association of spirochetal infection with Morgellons disease.

    PubMed

    Middelveen, Marianne J; Burugu, Divya; Poruri, Akhila; Burke, Jennie; Mayne, Peter J; Sapi, Eva; Kahn, Douglas G; Stricker, Raphael B

    2013-01-01

    Morgellons disease (MD) is an emerging multisystem illness characterized by skin lesions with unusual filaments embedded in or projecting from epithelial tissue. Filament formation results from abnormal keratin and collagen expression by epithelial-based keratinocytes and fibroblasts. Recent research comparing MD to bovine digital dermatitis, an animal infectious disease with similar skin features, provided clues that spirochetal infection could play an important role in the human disease as it does in the animal illness. Based on histological staining, immunofluorescent staining, electron microscopic imaging and polymerase chain reaction, we report the detection of Borrelia spirochetes in dermatological tissue of  four randomly-selected MD patients. The association of MD with spirochetal infection provides evidence that this infection may be a significant factor in the illness and refutes claims that MD lesions are self-inflicted and that people suffering from this disorder are delusional. Molecular characterization of the Borrelia spirochetes found in MD patients is warranted. PMID:24715950

  3. Association of spirochetal infection with Morgellons disease

    PubMed Central

    Stricker, Raphael B

    2013-01-01

    Morgellons disease (MD) is an emerging multisystem illness characterized by skin lesions with unusual filaments embedded in or projecting from epithelial tissue. Filament formation results from abnormal keratin and collagen expression by epithelial-based keratinocytes and fibroblasts. Recent research comparing MD to bovine digital dermatitis, an animal infectious disease with similar skin features, provided clues that spirochetal infection could play an important role in the human disease as it does in the animal illness. Based on histological staining, immunofluorescent staining, electron microscopic imaging and polymerase chain reaction, we report the detection of Borrelia spirochetes in dermatological tissue of  four randomly-selected MD patients. The association of MD with spirochetal infection provides evidence that this infection may be a significant factor in the illness and refutes claims that MD lesions are self-inflicted and that people suffering from this disorder are delusional. Molecular characterization of the Borrelia spirochetes found in MD patients is warranted. PMID:24715950

  4. Isolation of the Lyme disease spirochete from mammals in Minnesota.

    PubMed

    Loken, K I; Wu, C C; Johnson, R C; Bey, R F

    1985-07-01

    Lyme disease spirochetes were isolated from the kidneys of two Peromyscus spp. trapped in Minnesota in September and October 1983. No spirochetes were isolated from white-tailed deer (Odocoileus virginianus), red backed voles (Clethrionomys gapperi), or shrews (Sorexy cinereus and Blarina brevicauda). This is the first report of the isolation of the Lyme disease spirochete from the midwestern United States and isolations from these animals, which were free of ticks, suggest that the Lyme disease spirochete may persist in animal organs for months. PMID:4001130

  5. Swimming dynamics of the Lyme disease spirochete

    PubMed Central

    Vig, Dhruv K.; Wolgemuth, Charles W.

    2013-01-01

    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. PMID:23215618

  6. 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.

  7. Interaction of the Lyme disease spirochete with its tick vector.

    PubMed

    Caimano, Melissa J; Drecktrah, Dan; Kung, Faith; Samuels, D Scott

    2016-07-01

    Borrelia burgdorferi, the causative agent of Lyme disease (along with closely related genospecies), is in the deeply branching spirochete phylum. The bacterium is maintained in nature in an enzootic cycle that involves transmission from a tick vector to a vertebrate host and acquisition from a vertebrate host to a tick vector. During its arthropod sojourn, B. burgdorferi faces a variety of stresses, including nutrient deprivation. Here, we review some of the spirochetal factors that promote persistence, maintenance and dissemination of B. burgdorferi in the tick, and then focus on the utilization of available carbohydrates as well as the exquisite regulatory systems invoked to adapt to the austere environment between blood meals and to signal species transitions as the bacteria traverse their enzootic cycle. The spirochetes shift their source of carbon and energy from glucose in the vertebrate to glycerol in the tick. Regulation of survival under limiting nutrients requires the classic stringent response in which RelBbu controls the levels of the alarmones guanosine tetraphosphate and guanosine pentaphosphate (collectively termed (p)ppGpp), while regulation at the tick-vertebrate interface as well as regulation of protective responses to the blood meal require the two-component system Hk1/Rrp1 to activate production of the second messenger cyclic-dimeric-GMP (c-di-GMP). PMID:27147446

  8. The Cross-Talk between Spirochetal Lipoproteins and Immunity

    PubMed Central

    Kelesidis, Theodoros

    2014-01-01

    Spirochetal diseases such as syphilis, Lyme disease, and leptospirosis are major threats to public health. However, the immunopathogenesis of these diseases has not been fully elucidated. Spirochetes interact with the host through various structural components such as lipopolysaccharides (LPS), surface lipoproteins, and glycolipids. Although spirochetal antigens such as LPS and glycolipids may contribute to the inflammatory response during spirochetal infections, spirochetes such as Treponema pallidum and Borrelia burgdorferi lack LPS. Lipoproteins are most abundant proteins that are expressed in all spirochetes and often determine how spirochetes interact with their environment. Lipoproteins are pro-inflammatory, may regulate responses from both innate and adaptive immunity and enable the spirochetes to adhere to the host or the tick midgut or to evade the immune system. However, most of the spirochetal lipoproteins have unknown function. Herein, the immunomodulatory effects of spirochetal lipoproteins are reviewed and are grouped into two main categories: effects related to immune evasion and effects related to immune activation. Understanding lipoprotein-induced immunomodulation will aid in elucidating innate immunopathogenesis processes and subsequent adaptive mechanisms potentially relevant to spirochetal disease vaccine development and to inflammatory events associated with spirochetal diseases. PMID:25071771

  9. The Cross-Talk between Spirochetal Lipoproteins and Immunity.

    PubMed

    Kelesidis, Theodoros

    2014-01-01

    Spirochetal diseases such as syphilis, Lyme disease, and leptospirosis are major threats to public health. However, the immunopathogenesis of these diseases has not been fully elucidated. Spirochetes interact with the host through various structural components such as lipopolysaccharides (LPS), surface lipoproteins, and glycolipids. Although spirochetal antigens such as LPS and glycolipids may contribute to the inflammatory response during spirochetal infections, spirochetes such as Treponema pallidum and Borrelia burgdorferi lack LPS. Lipoproteins are most abundant proteins that are expressed in all spirochetes and often determine how spirochetes interact with their environment. Lipoproteins are pro-inflammatory, may regulate responses from both innate and adaptive immunity and enable the spirochetes to adhere to the host or the tick midgut or to evade the immune system. However, most of the spirochetal lipoproteins have unknown function. Herein, the immunomodulatory effects of spirochetal lipoproteins are reviewed and are grouped into two main categories: effects related to immune evasion and effects related to immune activation. Understanding lipoprotein-induced immunomodulation will aid in elucidating innate immunopathogenesis processes and subsequent adaptive mechanisms potentially relevant to spirochetal disease vaccine development and to inflammatory events associated with spirochetal diseases. PMID:25071771

  10. Historic evidence to support a causal relationship between spirochetal infections and Alzheimer’s disease

    PubMed Central

    Miklossy, Judith

    2015-01-01

    Following previous observations a statistically significant association between various types of spirochetes and Alzheimer’s disease (AD) fulfilled Hill’s criteria in favor of a causal relationship. If spirochetal infections can indeed cause AD, the pathological and biological hallmarks of AD should also occur in syphilitic dementia. To answer this question, observations and illustrations on the detection of spirochetes in the atrophic form of general paresis, which is known to be associated with slowly progressive dementia, were reviewed and compared with the characteristic pathology of AD. Historic observations and illustrations published in the first half of the 20th Century indeed confirm that the pathological hallmarks, which define AD, are also present in syphilitic dementia. Cortical spirochetal colonies are made up by innumerable tightly spiraled Treponema pallidum spirochetes, which are morphologically indistinguishable from senile plaques, using conventional light microscopy. Local brain amyloidosis also occurs in general paresis and, as in AD, corresponds to amyloid beta. These historic observations enable us to conclude that chronic spirochetal infections can cause dementia and reproduce the defining hallmarks of AD. They represent further evidence in support a causal relationship between various spirochetal infections and AD. They also indicate that local invasion of the brain by these helically shaped bacteria reproduce the filamentous pathology characteristic of AD. Chronic infection by spirochetes, and co-infection with other bacteria and viruses should be included in our current view on the etiology of AD. Prompt action is needed as AD might be prevented. PMID:25932012

  11. Cystitis induced by infection with the Lyme disease spirochete, Borrelia burgdorferi, in mice.

    PubMed Central

    Czub, S.; Duray, P. H.; Thomas, R. E.; Schwan, T. G.

    1992-01-01

    Previous studies have demonstrated that the urinary bladder is a consistent source for isolating the Lyme disease spirochete, Borrelia burgdorferi, from both experimentally infected and naturally exposed rodents. We examined histopathologic changes in the urinary bladder of different types of rodents experimentally infected with Lyme spirochetes, including BALB/c mice (Mus musculus), nude mice (M. musculus), white-footed mice (Peromyscus leucopus), and grasshopper mice (Onychomys leucogaster). Animals were inoculated intraperitoneally, subcutaneously, or intranasally with low-passaged spirochetes, high-passaged spirochetes, or phosphate-buffered saline. At various times after inoculation, animals were killed and approximately one-half of each urinary bladder and kidney were cultured separately in BSK-II medium while the other half of each organ was prepared for histologic examination. Spirochetes were cultured from the urinary bladder of all 35 mice inoculated with low-passaged spirochetes while we were unable to isolate spirochetes from any kidneys of the same mice. The pathologic changes observed most frequently in the urinary bladder of the infected mice were the presence of lymphoid aggregates, vascular changes, including an increase in the number of vessels and thickening of the vessel walls, and perivascular infiltrates. Our results demonstrate that nearly all individuals (93%) of the four types of mice examined had a cystitis associated with spirochetal infection. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:1443051

  12. Enhanced Adhesion and OspC Protein Synthesis of the Lyme Disease Spirochete Borrelia Burgdorferi Cultivated in a Host-Derived Tissue Co-Culture System

    PubMed Central

    Şen, Ece; Sigal, Leonard H.

    2013-01-01

    Background: The adhesion process of Borrelia burgdorferi to susceptible host cell has not yet been completely understood regarding the function of OspA, OspB and OspC proteins and a conflict exists in the infection process. Aims: The adhesion rates of pathogenic (low BSK medium passaged or susceptible rat joint tissue co-cultivated) or non-pathogenic Borrelia burgdorferi (high BSK medium passaged) isolate (FNJ) to human umbilical vein endothelial cells (HUVEC) cultured on coverslips and the synthesis of OspA and OspC proteins were investigated to analyze the infection process of this bacterium. Study Design: In-vitro study. Methods: Spirochetes were cultured in BSK medium or in a LEW/N rat tibiotarsal joint tissue feeder layer supported co-culture system using ESG co-culture medium and labelled with 3H-adenine for 48 hours. SDS-PAGE, Western Blotting, Immunogold A labeling as well as radiolabeling experiments were used to compare pathogenic or non pathogenic spirochetes during the adhesion process. Results: Tissue co-cultured B. burgdorferi adhered about ten times faster than BSK-grown spirochetes. Trypsin inhibited attachment to HUVEC and co-culture of trypsinized spirochetes with tissues reversed the inhibition. Also, the synthesis of OspC protein by spirochetes was increased in abundance after tissue co-cultures, as determined by SDS-PAGE and by electron microscopy analysis of protein A-immunogold staining by anti-OspC antibodies. OspA protein was synthesized in similar quantities in all Borrelia cultures analyzed by the same techniques. Conclusion: Low BSK passaged or tissue co-cultured pathogenic Lyme disease spirochetes adhere to HUVEC faster than non-pathogenic high BSK passaged forms of this bacterium. Spirochetes synthesized OspC protein during host tissue-associated growth. However, we did not observe a reduction of OspA synthesis during host tissue co-cultivation in vitro. PMID:25207103

  13. Lyme disease spirochetes in ticks from northeastern China.

    PubMed

    Takada, N; Ishiguro, F; Fujita, H; Wang, H P; Wang, J C; Masuzawa, T

    1998-06-01

    During May 1996, field surveys on Lyme disease spirochetes were conducted in Beijing, Shenyang, Fushun, and Inner Mongolia in northeastern China. The ticks collected consisted of 3 genera and 12 species. Of these, Ixodes persulcatus was dominant in sun-exposed vegetation in forests in Inner Mongolia; 57 Borrelia strains (55/123 unfed adults and 2/5 immature stages fed on a rodent) were obtained from this tick by BSK culture. Additionally, 2/2 Apodemus peninsulae were positive. Ixodes nipponensis, Ixodes pavlovskyi, Haemaphysalis douglasi, and Haemaphysalis megaspinosa, newly recorded in China, and other Haemaphysalis spp. were all negative for Borrelia. Based on a polymerase chain reaction restriction fragment length polymorphism analysis of the 45 strains successfully subcultured, these were classified as 29 Borrelia garinii and 16 Borrelia afelii. These strains seemed to be more closely related to Japanese strains in genetic features than to those from Europe. The result of sodium dodecyl sulfate-polyacrylamide gel electrophoresis suggested more diversity in both genospecies, but Borrelia burgdorferi sensu stricto was not found. PMID:9645846

  14. Interactions of phagocytes with the Lyme disease spirochete: role of the Fc receptor

    SciTech Connect

    Benach, J.L.; Fleit, H.B.; Habicht, G.S.; Coleman, J.L.; Bosler, E.M.; Lane, B.P.

    1984-10-01

    The phagocytic capacity of murine and human mononuclear and polymorphonuclear phagocytes (including peripheral blood monocytes and neutrophils), rabbit and murine peritoneal exudate cells, and the murine macrophage cell line P388D1 against the Lyme disease spirochete was studied. All of these cells were capable of phagocytosing the spirochete; phagocytosis was measured by the uptake of radiolabeled spirochetes, the appearance of immunofluorescent bodies in phagocytic cells, and electron microscopy. Both opsonized and nonopsonized organisms were phagocytosed. The uptake of opsonized organisms by neutrophils was blocked by a monoclonal antibody specific for the Fc receptor and by immune complexes; these findings suggested that most phagocytosis is mediated by the Fc receptor. Similarly, the uptake of opsonized organisms by human monocytes was inhibited by human monomeric IgG1 and by immune complexes. These results illustrate the role of immune phagocytosis of spirochetes in host defense against Lyme disease.

  15. Viscous Dynamics of Lyme Disease and Syphilis Spirochetes Reveal Flagellar Torque and Drag

    PubMed Central

    Harman, Michael; Vig, Dhruv K.; Radolf, Justin D.; Wolgemuth, Charles W.

    2013-01-01

    The spirochetes that cause Lyme disease (Borrelia burgdorferi) and syphilis (Treponema pallidum) swim through viscous fluids, such as blood and interstitial fluid, by undulating their bodies as traveling, planar waves. These undulations are driven by rotation of the flagella within the periplasmic space, the narrow (∼20–40 nm in width) compartment between the inner and outer membranes. We show here that the swimming speeds of B. burgdorferi and T. pallidum decrease with increases in viscosity of the external aqueous milieu, even though the flagella are entirely intracellular. We then use mathematical modeling to show that the measured changes in speed are consistent with the exertion of constant torque by the spirochetal flagellar motors. Comparison of simulations, experiments, and a simple model for power dissipation allows us to estimate the torque and resistive drag that act on the flagella of these major spirochetal pathogens. PMID:24268139

  16. Regulatory protein BBD18 of the lyme disease spirochete: essential role during tick acquisition?

    PubMed

    Hayes, Beth M; Dulebohn, Daniel P; Sarkar, Amit; Tilly, Kit; Bestor, Aaron; Ambroggio, Xavier; Rosa, Patricia A

    2014-01-01

    The Lyme disease spirochete Borrelia burgdorferi senses and responds to environmental cues as it transits between the tick vector and vertebrate host. Failure to properly adapt can block transmission of the spirochete and persistence in either vector or host. We previously identified BBD18, a novel plasmid-encoded protein of B. burgdorferi, as a putative repressor of the host-essential factor OspC. In this study, we investigate the in vivo role of BBD18 as a regulatory protein, using an experimental mouse-tick model system that closely resembles the natural infectious cycle of B. burgdorferi. We show that spirochetes that have been engineered to constitutively produce BBD18 can colonize and persist in ticks but do not infect mice when introduced by either tick bite or needle inoculation. Conversely, spirochetes lacking BBD18 can persistently infect mice but are not acquired by feeding ticks. Through site-directed mutagenesis, we have demonstrated that abrogation of spirochete infection in mice by overexpression of BBD18 occurs only with bbd18 alleles that can suppress OspC synthesis. Finally, we demonstrate that BBD18-mediated regulation does not utilize a previously described ospC operator sequence required by B. burgdorferi for persistence in immunocompetent mice. These data lead us to conclude that BBD18 does not represent the putative repressor utilized by B. burgdorferi for the specific downregulation of OspC in the mammalian host. Rather, we suggest that BBD18 exhibits features more consistent with those of a global regulatory protein whose critical role occurs during spirochete acquisition by feeding ticks. IMPORTANCE Lyme disease, caused by Borrelia burgdorferi, is the most common arthropod-borne disease in North America. B. burgdorferi is transmitted to humans and other vertebrate hosts by ticks as they take a blood meal. Transmission between vectors and hosts requires the bacterium to sense changes in the environment and adapt. However, the mechanisms

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

    PubMed

    Salkeld, Daniel J; Lane, Robert S

    2010-01-01

    Vector-borne zoonotic diseases are often maintained in complex transmission cycles involving multiple vertebrate hosts and their arthropod vectors. In the state of California, U.S.A., the spirochete Borrelia burgdorferi, which causes Lyme disease, is transmitted between vertebrate hosts by the western black-legged tick, Ixodes pacificus. Several mammalian species serve as reservoir hosts of the spirochete, but levels of tick infestation, reservoir competence, and Borrelia-infection prevalence vary widely among such hosts. Here, we model the host (lizards, Peromyscus mice, Californian meadow voles, dusky-footed wood rats, and western gray squirrels), vector, and pathogen community of oak woodlands in northwestern California to determine the relative importance of different tick hosts. Observed infection prevalence of B. burgdorferi in host-seeking I. pacificus nymphs was 1.8-5.3%, and our host-community model estimated an infection prevalence of 1.6-2.2%. The western gray squirrel (Sciurus griseus) was the only source of infected nymphs. Lizards, which are refractory to Borrelia infection, are important in feeding subadult ticks but reduce disease risk (nymphal infection prevalence). Species identity is therefore critical in understanding and determining the local disease ecology. PMID:20380218

  18. Absence of transplacental transmission of Lyme disease spirochetes from reservoir mice (Peromyscus leucopus) to their offspring.

    PubMed

    Mather, T N; Telford, S R; Adler, G H

    1991-09-01

    Lyme disease spirochetes (Borrelia burgdorferi) are naturally maintained in an enzootic cycle mainly by vector ticks (Ixodes dammini) infesting white-footed mice (Peromyscus leucopus). Suggestions that mice may become infected without exposure to ticks prompted a study to evaluate whether mice could transmit spirochetes transplacentally to their offspring. Mice were live-captured in two Massachusetts sites where Lyme disease spirochetes are intensely enzootic. Pregnant females were housed separately in the laboratory through delivery, and mothers and their offspring were caged together until weaning. Each female and two offspring were then examined for evidence of infection serologically and by tick xenodiagnosis. All 14 mother mice examined produced infected ticks and exhibited serum antibodies to B. burgdorferi. However, none of 28 offspring tested produced infected ticks and only a few had evidence of circulating antibody. In a separate experiment, no young CD-1 mice, born of infected mothers, had IgM antibody to B. burgdorferi. It would appear that immature mice are not transplacentally infected with spirochetes and must be exposed to infected ticks before becoming infected and infective themselves. PMID:1869842

  19. Population Bottlenecks during the Infectious Cycle of the Lyme Disease Spirochete Borrelia burgdorferi

    PubMed Central

    Rego, Ryan O. M.; Bestor, Aaron; Štefka, Jan; Rosa, Patricia A.

    2014-01-01

    Borrelia burgdorferi is a zoonotic pathogen whose maintenance in nature depends upon an infectious cycle that alternates between a tick vector and mammalian hosts. Lyme disease in humans results from transmission of B. burgdorferi by the bite of an infected tick. The population dynamics of B. burgdorferi throughout its natural infectious cycle are not well understood. We addressed this topic by assessing the colonization, dissemination and persistence of B. burgdorferi within and between the disparate mammalian and tick environments. To follow bacterial populations during infection, we generated seven isogenic but distinguishable B. burgdorferi clones, each with a unique sequence tag. These tags resulted in no phenotypic changes relative to wild type organisms, yet permitted highly sensitive and specific detection of individual clones by PCR. We followed the composition of the spirochete population throughout an experimental infectious cycle that was initiated with a mixed inoculum of all clones. We observed heterogeneity in the spirochete population disseminating within mice at very early time points, but all clones displayed the ability to colonize most mouse tissues by 3 weeks of infection. The complexity of clones subsequently declined as murine infection persisted. Larval ticks typically acquired a reduced and variable number of clones relative to what was present in infected mice at the time of tick feeding, and maintained the same spirochete population through the molt to nymphs. However, only a random subset of infectious spirochetes was transmitted to naïve mice when these ticks next fed. Our results clearly demonstrate that the spirochete population experiences stochastic bottlenecks during both acquisition and transmission by the tick vector, as well as during persistent infection of its murine host. The experimental system that we have developed can be used to further explore the forces that shape the population of this vector-borne bacterial pathogen

  20. Gut Microbiota of the Tick Vector Ixodes scapularis Modulate Colonization of the Lyme Disease Spirochete

    PubMed Central

    Narasimhan, Sukanya; Rajeevan, Nallakkandi; Liu, Lei; Zhao, Yang O.; Heisig, Julia; Pan, Jingyi; Eppler-Epstein, Rebecca; DePonte, Kathleen; Fish, Durland; Fikrig, Erol

    2014-01-01

    SUMMARY Arthopods, such as Ixodes ticks, serve as vectors for many human pathogens. The arthropod gut presents a pivotal microbial entry point and determines pathogen colonization and survival. We show that the gut microbiota of Ixodes scapularis, a major vector of the Lyme disease spirochete Borrelia burgdorferi, influence spirochete colonization of ticks. Perturbing the gut microbiota of larval ticks reduced Borrelia colonization, with dysbiosed larvae displaying decreased expression of the transcription factor STAT. Diminished STAT expression corresponded to lower expression of peritrophin, a key glycoprotein scaffold of the glycan-rich mucus-like peritrophic matrix (PM) that separates the gut lumen from the epithelium. The integrity of the I. scapularis PM was essential for B. burgdorferi to efficiently colonize the gut epithelium. These data elucidate a functional link between the gut microbiota, STAT-signaling, and pathogen colonization in the context of the gut epithelial barrier of an arthropod vector. PMID:24439898

  1. Fibronectin Binding Protein BBK32 of the Lyme Disease Spirochete Promotes Bacterial Attachment to Glycosaminoglycans

    PubMed Central

    Fischer, Joshua R.; LeBlanc, Kimberly T.; Leong, John M.

    2006-01-01

    Borrelia burgdorferi, the agent of Lyme disease, causes a multisystemic illness that can affect the skin, heart, joints, and nervous system and is capable of attachment to diverse cell types. Among the host components recognized by this spirochete are fibronectin and glycosaminoglycans (GAGs). Three surface-localized GAG-binding bacterial ligands, Bgp, DbpA, and DbpB, have been previously identified, but recent studies suggested that at least one additional GAG-binding ligand is expressed on the spirochetal surface when the spirochete is adapted to the mammalian host environment. BBK32 is a surface lipoprotein that is produced during infection and that has been shown to bind to fibronectin. In this study, we show that, when BBK32 was produced from a shuttle vector in an otherwise nonadherent high-passage B. burgdorferi strain, the protein localized on the bacterial surface and conferred attachment to fibronectin and to mammalian cell monolayers. In addition, the high-passage strain producing BBK32 bound to purified preparations of the GAGs dermatan sulfate and heparin, as well as to these GAGs on the surfaces of cultured mammalian cells. Recombinant BBK32 recognized purified heparin, indicating that the bacterial attachment to GAGs was due to direct binding by BBK32. This GAG-binding activity of BBK32 is apparently independent of fibronectin recognition, because exogenous heparin had no effect on BBK32-mediated bacterial binding to fibronectin. PMID:16368999

  2. Distribution and molecular analysis of Lyme disease spirochetes, Borrelia burgdorferi, isolated from ticks throughout California.

    PubMed Central

    Schwan, T G; Schrumpf, M E; Karstens, R H; Clover, J R; Wong, J; Daugherty, M; Struthers, M; Rosa, P A

    1993-01-01

    Previous studies describing the occurrence and molecular characteristics of Lyme disease spirochetes, Borrelia burgdorferi, from California have been restricted primarily to isolates obtained from the north coastal region of this large and ecologically diverse state. Our objective was to look for and examine B. burdorferi organisms isolated from Ixodes pacificus ticks collected from numerous regions spanning most parts of California where this tick is found. Thirty-one isolates of B. burgdorferi were examined from individual or pooled I. pacificus ticks collected from 25 counties throughout the state. One isolate was obtained from ticks collected at Wawona Campground in Yosemite National Park, documenting the occurrence of the Lyme disease spirochete in an area of intensive human recreational use. One isolate from an Ixodes neotomae tick from an additional county was also examined. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis, immunoblot analysis, agarose gel electrophoresis, Southern blot analysis, and the polymerase chain reaction were used to examine the molecular and genetic determinants of these uncloned, low-passage-number isolates. All of the isolates were identified as B. burgdorferi by their protein profiles and reactivities with monoclonal and polyclonal antibodies, and all the isolates were typed by the polymerase chain reaction as North American-type spirochetes (B. burgdorferi sensu stricto). Although products of the ospAB locus were identified in protein analyses in all of the isolates, several isolates contained deleted forms of this locus that would result in the expression of chimeric OspA-OspB proteins. The analysis of OspC demonstrated that this protein was widely conserved among the isolates but was also quite variable in its molecular mass and the amount of it that was expressed. Images PMID:8308101

  3. Hypothetical Protein BB0569 Is Essential for Chemotaxis of the Lyme Disease Spirochete Borrelia burgdorferi

    PubMed Central

    Zhang, Kai; Liu, Jun; Charon, Nyles W.

    2015-01-01

    ABSTRACT The Lyme disease spirochete Borrelia burgdorferi has five putative methyl-accepting chemotaxis proteins (MCPs). In this report, we provide evidence that a hypothetical protein, BB0569, is essential for the chemotaxis of B. burgdorferi. While BB0569 lacks significant homology to the canonical MCPs, it contains a conserved domain (spanning residues 110 to 170) that is often evident in membrane-bound MCPs such as Tar and Tsr of Escherichia coli. Unlike Tar and Tsr, BB0569 lacks transmembrane regions and recognizable HAMP and methylation domains and is similar to TlpC, a cytoplasmic chemoreceptor of Rhodobacter sphaeroides. An isogenic mutant of BB0569 constantly runs in one direction and fails to respond to attractants, indicating that BB0569 is essential for chemotaxis. Immunofluorescence, green fluorescent protein (GFP) fusion, and cryo-electron tomography analyses demonstrate that BB0569 localizes at the cell poles and is required for chemoreceptor clustering at the cell poles. Protein cross-linking studies reveal that BB0569 forms large protein complexes with MCP3, indicative of its interactions with other MCPs. Interestingly, analysis of B. burgdorferi mcp mutants shows that inactivation of either mcp2 or mcp3 reduces the level of BB0569 substantially and that such a reduction is caused by protein turnover. Collectively, these results demonstrate that the domain composition and function of BB0569 are similar in some respects to those of TlpC but that these proteins are different in their cellular locations, further highlighting that the chemotaxis of B. burgdorferi is unique and different from the Escherichia coli and Salmonella enterica paradigm. IMPORTANCE Spirochete chemotaxis differs substantially from the Escherichia coli and Salmonella enterica paradigm, and the basis for controlling the rotation of the bundles of periplasmic flagella at each end of the cell is unknown. In recent years, Borrelia burgdorferi, the causative agent of Lyme disease, has

  4. Archaeal-type lysyl-tRNA synthetase in the Lyme disease spirochete Borrelia burgdorferi

    PubMed Central

    Ibba, Michael; Bono, James L.; Rosa, Patricia A.; Söll, Dieter

    1997-01-01

    Lysyl-tRNAs are essential for protein biosynthesis by ribosomal mRNA translation in all organisms. They are synthesized by lysyl-tRNA synthetases (EC 6.1.1.6), a group of enzymes composed of two unrelated families. In bacteria and eukarya, all known lysyl-tRNA synthetases are subclass IIc-type aminoacyl-tRNA synthetases, whereas some archaea have been shown to contain an unrelated class I-type lysyl-tRNA synthetase. Examination of the preliminary genomic sequence of the bacterial pathogen Borrelia burgdorferi, the causative agent of Lyme disease, indicated the presence of an open reading frame with over 55% similarity at the amino acid level to archaeal class I-type lysyl-tRNA synthetases. In contrast, no coding region with significant similarity to any class II-type lysyl-tRNA synthetase could be detected. Heterologous expression of this open reading frame in Escherichia coli led to the production of a protein with canonical lysyl-tRNA synthetase activity in vitro. Analysis of B. burgdorferi mRNA showed that the lysyl-tRNA synthetase-encoding gene is highly expressed, confirming that B. burgdorferi contains a functional class I-type lysyl-tRNA synthetase. The detection of an archaeal-type lysyl-tRNA synthetase in B. burgdorferi and other pathogenic spirochetes, but not to date elsewhere in bacteria or eukarya, indicates that the gene that encodes this enzyme has a common origin with its orthologue from the archaeal kingdom. This difference between the lysyl-tRNA synthetases of spirochetes and their hosts may be readily exploitable for the development of anti-spirochete therapeutics. PMID:9405621

  5. Host cell heparan sulfate glycosaminoglycans are ligands for OspF-related proteins of the Lyme disease spirochete.

    PubMed

    Lin, Yi-Pin; Bhowmick, Rudra; Coburn, Jenifer; Leong, John M

    2015-10-01

    Borrelia burgdorferi, the agent of Lyme disease, spreads from the site of the tick bite to tissues such as heart, joints and the nervous tissues. Host glycosaminoglycans, highly modified repeating disaccharides that are present on cell surfaces and in extracellular matrix, are common targets of microbial pathogens during tissue colonization. While several dermatan sulfate-binding B. burgdorferi adhesins have been identified, B. burgdorferi adhesins documented to promote spirochetal binding to heparan sulfate have not yet been identified. OspEF-related proteins (Erps), a large family of plasmid-encoded surface lipoproteins that are produced in the mammalian host, can be divided into the OspF-related, OspEF-leader peptide (Elp) and OspE-related subfamilies. We show here that a member of the OspF-related subfamily, ErpG, binds to heparan sulfate and when produced on the surface of an otherwise non-adherent B. burgdorferi strain, ErpG promotes heparan sulfate-mediated bacterial attachment to the glial but not the endothelial, synovial or respiratory epithelial cells. Six other OspF-related proteins were capable of binding heparan sulfate, whereas representative OspE-related and Elp proteins lacked this activity. These results indicate that OspF-related proteins are heparan sulfate-binding adhesins, at least one of which promotes bacterial attachment to glial cells. PMID:25864455

  6. Pathological manifestations in murine Lyme disease: association with tissue invasion and spirochete persistence.

    PubMed

    Weis, J J; Yang, L; Seiler, K P; Silver, R M

    1997-07-01

    The clinical manifestations of human Lyme disease present with a spectrum of tissue or organ involvement and severity of symptoms. The murine model of Lyme disease has proved to be an accurate reflection of many of the human symptoms of disease and has been particularly useful for studying development of subacute arthritis and tendonitis. Direct tissue invasion by Borrelia burgdorferi and persistence of high levels of spirochetes in tissues are important components of arthritis development. The outer-surface lipoproteins contain a biologically active lipid-modified moiety with potent ability to stimulate inflammatory cytokine production and other inflammatory mediators such as nitric oxide. Localized inflammation stimulated by these lipoproteins may be the trigger for neutrophil infiltration, synovial proliferation, and other events associated with this arthritis. Invasion of maternal uterine tissue, but not direct invasion of fetal tissue, is associated with low levels of pregnancy loss in mice infected during gestation, consistent with the detrimental effect of inflammatory cytokines on pregnancy. PMID:9233659

  7. Reservoir competence of Microtus pennsylvanicus (Rodentia: Cricetidae) for the Lyme disease spirochete, Borrelia burgdorferi

    USGS Publications Warehouse

    Markowski, D.; Ginsberg, H.S.; Hyland, K.E.; Hu, R.

    1998-01-01

    The reservoir competence of the meadow vole, Microtus pennsylvanicus Ord, for the Lyme disease spirochete, Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner was established on Patience Island, RI. Meadow voles were collected from 5 locations throughout Rhode Island. At 4 of the field sites, M. pennsylvanicus represented only 4.0% (n = 141) of the animals captured. However, on Patience Island, M. pennsylvanicus was the sole small mammal collected (n = 48). Of the larval Ixodes scapularis Say obtained from the meadow voles on Patience Island, 62% (n = 78) was infected with B. burgdorferi. Meadow voles from all 5 locations were successfully infected with B. burgdorferi in the laboratory and were capable of passing the infection to xenodiagnostic I. scapularis larvae for 9 wk. We concluded that M. pennsylvanicus was physiologically capable of maintaining B. burgdorferi infection. However, in locations where Peromyscus leucopus (Rafinesque) is abundant, the role of M. pennsylvanicus as a primary reservoir for B. burgdorferi was reduced.

  8. Ability of experimentally infected chickens to infect ticks with the Lyme disease spirochete, Borrelia burgdorferi.

    PubMed

    Piesman, J; Dolan, M C; Schriefer, M E; Burkot, T R

    1996-03-01

    Chickens were used as a laboratory model to determine the conditions affecting the ability of birds to infect ticks with Lyme disease spirochetes. Chicks (Gallus gallus) were exposed to 12 nymphal Ixodes scapularis at one week or three weeks of age. Xenodiagnostic larval ticks fed these birds at weekly intervals thereafter. Chicks exposed to infected nymphs at one week of age infected 87% of larvae at three weeks of age, but only infected 3% of larvae at four weeks and 0% of larvae at five weeks. Chicks exposed to nymphs at three weeks of age infected only 12% of larvae at four weeks, and 0% thereafter. Thus, experimentally infected chicks can infect larval ticks, but only for a brief interval after exposure. Young chicks are more infectious than older chickens. The immune response of infected chicks was rapid and directed against diverse antigens. PMID:8600769

  9. Susceptibility to Ticks and Lyme Disease Spirochetes Is Not Affected in Mice Coinfected with Nematodes

    PubMed Central

    Maaz, Denny; Rausch, Sebastian; Richter, Dania; Krücken, Jürgen; Kühl, Anja A.; Demeler, Janina; Blümke, Julia; Matuschka, Franz-Rainer; von Samson-Himmelstjerna, Georg

    2016-01-01

    Small rodents serve as reservoir hosts for tick-borne pathogens, such as the spirochetes causing Lyme disease. Whether natural coinfections with other macroparasites alter the success of tick feeding, antitick immunity, and the host's reservoir competence for tick-borne pathogens remains to be determined. In a parasitological survey of wild mice in Berlin, Germany, approximately 40% of Ixodes ricinus-infested animals simultaneously harbored a nematode of the genus Heligmosomoides. We therefore aimed to analyze the immunological impact of the nematode/tick coinfection as well as its effect on the tick-borne pathogen Borrelia afzelii. Hosts experimentally coinfected with Heligmosomoides polygyrus and larval/nymphal I. ricinus ticks developed substantially stronger systemic type 2 T helper cell (Th2) responses, on the basis of the levels of GATA-3 and interleukin-13 expression, than mice infected with a single pathogen. During repeated larval infestations, however, anti-tick Th2 reactivity and an observed partial immunity to tick feeding were unaffected by concurrent nematode infections. Importantly, the strong systemic Th2 immune response in coinfected mice did not affect susceptibility to tick-borne B. afzelii. An observed trend for decreased local and systemic Th1 reactivity against B. afzelii in coinfected mice did not result in a higher spirochete burden, nor did it facilitate bacterial dissemination or induce signs of immunopathology. Hence, this study indicates that strong systemic Th2 responses in nematode/tick-coinfected house mice do not affect the success of tick feeding and the control of the causative agent of Lyme disease. PMID:26883594

  10. Susceptibility to Ticks and Lyme Disease Spirochetes Is Not Affected in Mice Coinfected with Nematodes.

    PubMed

    Maaz, Denny; Rausch, Sebastian; Richter, Dania; Krücken, Jürgen; Kühl, Anja A; Demeler, Janina; Blümke, Julia; Matuschka, Franz-Rainer; von Samson-Himmelstjerna, Georg; Hartmann, Susanne

    2016-05-01

    Small rodents serve as reservoir hosts for tick-borne pathogens, such as the spirochetes causing Lyme disease. Whether natural coinfections with other macroparasites alter the success of tick feeding, antitick immunity, and the host's reservoir competence for tick-borne pathogens remains to be determined. In a parasitological survey of wild mice in Berlin, Germany, approximately 40% of Ixodes ricinus-infested animals simultaneously harbored a nematode of the genus Heligmosomoides We therefore aimed to analyze the immunological impact of the nematode/tick coinfection as well as its effect on the tick-borne pathogen Borrelia afzelii Hosts experimentally coinfected with Heligmosomoides polygyrus and larval/nymphal I. ricinus ticks developed substantially stronger systemic type 2 T helper cell (Th2) responses, on the basis of the levels of GATA-3 and interleukin-13 expression, than mice infected with a single pathogen. During repeated larval infestations, however, anti-tick Th2 reactivity and an observed partial immunity to tick feeding were unaffected by concurrent nematode infections. Importantly, the strong systemic Th2 immune response in coinfected mice did not affect susceptibility to tick-borne B. afzelii An observed trend for decreased local and systemic Th1 reactivity against B. afzelii in coinfected mice did not result in a higher spirochete burden, nor did it facilitate bacterial dissemination or induce signs of immunopathology. Hence, this study indicates that strong systemic Th2 responses in nematode/tick-coinfected house mice do not affect the success of tick feeding and the control of the causative agent of Lyme disease. PMID:26883594

  11. Characterization of outer membranes isolated from Borrelia burgdorferi, the Lyme disease spirochete.

    PubMed Central

    Radolf, J D; Goldberg, M S; Bourell, K; Baker, S I; Jones, J D; Norgard, M V

    1995-01-01

    The lack of methods for isolating Borrelia burgdorferi outer membranes (OMs) has hindered efforts to characterize borrelial surface-exposed proteins. Here we isolated OMs by immersion of motile spirochetes in hypertonic sucrose followed by isopycnic ultracentrifugation of the plasmolyzed cells. The unilamellar vesicles thus obtained were shown to be OMs by the following criteria: (i) they contained OspA and OspB; (ii) they did not contain flagellin, NADH oxidase activity, or the 60-kDa heat shock protein; and (iii) their morphology by freeze-fracture electron microscopy was identical to that of OMs of intact organisms. Consistent with previous studies which employed immunoelectron microscopy and detergent-based solubilization of B. burgdorferi OMs, only small proportions of the total cellular content of OspA or OspB were OM associated. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) fluorography of OMs from spirochetes metabolically radiolabeled with [3H]palmitate or 35S-amino acids demonstrated that the OMs contained both nonlipidated and lipidated proteins. This fractionation procedure was also used to isolate OMs from virulent and avirulent isolates of the well-characterized B. burgdorferi N40 strain. SDS-PAGE fluorography revealed that OMs from the two isolates differed with respect to both nonlipoprotein and lipoprotein constituents. When whole cells, protoplasmic cylinders, and OMs were immunoblotted against sera from mice persistently infected with B. burgdorferi N40, the majority of antibody reactivity was directed against intracellular proteins. The availability of isolated OMs should facilitate efforts to elucidate the complex relationship(s) between B. burgdorferi membrane composition and Lyme disease pathogenesis. PMID:7768594

  12. Identification and function of the RNA chaperone Hfq in the Lyme disease spirochete Borrelia burgdorferi

    PubMed Central

    Lybecker, Meghan C.; Abel, Cassandra A.; Feig, Andrew L.; Samuels, D. Scott

    2010-01-01

    Summary Hfq is a global regulatory RNA-binding protein. We have identified and characterized an atypical Hfq required for gene regulation and infectivity in the Lyme disease spirochete Borrelia burgdorferi. Sequence analyses of the putative B. burgdorferi Hfq protein revealed only a modest level of similarity with the Hfq from Escherichia coli, although a few key residues are retained and the predicted tertiary structure is similar. Several lines of evidence suggest that the B. burgdorferi bb0268 gene encodes a functional Hfq homolog. First, the hfqBb gene (bb0268) restores the efficient translation of an rpoS::lacZ fusion in an E. coli hfq null mutant. Second, the Hfq from B. burgdorferi binds to the small RNA DsrABb and the rpoS mRNA. Third, a B. burgdorferi hfq null mutant was generated and has a pleiotropic phenotype that includes increased cell length and decreased growth rate, as found in hfq mutants in other bacteria. The hfqBb mutant phenotype is complemented in trans with the hfq gene from either B. burgdorferi or, surprisingly, E. coli. This is the first example of a heterologous bacterial gene complementing a B. burgdorferi mutant. The alternative sigma factor RpoS and the outer membrane lipoprotein OspC, which are induced by increased temperature and required for mammalian infection, are not upregulated in the hfq mutant. Consequently, the hfq mutant is not infectious by needle inoculation in the murine model. These data suggest that Hfq plays a key role in the regulation of pathogenicity factors in B. burgdorferi and we hypothesize that the spirochete has a complex Hfq-dependent sRNA network. PMID:20815822

  13. Medication Adherence in People With Parkinson Disease.

    PubMed

    Shin, Ju Young; Habermann, Barbara

    2016-01-01

    Parkinson disease (PD) is the second most common neurodegenerative disorder in the United States. Because there is no cure for PD currently, pharmacological therapy is the mainstay of PD symptom management. Despite the importance of medication adherence in PD, several studies have reported medication nonadherence and/or suboptimal adherence. This literature review provides an overview of medication adherence issues in people with PD. Articles were identified for this study using computerized database searches and journal hand searches. Of the 72 medication adherence articles reviewed, the following articles were eligible for this review: (a) 10 articles measuring medication adherence in people with PD, (b) four medication adherence intervention articles, and (c) six studies of medication adherence in hospitalized settings. The importance of adherence assessment and strategies in improving medication adherence are discussed with the goal of improving symptom management and clinical outcomes in people with PD. Because medication taking is a complex and multifaceted phenomena, patient-centered, theory-driven interventions are needed to improve medication adherence and quality of care and life in people with PD. PMID:27224682

  14. Filament formation associated with spirochetal infection: a comparative approach to Morgellons disease

    PubMed Central

    Middelveen, Marianne J; Stricker, Raphael B

    2011-01-01

    Bovine digital dermatitis is an emerging infectious disease that causes lameness, decreased milk production, and weight loss in livestock. Proliferative stages of bovine digital dermatitis demonstrate keratin filament formation in skin above the hooves in affected animals. The multifactorial etiology of digital dermatitis is not well understood, but spirochetes and other coinfecting microorganisms have been implicated in the pathogenesis of this veterinary illness. Morgellons disease is an emerging human dermopathy characterized by the presence of filamentous fibers of undetermined composition, both in lesions and subdermally. While the etiology of Morgellons disease is unknown, there is serological and clinical evidence linking this phenomenon to Lyme borreliosis and coinfecting tick-borne agents. Although the microscopy of Morgellons filaments has been described in the medical literature, the structure and pathogenesis of these fibers is poorly understood. In contrast, most microscopy of digital dermatitis has focused on associated pathogens and histology rather than the morphology of late-stage filamentous fibers. Clinical, laboratory, and microscopic characteristics of these two diseases are compared. PMID:22253541

  15. Filament formation associated with spirochetal infection: a comparative approach to Morgellons disease.

    PubMed

    Middelveen, Marianne J; Stricker, Raphael B

    2011-01-01

    Bovine digital dermatitis is an emerging infectious disease that causes lameness, decreased milk production, and weight loss in livestock. Proliferative stages of bovine digital dermatitis demonstrate keratin filament formation in skin above the hooves in affected animals. The multifactorial etiology of digital dermatitis is not well understood, but spirochetes and other coinfecting microorganisms have been implicated in the pathogenesis of this veterinary illness. Morgellons disease is an emerging human dermopathy characterized by the presence of filamentous fibers of undetermined composition, both in lesions and subdermally. While the etiology of Morgellons disease is unknown, there is serological and clinical evidence linking this phenomenon to Lyme borreliosis and coinfecting tick-borne agents. Although the microscopy of Morgellons filaments has been described in the medical literature, the structure and pathogenesis of these fibers is poorly understood. In contrast, most microscopy of digital dermatitis has focused on associated pathogens and histology rather than the morphology of late-stage filamentous fibers. Clinical, laboratory, and microscopic characteristics of these two diseases are compared. PMID:22253541

  16. Temporal Changes in Outer Surface Proteins A and C of the Lyme Disease-Associated Spirochete, Borrelia burgdorferi, during the Chain of Infection in Ticks and Mice

    PubMed Central

    Schwan, Tom G.; Piesman, Joseph

    2000-01-01

    The Lyme disease-associated spirochete, Borrelia burgdorferi, is maintained in enzootic cycles involving Ixodes ticks and small mammals. Previous studies demonstrated that B. burgdorferi expresses outer surface protein A (OspA) but not OspC when residing in the midgut of unfed ticks. However, after ticks feed on blood, some spirochetes stop making OspA and express OspC. Our current work examined the timing and frequency of OspA and OspC expression by B. burgdorferi in infected Ixodes scapularis nymphs as they fed on uninfected mice and in uninfected I. scapularis larvae and nymphs as they first acquired spirochetes from infected mice. Smears of midguts from previously infected ticks were prepared at 12- or 24-h intervals following attachment through repletion at 96 h, and spirochetes were stained for immunofluorescence for detection of antibodies to OspA and OspC. As shown previously, prior to feeding spirochetes in nymphs expressed OspA but not OspC. During nymphal feeding, however, the proportion of spirochetes expressing OspA decreased, while spirochetes expressing OspC became detectable. In fact, spirochetes rapidly began to express OspC, with the greatest proportion of spirochetes having this protein at 48 h of attachment and then with the proportion decreasing significantly by the time that the ticks had completed feeding. In vitro cultivation of the spirochete at different temperatures showed OspC to be most abundant when the spirochetes were grown at 37°C. Yet, the synthesis of this protein waned with continuous passage at this temperature. Immunofluorescence staining of spirochetes in smears of midguts from larvae and nymphs still attached or having completed feeding on infected mice demonstrated that OspA but not OspC was produced by these spirochetes recently acquired from mice. Therefore, the temporal synthesis of OspC by spirochetes only in feeding ticks that were infected prior to the blood meal suggests that this surface protein is involved in

  17. Intestinal spirochete infections of chickens: a review of disease associations, epidemiology and control.

    PubMed

    Stephens, C P; Hampson, D J

    2001-06-01

    This paper presents an overview of intestinal spirochete infections of chickens. It focuses particularly on studies in Australia, where recent surveys of 136 layer and broiler breeder flocks have revealed a high rate of infection (>40%) with intestinal spirochetes. Infection was not detected in broiler flocks. Approximately 50% of isolates from infected flocks were Brachyspira (Serpulina) intermedia or B. pilosicoli, with the other isolates being B. innocens, B. murdochii or the proposed species 'B. pulli'. No isolates of B. alvinipulli were found. Intestinal spirochetes were significantly associated with wet litter problems and/or reduced egg production. Experimental infection of point-of-lay birds with either B. intermedia or B. pilosicoli caused reduced egg production, and, with B. intermedia, a significant increase in fecal moisture content. Infection with B. innocens caused no significant changes. In-water treatment of a flock with a mixed spirochete infection using lincospectin resulted in a slimy diarrhea lasting for 2-3 weeks, followed by absence of spirochetes for 3 months. Birds treated with tiamulin remained healthy, and had a reduced level of infection with intestinal spirochetes (30%) for 3 months. Trials are under way to test the efficacy of antimicrobials in point-of-lay chickens experimentally infected with either B. intermedia or B. pilosicoli. PMID:11708751

  18. CSM murray award lecture - functional studies of the Lyme disease spirochete - from molecules to mice.

    PubMed

    Chaconas, George

    2012-03-01

    Lyme borreliosis, also known as Lyme disease, is now the most common vector transmitted disease in the northern hemisphere. It is caused by the spirochete Borrelia burgdorferi and related species. In addition to their clinical importance, these organisms are fascinating to study because of the wide variety of unusual features they possess. Ongoing work in the laboratory in several areas will be described. (1) The segmented genomes contain up to two dozen genetic elements, the majority of which are linear with covalently closed hairpin ends. These linear DNAs also display a very high degree of ongoing genetic rearrangement. Mechanisms for these processes will be described. (2) Persistent infection by Borrelia species requires antigenic variation through a complex DNA rearrangement process at the vlsE locus on the linear plasmid lp28-1. Novel features of this recombination process will be presented. (3) Evidence for a new global regulatory pathway of B. burgdorferi gene expression that is required for pathogenicity will be described. The DEAH box RNA helicase HrpA is involved in this pathway, which may be relevant in other bacteria. (4) The mechanism of B. burgdorferi to effectively disseminate throughout its host is being studied in real time by high resolution intravital imaging in live mice. Recent work will be presented. PMID:22339274

  19. The cyclic-di-GMP signaling pathway in the Lyme disease spirochete, Borrelia burgdorferi

    PubMed Central

    Novak, Elizabeth A.; Sultan, Syed Z.; Motaleb, Md. A.

    2014-01-01

    In nature, the Lyme disease spirochete Borrelia burgdorferi cycles between the unrelated environments of the Ixodes tick vector and mammalian host. In order to survive transmission between hosts, B. burgdorferi must be able to not only detect changes in its environment, but also rapidly and appropriately respond to these changes. One manner in which this obligate parasite regulates and adapts to its changing environment is through cyclic-di-GMP (c-di-GMP) signaling. c-di-GMP has been shown to be instrumental in orchestrating the adaptation of B. burgdorferi to the tick environment. B. burgdorferi possesses only one set of c-di-GMP-metabolizing genes (one diguanylate cyclase and two distinct phosphodiesterases) and one c-di-GMP-binding PilZ-domain protein designated as PlzA. While studies in the realm of c-di-GMP signaling in B. burgdorferi have exploded in the last few years, there are still many more questions than answers. Elucidation of the importance of c-di-GMP signaling to B. burgdorferi may lead to the identification of mechanisms that are critical for the survival of B. burgdorferi in the tick phase of the enzootic cycle as well as potentially delineate a role (if any) c-di-GMP may play in the transmission and virulence of B. burgdorferi during the enzootic cycle, thereby enabling the development of effective drugs for the prevention and/or treatment of Lyme disease. PMID:24822172

  20. Outer Surface Protein A Protects Lyme Disease Spirochetes from Acquired Host Immunity in the Tick Vector▿

    PubMed Central

    Battisti, James M.; Bono, James L.; Rosa, Patricia A.; Schrumpf, Merry E.; Schwan, Tom G.; Policastro, Paul F.

    2008-01-01

    The Lyme disease spirochete Borrelia burgdorferi alters the expression of outer surface protein (osp) genes as the bacterium cycles between ticks and mammals. OspA is produced as borreliae enter the tick vector and remains a major surface antigen during midgut colonization. To elucidate the role of OspA in the vector, we created an insertional deletion of ospA in strain B31-A3. The ospA mutant infects mice when it is injected intradermally and is acquired by larval ticks fed on these mice, where it persists through the molt to the nymph stage. Bacterial survival rates in artificially infected tick larvae fed on naïve mice were compared with those in the vector fed on immune mice. The ospA mutant proliferates in larvae if it is exposed to blood from naïve mice, but it declines in density after larval feeding if the blood is from immune mice. When uninfected larvae are fed on B-cell-deficient mice infected with the ospA mutant, larvae show borrelial densities and persistence that are significantly greater than those fed on infected, immunocompetent mice. We conclude that OspA serves a critical antibody-shielding role during vector blood meal uptake from immune hosts and is not required for persistence in the tick vector. PMID:18779341

  1. Reservoir competence of native North American birds for the Lyme disease spirochete, Borrelia burgdorferi

    USGS Publications Warehouse

    Ginsberg, H.S.; Buckley, P.A.; Balmforth, M.G.; Zhioua, E.; Mitra, Siddhartha; Buckley, F.G.

    2005-01-01

    Reservoir competence of the Lyme disease spirochete, Borrelia burgdorferi, was tested for six species of native North American birds: American Robin, Gray Catbird, Brown Thrasher, Eastern Towhee, Song Sparrow, and Northern Cardinal. Wild birds collected by mistnetting on Fire Island, NY, were held in a field lab in cages over water, and locally collected larval ticks were placed on the birds, harvested from the water after engorgement, and tested for infection by DFA after molting to the nymphal stage. American Robins were competent reservoirs, infecting 16.1% of larvae applied to wild-caught birds, compared to 0% of control ticks placed on uninfected lab mice. Robins that were previously infected in the lab by nymphal feeding infected 81.8% of applied larvae. Wild-caught Song Sparrows infected 4.8% of applied larvae, and 21.1% when infected by nymphal feeding. Results suggest moderate levels of reservoir competence for Northern Cardinals, lower levels for Gray Catbirds, and little evidence of reservoir competence for Eastern Towhees or Brown Thrashers. Lower infection rates in larvae applied to wild-caught birds compared to birds infected in the lab suggest that infected birds display temporal variability in infectiousness to larval ticks. Engorged larvae drop from birds abundantly during daylight hours, so the abundance of these bird species in the peridomestic environment suggests that they might contribute infected ticks to lawns and gardens.

  2. Reservoir competence of native North American birds for the lyme disease spirochete, Borrelia burgdorfieri.

    PubMed

    Ginsberg, Howard S; Buckley, P A; Balmforth, Maxon G; Zhioua, Elyes; Mitra, Shaibal; Buckley, Francine G

    2005-05-01

    Reservoir competence for the Lyme disease spirochete, Borrelia burgdorferi, was tested for six species of native North American birds: American robin, gray catbird, brown thrasher, eastern towhee, song sparrow, and northern cardinal. Wild birds collected by mist netting on Fire Island, NY, were held in a field laboratory in cages over water and locally collected larval ticks were placed on the birds, harvested from the water after engorgement, and tested for infection by direct fluorescentantibody staining after molting to the nymphal stage. American robins were competent reservoirs, infecting 16.1% of larvae applied to wild-caught birds, compared with 0% of control ticks placed on uninfected laboratory mice. Robins that were previously infected in the laboratory by nymphal feeding infected 81.8% of applied larvae. Wild-caught song sparrows infected 4.8% of applied larvae and 21.1% when infected by nymphal feeding. Results suggest moderate levels of reservoir competence for northern cardinals, lower levels for gray catbirds, and little evidence of reservoir competence for eastern towhees or brown thrashers. Lower infection rates in larvae applied to wild-caught birds compared with birds infected in the laboratory suggest that infected birds display temporal variability in infectiousness to larval ticks. Engorged larvae drop from birds abundantly during daylight, so the abundance of these bird species in the peridomestic environment suggests that they might contribute infected ticks to lawns and gardens. PMID:15962798

  3. Distribution of the Lyme Disease Spirochete Borrelia burgdorferi in Naturally and Experimentally Infected Western Gray Squirrels (Sciurus griseus)

    PubMed Central

    Jensen, Kelly; Salkeld, Daniel J.; Lane, Robert S.

    2010-01-01

    Abstract The dynamics of Borrelia burgdorferi infections within its natural hosts are poorly understood. We necropsied four wild-caught western gray squirrels (Sciurus griseus) that were acquired during a previous study that evaluated the reservoir competence of this rodent for the Lyme disease spirochete. One animal was infected experimentally, whereas the others were infected in the wild before capture. To investigate dissemination of B. burgdorferi and concurrent histopathologic lesions in different tissues, blood specimens, synovial and cerebrospinal fluid, ear-punch biopsies, and diverse tissue samples from skin and various organs were taken and examined by culture, polymerase chain reaction, and histology. Borrelia-positive cultures were obtained from three of the squirrels, that is, from skin biopsies (7 of 20 samples), ear-punch biopsies (2 of 8), and one (1 of 5) lymph node. Sequencing of amplicons confirmed B. burgdorferi sensu stricto (s.s.) infection in 9 of 10 culture-positive samples and in DNA extracted from all 10 positive cultures. The experimentally infected squirrel yielded most of the positive samples. In contrast, bodily fluids, all other organ specimens from these animals, and all samples from one naturally infected squirrel were negative for Borrelia for both assays. None of the necropsied squirrels exhibited specific clinical signs associated with B. burgdorferi. Similarly, necropsy and histological examination of tissues indicated the presence of underlying infectious processes, none of which could be ascribed conclusively to B. burgdorferi infection. Based on these results, obtained from a small number of animals investigated at a single time point, we suggest that B. burgdorferi s.s. infection in S. griseus may result in rather localized dissemination of spirochetes, and that mild or nonclinical disease might be more common after several months of infection duration. Since spirochetes could be detected in squirrels 7–21 months

  4. Statins reduce spirochetal burden and modulate immune responses in the C3H/HeN mouse model of Lyme disease.

    PubMed

    Van Laar, Tricia A; Hole, Camaron; Rajasekhar Karna, S L; Miller, Christine L; Reddick, Robert; Wormley, Floyd L; Seshu, J

    2016-06-01

    Lyme disease (LD) is a systemic disorder caused by Borrelia burgdorferi. Lyme spirochetes encode for a functional 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGR EC 1.1.1.88) serving as a rate limiting enzyme of the mevalonate pathway that contribute to components critical for cell wall biogenesis. Statins have been shown to inhibit B. burgdorferi in vitro. Using a mouse model of Lyme disease, we found that statins contribute to reducing bacterial burden and altering the murine immune response to favor clearance of spirochetes. PMID:26993029

  5. Alzheimer's Disease: Assessing the Role of Spirochetes, Biofilms, the Immune System, and Amyloid-β with Regard to Potential Treatment and Prevention.

    PubMed

    Allen, Herbert B

    2016-06-27

    Alzheimer's disease (AD) is an infectious disease caused by spirochetes, and these spirochetes form biofilms, which attract the innate immune system. The innate immune system first responder, Toll-like receptor 2, generates both NF-κB and TNF-α which try to kill the spirochetes in the biofilm, but cannot penetrate the "slime". NF-κB is also responsible for the generation of amyloid-β (Aβ) which itself is anti-microbial. Aβ cannot penetrate the biofilm either, and its accumulation leads to destruction of the cerebral neurocircuitry. Treatment with penicillin (as in tertiary syphilis, the comparator to AD) is outlined; a biofilm dispersing agent may need to be added to the protocol. PMID:27372648

  6. Alzheimer’s Disease: Assessing the Role of Spirochetes, Biofilms, the Immune System, and Amyloid-β with Regard to Potential Treatment and Prevention

    PubMed Central

    Allen, Herbert B.

    2016-01-01

    Alzheimer’s disease (AD) is an infectious disease caused by spirochetes, and these spirochetes form biofilms, which attract the innate immune system. The innate immune system first responder, Toll-like receptor 2, generates both NF-κB and TNF-α which try to kill the spirochetes in the biofilm, but cannot penetrate the “slime”. NF-κB is also responsible for the generation of amyloid-β (Aβ) which itself is anti-microbial. Aβ cannot penetrate the biofilm either, and its accumulation leads to destruction of the cerebral neurocircuitry. Treatment with penicillin (as in tertiary syphilis, the comparator to AD) is outlined; a biofilm dispersing agent may need to be added to the protocol. PMID:27372648

  7. Phagocytosis of Borrelia burgdorferi, the Lyme Disease Spirochete, Potentiates Innate Immune Activation and Induces Apoptosis in Human Monocytes▿

    PubMed Central

    Cruz, Adriana R.; Moore, Meagan W.; La Vake, Carson J.; Eggers, Christian H.; Salazar, Juan C.; Radolf, Justin D.

    2008-01-01

    We have previously demonstrated that phagocytosed Borrelia burgdorferi induces activation programs in human peripheral blood mononuclear cells that differ qualitatively and quantitatively from those evoked by equivalent lipoprotein-rich lysates. Here we report that ingested B. burgdorferi induces significantly greater transcription of proinflammatory cytokine genes than do lysates and that live B. burgdorferi, but not B. burgdorferi lysate, is avidly internalized by monocytes, where the bacteria are completely degraded within phagolysosomes. In the course of these experiments, we discovered that live B. burgdorferi also induced a dose-dependent decrease in monocytes but not a decrease in dendritic cells or T cells and that the monocyte population displayed morphological and biochemical hallmarks of apoptosis. Particularly noteworthy was the finding that apoptotic changes occurred predominantly in monocytes that had internalized spirochetes. Abrogation of phagocytosis with cytochalasin D prevented the death response. Heat-killed B. burgdorferi, which was internalized as well as live organisms, induced a similar degree of apoptosis of monocytes but markedly less cytokine production. Surprisingly, opsonophagocytosis of Treponema pallidum did not elicit a discernible cell death response. Our combined results demonstrate that B. burgdorferi confined to phagolysosomes is a potent inducer of cytosolic signals that result in (i) production of NF-κB-dependent cytokines, (ii) assembly of the inflammasome and activation of caspase-1, and (iii) induction of programmed cell death. We propose that inflammation and apoptosis represent mutually reinforcing components of the immunologic arsenal that the host mobilizes to defend itself against infection with Lyme disease spirochetes. PMID:17938216

  8. Outer membrane proteins of pathogenic spirochetes

    PubMed Central

    Cullen, Paul A.; Haake, David A.; Adler, Ben

    2009-01-01

    Pathogenic spirochetes are the causative agents of several important diseases including syphilis, Lyme disease, leptospirosis, swine dysentery, periodontal disease and some forms of relapsing fever. Spirochetal bacteria possess two membranes and the proteins present in the outer membrane are at the site of interaction with host tissue and the immune system. This review describes the current knowledge in the field of spirochetal outer membrane protein (OMP) biology. What is known concerning biogenesis and structure of OMPs, with particular regard to the atypical signal peptide cleavage sites observed amongst the spirochetes, is discussed. We examine the functions that have been determined for several spirochetal OMPs including those that have been demonstrated to function as adhesins, porins or to have roles in complement resistance. A detailed description of the role of spirochetal OMPs in immunity, including those that stimulate protective immunity or that are involved in antigenic variation, is given. A final section is included which covers experimental considerations in spirochetal outer membrane biology. This section covers contentious issues concerning cellular localization of putative OMPs, including determination of surface exposure. A more detailed knowledge of spirochetal OMP biology will hopefully lead to the design of new vaccines and a better understanding of spirochetal pathogenesis. PMID:15449605

  9. Bacterial Heterogeneity Is a Requirement for Host Superinfection by the Lyme Disease Spirochete

    PubMed Central

    Rogovskyy, Artem S.

    2014-01-01

    In nature, mixed Borrelia burgdorferi infections are common and possibly can be acquired by either superinfection or coinfection. Superinfection by heterologous B. burgdorferi strains has been established experimentally, although the ability of homologous B. burgdorferi clones to superinfect a host has not been studied in detail. Information regarding any potential immune barriers to secondary infection also currently is unavailable. In the present study, the ability to superinfect various mouse models by homologous wild-type clones was examined and compared to superinfection by heterologous strains. To assess the ability of homologous B. burgdorferi clones to successfully superinfect a mouse host, primary- and secondary-infecting spirochetes were recovered via in vitro cultivation of collected blood or tissue samples. This was accomplished by generating two different antibiotic-resistant versions of the wild-type B31-A3 clone in order to distinguish superinfecting B. burgdorferi from primary-infecting spirochetes. The data demonstrate an inability of homologous B. burgdorferi to superinfect immunocompetent mice as opposed to heterologous strains. Attempts to superinfect different types of immunodeficient mice with homologous B. burgdorferi indicate that the murine innate immune system represents a major barrier to intrastrain superinfection. Consequently, the possibility of innate immunity as a driving force for B. burgdorferi heterogeneity during the enzootic cycle is discussed. PMID:25114120

  10. Cyclic di-GMP Modulates Gene Expression in Lyme Disease Spirochetes at the Tick-Mammal Interface To Promote Spirochete Survival during the Blood Meal and Tick-to-Mammal Transmission

    PubMed Central

    Dunham-Ems, Star; Allard, Anna M.; Cassera, Maria B.; Kenedy, Melisha; Radolf, Justin D.

    2015-01-01

    Borrelia burgdorferi, the Lyme disease spirochete, couples environmental sensing and gene regulation primarily via the Hk1/Rrp1 two-component system (TCS) and Rrp2/RpoN/RpoS pathways. Beginning with acquisition, we reevaluated the contribution of these pathways to spirochete survival and gene regulation throughout the enzootic cycle. Live imaging of B. burgdorferi caught in the act of being acquired revealed that the absence of RpoS and the consequent derepression of tick-phase genes impart a Stay signal required for midgut colonization. In addition to the behavioral changes brought on by the RpoS-off state, acquisition requires activation of cyclic di-GMP (c-di-GMP) synthesis by the Hk1/Rrp1 TCS; B. burgdorferi lacking either component is destroyed during the blood meal. Prior studies attributed this dramatic phenotype to a metabolic lesion stemming from reduced glycerol uptake and utilization. In a head-to-head comparison, however, the B. burgdorferi Δglp mutant had a markedly greater capacity to survive tick feeding than B. burgdorferi Δhk1 or Δrrp1 mutants, establishing unequivocally that glycerol metabolism is only one component of the protection afforded by c-di-GMP. Data presented herein suggest that the protective response mediated by c-di-GMP is multifactorial, involving chemotactic responses, utilization of alternate substrates for energy generation and intermediary metabolism, and remodeling of the cell envelope as a means of defending spirochetes against threats engendered during the blood meal. Expression profiling of c-di-GMP-regulated genes through the enzootic cycle supports our contention that the Hk1/Rrp1 TCS functions primarily, if not exclusively, in ticks. These data also raise the possibility that c-di-GMP enhances the expression of a subset of RpoS-dependent genes during nymphal transmission. PMID:25987708

  11. Cyclic di-GMP modulates gene expression in Lyme disease spirochetes at the tick-mammal interface to promote spirochete survival during the blood meal and tick-to-mammal transmission.

    PubMed

    Caimano, Melissa J; Dunham-Ems, Star; Allard, Anna M; Cassera, Maria B; Kenedy, Melisha; Radolf, Justin D

    2015-08-01

    Borrelia burgdorferi, the Lyme disease spirochete, couples environmental sensing and gene regulation primarily via the Hk1/Rrp1 two-component system (TCS) and Rrp2/RpoN/RpoS pathways. Beginning with acquisition, we reevaluated the contribution of these pathways to spirochete survival and gene regulation throughout the enzootic cycle. Live imaging of B. burgdorferi caught in the act of being acquired revealed that the absence of RpoS and the consequent derepression of tick-phase genes impart a Stay signal required for midgut colonization. In addition to the behavioral changes brought on by the RpoS-off state, acquisition requires activation of cyclic di-GMP (c-di-GMP) synthesis by the Hk1/Rrp1 TCS; B. burgdorferi lacking either component is destroyed during the blood meal. Prior studies attributed this dramatic phenotype to a metabolic lesion stemming from reduced glycerol uptake and utilization. In a head-to-head comparison, however, the B. burgdorferi Δglp mutant had a markedly greater capacity to survive tick feeding than B. burgdorferi Δhk1 or Δrrp1 mutants, establishing unequivocally that glycerol metabolism is only one component of the protection afforded by c-di-GMP. Data presented herein suggest that the protective response mediated by c-di-GMP is multifactorial, involving chemotactic responses, utilization of alternate substrates for energy generation and intermediary metabolism, and remodeling of the cell envelope as a means of defending spirochetes against threats engendered during the blood meal. Expression profiling of c-di-GMP-regulated genes through the enzootic cycle supports our contention that the Hk1/Rrp1 TCS functions primarily, if not exclusively, in ticks. These data also raise the possibility that c-di-GMP enhances the expression of a subset of RpoS-dependent genes during nymphal transmission. PMID:25987708

  12. Stage-specific global alterations in the transcriptomes of Lyme disease spirochetes during tick feeding and following mammalian host adaptation.

    PubMed

    Iyer, Radha; Caimano, Melissa J; Luthra, Amit; Axline, David; Corona, Arianna; Iacobas, Dumitru A; Radolf, Justin D; Schwartz, Ira

    2015-02-01

    Borrelia burgdorferi, the agent of Lyme disease, is maintained in nature within an enzootic cycle involving a mammalian reservoir and an Ixodes sp. tick vector. The transmission, survival and pathogenic potential of B. burgdorferi depend on the bacterium's ability to modulate its transcriptome as it transits between vector and reservoir host. Herein, we employed an amplification-microarray approach to define the B. burgdorferi transcriptomes in fed larvae, fed nymphs and in mammalian host-adapted organisms cultivated in dialysis membrane chambers. The results show clearly that spirochetes exhibit unique expression profiles during each tick stage and during cultivation within the mammal; importantly, none of these profiles resembles that exhibited by in vitro grown organisms. Profound shifts in transcript levels were observed for genes encoding known or predicted lipoproteins as well as proteins involved in nutrient uptake, carbon utilization and lipid synthesis. Stage-specific expression patterns of chemotaxis-associated genes also were noted, suggesting that the composition and interactivities of the chemotaxis machinery components vary considerably in the feeding tick and mammal. The results as a whole make clear that environmental sensing by B. burgdorferi directly or indirectly drives an extensive and tightly integrated modulation of cell envelope constituents, chemotaxis/motility machinery, intermediary metabolism and cellular physiology. These findings provide the necessary transcriptional framework for delineating B. burgdorferi regulatory pathways throughout the enzootic cycle as well as defining the contribution(s) of individual genes to spirochete survival in nature and virulence in humans. PMID:25425211

  13. Dietary guideline adherence for gastroesophageal reflux disease

    PubMed Central

    2014-01-01

    Background Gastroesophageal reflux disease (GERD) is the most common gastrointestinal disease, and the cost of health care and lost productivity due to GERD is extremely high. Recently described side effects of long-term acid suppression have increased the interest in nonpharmacologic methods for alleviating GERD symptoms. We aimed to examine whether GERD patients follow recommended dietary guidelines, and if adherence is associated with the severity and frequency of reflux symptoms. Methods We conducted a population-based cross-sectional study within the Kaiser Permanente Northern California population, comparing 317 GERD patients to 182 asymptomatic population controls. All analyses adjusted for smoking and education. Results GERD patients, even those with moderate to severe symptoms or frequent symptoms, were as likely to consume tomato products and large portion meals as GERD-free controls and were even more likely to consume soft drinks and tea [odds ratio (OR) = 2.01 95% confidence interval (CI) 1.12-3.61; OR = 2.63 95% CI 1.24-5.59, respectively] and eat fried foods and high fat diet. The only reflux-triggering foods GERD patients were less likely to consume were citrus and alcohol [OR = 0.59; 95% CI: 0.35-0.97 for citrus; OR = 0.41 95% CI 0.19-0.87 for 1 + drink/day of alcohol]. The associations were similar when we excluded users of proton pump inhibitors. Conclusions GERD patients consume many putative GERD causing foods as frequently or even more frequently than asymptomatic patients despite reporting symptoms. These findings suggest that, if dietary modification is effective in reducing GERD, substantial opportunities for nonpharmacologic interventions exist for many GERD patients. PMID:25125219

  14. Host cell heparan sulfate glycosaminoglycans are ligands for OspF-related proteins of the Lyme disease spirochete

    PubMed Central

    Lin, Yi-Pin; Bhowmick, Rudra; Coburn, Jenifer; Leong, John M.

    2015-01-01

    Borrelia burgdorferi , the agent of Lyme disease, spreads from the site of the tick bite to tissues such as heart, joints and the nervous system. Host glycosaminoglycans (GAGs), highly modified repeating disaccharides that are present on cell surfaces and in extracellular matrix, are common targets of microbial pathogens during tissue colonization. While several dermatan sulfate-binding B. burgdorferi adhesins have been identified, B. burgdorferi adhesins documented to promote spirochetal binding to heparan sulfate have not yet been identified. OspEF-related proteins (Erps), a large family of plasmid-encoded surface lipoproteins that are produced in the mammalian host, can be divided into the OspF-related, OspEF leader peptide (Elp), and OspE-related subfamilies. We show here that a member of the OspF-related subfamily, ErpG, binds to heparan sulfate, and when produced on the surface of an otherwise nonadherent B. burgdorferi strain, ErpG promotes heparan sulfate-mediated bacterial attachment to glial but not endothelial, synovial or respiratory epithelial cells. Six other OspF-related proteins were capable of binding heparan sulfate, whereas representative OspE-related and Elp proteins lacked this activity. These results indicate that OspF-related proteins are heparan sulfate-binding adhesins, at least one of which promotes bacterial attachment to glial cells. PMID:25864455

  15. Oral Spirochetes Implicated in Dental Diseases Are Widespread in Normal Human Subjects and Carry Extremely Diverse Integron Gene Cassettes

    PubMed Central

    Wu, Yu-Wei; Rho, Mina; Doak, Thomas G.

    2012-01-01

    The NIH Human Microbiome Project (HMP) has produced several hundred metagenomic data sets, allowing studies of the many functional elements in human-associated microbial communities. Here, we survey the distribution of oral spirochetes implicated in dental diseases in normal human individuals, using recombination sites associated with the chromosomal integron in Treponema genomes, taking advantage of the multiple copies of the integron recombination sites (repeats) in the genomes, and using a targeted assembly approach that we have developed. We find that integron-containing Treponema species are present in ∼80% of the normal human subjects included in the HMP. Further, we are able to de novo assemble the integron gene cassettes using our constrained assembly approach, which employs a unique application of the de Bruijn graph assembly information; most of these cassette genes were not assembled in whole-metagenome assemblies and could not be identified by mapping sequencing reads onto the known reference Treponema genomes due to the dynamic nature of integron gene cassettes. Our study significantly enriches the gene pool known to be carried by Treponema chromosomal integrons, totaling 826 (598 97% nonredundant) genes. We characterize the functions of these gene cassettes: many of these genes have unknown functions. The integron gene cassette arrays found in the human microbiome are extraordinarily dynamic, with different microbial communities sharing only a small number of common genes. PMID:22635997

  16. Challenges of treatment adherence in older patients with Parkinson's disease.

    PubMed

    Bainbridge, Jacquelyn L; Ruscin, J Mark

    2009-01-01

    Patient adherence to a medication regimen is critical to treatment outcome, quality of life and future healthcare costs. For elderly patients with Parkinson's disease, obstacles to adherence can be particularly complex. Beyond age-related and economic factors, elderly patients with Parkinson's disease often require complicated dosing or titration schedules and have multiple co-morbidities that necessitate administration of therapies from multiple drug classes. In addition, neuropsychiatric disturbances and cognitive impairment, which are often part of the disease process, can affect adherence, as can variable responses to anti-parkinsonian agents as the disease progresses. Several recent studies in patients with Parkinson's disease point to the need for establishing good adherence patterns early and maintaining these throughout the course of treatment. To achieve optimal adherence in elderly patients with Parkinson's disease, a combination of pharmacological and non-pharmacological approaches appears to be the best strategy for success. Examples include a strong provider-patient relationship, educational intervention by phone or face-to-face contact, simplified dosing and administration schedules, management and understanding of medication adverse events, and the use of adherence aids such as pill boxes and hour-by-hour organizational charts. Research into new avenues that include improved drug monitoring, pharmacogenetics and neuroprotective regimens may give rise to better adherence in elderly patients with Parkinson's disease in the future. PMID:19220071

  17. Adherence with drug therapy in the rheumatic diseases Part one: a review of adherence rates.

    PubMed

    Hill, Jackie

    2005-01-01

    Drug therapy plays a major role in the management of many rheumatic diseases and is particularly important in rheumatoid arthritis (RA) because of the significant rates of morbidity and mortality (Pincus, 1995). Understanding of the pathogenesis of RA has led to the development of new and more effective drugs (Emery et al., 1999), but the ultimate efficacy of any drug therapy depends upon the patient's decision to take it. There is widespread agreement that many people with rheumatic disease do not adhere to their medication regimens (Deyo et al., 1981; Belcon et al., 1984; Pullar et al., 1988; Hill et al., 2001). Research has demonstrated that 50% of women taking hormone replacement therapy for the prevention of osteoporosis discontinue treatment after a year (Fordham, 2000) and similar rates of discontinuation are found in other chronic diseases (Haynes et al., 1996, 2000). This is bewildering as, in asymptomatic illnesses such as hypertension and diabetes, the expectation is that levels of adherence would be lower than in diseases where pain and stiffness are present. The picture becomes even more confusing when we consider the findings from a recent multi-country study of RA, which found no association between adherence and disease severity, nor with the treatment prescribed (Viller et al., 1999). In chronic disease poor adherence is commonplace. The World Health Organization (WHO) recognizes this and has recently stated that 'poor adherence to treatment of chronic diseases is a worldwide problem of striking magnitude' and cites adherence to long-term therapy for chronic illnesses in developed countries averaging just 50% (WHO, 2003). The first part of this two part review focuses on adherence with drug therapy, and the second part discusses different methods of measuring it. PMID:17041995

  18. Nuclear Markers Reveal Predominantly North to South Gene Flow in Ixodes scapularis, the Tick Vector of the Lyme Disease Spirochete

    PubMed Central

    Van Zee, Janice; Piesman, Joseph F.; Hojgaard, Andrias; Black IV, William Cormack

    2015-01-01

    Ixodes scapularis, the tick vector of the Lyme disease spirochete, is distributed over most of the eastern United States, but >80% of all Lyme disease cases occur in the northeast. The role that genetic differences between northern and southern tick populations play in explaining this disparate distribution of Lyme disease cases is unclear. The present study was conducted with 1,155 SNP markers in eight nuclear genes; the 16S mitochondrial gene was examined for comparison with earlier studies. We examined 350 I. scapularis from 7 states covering a representative area of the species. A demographic analysis using Bayesian Extended Skyline Analysis suggested that I. scapularis populations in Mississippi and Georgia began expanding 500,000 years ago, those in Florida and North Carolina 200,000 years ago and those from Maryland and New Jersey only during the past 50,000 years with an accompanying bottleneck. Wisconsin populations only began expanding in the last 20,000 years. Analysis of current migration patterns suggests large amounts of gene flow in northern collections and equally high rates of gene flow among southern collections. In contrast there is restricted and unidirectional gene flow between northern and southern collections, mostly occurring from northern into southern populations. Northern populations are characterized by nymphs that quest above the leaf litter, are easy to collect by flagging, frequently feed on mammals such as rodents and shrews, commonly attach to people, and about 25% of which are infected with B. burgdorferi. If there is a genetic basis for these behaviors, then the patterns detected in this study are of concern because they suggest that northern I. scapularis populations with a greater ability to vector B. burgdorferi to humans are expanding south. PMID:26536360

  19. Prevalence of the Lyme Disease Spirochete, Borrelia burgdorferi, in Blacklegged Ticks, Ixodes scapularis at Hamilton-Wentworth, Ontario.

    PubMed

    Scott, John D; Anderson, John F; Durden, Lance A; Smith, Morgan L; Manord, Jodi M; Clark, Kerry L

    2016-01-01

    Lyme disease has emerged as a major health concern in Canada, where the etiological agent, Borrelia burgdorferi sensu lato (s.l.), a spirochetal bacterium, is typically spread by the bite of certain ticks. This study explores the presence of B. burgdorferi s.l. in blacklegged ticks, Ixodes scapularis, collected at Dundas, Ontario (a locality within the region of Hamilton-Wentworth). Using passive surveillance, veterinarians and pet groomers were asked to collect blacklegged ticks from dogs and cats with no history of travel. Additionally, I. scapularis specimens were submitted from local residents and collected by flagging. Overall, 12 (41%) of 29 blacklegged ticks were infected with B. burgdorferi s.l. Using polymerase chain reaction (PCR) and DNA sequencing, two borrelial amplicons were characterized as B. burgdorferi sensu stricto (s.s.), a genospecies pathogenic to humans and certain domestic animals. Notably, three different vertebrate hosts each had two engorged I. scapularis females removed on the same day and, likewise, one cat had three repeat occurrences of this tick species. These multiple infestations suggest that a population of I. scapularis may be established in this area. The local public health unit has been underreporting the presence of B. burgdorferi s.l.-infected I. scapularis in the area encompassing Dundas. Our findings raise concerns about the need to erect tick warning signs in parkland areas. Veterinarians, medical professionals, public health officials, and the general public must be vigilant that Lyme disease-carrying blacklegged ticks pose a public health risk in the Dundas area and the surrounding Hamilton-Wentworth region. PMID:27226771

  20. Prevalence of the Lyme Disease Spirochete, Borrelia burgdorferi, in Blacklegged Ticks, Ixodes scapularis at Hamilton-Wentworth, Ontario

    PubMed Central

    Scott, John D.; Anderson, John F.; Durden, Lance A.; Smith, Morgan L.; Manord, Jodi M.; Clark, Kerry L.

    2016-01-01

    Lyme disease has emerged as a major health concern in Canada, where the etiological agent, Borrelia burgdorferi sensu lato (s.l.), a spirochetal bacterium, is typically spread by the bite of certain ticks. This study explores the presence of B. burgdorferi s.l. in blacklegged ticks, Ixodes scapularis, collected at Dundas, Ontario (a locality within the region of Hamilton-Wentworth). Using passive surveillance, veterinarians and pet groomers were asked to collect blacklegged ticks from dogs and cats with no history of travel. Additionally, I. scapularis specimens were submitted from local residents and collected by flagging. Overall, 12 (41%) of 29 blacklegged ticks were infected with B. burgdorferi s.l. Using polymerase chain reaction (PCR) and DNA sequencing, two borrelial amplicons were characterized as B. burgdorferi sensu stricto (s.s.), a genospecies pathogenic to humans and certain domestic animals. Notably, three different vertebrate hosts each had two engorged I. scapularis females removed on the same day and, likewise, one cat had three repeat occurrences of this tick species. These multiple infestations suggest that a population of I. scapularis may be established in this area. The local public health unit has been underreporting the presence of B. burgdorferi s.l.-infected I. scapularis in the area encompassing Dundas. Our findings raise concerns about the need to erect tick warning signs in parkland areas. Veterinarians, medical professionals, public health officials, and the general public must be vigilant that Lyme disease-carrying blacklegged ticks pose a public health risk in the Dundas area and the surrounding Hamilton-Wentworth region. PMID:27226771

  1. What ticks do under your skin: two-photon intravital imaging of Ixodes scapularis feeding in the presence of the lyme disease spirochete.

    PubMed

    Bockenstedt, Linda K; Gonzalez, David; Mao, Jialing; Li, Ming; Belperron, Alexia A; Haberman, Ann

    2014-03-01

    Lyme disease, due to infection with the Ixodes-tick transmitted spirochete Borrelia burgdorferi, is the most common tick-transmitted disease in the northern hemisphere. Our understanding of the tick-pathogen-vertebrate host interactions that sustain an enzootic cycle for B. burgdorferi is incomplete. In this article, we describe a method for imaging the feeding of Ixodes scapularis nymphs in real-time using two-photon intravital microscopy and show how this technology can be applied to view the response of Lyme borrelia in the skin of an infected host to tick feeding. PMID:24600332

  2. What Ticks Do Under Your Skin: Two-Photon Intravital Imaging of Ixodes Scapularis Feeding in the Presence of the Lyme Disease Spirochete

    PubMed Central

    Bockenstedt, Linda K.; Gonzalez, David; Mao, Jialing; Li, Ming; Belperron, Alexia A.; Haberman, Ann

    2014-01-01

    Lyme disease, due to infection with the Ixodes-tick transmitted spirochete Borrelia burgdorferi, is the most common tick-transmitted disease in the northern hemisphere. Our understanding of the tick-pathogen-vertebrate host interactions that sustain an enzootic cycle for B. burgdorferi is incomplete. In this article, we describe a method for imaging the feeding of Ixodes scapularis nymphs in real-time using two-photon intravital microscopy and show how this technology can be applied to view the response of Lyme borrelia in the skin of an infected host to tick feeding. PMID:24600332

  3. [Concept analysis of medication adherence in patients with chronic disease].

    PubMed

    Huang, Jen-Ying; Chen, Hsing-Mei

    2014-06-01

    Pharmacotherapy plays an important role in the management of chronic diseases. However, many patients with chronic disease do not adhere to their medication regimen. This results in worsening symptoms and frequent re-hospitalizations. As a result, healthcare providers may view these patients as bad. Medication adherence is a complex concept. Analyzing this concept may assist nurses to improve patient-centered care. This paper uses Walker & Avant's method to conduct a concept analysis of medication adherence. Results show the defining attributes of medication adherence as: (1) knowing and agreeing to the medication; (2) communicating and negotiating the regimen; and (3) active, continuous involvement in and appraisal of the treatment effect. Identified antecedents of medication adherence included the patient having: (1) a prescribed medication regimen; (2) cognitive and action abilities in her / his role as a patient; and (3) level of preparation for medication treatment. Identified consequences of medication adherence include: (1) improving symptom control; (2) decreasing re-hospitalizations and mortality; (3) reducing medical care costs; (4) restoring self-esteem; and (5) diminishing depression. It is hoped that this concept analysis provides a reference for nurses to achieve a better understanding of medication adherence and further improve nursing practice. PMID:24899565

  4. HrpA, an RNA Helicase Involved in RNA Processing, Is Required for Mouse Infectivity and Tick Transmission of the Lyme Disease Spirochete

    PubMed Central

    Salman-Dilgimen, Aydan; Hardy, Pierre-Olivier; Radolf, Justin D.; Caimano, Melissa J.; Chaconas, George

    2013-01-01

    The Lyme disease spirochete Borrelia burgdorferi must differentially express genes and proteins in order to survive in and transit between its tick vector and vertebrate reservoir. The putative DEAH-box RNA helicase, HrpA, has been recently identified as an addition to the spirochete's global regulatory machinery; using proteomic methods, we demonstrated that HrpA modulates the expression of at least 180 proteins. Although most bacteria encode an HrpA helicase, RNA helicase activity has never been demonstrated for HrpAs and the literature contains little information on the contribution of this protein to bacterial physiology or pathogenicity. In this work, we report that B. burgdorferi HrpA has RNA-stimulated ATPase activity and RNA helicase activity and that this enzyme is essential for both mammalian infectivity by syringe inoculation and tick transmission. Reduced infectivity of strains carrying mutations in the ATPase and RNA binding motif mutants suggests that full virulence expression requires both ATPase and coupled helicase activity. Microarray profiling revealed changes in RNA levels of two-fold, or less in an hrpA mutant versus wild-type, suggesting that the enzyme functions largely or exclusively at the post-transcriptional level. In this regard, northern blot analysis of selected gene products highly regulated by HrpA (bb0603 [p66], bba74, bb0241 [glpK], bb0242 and bb0243 [glpA]) suggests a role for HrpA in the processing and translation of transcripts. In addition to being the first demonstration of RNA helicase activity for a bacterial HrpA, our data indicate that the post-transcriptional regulatory functions of this enzyme are essential for maintenance of the Lyme disease spirochete's enzootic cycle. PMID:24367266

  5. Evidence of a conjugal erythromycin resistance element in the Lyme disease spirochete Borrelia burgdorferi

    PubMed Central

    Jackson, Charlene R.; Boylan, Julie; Frye, Jonathan G.; Gherardini, Frank C.

    2007-01-01

    We report the identification of isolates of Borrelia burgdorferi strain B31 that exhibit an unusual macrolide–lincosamide (ML) or macrolide–lincosamide–streptogramin A (MLSA) antibiotic resistance pattern. Low-passage isolates were resistant to high levels (>100 μg/mL) of erythromycin, spiramycin and the lincosamides but were sensitive to dalfopristin, an analogue of streptogramin B. Interestingly, the high-passage erythromycin-resistant strain B31 was resistant to quinupristin, an analogue of streptogramin A (25 μg/mL). Biochemical analysis revealed that resistance was not due to antibiotic inactivation or energy-dependent efflux but was instead due to modification of ribosomes in these isolates. Interestingly, we were able to demonstrate high-frequency transfer of the resistance phenotype via conjugation from B. burgdorferi to Bacillus subtilis (10−2–10−4) or Enterococcus faecalis (10−5). An intergeneric conjugal system in B. burgdorferi suggests that horizontal gene transfer may play a role in its evolution and is a potential tool for developing new genetic systems to study the pathogenesis of Lyme disease. PMID:17905571

  6. Genome Stability of Lyme Disease Spirochetes: Comparative Genomics of Borrelia burgdorferi Plasmids

    PubMed Central

    Casjens, Sherwood R.; Mongodin, Emmanuel F.; Qiu, Wei-Gang; Luft, Benjamin J.; Schutzer, Steven E.; Gilcrease, Eddie B.; Huang, Wai Mun; Vujadinovic, Marija; Aron, John K.; Vargas, Levy C.; Freeman, Sam; Radune, Diana; Weidman, Janice F.; Dimitrov, George I.; Khouri, Hoda M.; Sosa, Julia E.; Halpin, Rebecca A.; Dunn, John J.; Fraser, Claire M.

    2012-01-01

    Lyme disease is the most common tick-borne human illness in North America. In order to understand the molecular pathogenesis, natural diversity, population structure and epizootic spread of the North American Lyme agent, Borrelia burgdorferi sensu stricto, a much better understanding of the natural diversity of its genome will be required. Towards this end we present a comparative analysis of the nucleotide sequences of the numerous plasmids of B. burgdorferi isolates B31, N40, JD1 and 297. These strains were chosen because they include the three most commonly studied laboratory strains, and because they represent different major genetic lineages and so are informative regarding the genetic diversity and evolution of this organism. A unique feature of Borrelia genomes is that they carry a large number of linear and circular plasmids, and this work shows that strains N40, JD1, 297 and B31 carry related but non-identical sets of 16, 20, 19 and 21 plasmids, respectively, that comprise 33–40% of their genomes. We deduce that there are at least 28 plasmid compatibility types among the four strains. The B. burgdorferi ∼900 Kbp linear chromosomes are evolutionarily exceptionally stable, except for a short ≤20 Kbp plasmid-like section at the right end. A few of the plasmids, including the linear lp54 and circular cp26, are also very stable. We show here that the other plasmids, especially the linear ones, are considerably more variable. Nearly all of the linear plasmids have undergone one or more substantial inter-plasmid rearrangements since their last common ancestor. In spite of these rearrangements and differences in plasmid contents, the overall gene complement of the different isolates has remained relatively constant. PMID:22432010

  7. Genome Stability of Lyme Disease Spirochetes: Comparative Genomics of Borrelia burgdorferi Plasmids

    SciTech Connect

    Casjens S. R.; Dunn J.; Mongodin, E. F.; Qiu, W.-G.; Luft, B. J.; Schutzer, S. E.; Gilcrease, E. B.; Huang, W. M.; Vujadinovic, M.; Aron, J. K.; Vargas, L. C.; Freeman, S.; Radune, D.; Weidman, J. F.; Dimitrov, G. I.; Khouri, H. M.; Sosa, J. E.; Halpin, R. A.; Fraser, C. M.

    2012-03-14

    Lyme disease is the most common tick-borne human illness in North America. In order to understand the molecular pathogenesis, natural diversity, population structure and epizootic spread of the North American Lyme agent, Borrelia burgdorferi sensu stricto, a much better understanding of the natural diversity of its genome will be required. Towards this end we present a comparative analysis of the nucleotide sequences of the numerous plasmids of B. burgdorferi isolates B31, N40, JD1 and 297. These strains were chosen because they include the three most commonly studied laboratory strains, and because they represent different major genetic lineages and so are informative regarding the genetic diversity and evolution of this organism. A unique feature of Borrelia genomes is that they carry a large number of linear and circular plasmids, and this work shows that strains N40, JD1, 297 and B31 carry related but non-identical sets of 16, 20, 19 and 21 plasmids, respectively, that comprise 33-40% of their genomes. We deduce that there are at least 28 plasmid compatibility types among the four strains. The B. burgdorferi {approx}900 Kbp linear chromosomes are evolutionarily exceptionally stable, except for a short {le}20 Kbp plasmid-like section at the right end. A few of the plasmids, including the linear lp54 and circular cp26, are also very stable. We show here that the other plasmids, especially the linear ones, are considerably more variable. Nearly all of the linear plasmids have undergone one or more substantial inter-plasmid rearrangements since their last common ancestor. In spite of these rearrangements and differences in plasmid contents, the overall gene complement of the different isolates has remained relatively constant.

  8. Global Repression of Host-Associated Genes of the Lyme Disease Spirochete through Post-Transcriptional Modulation of the Alternative Sigma Factor RpoS

    PubMed Central

    Dulebohn, Daniel P.; Hayes, Beth M.; Rosa, Patricia A.

    2014-01-01

    Borrelia burgdorferi, the agent of Lyme disease, is a vector-borne pathogen that transits between Ixodes ticks and vertebrate hosts. During the natural infectious cycle, spirochetes must globally adjust their transcriptome to survive in these dissimilar environments. One way B. burgdorferi accomplishes this is through the use of alternative sigma factors to direct transcription of specific genes. RpoS, one of only three sigma factors in B. burgdorferi, controls expression of genes required during tick-transmission and infection of the mammalian host. How spirochetes switch between different sigma factors during the infectious cycle has remained elusive. Here we establish a role for a novel protein, BBD18, in the regulation of the virulence-associated sigma factor RpoS. Constitutive expression of BBD18 repressed transcription of RpoS-dependent genes to levels equivalent to those observed in an rpoS mutant. Consistent with the global loss of RpoS-dependent transcripts, we were unable to detect RpoS protein. However, constitutive expression of BBD18 did not diminish the amount of rpoS transcript, indicating post-transcriptional regulation of RpoS by BBD18. Interestingly, BBD18-mediated repression of RpoS is independent of both the rpoS promoter and the 5’ untranslated region, suggesting a mechanism of protein destabilization rather than translational control. We propose that BBD18 is a novel regulator of RpoS and its activity likely represents a first step in the transition from an RpoS-ON to an RpoS-OFF state, when spirochetes transition from the host to the tick vector. PMID:24671196

  9. Treatment Adherence in Adolescents With Inflammatory Bowel Disease: The Collective Impact of Barriers to Adherence and Anxiety/Depressive Symptoms

    PubMed Central

    Gray, Wendy N.; Denson, Lee A.; Baldassano, Robert N.

    2012-01-01

    Objective Knowledge of factors impacting adolescents’ ability to adhere to their inflammatory bowel disease (IBD) regimen is limited. The current study examines the collective impact of barriers to adherence and anxiety/depressive symptoms on adolescent adherence to the IBD regimen. Methods Adolescents (n = 79) completed measures of barriers to adherence, adherence, and anxiety/depressive symptoms at one of two specialty pediatric IBD clinics. Results Most adolescents reported barriers to adherence and 1 in 8 reported borderline or clinically elevated levels of anxiety/depressive symptoms. Anxiety/depressive symptoms moderated the relationship between barriers to adherence and adherence. Post hoc probing revealed a significant, additive effect of higher anxiety/depressive symptoms in the barriers–adherence relationship, with adherence significantly lower among adolescents with higher barriers and higher anxiety/depressive symptoms. Conclusions In order to optimize adherence in adolescents, interventions should target not only barriers to adherence but also any anxiety/depressive symptoms that may negatively impact efforts to adhere to recommended treatment. PMID:22080456

  10. Use of T7 RNA polymerase to direct expression of outer Surface Protein A (OspA) from the Lyme disease Spirochete, Borrelia burgdorferi

    NASA Technical Reports Server (NTRS)

    Dunn, John J.; Lade, Barbara N.

    1991-01-01

    The OspA gene from a North American strain of the Lyme disease Spirochete, Borrelia burgdorferi, was cloned under the control of transciption and translation signals from bacteriophage T7. Full-length OspA protein, a 273 amino acid (31kD) lipoprotein, is expressed poorly in Escherichia coli and is associated with the insoluble membrane fraction. In contrast, a truncated form of OspA lacking the amino-terminal signal sequence which normally would direct localization of the protein to the outer membrane is expressed at very high levels (less than or equal to 100 mg/liter) and is soluble. The truncated protein was purified to homogeneity and is being tested to see if it will be useful as an immunogen in a vaccine against Lyme disease. Circular dichroism and fluorescence spectroscopy was used to characterize the secondary structure and study conformational changes in the protein. Studies underway with other surface proteins from B burgdorferi and a related spirochete, B. hermsii, which causes relapsing fever, leads us to conclude that a strategy similar to that used to express the truncated OspA can provide a facile method for producing variations of Borrelia lipoproteins which are highly expressed in E. coli and soluble without exposure to detergents.

  11. Spirochete motility and morpholgy

    NASA Astrophysics Data System (ADS)

    Charon, Nyles

    2004-03-01

    Spirochetes have a unique structure, and as a result their motility is different from that of other bacteria. These organisms can swim in a highly viscous, gel-like medium, such as that found in connective tissue, that inhibits the motility of most other bacteria. In spirochetes, the organelles for motility, the periplasmic flagella, reside inside the cell within the periplasmic space. A given periplasmic flagellum is attached only at one end of the cell, and depending on the species, may or may not overlap in the center of the cell. The number of periplasmic flagella varies from species to species. These structures have been shown to be directly involved in motility and function by rotating within the periplasmic space (1). The present talk focuses on the spirochete that causes Lyme disease, Borrelia burgdorferi. In many bacterial species, cell shape is usually dictated by the peptidoyglycan layer of the cell wall. In the first part of the talk, results will be presented that the morphology of B. burgdorferi is the result of a complex interaction between the cell cylinder and the internal periplasmic flagella resulting in a cell with a flat-wave morphology. Backward moving, propagating waves enable these bacteria to swim and translate in a given direction. Using targeted mutagenesis, we inactivated the gene encoding the major periplasmic flagellar filament protein FlaB. The resulting flaB mutants not only were non-motile, but were rod-shaped (2). Western blot analysis indicated that flaB was no longer synthesized, and electron microscopy revealed that the mutants were completely deficient in periplasmic flagella. Our results indicate that the periplasmic flagella of B. burgdorferi have a skeletal function. These organelles dynamically interact with the rod-shaped cell cylinder to enable the cell to swim, and to confer in part its flat-wave morphology The latter part of the talk concerns the basis for asymmetrical rotation of the periplasmic flagella of B

  12. Stage-Specific Global Alterations in the Transcriptomes of Lyme Disease Spirochetes During Tick Feeding and Following Mammalian Host-Adaptation

    PubMed Central

    Iyer, Radha; Caimano, Melissa J.; Luthra, Amit; Axline, David; Corona, Arianna; Iacobas, Dumitru A.; Radolf, Justin D.; Schwartz, Ira

    2015-01-01

    Borrelia burgdorferi, the agent of Lyme disease, is maintained in nature within an enzootic cycle involving a mammalian reservoir and an Ixodes sp. tick vector. The transmission, survival and pathogenic potential of B. burgdorferi depend on the bacterium’s ability to modulate its transcriptome as it transits between vector and reservoir host. Herein, we employed an amplification-microarray approach to define the B. burgdorferi transcriptomes in fed larvae, fed nymphs and in mammalian host-adapted organisms cultivated in dialysis membrane chambers. The results show clearly that spirochetes exhibit unique expression profiles during each tick stage and during cultivation within the mammal; importantly, none of these profiles resembles that exhibited by in vitro-grown organisms. Profound shifts in transcript levels were observed for genes encoding known or predicted lipoproteins as well as proteins involved in nutrient uptake, carbon utilization and lipid synthesis. Stage-specific expression patterns of chemotaxis-associated genes also were noted, suggesting that the composition and interactivities of the chemotaxis machinery components vary considerably in the feeding tick and mammal. The results as a whole make clear that environmental sensing by B. burgdorferi directly or indirectly drives an extensive and tightly integrated modulation of cell envelope constituents, chemotaxis/motility machinery, intermediary metabolism and cellular physiology. These findings provide the necessary transcriptional framework for delineating B. burgdorferi regulatory pathways throughout the enzootic cycle as well as defining the contribution(s) of individual genes to spirochete survival in nature and virulence in humans. PMID:25425211

  13. Procedure volume influences adherence to celiac disease guidelines

    PubMed Central

    Lebwohl, Benjamin; Genta, Robert M.; Kapel, Robert C.; Sheehan, Daniel; Lerner, Nina S.; Green, Peter H.; Neugut, Alfred I.; Rundle, Andrew

    2014-01-01

    Background Although the prevalence of celiac disease in the USA approaches 1%, most cases are undiagnosed, in part, because of low adherence to the recommendation of submitting at least four specimens during duodenal biopsy. We aimed to determine whether physician and practice characteristics are associated with adherence to this recommendation. Materials and methods We used a large national pathology database to identify all adult patients who underwent duodenal biopsy during 2006–2009. Hierarchical modeling was used to determine whether procedure volume, the number of gastroenterologists per endoscopy suite, and the number of gastroenterologists per capita of the zip code of the practice were associated with adherence. Results We identified 92 580 patients (67% female, mean age 53.5 years) who met our inclusion/exclusion criteria. Specimens were submitted by 669 gastroenterologists from 200 endoscopy suites, located in 191 zip codes, with a mean of 3.4 gastroenterologists per suite. On multivariate analysis, a higher procedure volume was associated with a decreased adherence [odds ratio (OR) for each additional 100 procedures, 0.92; 95% confidence interval (CI), 0.88–0.97; P = 0.002]. An increased adherence was reported for gastroenterologists working at suites with higher numbers of gastroenterologists (OR for each additional gastroenterologist, 1.08; 95% CI, 1.04–1.13; P < 0.001) but not for a higher gastroenterologist density in the zip code of the practice (OR for each additional gastroenterologist per capita, 1.01; 95% CI, 0.99–1.03; P = 0.21). Conclusion High-volume physicians exhibit lower rates of adherence to biopsy guidelines, possibly because of the additional time required to submit at least four specimens. In contrast, a greater number of endoscopists working in an endoscopy suite are associated with an increased adherence, possibly because of peer education. PMID:23995767

  14. Decorin-binding proteins A and B confer distinct mammalian cell type-specific attachment by Borrelia burgdorferi, the Lyme disease spirochete

    PubMed Central

    Fischer, Joshua R.; Parveen, Nikhat; Magoun, Loranne; Leong, John M.

    2003-01-01

    Host cell binding is an essential step in colonization by many bacterial pathogens, and the Lyme disease agent, Borrelia burgdorferi, which colonizes multiple tissues, is capable of attachment to diverse cell types. Glycosaminoglycans (GAGs) are ubiquitously expressed on mammalian cells and are recognized by multiple B. burgdorferi surface proteins. We previously showed that B. burgdorferi strains differ in the particular spectrum of GAGs that they recognize, leading to differences in the cultured mammalian cell types that they efficiently bind. The molecular basis of these binding specificities remains undefined, due to the difficulty of analyzing multiple, potentially redundant cell attachment pathways and to the paucity of genetic tools for this pathogen. In the current study, we show that the expression of decorin-binding protein (Dbp) A and/or DbpB, two B. burgdorferi surface proteins that bind GAGs, is sufficient to convert a high-passage nonadherent B. burgdorferi strain into one that efficiently binds 293 epithelial cells. Epithelial cell attachment was mediated by dermatan sulfate, and, consistent with this GAG-binding specificity, these recombinant strains did not bind EA-Hy926 endothelial cells. The GAG-binding properties of bacteria expressing DbpB or DbpA were distinguishable, and DbpB but not DbpA promoted spirochetal attachment to C6 glial cells. Thus, DbpA and DbpB may each play central but distinct roles in cell type-specific binding by Lyme disease spirochetes. This study illustrates that transformation of high-passage B. burgdorferi strains may provide a relatively simple genetic approach to analyze virulence-associated phenotypes conferred by multiple bacterial factors. PMID:12773620

  15. A Single-Domain FlgJ Contributes to Flagellar Hook and Filament Formation in the Lyme Disease Spirochete Borrelia burgdorferi

    PubMed Central

    Zhang, Kai; Tong, Brian A.; Liu, Jun

    2012-01-01

    FlgJ plays a very important role in flagellar assembly. In the enteric bacteria, flgJ null mutants fail to produce the flagellar rods, hooks, and filaments but still assemble the integral membrane-supramembrane (MS) rings. These mutants are nonmotile. The FlgJ proteins consist of two functional domains. The N-terminal rod-capping domain acts as a scaffold for rod assembly, and the C-terminal domain acts as a peptidoglycan (PG) hydrolase (PGase), which allows the elongating flagellar rod to penetrate through the PG layer. However, the FlgJ homologs in several bacterial phyla (including spirochetes) often lack the PGase domain. The function of these single-domain FlgJ proteins remains elusive. Herein, a single-domain FlgJ homolog (FlgJBb) was studied in the Lyme disease spirochete Borrelia burgdorferi. Cryo-electron tomography analysis revealed that the flgJBb mutant still assembled intact flagellar basal bodies but had fewer and disoriented flagellar hooks and filaments. Consistently, Western blots showed that the levels of flagellar hook (FlgE) and filament (FlaB) proteins were substantially decreased in the flgJBb mutant. Further studies disclosed that the decreases of FlgE and FlaB in the mutant occurred at the posttranscriptional level. Microscopic observation and swarm plate assay showed that the motility of the flgJBb mutant was partially deficient. The altered phenotypes were completely restored when the mutant was complemented. Collectively, these results indicate that FlgJBb is involved in the assembly of the flagellar hook and filament but not the flagellar rod in B. burgdorferi. The observed phenotype is different from that of flgJ mutants in the enteric bacteria. PMID:22155773

  16. [Adherence to cardioprotective medications in coronary heart disease].

    PubMed

    Scardi, Sabino; Mazzone, Carmine; Di Lenarda, Andrea

    2009-04-01

    Treatment of patients with ischemic heart disease relies on evidence-based medications such as beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, aspirin and statins, which are considered cornerstones to control symptoms, improve quality of life, reduce future events, and prolong survival. In spite of the clear benefits of therapy, previous studies have shown differences between the large randomized populations and the "real world" about long-term treatment in terms of efficacy, tolerability, costs, side effects and drug interactions. Moreover, a different awareness of the patient's compliance has been highlighted in relation to the setting (hospital, family doctor, etc.). The analysis and assessment of the prescription and efficacy of therapy for secondary prevention of coronary artery disease represent one of the most important challenges for the healthcare system, because reliable data are necessary to verify usefulness and results of therapy, prescribed at discharge after an acute coronary syndrome and/or coronary artery bypass graft, but above all the actual application of treatments should be pursued in every clinical setting. The Cardiology School of the Trieste University has constituted a working group of cardiology students that during the year 2009 will enroll and follow for 1 year all patients with coronary artery disease discharged from the Cardiovascular Department and Emergency Unit of the University Hospital of Trieste to assess: (1) if evidence-based medicine for secondary prevention of coronary artery disease is applied in the Trieste area; (2) adherence to prescribed treatment; (3) factors that are associated with non-adherence and consequences of non-adherence. PMID:19475879

  17. The OspE-Related Proteins Inhibit Complement Deposition and Enhance Serum Resistance of Borrelia burgdorferi, the Lyme Disease Spirochete

    PubMed Central

    Kenedy, Melisha R.; Akins, Darrin R.

    2011-01-01

    Borrelia burgdorferi, the Lyme disease spirochete, binds the host complement inhibitors factor H (FH) and FH-like protein 1 (FHL-1). Binding of FH/FHL-1 by the B. burgdorferi proteins CspA and the OspE-related proteins is thought to enhance resistance to serum-mediated killing. While previous reports have shown that CspA confers serum resistance in B. burgdorferi, it is unclear whether the OspE-related proteins are relevant in B. burgdorferi serum resistance when OspE is expressed on the borrelial surface. To assess the role of the OspE-related proteins, we overexpressed them in a serum-sensitive CspA mutant strain. OspE overexpression enhanced serum resistance of the CspA-deficient organisms. Furthermore, FH was more efficiently bound to the B. burgdorferi surface when OspE was overexpressed. Deposition of complement components C3 and C5b-9 (the membrane attack complex), however, was reduced on the surface of the OspE-overexpressing strain compared to that on the CspA mutant strain. These data demonstrate that OspE proteins expressed on the surface of B. burgdorferi bind FH and protect the organism from complement deposition and subsequent serum-mediated destruction. PMID:21282413

  18. Invasion of oral and aortic tissues by oral spirochete Treponema denticola in ApoE(-/-) mice causally links periodontal disease and atherosclerosis.

    PubMed

    Chukkapalli, Sasanka S; Rivera, Mercedes F; Velsko, Irina M; Lee, Ju-Youn; Chen, Hao; Zheng, Donghang; Bhattacharyya, Indraneel; Gangula, Pandu R; Lucas, Alexandra R; Kesavalu, Lakshmyya

    2014-05-01

    Treponema denticola is a predominantly subgingival oral spirochete closely associated with periodontal disease and has been detected in atherosclerosis. This study was designed to evaluate causative links between periodontal disease induced by chronic oral T. denticola infection and atherosclerosis in hyperlipidemic ApoE(-/-) mice. ApoE(-/-) mice (n = 24) were orally infected with T. denticola ATCC 35404 and were euthanized after 12 and 24 weeks. T. denticola genomic DNA was detected in oral plaque samples, indicating colonization of the oral cavity. Infection elicited significantly (P = 0.0172) higher IgG antibody levels and enhanced intrabony defects than sham infection. T. denticola-infected mice had higher levels of horizontal alveolar bone resorption than sham-infected mice and an associated significant increase in aortic plaque area (P ≤ 0.05). Increased atherosclerotic plaque correlated with reduced serum nitric oxide (NO) levels and increased serum-oxidized low-density lipoprotein (LDL) levels compared to those of sham-infected mice. T. denticola infection altered the expression of genes known to be involved in atherosclerotic development, including the leukocyte/endothelial cell adhesion gene (Thbs4), the connective tissue growth factor gene (Ctgf), and the selectin-E gene (Sele). Fluorescent in situ hybridization (FISH) revealed T. denticola clusters in both gingival and aortic tissue of infected mice. This is the first study examining the potential causative role of chronic T. denticola periodontal infection and vascular atherosclerosis in vivo in hyperlipidemic ApoE(-/-) mice. T. denticola is closely associated with periodontal disease and the rapid progression of atheroma in ApoE(-/-) mice. These studies confirm a causal link for active oral T. denticola infection with both atheroma and periodontal disease. PMID:24566627

  19. The unique paradigm of spirochete motility and chemotaxis

    PubMed Central

    Charon, Nyles W.; Cockburn, Andrew; Li, Chunhao; Liu, Jun; Miller, Kelly A.; Miller, Michael R.; Motaleb, Md.; Wolgemuth, Charles W.

    2013-01-01

    Spirochete motility is enigmatic: It differs from the motility of most other bacteria in that the entire bacterium is involved in translocation in the absence of external appendages. Using the Lyme disease spirochete Borrelia burgdorferi (Bb) as a model system, we explore the current research on spirochete motility and chemotaxis. Bb has periplasmic flagella (PFs) subterminally attached to each end of the protoplasmic cell cylinder, and surrounding the cell is an outer membrane. These internal helically shaped PFs allow the spirochete to swim by generating backward-moving waves by rotation. Exciting advances using cryoelectron microscopy tomography are presented with respect to in situ analysis of cell, PF, and motor structure. In addition, advances in the dynamics of motility, chemotaxis, gene regulation, and the role of motility and chemotaxis in the life cycle of Bb are summarized. The results indicate that the motility paradigms of flagellated bacteria do not apply to these unique bacteria. PMID:22994496

  20. Geographic uniformity of the Lyme disease spirochete (Borrelia burgdorferi) and its shared history with tick vector (Ixodes scapularis) in the Northeastern United States.

    PubMed

    Qiu, Wei-Gang; Dykhuizen, Daniel E; Acosta, Michael S; Luft, Benjamin J

    2002-03-01

    Over 80% of reported cases of Lyme disease in the United States occur in coastal regions of northeastern and mid-Atlantic states. The genetic structure of the Lyme disease spirochete (Borrelia burgdorferi) and its main tick vector (Ixodes scapularis) was studied concurrently and comparatively by sampling natural populations of I. scapularis ticks along the East Coast from 1996 to 1998. Borrelia is genetically highly diverse at the outer surface protein ospC. Since Borrelia is highly clonal, the ospC alleles can be used to define clones. A newly designed reverse line blotting (RLB) assay shows that up to 10 Borrelia clones can infect a single tick. The clone frequencies in Borrelia populations are the same across the Northeast. On the other hand, I. scapularis populations show strong regional divergence (among northeastern, mid-Atlantic, and southern states) as well as local differentiation. The high genetic diversity within Borrelia populations and the disparity in the genetic structure between Borrelia and its tick vector are likely consequences of strong balancing selection on local Borrelia clones. Demographically, both Borrelia and I. scapularis populations in the Northeast show the characteristics of a species that has recently expanded from a population bottleneck. Major geological and ecological events, such as the last glacial maximum (18,000 years ago) and the modern-day expansion of tick habitats, are likely causes of the observed "founder effects" for the two organisms in the Northeast. We therefore conclude that the genetic structure of B. burgdorferi has been intimately shaped by the natural history of its main vector, the northern lineage of I. scapularis ticks. PMID:11901105

  1. Geographic uniformity of the Lyme disease spirochete (Borrelia burgdorferi) and its shared history with tick vector (Ixodes scapularis) in the Northeastern United States.

    PubMed Central

    Qiu, Wei-Gang; Dykhuizen, Daniel E; Acosta, Michael S; Luft, Benjamin J

    2002-01-01

    Over 80% of reported cases of Lyme disease in the United States occur in coastal regions of northeastern and mid-Atlantic states. The genetic structure of the Lyme disease spirochete (Borrelia burgdorferi) and its main tick vector (Ixodes scapularis) was studied concurrently and comparatively by sampling natural populations of I. scapularis ticks along the East Coast from 1996 to 1998. Borrelia is genetically highly diverse at the outer surface protein ospC. Since Borrelia is highly clonal, the ospC alleles can be used to define clones. A newly designed reverse line blotting (RLB) assay shows that up to 10 Borrelia clones can infect a single tick. The clone frequencies in Borrelia populations are the same across the Northeast. On the other hand, I. scapularis populations show strong regional divergence (among northeastern, mid-Atlantic, and southern states) as well as local differentiation. The high genetic diversity within Borrelia populations and the disparity in the genetic structure between Borrelia and its tick vector are likely consequences of strong balancing selection on local Borrelia clones. Demographically, both Borrelia and I. scapularis populations in the Northeast show the characteristics of a species that has recently expanded from a population bottleneck. Major geological and ecological events, such as the last glacial maximum (18,000 years ago) and the modern-day expansion of tick habitats, are likely causes of the observed "founder effects" for the two organisms in the Northeast. We therefore conclude that the genetic structure of B. burgdorferi has been intimately shaped by the natural history of its main vector, the northern lineage of I. scapularis ticks. PMID:11901105

  2. Factors that Influence Adherence to a Gluten-Free Diet in Adults with Celiac Disease

    PubMed Central

    Edwards-George, Jessica; Dennis, Melinda; Schuppan, Detlef; Cook, Francis; Franko, Debra L.; Blom-Hoffman, Jessica; Kelly, Ciaran P.

    2013-01-01

    Objective The only treatment for celiac disease is lifelong adherence to a gluten-free diet, yet adherence is limited and factors influencing adherence are poorly understood. The purpose of this study was to determine factors influencing gluten-free diet adherence in adults with celiac disease. Methods A questionnaire was developed and administered to 154 adults with celiac disease who then underwent a standardized gluten-free diet evaluation by an experienced nutritionist. Multivariate analysis was conducted to determine factors associated with adherence level. Results Thirteen factors hypothesized to contribute to gluten-free diet adherence were found to be significantly associated with improved adherence including: understanding of the gluten-free diet, membership of a celiac disease advocacy group, and perceived ability to maintain adherence despite travel or changes in mood or stress (P < 0.001). Conclusions This study identified specific factors correlated with gluten-free diet adherence. These results provide a foundation for the design of educational interventions to improve adherence. PMID:17990115

  3. Composite, large spirochetes from microbial mats: spirochete structure review

    NASA Technical Reports Server (NTRS)

    Margulis, L.; Ashen, J. B.; Sole, M.; Guerrero, R.

    1993-01-01

    Phenomena previously unknown in free-living spirochetes are reported: large-sized cells with variable diameter (length to 100 microns, width between 0.4 and 3.0 microns), composite structure (smaller spirochetes inside larger ones), and positive phototropic behavior. These bacteria, Spirosymplokos, are compared with all other spirochete genera. The large spirochete, grown in mixed culture, was studied live and by transmission EM. The protoplasmic cylinder was replete with spherical granules 20-32 nm in diameter, and three to six periplasmic 26-nm flagella were inserted subterminally. Comparably granulated and flagellated small spirochetes were located inside the protoplasmic cylinder and in the periplasm of the large ones. When exposed to air, movement became erratic, protoplasmic cylinders retracted to lie folded inside the outer membrane, and refractile membranous structures formed. From one to four structures per still-moving spirochete were seen. Spirosymplokos was enriched from laboratory samples exposed to oxygen-rich and desiccating, but not dry, conditions for at least 4 mo after removal of microbial mat from the field.

  4. Injectable disease-modifying therapy for relapsing-remitting multiple sclerosis: a review of adherence data.

    PubMed

    Caon, Christina; Saunders, Carol; Smrtka, Jennifer; Baxter, Nancy; Shoemaker, Jennifer

    2010-10-01

    Long-term adherence to disease-modifying therapy in relapsing-remitting multiple sclerosis (RRMS) is associated with improved patient outcomes, including a reduced risk of relapse and a better preserved quality of life. However, the unpredictable nature of the disease--even when it is being treated--may make it difficult to convince patients of the importance of treatment adherence. A number of studies have attempted to pinpoint factors that affect adherence. Nursing interventions that address some of these factors may improve adherence and, thus, the disease course for a variety of RRMS patients. This article summarizes literature that approximates the prevalence and impact of nonadherence and reviews factors identified in clinical trials that affect adherence. Nursing interventions that can improve adherence, including telephone counseling and motivational interview techniques, are also addressed. PMID:21049828

  5. Adherence to prescribed medications of Iranian traditional medicine in a group of patients with chronic disease

    PubMed Central

    Dabaghian, Fataneh Hashem; Rassouli, Maryam; Sadighi, Jila; Ghods, Roshanak

    2016-01-01

    Objective: The extent to which a person's health-related behavior corresponds with medical instructions (adherence) is an important modifier of health system effectiveness. This study was designed to determine the patients’ adherence to Iranian traditional medicine in a group of patients with chronic disease. Methods: Convenience sampling was used to enroll 320 patients with chronic diseases from January 2014 to January 2015 in clinics of traditional medicine affiliated with medical universities in Tehran. Morisky Medication Adherence Scale (MMAS) was used to measure the adherence. After describing the variables and the frequency of adherence, logistic regression analysis was used to determine the influencing factors. Findings: Mean age was 40.8 (standard deviation [SD] =13) years. The mean of the duration of disease was 54.6 (SD = 56.1) months and mean of the duration of referring to the clinics 6.5 (SD = 6.9) months. Total score of MMAS was zero in 33 (10.3%) of patients (high adherence), one or two in 128 (40%) of patients (moderate adherence), and more than two in 159 (49.7%) of patients (low adherence). Forgetfulness, bad taste, not availability, and the high cost of the drugs were the most commonly reported causes of non-adherence. Adherence was associated with age (odds ratio [OR] =1.05, 95% confidence interval [95% CI] 1–1.1), marriage (OR = 10.8, 95% CI 2.05–57.6), number of prescribed drugs (OR = 0.05, 95% CI 0.02–0.14), and duration of disease (OR = 1.01, 95% CI 1–1.02). Conclusion: Considering the low adherence in users of medications of Iranian traditional medicine, health care practitioners need to be trained in adherence and the influencing factors and also to use some interventions to increase the adherence. PMID:26985436

  6. Evaluation of adherence to therapy in patients of chronic kidney disease

    PubMed Central

    Sontakke, Smita; Budania, Ritu; Bajait, Chaitali; Jaiswal, Kavita; Pimpalkhute, Sonali

    2015-01-01

    Objective: To evaluate adherence to medication and study factors associated with non-adherence in chronic kidney disease (CKD) patients. Methods: A prospective, cross-sectional, questionnaire based study was conducted in Nephrology department of a super specialty hospital. Patients above 18 years of age, suffering from CKD from six months or more were interviewed using self-designed, semi-structured questionnaire to get information about adherence to medication, diet restriction and lifestyle modification (n = 150). Morisky medication adherence questionnaire was used to calculate overall adherence. In this higher score indicates poor adherence. Main outcome measures included prevalence of non-adherence and factors associated with the same. Results: Average number of medicines taken by each patient was 8.0+1.612 (mean+SD) per day. Non-adherence to medication schedule was reported in 34% patients. Common causes of non-adherence were high cost (21.3%), complex dosing schedule (20%), fear of adverse effects (16%). Sixty-eight% patients were not aware about importance of taking each medicine. Sixteen% stopped taking medicines due to high cost. Forty-two% suggested that government should adopt measures to provide free medicines to poor patients. In Morisky medication adherence questionnaire high, medium and low adherence was reported in 7.3%, 55.3% and 37.3% of patients, respectively. Moderately positive correlation was observed between poor adherence and number of concurrent illnesses and number of medicines taken. Conclusion: Since majority of patients were not aware about importance of taking each medicine, creating awareness about the same is essential for improving adherence to therapy. Measures to provide free medicines to non-affording patients need to be implemented since high cost was other major cause of non-adherence. PMID:26729961

  7. The bdr gene families of the Lyme disease and relapsing fever spirochetes: potential influence on biology, pathogenesis, and evolution.

    PubMed

    Roberts, D M; Carlyon, J A; Theisen, M; Marconi, R T

    2000-01-01

    Species of the genus Borrelia cause human and animal infections, including Lyme disease, relapsing fever, and epizootic bovine abortion. The borrelial genome is unique among bacterial genomes in that it is composed of a linear chromosome and a series of linear and circular plasmids. The plasmids exhibit significant genetic redundancy and carry 175 paralogous gene families, most of unknown function. Homologous alleles on different plasmids could influence the organization and evolution of the Borrelia genome by serving as foci for interplasmid homologous recombination. The plasmid-carried Borrelia direct repeat (bdr) gene family encodes polymorphic, acidic proteins with putative phosphorylation sites and transmembrane domains. These proteins may play regulatory roles in Borrelia. We describe recent progress in the characterization of the Borrelia bdr genes and discuss the possible influence of this gene family on the biology, pathogenesis, and evolution of the Borrelia genome. PMID:10756144

  8. Suboptimal inhaler medication adherence and incorrect technique are common among chronic obstructive pulmonary disease patients.

    PubMed

    Sriram, Krishna B; Percival, Matthew

    2016-02-01

    Patients with chronic obstructive pulmonary disease (COPD) are routinely prescribed one or more inhaled medications. Adherence to inhaler medications and correct inhaler device technique are crucial to successful COPD management. The goals of this study were to estimate adherence and inhaler technique in a cohort of COPD patients. This was an observational study conducted on a sample of 150 COPD patients. Medication adherence was assessed using the Medication Adherence Report Scale (MARS). Inhaler technique was assessed using standardized checklists. Clinical data were collected using a proforma. Of the 150 patients (mean age 70.3 years, 52% male), 58% reported suboptimal adherence (MARS ≤ 24). High adherence to therapy (MARS = 25) was associated with older age (p = 0.001), but not any of the other studied variables. Medication non-adherence was not associated with COPD exacerbations. Errors (≥ 1) in inhaler technique were common across all of the types of inhaler devices reportedly used by patients, with the highest proportion of errors among Turbuhaler users (83%) and the least proportion of errors among Handihaler users (50%). No clinical variables were associated with errors in inhaler technique. Suboptimal adherence and errors in inhaler technique are common among COPD patients. No clinical variables to assist in the prediction of medication non-adherence and poor inhaler technique were identifiable. Consequently, regular assessment of medication adherence and inhaler technique should be incorporated into routine clinical practice to facilitate improved health outcomes among patients with COPD. PMID:26396159

  9. A validated measure of adherence to antibiotic prophylaxis in children with sickle cell disease

    PubMed Central

    Duncan, Natalie A; Kronenberger, William G; Hampton, Kisha C; Bloom, Ellen M; Rampersad, Angeli G; Roberson, Christopher P; Shapiro, Amy D

    2016-01-01

    Background Antibiotic prophylaxis is a mainstay in sickle cell disease management. However, adherence is estimated at only 66%. This study aimed to develop and validate a Sickle Cell Antibiotic Adherence Level Evaluation (SCAALE) to promote systematic and detailed adherence evaluation. Methods A 28-item questionnaire was created, covering seven adherence areas. General Adherence Ratings from the parent and one health care provider and medication possession ratios were obtained as validation measures. Results Internal consistency was very good to excellent for the total SCAALE (α=0.89) and four of the seven subscales. Correlations between SCAALE scores and validation measures were strong for the total SCAALE and five of the seven subscales. Conclusion The SCAALE provides a detailed, quantitative, multidimensional, and global measurement of adherence and can promote clinical care and research. PMID:27354768

  10. Factors affecting adherence to a gluten-free diet in children with celiac disease

    PubMed Central

    MacCulloch, Katherine; Rashid, Mohsin

    2014-01-01

    BACKGROUND: The treatment of celiac disease is a strict, life-long gluten-free (GF) diet. This diet is complex and can be challenging. Factors affecting adherence to the GF diet are important to identify for improving adherence. OBJECTIVE: To identify factors that inhibit or improve adherence to a GF diet in children with celiac disease. METHODS: Patients (<18 years of age) with biopsy-confirmed celiac disease followed by the gastroenterology service at a tertiary care paediatric institution were surveyed using a mailed questionnaire. Factors influencing adherence to a GF diet were scored from 1 to 10 based on how often they were problematic (1 = never, 10 = always). Parents of patients <13 years of age were instructed to complete the survey with their child. Adolescents ≥13 years of age were asked to complete the survey themselves. RESULTS: Of 253 subjects, 126 completed the survey; the median age was 12 years (range two to 18 years). Forty percent were adolescents. Overall, participants reported good adherence at home and school, but lower adherence at social events. Adolescents reported lower adherence compared with parents. Availability of GF foods and cost were the most significant barriers. Other factors identified to help with a GF diet included education for schools/restaurants and improved government support. CONCLUSIONS: Availability, cost and product labelling are major barriers to adherence to a GF diet. Better awareness, improved labelling and income support are needed to help patients. PMID:25332660

  11. Polymorphonuclear leucocytes in Crohn's disease and ulcerative proctocolitis: association between enhanced adherence to nylon fibre and disease variables.

    PubMed

    Cason, J; Ainley, C C; Wolstencroft, R A; Thompson, R P

    1988-03-01

    The adherence of polymorphonuclear leucocytes (PMN) to nylon fibre was investigated in patients with Crohn's disease, ulcerative proctocolitis, and anorexia nervosa, and compared with changes of circulating PMNs, C reactive protein concentrations, erythrocyte sedimentation rates, and clinical assessment of disease activity. PMN adherence was in excess of the maximum value detected for healthy subjects in 14 of 25 patients with Crohn's disease and two of 10 with proctocolitis, but it was within the normal range for all eight with anorexia nervosa. High adherence in Crohn's disease, however, was not associated with quantitative or qualitative changes of PMN populations, absolute concentrations of C reactive protein, erythrocyte sedimentation rates, disease severity, drug regimens, malnutrition, or zinc deficiency. High PMN adherence in Crohn's disease may therefore reflect the activation in vivo of normal PMN by humoral factors. PMID:3360954

  12. Complete genome sequence of Treponema pallidum, the syphilis spirochete.

    PubMed

    Fraser, C M; Norris, S J; Weinstock, G M; White, O; Sutton, G G; Dodson, R; Gwinn, M; Hickey, E K; Clayton, R; Ketchum, K A; Sodergren, E; Hardham, J M; McLeod, M P; Salzberg, S; Peterson, J; Khalak, H; Richardson, D; Howell, J K; Chidambaram, M; Utterback, T; McDonald, L; Artiach, P; Bowman, C; Cotton, M D; Fujii, C; Garland, S; Hatch, B; Horst, K; Roberts, K; Sandusky, M; Weidman, J; Smith, H O; Venter, J C

    1998-07-17

    The complete genome sequence of Treponema pallidum was determined and shown to be 1,138,006 base pairs containing 1041 predicted coding sequences (open reading frames). Systems for DNA replication, transcription, translation, and repair are intact, but catabolic and biosynthetic activities are minimized. The number of identifiable transporters is small, and no phosphoenolpyruvate:phosphotransferase carbohydrate transporters were found. Potential virulence factors include a family of 12 potential membrane proteins and several putative hemolysins. Comparison of the T. pallidum genome sequence with that of another pathogenic spirochete, Borrelia burgdorferi, the agent of Lyme disease, identified unique and common genes and substantiates the considerable diversity observed among pathogenic spirochetes. PMID:9665876

  13. [Modifying habits and treatment adherence, essential for controlling the chronic disease].

    PubMed

    Pisano González, Marta M; González Pisano, Ana

    2014-01-01

    Therapeutic adherence is defined as the extent to which a person's behavior (taking medications, following a diet and changes in lifestyle) coincides with health recommendations (WHO, 2004). We can deduce that is a multiple, complex and changing phenomenon, that there can be total or partial adherence to a treatment, and depending on timing and circumstances. Lack of adherence is a worrying problem; due to its great magnitude and complexity (over two hundred factors) it is responsible for the increased morbid-mortality, complications, hospital admissions, health costs, and dissatisfaction of the user and health professionals. In this paper we develop effective interventions in changing habits and improving adherence: cognitive (education and improved communication), behavior and motivation. Interventions areas include pharmacological treatments, habits and life style, as well as social and family support. The most effective model emphasizes self-care and self-responsibility of the user to manage their disease and increase adherence. PMID:24369770

  14. Phylogenetic analysis of the spirochetes.

    PubMed Central

    Paster, B J; Dewhirst, F E; Weisburg, W G; Tordoff, L A; Fraser, G J; Hespell, R B; Stanton, T B; Zablen, L; Mandelco, L; Woese, C R

    1991-01-01

    The 16S rRNA sequences were determined for species of Spirochaeta, Treponema, Borrelia, Leptospira, Leptonema, and Serpula, using a modified Sanger method of direct RNA sequencing. Analysis of aligned 16S rRNA sequences indicated that the spirochetes form a coherent taxon composed of six major clusters or groups. The first group, termed the treponemes, was divided into two subgroups. The first treponeme subgroup consisted of Treponema pallidum, Treponema phagedenis, Treponema denticola, a thermophilic spirochete strain, and two species of Spirochaeta, Spirochaeta zuelzerae and Spirochaeta stenostrepta, with an average interspecies similarity of 89.9%. The second treponeme subgroup contained Treponema bryantii, Treponema pectinovorum, Treponema saccharophilum, Treponema succinifaciens, and rumen strain CA, with an average interspecies similarity of 86.2%. The average interspecies similarity between the two treponeme subgroups was 84.2%. The division of the treponemes into two subgroups was verified by single-base signature analysis. The second spirochete group contained Spirochaeta aurantia, Spirochaeta halophila, Spirochaeta bajacaliforniensis, Spirochaeta litoralis, and Spirochaeta isovalerica, with an average similarity of 87.4%. The Spirochaeta group was related to the treponeme group, with an average similarity of 81.9%. The third spirochete group contained borrelias, including Borrelia burgdorferi, Borrelia anserina, Borrelia hermsii, and a rabbit tick strain. The borrelias formed a tight phylogenetic cluster, with average similarity of 97%. THe borrelia group shared a common branch with the Spirochaeta group and was closer to this group than to the treponemes. A single spirochete strain isolated fromt the shew constituted the fourth group. The fifth group was composed of strains of Serpula (Treponema) hyodysenteriae and Serpula (Treponema) innocens. The two species of this group were closely related, with a similarity of greater than 99%. Leptonema illini

  15. Interaction of the Lyme Disease Spirochete Borrelia burgdorferi with Brain Parenchyma Elicits Inflammatory Mediators from Glial Cells as Well as Glial and Neuronal Apoptosis

    PubMed Central

    Ramesh, Geeta; Borda, Juan T.; Dufour, Jason; Kaushal, Deepak; Ramamoorthy, Ramesh; Lackner, Andrew A.; Philipp, Mario T.

    2008-01-01

    Lyme neuroborreliosis, caused by the spirochete Borrelia burgdorferi, often manifests by causing neurocognitive deficits. As a possible mechanism for Lyme neuroborreliosis, we hypothesized that B. burgdorferi induces the production of inflammatory mediators in the central nervous system with concomitant neuronal and/or glial apoptosis. To test our hypothesis, we constructed an ex vivo model that consisted of freshly collected slices from brain cortex of a rhesus macaque and allowed live B. burgdorferi to penetrate the tissue. Numerous transcripts of genes that regulate inflammation as well as oligodendrocyte and neuronal apoptosis were significantly altered as assessed by DNA microarray analysis. Transcription level increases of 7.43-fold (P = 0.005) for the cytokine tumor necrosis factor-α and 2.31-fold (P = 0.016) for the chemokine interleukin (IL)-8 were also detected by real-time-polymerase chain reaction array analysis. The immune mediators IL-6, IL-8, IL-1β, COX-2, and CXCL13 were visualized in glial cells in situ by immunofluorescence staining and confocal microscopy. Concomitantly, significant proportions of both oligodendrocytes and neurons undergoing apoptosis were present in spirochete-stimulated tissues. IL-6 production by astrocytes in addition to oligodendrocyte apoptosis were also detected, albeit at lower levels, in rhesus macaques that had received in vivo intraparenchymal stereotaxic inoculations of live B. burgdorferi. These results provide proof of concept for our hypothesis that B. burgdorferi produces inflammatory mediators in the central nervous system, accompanied by glial and neuronal apoptosis. PMID:18832582

  16. Interaction of the Lyme disease spirochete Borrelia burgdorferi with brain parenchyma elicits inflammatory mediators from glial cells as well as glial and neuronal apoptosis.

    PubMed

    Ramesh, Geeta; Borda, Juan T; Dufour, Jason; Kaushal, Deepak; Ramamoorthy, Ramesh; Lackner, Andrew A; Philipp, Mario T

    2008-11-01

    Lyme neuroborreliosis, caused by the spirochete Borrelia burgdorferi, often manifests by causing neurocognitive deficits. As a possible mechanism for Lyme neuroborreliosis, we hypothesized that B. burgdorferi induces the production of inflammatory mediators in the central nervous system with concomitant neuronal and/or glial apoptosis. To test our hypothesis, we constructed an ex vivo model that consisted of freshly collected slices from brain cortex of a rhesus macaque and allowed live B. burgdorferi to penetrate the tissue. Numerous transcripts of genes that regulate inflammation as well as oligodendrocyte and neuronal apoptosis were significantly altered as assessed by DNA microarray analysis. Transcription level increases of 7.43-fold (P = 0.005) for the cytokine tumor necrosis factor-alpha and 2.31-fold (P = 0.016) for the chemokine interleukin (IL)-8 were also detected by real-time-polymerase chain reaction array analysis. The immune mediators IL-6, IL-8, IL-1beta, COX-2, and CXCL13 were visualized in glial cells in situ by immunofluorescence staining and confocal microscopy. Concomitantly, significant proportions of both oligodendrocytes and neurons undergoing apoptosis were present in spirochete-stimulated tissues. IL-6 production by astrocytes in addition to oligodendrocyte apoptosis were also detected, albeit at lower levels, in rhesus macaques that had received in vivo intraparenchymal stereotaxic inoculations of live B. burgdorferi. These results provide proof of concept for our hypothesis that B. burgdorferi produces inflammatory mediators in the central nervous system, accompanied by glial and neuronal apoptosis. PMID:18832582

  17. Interventions to enhance adherence to dietary advice for preventing and managing chronic diseases in adults

    PubMed Central

    Desroches, Sophie; Lapointe, Annie; Ratté, Stéphane; Gravel, Karine; Légaré, France; Turcotte, Stéphane

    2016-01-01

    Background It has been recognized that poor adherence can be a serious risk to the health and wellbeing of patients, and greater adherence to dietary advice is a critical component in preventing and managing chronic diseases. Objectives To assess the effects of interventions for enhancing adherence to dietary advice for preventing and managing chronic diseases in adults. Search methods We searched the following electronic databases up to 29 September 2010: The Cochrane Library (issue 9 2010), PubMed, EMBASE (Embase.com), CINAHL (Ebsco) and PsycINFO (PsycNET) with no language restrictions. We also reviewed: a) recent years of relevant conferences, symposium and colloquium proceedings and abstracts; b) web-based registries of clinical trials; and c) the bibliographies of included studies. Selection criteria We included randomized controlled trials that evaluated interventions enhancing adherence to dietary advice for preventing and managing chronic diseases in adults. Studies were eligible if the primary outcome was the client’s adherence to dietary advice. We defined ‘client’ as an adult participating in a chronic disease prevention or chronic disease management study involving dietary advice. Data collection and analysis Two review authors independently assessed the eligibility of the studies. They also assessed the risk of bias and extracted data using a modified version of the Cochrane Consumers and Communication Review Group data extraction template. Any discrepancies in judgement were resolved by discussion and consensus, or with a third review author. Because the studies differed widely with respect to interventions, measures of diet adherence, dietary advice, nature of the chronic diseases and duration of interventions and follow-up, we conducted a qualitative analysis. We classified included studies according to the function of the intervention and present results in a narrative table using vote counting for each category of intervention. Main results

  18. Systemic Arterial Hypertension in the Emergency Service: medication adherence and understanding of this disease

    PubMed Central

    Vancini-Campanharo, Cássia Regina; Oliveira, Gabriella Novelli; Andrade, Thaisa Fernanda Landim; Okuno, Meiry Fernanda Pinto; Lopes, Maria Carolina Barbosa Teixeira; Batista, Ruth Ester Assayag

    2015-01-01

    Objective: to identify the epidemiological profile of hypertension patients, how much they understand about the disease and the rate of adherence to treatment by these patients who had been hospitalized in the Brazilian emergency service. Methods: this cross-sectional study was performed with 116 patients, both male and female and aged over 18 years, who had been hospitalized in the Emergency Service of a University Hospital between March and June, 2013. The studied variables were data referring to socio-demographics, comorbidities, physical activity and knowledge regarding the disease. Patient adherence to treatment and the identification of the barriers were respectively evaluated using the Morisky test and the Brief Medication Questionnaire. Results: most of the patients involved in this study were women (55%), with white skin color (55%), married (51%), retirees or pensioners (64%) and with a low educational level (58%). Adherence to treatment, in most cases (55%), was moderate and the most prevalent adherence barrier was recall (67%). When medication was acquired at no cost to the patient, there was greater adherence to treatment. Conclusion: this study's patients had a moderate understanding about the disease. The high correlation between the number of drugs used and the recall barrier suggests that monotherapy is an option that can facilitate treatment adherence and reduce how often the patients forget to take their medication. PMID:26626007

  19. Measuring beliefs about gluten free diet adherence in adult coeliac disease using the theory of planned behaviour.

    PubMed

    Sainsbury, Kirby; Mullan, Barbara

    2011-04-01

    The theory of planned behaviour (TPB) was used to elicit the salient beliefs about gluten free diet (GFD) adherence in adults with coeliac disease (CD) and to design a TPB questionnaire to predict adherence levels. This questionnaire was administered to 265 CD participants with adherence and quality of life (QOL) measures, a GFD knowledge test, and self-reported psychiatric history. Regression analyses were used to test the fit of the TPB in predicting adherence, and to determine the nature of the relationships between adherence, QOL, knowledge, and psychiatric history. The TPB combined with self-reported depression and anxiety, and QOL explained significant variance in intention (41.0%) and adherence (33.7%). Poorer dietary adherence and psychiatric history were also associated with lower QOL. Findings suggest that the TPB provides an adequate model for predicting GFD adherence in CD, and the presence of psychiatric conditions represents a potential intervention target to improve adherence and QOL. PMID:21277925

  20. Practical strategies for enhancing adherence to treatment regimen in inflammatory bowel disease.

    PubMed

    Greenley, Rachel N; Kunz, Jennifer H; Walter, Jennifer; Hommel, Kevin A

    2013-06-01

    Promoting adherence to treatment among pediatric and adult patients with inflammatory bowel disease (IBD) is a critical yet challenging task for health care providers. Several existing interventions to enhance adherence among individuals with IBD offer useful information about practical strategies to enhance adherence. The current review article has 3 goals. First, the review provides a context for understanding treatment regimen adherence in IBD by reviewing key definitional, measurement, and conceptual challenges in this area. Next, published studies focused on interventions to enhance adherence in IBD are briefly summarized, followed by a synthesis of practical adherence promotion strategies for use in IBD by health care providers. Strategies are distinguished by the level of evidence supporting their utility as well as by age group. Finally, recommendations for future research to facilitate the development and implementation of practical, evidence-based strategies for adherence promotion in IBD are provided. Findings from the literature review suggest that strategies including education, regimen simplification, and use of reminder systems and organizational strategies (e.g., pill boxes) are likely to be best suited for addressing accidental nonadherence. In contrast, addressing motivational issues, teaching problem-solving skills, and addressing problematic patterns of family functioning are more likely to benefit individuals displaying intentional nonadherence. PMID:23635715

  1. Practical Strategies for Enhancing Adherence to Treatment Regimen in Inflammatory Bowel Disease

    PubMed Central

    Greenley, Rachel N.; Kunz, Jennifer H.; Walter, Jennifer; Hommel, Kevin A.

    2013-01-01

    Promoting adherence to treatment among pediatric and adult patients with inflammatory bowel disease (IBD) is a critical yet challenging task for health care providers. Several existing interventions to enhance adherence among individuals with IBD offer useful information about practical strategies to enhance adherence. The current review article has 3 goals. First, the review provides a context for understanding treatment regimen adherence in IBD by reviewing key definitional, measurement, and conceptual challenges in this area. Next, published studies focused on interventions to enhance adherence in IBD are briefly summarized, followed by a synthesis of practical adherence promotion strategies for use in IBD by health care providers. Strategies are distinguished by the level of evidence supporting their utility as well as by age group. Finally, recommendations for future research to facilitate the development and implementation of practical, evidence-based strategies for adherence promotion in IBD are provided. Findings from the literature review suggest that strategies including education, regimen simplification, and use of reminder systems and organizational strategies (e.g., pill boxes) are likely to be best suited for addressing accidental nonadherence. In contrast, addressing motivational issues, teaching problem-solving skills, and addressing problematic patterns of family functioning are more likely to benefit individuals displaying intentional nonadherence. PMID:23635715

  2. Spirochete antigens persist near cartilage after murine Lyme borreliosis therapy

    PubMed Central

    Bockenstedt, Linda K.; Gonzalez, David G.; Haberman, Ann M.; Belperron, Alexia A.

    2012-01-01

    An enigmatic feature of Lyme disease is the slow resolution of musculoskeletal symptoms that can continue after treatment, with some patients developing an inflammatory arthritis that becomes refractory to antibiotic therapy. Using intravital microscopy and the mouse model of Lyme borreliosis, we observed that Borrelia burgdorferi antigens, but not infectious spirochetes, can remain adjacent to cartilage for extended periods after antibiotic treatment. B. burgdorferi was not recovered by culture or xenodiagnosis with ticks after antibiotic treatment of WT mice and all but one of the immunodeficient mice with heightened pathogen burden due to impaired TLR responsiveness. Amorphous GFP+ deposits were visualized by intravital microscopy in the entheses of antibiotic-treated mice infected with GFP-expressing spirochetes and on the ear cartilage surface in sites where immunofluorescence staining detected spirochete antigens. Naive mice were not infected by tissue transplants from antibiotic-treated mice even though transplants contained spirochete DNA. Tissue homogenates from antibiotic-treated mice induced IgG reactive with B. burgdorferi antigens after immunization of naive mice and stimulated TNF-α production from macrophages in vitro. This is the first direct demonstration that inflammatory B. burgdorferi components can persist near cartilaginous tissue after treatment for Lyme disease. We propose that these deposits could contribute to the development of antibiotic-refractory Lyme arthritis. PMID:22728937

  3. Improving medication adherence for chronic disease using integrated e-technologies.

    PubMed

    Dixon, Brian E; Jabour, Abdulrahman M; Phillips, Erin O'Kelly; Marrero, David G

    2013-01-01

    Diabetes mellitus (DM) is a chronic disease affecting more than 285 people worldwide and the fourth leading cause of death. Increasing evidence suggests that many DM patients have poor adherence with prescribed medication therapies, impacting clinical outcomes. Patients' barriers to medication adherence and the extent to which barriers contribute to poor outcomes, however, are not routinely assessed. We designed a dashboard for an electronic health record system to integrate DM disease and medication data, including patient-reported barriers to adherence. Processes to support routine capture of data from patients are also being explored. The dashboard is being evaluated at multiple ambulatory clinics to examine whether integrated electronic tools can support patient-centered decision-making processes involving complex medication regimens for DM and other chronic diseases. PMID:23920703

  4. Treatment adherence to disease-modifying antirheumatic drugs in Chinese patients with rheumatoid arthritis

    PubMed Central

    Xia, Yunfei; Yin, Rulan; Fu, Ting; Zhang, Lijuan; Zhang, Qiuxiang; Guo, Genkai; Li, Liren; Gu, Zhifeng

    2016-01-01

    Objective Nonadherence in rheumatoid arthritis (RA) patients using disease-modifying antirheumatic drugs (DMARDs) may lead to joint damage and function loss. The aim of this cross-sectional study was to explore Chinese RA patients’ adherence rates and investigate potential risk factors for nonadherence. Methods A total of 122 RA patients were recruited from the Affiliated Hospital of Nantong University from January 2014 to April 2015. Patients were asked to complete a set of standardized self-report questionnaires (Compliance Questionnaire on Rheumatology, Health Assessment Questionnaire, Short Form-36 questionnaire, 28-joint Disease Activity Score, Hospital Anxiety and Depression Scale, and Visual Analog Scale). Independent samples t-tests, chi-square analyses, and logistic regression modeling were used to analyze these data. Results Based on Compliance Questionnaire on Rheumatology, 38% of the patients adhered to DMARDs. Adherence was associated with education, income, depression, and the total number of DMARDs. Other demographic and clinical characteristics were not associated with adherence. Logistic regression models identified income, depression, and the total number of DMARDs as predictors of medication nonadherence. Conclusion In this study, 62% of patients with RA were not adherent to their DMARD prescription. Education, income, depression, and the total number of DMARDs were associated with medication adherence, and income, depression, and the total number of DMARDs were independent predictors of medication adherence in patients with RA. These findings could help medical personnel develop helpful interventions to improve adherence in RA patients by paying more attention to the patients with these accompanying risk factors and, finally, improve RA patients’ quality of life. PMID:27217726

  5. Cristispira from oyster styles: complex morphology of large symbiotic spirochetes

    NASA Technical Reports Server (NTRS)

    Margulis, L.; Nault, L.; Sieburth, J. M.

    1991-01-01

    Crystalline styles (digestive organs) of bivalve mollusks provide the habitat for highly motile bacteria. Styles from freshly-collected oysters, Crassostrea virginica, were studied by electron microscopy; Cristispira spirochetes were abundant in these organs. Detailed study reveals these spirochetes to be among the most complex prokaryotic cells known. More than 600 periplasmic flagella and an adhering outer lipoprotein membrane (e.g., a 270 degrees sillon) form the ultrastructural basis for the "crista," first described by light microscopy. Unique rosette structures corresponding to the "chambers" or "ovoid inclusions" of light microscopy were detected at the periphery of all protoplasmic cylinders. Polar organelles and linearly aligned flagellar insertions are conspicuous. In size and complexity, Cristispira more resembles Pillotina, Diplocalyx, Clevelandina and Hollandina (large spirochetes symbiotic in termites) than it does Treponema. Cristispira pectinis (Gross, 1910), the type species; Spirillum ostrea (Noguchi, 1921); and another, less frequent bacterial symbiont are the predominant inhabitants of the dense style matrix. The ultrastructure of the spirillum and an electron micrograph of the third bacterium are shown.

  6. Chemoreceptors and Flagellar Motors Are Subterminally Located in Close Proximity at the Two Cell Poles in Spirochetes ▿ ‡

    PubMed Central

    Xu, Hongbin; Raddi, Gianmarco; Liu, Jun; Charon, Nyles W.; Li, Chunhao

    2011-01-01

    Green fluorescent protein (GFP) fusions, immunofluorescence microscopy, and cryo-electron tomography revealed that the chemoreceptors of the Lyme disease spirochete Borrelia burgdorferi form long, thin arrays near both cell poles. These arrays are in close proximity to the flagellar motors. This information provides a basis for further understanding motility, chemotaxis, and protein localization in spirochetes. PMID:21441520

  7. Destruction of spirochete Borrelia burgdorferi round-body propagules (RBs) by the antibiotic Tigecycline

    PubMed Central

    Brorson, Øystein; Brorson, Sverre-Henning; Scythes, John; MacAllister, James; Wier, Andrew; Margulis, Lynn

    2009-01-01

    Persistence of tissue spirochetes of Borrelia burgdorferi as helices and round bodies (RBs) explains many erythema-Lyme disease symptoms. Spirochete RBs (reproductive propagules also called coccoid bodies, globular bodies, spherical bodies, granules, cysts, L-forms, sphaeroplasts, or vesicles) are induced by environmental conditions unfavorable for growth. Viable, they grow, move and reversibly convert into motile helices. Reversible pleiomorphy was recorded in at least six spirochete genera (>12 species). Penicillin solution is one unfavorable condition that induces RBs. This antibiotic that inhibits bacterial cell wall synthesis cures neither the second “Great Imitator” (Lyme borreliosis) nor the first: syphilis. Molecular-microscopic techniques, in principle, can detect in animals (insects, ticks, and mammals, including patients) helices and RBs of live spirochetes. Genome sequences of B. burgdorferi and Treponema pallidum spirochetes show absence of >75% of genes in comparison with their free-living relatives. Irreversible integration of spirochetes at behavioral, metabolic, gene product and genetic levels into animal tissue has been documented. Irreversible integration of spirochetes may severely impair immunological response such that they persist undetected in tissue. We report in vitro inhibition and destruction of B. burgdorferi (helices, RBs = “cysts”) by the antibiotic Tigecycline (TG; Wyeth), a glycylcycline protein-synthesis inhibitor (of both 30S and 70S ribosome subunits). Studies of the pleiomorphic life history stages in response to TG of both B. burgdorferi and Treponema pallidum in vivo and in vitro are strongly encouraged. PMID:19843691

  8. Cysteinyl leukotriene overproduction in aspirin-exacerbated respiratory disease is driven by platelet-adherent leukocytes

    PubMed Central

    Laidlaw, Tanya M.; Kidder, Molly S.; Bhattacharyya, Neil; Xing, Wei; Shen, Shiliang; Milne, Ginger L.; Castells, Mariana C.; Chhay, Heng

    2012-01-01

    Cysteinyl leukotriene (cysLT) overproduction is a hallmark of aspirin-exacerbated respiratory disease (AERD), but its mechanism is poorly understood. Because adherent platelets can convert the leukocyte-derived precursor leukotriene (LT)A4 to LTC4, the parent cysLT, through the terminal enzyme LTC4 synthase, we investigated the contribution of platelet-dependent transcellular cysLT production in AERD. Nasal polyps from subjects with AERD contained many extravascular platelets that colocalized with leukocytes, and the percentages of circulating neutrophils, eosinophils, and monocytes with adherent platelets were markedly higher in the blood of subjects with AERD than in aspirin-tolerant controls. Platelet-adherent subsets of leukocytes had higher expression of several adhesion markers than did platelet nonadherent subsets. Adherent platelets contributed more than half of the total LTC4 synthase activity of peripheral blood granulocytes, and they accounted for the higher level of LTC4 generation by activated granulocytes from subjects with AERD compared with aspirin-tolerant controls. Urinary LTE4 levels, a measure of systemic cysLT production, correlated strongly with percentages of circulating platelet-adherent granulocytes. Because platelet adherence to leukocytes allows for both firm adhesion to endothelial cells and augmented transcellular conversion of leukotrienes, a disturbance in platelet-leukocyte interactions may be partly responsible for the respiratory tissue inflammation and the overproduction of cysLTs that characterize AERD. PMID:22262771

  9. The Seven Stages of Man: The Role of Developmental Stage on Medication Adherence in Respiratory Diseases.

    PubMed

    Costello, Richard W; Foster, Juliet M; Grigg, Jonathan; Eakin, Michelle N; Canonica, Walter; Yunus, Fasail; Ryan, Dermot

    2016-01-01

    The circumstances and drivers of the decision to initiate, implement, or persist with a medication differ for individuals at each developmental stage. For school-age children with asthma, the social environment of their family's cultural beliefs and the influence of peer networks and school policies are strong determinants of medication adherence. The stage of adolescence can be a particularly challenging time because there is a reduction in parental supervision of asthma management as the young person strives to become more autonomous. To illustrate the importance of such factors, adherence interventions in children and young adults with asthma have used peer-based supports and social supports, particularly social media platforms. In older patients, it is internal rather than external factors and age-related decline that pose challenges to medication adherence. Seniors face the challenges of polypharmacy, reduced social support, increased isolation, and loss of cognitive function. Strategies to promote adherence must be tailored to the developmental stage and respective behavioral determinants of the target group. This review considers the different attitudes toward medication and the different adherence behaviors in young and elderly patients with chronic respiratory conditions, specifically asthma and chronic obstructive pulmonary disease. Opportunities to intervene to optimize adherence are suggested. PMID:27587315

  10. Treatment adherence in paediatric inflammatory bowel disease: perceptions from adolescent patients and their families.

    PubMed

    Hommel, Kevin A; Odell, Shannon; Sander, Emily; Baldassano, Robert N; Barg, Frances K

    2011-01-01

    The objective of this study was to examine patient- and parent-perceived factors that impact adherence to inflammatory bowel disease treatment using a qualitative descriptive individual interview approach. Sixteen adolescents and their parents were recruited from May through August 2007 and interviewed about medication adherence using an open-ended semi-structured interview format. Interviews were audio recorded, transcribed, and coded into themes. Parent-child dyads identified forgetting, interfering activities, parent-child conflict and oppositional behaviour and inadequate planning for treatment as challenges to adherence. Participants reported that family support and good parent-child relationships, routines, monitoring and reminding and organisational tools such as pill boxes facilitated treatment adherence. Other issues that emerged included immediacy of treatment effects and parent-adolescent responsibility for treatment. Patients and parents experience a number of challenges related to adherence within behavioural, educational, organisational and health belief domains. Behavioural interventions should focus on these issues, reduction of perceived barriers, and effective transition of responsibility for treatment adherence. Future research considerations are discussed. PMID:21143544

  11. Alexithymia, Assertiveness and Psychosocial Functioning in HIV: Implications for Medication Adherence and Disease Severity.

    PubMed

    McIntosh, Roger C; Ironson, Gail; Antoni, Michael; Fletcher, Mary Ann; Schneiderman, Neil

    2016-02-01

    Psychosocial function and adherence to antiretroviral regimen are key factors in human immunodeficiency virus (HIV) disease management. Alexithymia (AL) is a trait deficit in the ability to identify and describe feelings, emotions and bodily sensations. A structural equation model was used to test whether high levels of AL indirectly relate to greater non-adherent behavior and HIV disease severity via psychosocial dysfunction. Blood draws for HIV-1 viral load and CD4 T-lymphocyte, along with psychosocial surveys were collected from 439 HIV positive adults aged 18-73 years. The structural model supports significant paths from: (1) AL to non-active patient involvement, psychological distress, and lower social support, (2) psychological distress and non-active involvement to non-adherent behavior, and (3) non-adherence to greater HIV disease severity (CFI = .97, RMSEA = .04, SRMR = .05). A second model confirmed the intermediary effect of greater patient assertiveness on the path from AL to social support and non-active patient involvement (CFI = .94, RMSEA = .04, SRMR = .05). Altogether, AL is indirectly linked with HIV disease management through it's association with poor psychosocial function, however greater patient assertiveness buffers the negative impact of AL on relationship quality with healthcare providers and members of one's social support network. PMID:26143246

  12. Sulfated carbohydrate compounds prevent microbial adherence by sexually transmitted disease pathogens.

    PubMed Central

    Herold, B C; Siston, A; Bremer, J; Kirkpatrick, R; Wilbanks, G; Fugedi, P; Peto, C; Cooper, M

    1997-01-01

    Heparan sulfate (HS) serves as a receptor for adherence of herpes simplex viruses, Chlamydia trachomatis, Neisseria gonorrhoeae, and, indirectly, human immunodeficiency virus. Using primary human culture systems, we identified sulfated carbohydrate compounds that resemble HS and competitively inhibit infection by these pathogens. These compounds are candidates for intravaginal formulations for the prevention of sexually transmitted diseases. PMID:9420059

  13. Impact of mHealth Chronic Disease Management on Treatment Adherence and Patient Outcomes: A Systematic Review

    PubMed Central

    Hamine, Saee; Faulx, Dunia; Green, Beverly B; Ginsburg, Amy Sarah

    2015-01-01

    Background Adherence to chronic disease management is critical to achieving improved health outcomes, quality of life, and cost-effective health care. As the burden of chronic diseases continues to grow globally, so does the impact of non-adherence. Mobile technologies are increasingly being used in health care and public health practice (mHealth) for patient communication, monitoring, and education, and to facilitate adherence to chronic diseases management. Objective We conducted a systematic review of the literature to evaluate the effectiveness of mHealth in supporting the adherence of patients to chronic diseases management (“mAdherence”), and the usability, feasibility, and acceptability of mAdherence tools and platforms in chronic disease management among patients and health care providers. Methods We searched PubMed, Embase, and EBSCO databases for studies that assessed the role of mAdherence in chronic disease management of diabetes mellitus, cardiovascular disease, and chronic lung diseases from 1980 through May 2014. Outcomes of interest included effect of mHealth on patient adherence to chronic diseases management, disease-specific clinical outcomes after intervention, and the usability, feasibility, and acceptability of mAdherence tools and platforms in chronic disease management among target end-users. Results In all, 107 articles met all inclusion criteria. Short message service was the most commonly used mAdherence tool in 40.2% (43/107) of studies. Usability, feasibility, and acceptability or patient preferences for mAdherence interventions were assessed in 57.9% (62/107) of studies and found to be generally high. A total of 27 studies employed randomized controlled trial (RCT) methods to assess impact on adherence behaviors, and significant improvements were observed in 15 of those studies (56%). Of the 41 RCTs that measured effects on disease-specific clinical outcomes, significant improvements between groups were reported in 16 studies (39

  14. Pyruvate Protects Pathogenic Spirochetes from H2O2 Killing

    PubMed Central

    Troxell, Bryan; Zhang, Jun-Jie; Bourret, Travis J.; Zeng, Melody Yue; Blum, Janice; Gherardini, Frank; Hassan, Hosni M.; Yang, X. Frank

    2014-01-01

    Pathogenic spirochetes cause clinically relevant diseases in humans and animals, such as Lyme disease and leptospirosis. The causative agent of Lyme disease, Borrelia burgdorferi, and the causative agent of leptospirosis, Leptospria interrogans, encounter reactive oxygen species (ROS) during their enzootic cycles. This report demonstrated that physiologically relevant concentrations of pyruvate, a potent H2O2 scavenger, and provided passive protection to B. burgdorferi and L. interrogans against H2O2. When extracellular pyruvate was absent, both spirochetes were sensitive to a low dose of H2O2 (≈0.6 µM per h) generated by glucose oxidase (GOX). Despite encoding a functional catalase, L. interrogans was more sensitive than B. burgdorferi to H2O2 generated by GOX, which may be due to the inherent resistance of B. burgdorferi because of the virtual absence of intracellular iron. In B. burgdorferi, the nucleotide excision repair (NER) and the DNA mismatch repair (MMR) pathways were important for survival during H2O2 challenge since deletion of the uvrB or the mutS genes enhanced its sensitivity to H2O2 killing; however, the presence of pyruvate fully protected ΔuvrB and ΔmutS from H2O2 killing further demonstrating the importance of pyruvate in protection. These findings demonstrated that pyruvate, in addition to its classical role in central carbon metabolism, serves as an important H2O2 scavenger for pathogenic spirochetes. Furthermore, pyruvate reduced ROS generated by human neutrophils in response to the Toll-like receptor 2 (TLR2) agonist zymosan. In addition, pyruvate reduced neutrophil-derived ROS in response to B. burgdorferi, which also activates host expression through TLR2 signaling. Thus, pathogenic spirochetes may exploit the metabolite pyruvate, present in blood and tissues, to survive H2O2 generated by the host antibacterial response generated during infection. PMID:24392147

  15. European hospital adherence to GOLD recommendations for chronic obstructive pulmonary disease (COPD) exacerbation admissions.

    PubMed

    Roberts, C Michael; Lopez-Campos, Jose Luis; Pozo-Rodriguez, Francisco; Hartl, Sylvia

    2013-12-01

    Understanding how European care of chronic obstructive pulmonary disease (COPD) admissions vary against guideline standards provides an opportunity to target appropriate quality improvement interventions. In 2010-2011 an audit of care against the 2010 'Global initiative for chronic Obstructive Lung Disease' (GOLD) standards was performed in 16 018 patients from 384 hospitals in 13 countries. Clinicians prospectively identified consecutive COPD admissions over a period of 8 weeks, recording clinical care measures on a web-based data tool. Data were analysed comparing adherence to 10 key management recommendations. Adherence varied between hospitals and across countries. The lack of available spirometry results and variable use of oxygen and non-invasive ventilation (NIV) are high impact areas identified for improvement. PMID:23729193

  16. Adherence to Disease Modifying Anti-Rheumatic Drugs in Rheumatoid Arthritis Patients: A Narrative Review of the Literature

    PubMed Central

    Salt, Elizabeth; Frazier, Susan

    2010-01-01

    Aim This paper synthesizes findings from available research about medication adherence to disease modifying anti-rheumatic drugs (DMARDs) in the rheumatoid arthritis (RA) population. Results This review of literature included 35 articles. Medication adherence to DMARDs ranged from 30% to 107%. Adherence rates greater than 100% indicated that patients took more than the prescribed amount of medication. There were no consistent risk factors for nonadherence to DMARD prescriptions identified, but some evidence was provided for self-efficacy, patient-health care provider relationships, social support, patient beliefs about medications, and age as factors affecting medication adherence. Support for educational interventions focused on medication adherence was equivocal. Conclusion Further research is necessary to develop a comprehensive, theoretically-based understanding of medication adherence in RA patients. PMID:20664466

  17. Mutation and Recombination in the Upstream Homology Box-Flanked ospE-Related Genes of the Lyme Disease Spirochetes Result in the Development of New Antigenic Variants during Infection

    PubMed Central

    Sung, Shian Ying; McDowell, John V.; Carlyon, Jason A.; Marconi, Richard T.

    2000-01-01

    The ospE gene family of the Lyme disease spirochetes encodes a polymorphic group of immunogenic lipoproteins. The ospE genes are one of several gene families that are flanked by a highly conserved upstream sequence called the upstream homology box, or UHB, element. Earlier analyses in our lab demonstrated that ospE-related genes are characterized by defined hypervariable domains (domains 1 and 2) that are predicted to be hydrophilic, surface exposed, and antigenic. The flanking of hypervariable domain 1 by DNA repeats may indicate that recombination contributes to ospE diversity and thus ultimately to antigenic variation. Using an isogeneic clone of Borrelia burgdorferi B31G (designated B31Gc1), we demonstrate that the ospE-related genes undergo mutation and rearrangement during infection in mice. The mutations that develop during infection resulted in the generation of OspE proteins with altered antigenic characteristics. The data support the hypothesized role of OspE-related proteins in immune system evasion. PMID:10678944

  18. Relapsing Fever Spirochetes Retain Infectivity After Prolonged in vitro Cultivation

    PubMed Central

    Schrumpf, Merry E.; Raffel, Sandra J.; Policastro, Paul F.; Porcella, Stephen F.; Schwan, Tom G.

    2008-01-01

    Abstract Borrelia hermsii and Borrelia burgdorferi, two closely related spirochetes, are the etiological agents of tick-borne relapsing fever and Lyme disease, respectively. Previous studies have shown the loss of infectivity of B. burgdorferi is associated with in vitro cultivation. This diminished infectivity of B. burgdorferi has occurred as early as three in vitro passages, and the loss of plasmids have been observed with these less virulent to noninfective cultures. The effects of long-term in vitro cultivation on B. hermsii have not been investigated. However, understanding the degree of genomic degradation during in vitro cultivation is important for investigating pathogenic mechanisms of spirochetes. In this study, we analyzed the effects of continuous in vitro cultivation on the genomic composition and infectivity of B. hermsii and B. turicatae. We report that all seven isolates of B. hermsii and the one isolate of B. turicatae examined retained infectivity in mice after 1 year of continuous in vitro cultivation. Furthermore, there were few apparent differences in the plasmid profiles after long-term cultivation. Two isolates of B. hermsii remained infective after high passage despite losing a portion of the 200-kb linear plasmid containing the fhbA gene encoding the factor H binding protein. Also, sequence analysis of multiple B. hermsii isolates demonstrated two types of fhbA with complete congruence with the two genomic groups of B. hermsii spirochetes. Therefore, these results suggest that relapsing fever spirochetes are genetically stable during in vitro cultivation, and the fhbA-containing segment of DNA that is lost during cultivation is not required for infection. PMID:18637723

  19. Dietitians’ Perspectives on Interventions to Enhance Adherence to Dietary Advice for Chronic Diseases in Adults

    PubMed Central

    DESROCHES, SOPHIE; LAPOINTE, ANNIE; DESCHÊNES, SARAH-MAUDE; BISSONNETTE-MAHEUX, VÉRONIQUE; GRAVEL, KARINE; THIRSK, JAYNE; LÉGARÉ, FRANCE

    2016-01-01

    Purpose To assess dietitians’ perspectives on the importance and applicability of interventions to enhance adherence to dietary advice for preventing and managing chronic diseases in adults in the Canadian context. Methods Based on a Cochrane systematic review, we identified 8 promising interventions for enhancing adherence to dietary advice: behavioural contracts, exchange lists, feedback based on self-monitoring, individualized menu suggestions, multiple interventions, portion size awareness, telephone follow-up, and videos. Thirty-two dietitians then completed a 3-round Delphi study by responding to an electronic questionnaire asking them to rate the importance and applicability in their practice of the 8 interventions on a 7-point Likert scale. Results Using a ≥75% level of agreement, 4 interventions showed strong consensus: multiple interventions, feedback based on self-monitoring, portion size awareness, and videos. Among these, the most significant were (means ± SD for importance and applicability, respectively) feedback based on self-monitoring (6.97 ± 0.18 and 6.72 ± 0.46), portion size awareness (6.69 ± 0.54 and 6.75 ± 0.51), and multiple interventions (6.94 ± 0.25 and 6.81 ± 0.40). Conclusions These findings can guide the development of educational training sessions for dietitians to help them provide practice-relevant interventions that will increase the likelihood that patients adhere to their advice regarding prevention and management of chronic diseases. PMID:26280789

  20. Type of hemodialysis and preference for behavioral involvement: interactive effects on adherence in end-stage renal disease.

    PubMed

    Christensen, A J; Smith, T W; Turner, C W; Holman, J M; Gregory, M C

    1990-01-01

    Examined the effects of hemodialysis type (i.e., staff controlled, in center vs. patient controlled, home) and patient preference for behavioral involvement on adherence and emotional adjustment in a sample of 53 patients with end-stage renal disease. Consistent with person x treatment interaction models, higher levels of preference for behavioral involvement were associated with better dietary adherence (i.e., lower serum potassium) for patients receiving dialysis at home but worse dietary adherence for patients receiving treatment in a dialysis center. A similar though weaker patient x treatment type matching pattern was observed for fluid-intake adherence (i.e., interdialytic weight gain). No effects were observed for patients' self-reported depression levels. Possible mechanisms for the interactional effect on adherence are discussed. PMID:2331980

  1. BB0347, from the Lyme Disease Spirochete Borrelia burgdorferi, Is Surface Exposed and Interacts with the CS1 Heparin-Binding Domain of Human Fibronectin

    PubMed Central

    Gaultney, Robert A.; Gonzalez, Tammy; Floden, Angela M.; Brissette, Catherine A.

    2013-01-01

    The causative agent of Lyme disease, Borrelia burgdorferi, codes for several known fibronectin-binding proteins. Fibronectin a common the target of diverse bacterial pathogens, and has been shown to be essential in allowing for the development of certain disease states. Another borrelial protein, BB0347, has sequence similarity with these other known fibronectin-binding proteins, and may be important in Lyme disease pathogenesis. Herein, we perform an initial characterization of BB0347 via the use of molecular and biochemical techniques. We found that BB0347 is expressed, produced, and presented on the outer surface of intact B. burgdorferi. We also demonstrate that BB0347 has the potential to be important in Lyme disease progression, and have begun to characterize the nature of the interaction between human fibronectin and this bacterial protein. Further work is needed to define the role of this protein in the borrelial infection process. PMID:24086600

  2. The Effectiveness of Mobile Phone Text Messaging in Improving Medication Adherence for Patients with Chronic Diseases: A Systematic Review

    PubMed Central

    Ershad Sarabi, Roghayeh; Sadoughi, Farahnaz; Jamshidi Orak, Roohangiz; Bahaadinbeigy, Kambiz

    2016-01-01

    Context Medication non-adherence is a commonly observed problem in the self-administration of treatment, regardless of the disease type. Text messaging reminders, as electronic reminders, provide an opportunity to improve medication adherence. In this study, we aimed to provide evidence addressing the question of whether text message reminders were effective in improving patients’ adherence to medication. Evidence Acquisition We carried out a systematic literature search, using the five electronic bibliographic databases: PubMed, Embase, PsycINFO, CINAHL, and the Cochrane central register of controlled trials. Studies were included on the basis of whether they examined the benefits and effects of short-message service (SMS) interventions on medication adherence. Results The results of this systematic review indicated that text messaging interventions have improved patients’ medication adherence rate (85%, 29.34). Included in the review, those who had problems with adherence, or those whom text messaging was most helpful had HIV, asthma, diabetes, schizophrenia and heart disease (73.5%). The period of intervention varied from 1 week to 14 months. The most common study design was randomized controlled trials (RCTs) (66%) carried out in the developed countries. Conclusions This study demonstrated the potential of mobile phone text messaging for medication non-adherence problem solving. PMID:27437126

  3. Quality of life of coronary artery disease patients after the implementation of planning strategies for medication adherence 1

    PubMed Central

    Lourenço, Laura Bacelar de Araujo; Rodrigues, Roberta Cunha Matheus; São-João, Thaís Moreira; Gallani, Maria Cecilia; Cornélio, Marilia Estevam

    2015-01-01

    OBJECTIVE: to compare the general and specific health-related quality of life (HRQoL) between the Intervention (IG) and Control (CG) groups of coronary artery disease patients after the implementation of Action Planning and Coping Planning strategies for medication adherence and to verify the relationship between adherence and HRQoL. METHOD: this was a controlled and randomized study. RESULTS: the sample (n=115) was randomized into two groups, IG (n=59) and CG (n=56). Measures of medication adherence and general and specific HRQoL were obtained in the baseline and after two months of monitoring. CONCLUSION: the findings showed that the combination of intervention strategies - Action Planning and Coping Planning for medication adherence did not affect the HRQoL of coronary artery disease patients in outpatient monitoring. PMID:25806626

  4. Predictors of participant adherence and retention in the African American Study of Kidney Disease and Hypertension.

    PubMed

    Brooks, Deborah; Charleston, Jeanne; Dowie, Donna; Gabriel, Avril; Hall, Yvette Baxter; Hiremath, Leena; Lightfoot, Tammy; Sika, Mohammed; Smith, Winifred C; Wang, Xuelei

    2008-01-01

    The African American Study of Kidney Disease and Hypertension (AASK) was conducted over a 7-year period at 21 clinical centers across the United States to investigate whether one of two levels of blood pressure control and/or one of three classes of antihypertensive medications was more effective at slowing the rate of renal disease in African Americans with renal insufficiency presumed secondary to hypertension. Analysis at the end of the study revealed an overall participant retention rate of 90% (still alive and not on dialysis); defined as having had at least one 125I-iothalamate GFR, the primary data collection element, measured in the final year of the study. Adherence, defined as not missing 3 consecutive protocol visits (6 months) during the study, was 77%. Adherence to protocol visits showed that participants assigned to a low blood pressure goal (mean arterial pressure [MAP] of 92 mm/Hg or lower) had a 30% (95% CI, 9%-45%) lower risk of nonadherence as compared to those assigned to the usual goal [MAP of 102-107] (p = 0.006). No statistically significant difference was observed between randomized drug assignments. Higher baseline systolic (p = 0.0001) and diastolic (p = 0.007) blood pressures were associated with a higher risk of nonadherence. Declining to provide an annual income is associated with a higher risk of nonadherence compared to those with incomes of $15,000 or higher (p = 0.04). In discussing the identifying factors that may predict nonadherence and the strategies that assisted in improving adherence and retention, this article offers insights for researchers in achieving high levels of participation in long-term clinical studies. PMID:18472682

  5. Suppression of fibroblast proliferation by oral spirochetes.

    PubMed Central

    Boehringer, H; Taichman, N S; Shenker, B J

    1984-01-01

    Soluble sonic extracts of several strains of Treponema denticola and Treponema vincentii were examined for their abilities to alter proliferation of both murine and human fibroblasts. We found that sonic extracts of all tested strains of T. denticola caused a dose-dependent inhibition of murine and human fibroblast proliferation when assessed by both DNA synthesis ([3H]thymidine incorporation) and direct cell counts. T. vincentii had only a minimal inhibitory effect at comparable doses. No inhibition was observed when sonic extracts were added simultaneously with [3H]thymidine, indicating that suppression was not due to the presence of excessive amounts of cold thymidine in the extract, nonspecific effects on thymidine utilization by the cells (transport and incorporation), or degradation of label. RNA ([3H]uridine incorporation) and protein ([3H]leucine incorporation) synthesis were similarly altered after exposure to the T. denticola sonic extracts. There was no effect on cell viability as measured by trypan blue exclusion. Inhibition could be reversed by extensive washing of the cells within the first few hours of exposure to sonic extracts. Preliminary characterization and purification indicated that the inhibitory factor(s) is not endotoxin since it is heat labile, and elutes in a single, well-defined peak on a Sephadex G-150 chromatography column corresponding to a molecular weight of approximately 50,000. Since oral spirochetes have been implicated in the pathogenesis of periodontal disorders, it is possible that they contribute to the disease process by inhibition of fibroblast growth and therefore may, at least in part, account for the loss of collagen seen in diseased tissue. PMID:6735466

  6. Bacterial Amyloid and DNA are Important Constituents of Senile Plaques: Further Evidence of the Spirochetal and Biofilm Nature of Senile Plaques

    PubMed Central

    Miklossy, Judith

    2016-01-01

    It has long been known that spirochetes form clumps or micro colonies in vitro and in vivo. Cortical spirochetal colonies in syphilitic dementia were considered as reproductive centers for spirochetes. Historic and recent data demonstrate that senile plaques in Alzheimer’s disease (AD) are made up by spirochetes. Spirochetes, are able to form biofilm in vitro. Senile plaques are also reported to contain elements of biofilm constituents. We expected that AβPP and Aβ (the main components of senile plaques) also occur in pure spirochetal biofilms, and bacterial DNA (an important component of biofilm) is also present in senile plaques. Histochemical, immunohistochemical, and in situ hybridization techniques and the TUNEL assay were used to answer these questions. The results obtained demonstrate that Aβ and DNA, including spirochete-specific DNA, are key components of both pure spirochetal biofilms and senile plaques in AD and confirm the biofilm nature of senile plaques. These results validate validate previous observations that AβPP and/or an AβPP-like amyloidogenic protein are an integral part of spirochetes, and indicate that bacterial and host derived Aβ are both constituents of senile plaques. DNA fragmentation in senile plaques further confirms their bacterial nature and provides biochemical evidence for spirochetal cell death. Spirochetes evade host defenses, locate intracellularly, form more resistant atypical forms and notably biofilms, which contribute to sustain chronic infection and inflammation and explain the slowly progressive course of dementia in AD. To consider co-infecting microorganisms is equally important, as multi-species biofilms result in a higher resistance to treatments and a more severe dementia. PMID:27314530

  7. Escherichia coli in chronic inflammatory bowel diseases: An update on adherent invasive Escherichia coli pathogenicity

    PubMed Central

    Martinez-Medina, Margarita; Garcia-Gil, Librado Jesus

    2014-01-01

    Escherichia coli (E. coli), and particularly the adherent invasive E. coli (AIEC) pathotype, has been increasingly implicated in the ethiopathogenesis of Crohn’s disease (CD). E. coli strains with similar pathogenic features to AIEC have been associated with other intestinal disorders such as ulcerative colitis, colorectal cancer, and coeliac disease, but AIEC prevalence in these diseases remains largely unexplored. Since AIEC was described one decade ago, substantial progress has been made in deciphering its mechanisms of pathogenicity. However, the molecular bases that characterize the phenotypic properties of this pathotype are still not well resolved. A review of studies focused on E. coli populations in inflammatory bowel disease (IBD) is presented here and we discuss about the putative role of this species on each IBD subtype. Given the relevance of AIEC in CD pathogenesis, we present the latest research findings concerning AIEC host-microbe interactions and pathogenicity. We also review the existing data regarding the prevalence and abundance of AIEC in CD and its association with other intestinal diseases from humans and animals, in order to discuss the AIEC disease- and host-specificity. Finally, we highlight the fact that dietary components frequently found in industrialized countries may enhance AIEC colonization in the gut, which merits further investigation and the implementation of preventative measures. PMID:25133024

  8. Lack of Adherence to Evidence-based Treatment Guidelines for Nontuberculous Mycobacterial Lung Disease

    PubMed Central

    Prevots, D. Rebecca; Gallagher, Jack; Heap, Kylee; Gupta, Renu; Griffith, David

    2014-01-01

    Rationale: The 2007 American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA) recommend that patients with pulmonary nontuberculous mycobacterial (PNTM) disease caused by Mycobacterium avium complex (MAC) or M. abscessus be treated with a macrolide-based multidrug antibiotic regimen until sputum culture negative for 1 year. After 6 years, the degree of adherence to recommended guidelines among physicians remains unknown. Objective: To describe antibiotic treatment practices among physicians treating patients with PNTM in the United States. Methods: A nationally representative sample of 1,286 U.S. physicians was contacted in December 2011 through January 2012; 582 of the responding physicians were treating patients with PNTM and were eligible to participate. Physicians were asked to extract medical record data on the last four patients they treated in the past year with PNTM disease from either MAC or M. abscessus. Treatment patterns were assessed for all patients by NTM species and physician specialty, and compared with the 2007 recommended ATS/IDSA guidelines. Main Results: Questionnaires were completed by 349 physicians on 915 patients with PNTM, including 744 (81%) with MAC and 174 (19%) with M. abscessus; 3 patients were positive for both. Physicians treated 76 (44%) patients with M. abscessus and 411 (55%) patients with MAC. Only 13% of antibiotic regimens prescribed to patients with MAC met ATS/IDSA guidelines, 56% did not include a macrolide, and 16% were for macrolide monotherapy. Among patients with M. abscessus, 64% of regimens prescribed did not include a macrolide. Conclusions: Adherence to the 2007 ATS/IDSA guidelines for treating PNTM disease is poor. Across all physician specialties evaluated, suboptimal or potentially harmful antibiotic regimens were commonly prescribed. PMID:24236749

  9. Beta-Amyloid Deposition and Alzheimer's Type Changes Induced by Borrelia Spirochetes

    SciTech Connect

    Miklossy,J.; Kis, A.; Radenovic, A.; Miller, L.; Forro, L.; Martins, R.; Reiss, K.; Darbinian, N.; Darekar, P.; et al.

    2006-01-01

    The pathological hallmarks of Alzheimer's disease (AD) consist of {beta}-amyloid plaques and neurofibrillary tangles in affected brain areas. The processes, which drive this host reaction are unknown. To determine whether an analogous host reaction to that occurring in AD could be induced by infectious agents, we exposed mammalian glial and neuronal cells in vitro to Borrelia burgdorferi spirochetes and to the inflammatory bacterial lipopolysaccharide (LPS). Morphological changes analogous to the amyloid deposits of AD brain were observed following 2-8 weeks of exposure to the spirochetes. Increased levels of {beta}-amyloid presursor protein (A{beta}PP) and hyperphosphorylated tau were also detected by Western blots of extracts of cultured cells that had been treated with spirochetes or LPS. These observations indicate that, by exposure to bacteria or to their toxic products, host responses similar in nature to those observed in AD may be induced.

  10. Adherence of Myxobolus cerebralis myxospores to waders: Implications for disease dissemination

    USGS Publications Warehouse

    Gates, K.K.; Guy, C.S.; Zale, A.V.; Horton, T.B.

    2008-01-01

    The vectors involved in the spread of whirling disease, which is caused by Myxobolus cerebralis, are only partly understood. However, the parasite has rapidly become established in many regions, suggesting that it is easily disseminated. We gained insight into transport vectors by examining the surface porosity of common wading equipment materials and the adherence of M. cerebralis myxospores to them. Interstitial spaces within rubber, felt, lightweight nylon, and neoprene were measured on scanning electron microscope images. Myxospores were applied to each material, the material was rinsed, and the myxospores recovered to assess adherence. The mean interstitial space size of rubber was the smallest (2.0 ??m), whereas that of felt was the largest (31.3 ??m). The highest recovery rates were from rubber and the glass control. Percent myxospore recovery varied by material, the recovery from felt being lower than that from all other materials. The potential for felt to carry even small numbers of myxospores suggests that the introduction of M. cerebralis by felt-soled wading boots is possible. ?? Copyright by the American Fisheries Society 2008.

  11. Understanding Host-Adherent-Invasive Escherichia coli Interaction in Crohn's Disease: Opening Up New Therapeutic Strategies

    PubMed Central

    Massier, Sébastien; Darfeuille-Michaud, Arlette; Billard, Elisabeth; Barnich, Nicolas

    2014-01-01

    A trillion of microorganisms colonize the mammalian intestine. Most of them have coevolved with the host in a symbiotic relationship and some of them have developed strategies to promote their replication in the presence of competing microbiota. Recent evidence suggests that perturbation of the microbial community favors the emergence of opportunistic pathogens, in particular adherent-invasive Escherichia coli (AIEC) that can increase incidence and severity of gut inflammation in the context of Crohn's disease (CD). This review will report the importance of AIEC as triggers of intestinal inflammation, focusing on their impact on epithelial barrier function and stimulation of mucosal inflammation. Beyond manipulation of immune response, restoration of gut microbiota as a new treatment option for CD patients will be discussed. PMID:25580435

  12. CEACAM6 acts as a receptor for adherent-invasive E. coli, supporting ileal mucosa colonization in Crohn disease.

    PubMed

    Barnich, Nicolas; Carvalho, Frédéric A; Glasser, Anne-Lise; Darcha, Claude; Jantscheff, Peter; Allez, Matthieu; Peeters, Harald; Bommelaer, Gilles; Desreumaux, Pierre; Colombel, Jean-Frédéric; Darfeuille-Michaud, Arlette

    2007-06-01

    The ileal mucosa of Crohn disease (CD) patients is abnormally colonized by adherent-invasive E. coli (AIEC) that are able to adhere to and invade intestinal epithelial cells. Here, we show that CD-associated AIEC strains adhere to the brush border of primary ileal enterocytes isolated from CD patients but not controls without inflammatory bowel disease. AIEC adhesion is dependent on type 1 pili expression on the bacterial surface and on carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) expression on the apical surface of ileal epithelial cells. We report also that CEACAM6 acts as a receptor for AIEC adhesion and is abnormally expressed by ileal epithelial cells in CD patients. In addition, our in vitro studies show that there is increased CEACAM6 expression in cultured intestinal epithelial cells after IFN-gamma or TNF-alpha stimulation and after infection with AIEC bacteria, indicating that AIEC can promote its own colonization in CD patients. PMID:17525800

  13. Interaction of spirochetes with the host fibrinolytic system and potential roles in pathogenesis.

    PubMed

    Vieira, Mônica Larucci; Nascimento, Ana Lucia T O

    2016-08-01

    The pathogenic spirochetes Borrelia burgdorferi, B. hermsii, B. recurrentis, Treponema denticola and Leptospira spp. are the etiologic agents of Lyme disease, relapsing fever, periodontitis and leptospirosis, respectively. Lyme borreliosis is a multi-systemic disorder and the most prevalent tick-borne disease in the northern hemisphere. Tick-borne relapsing fever is persistent in endemic areas worldwide, representing a significant burden in some African regions. Periodontal disease, a chronic inflammatory disorder that often leads to tooth loss, is caused by several potential pathogens found in the oral cavity including T. denticola. Leptospirosis is considered the most widespread zoonosis, and the predominant human disease in tropical, undeveloped regions. What these diseases have in common is that they are a significant burden to healthcare costs in the absence of prophylactic measures. This review addresses the interaction of these spirochetes with the fibrinolytic system, plasminogen (Plg) binding to the surface of bacteria and the generation of plasmin (Pla) on their surface. The consequences on host-pathogen interactions when the spirochetes are endowed with this proteolytic activity are discussed on the basis of the results reported in the literature. Spirochetes equipped with Pla activity have been shown to degrade extracellular matrix (ECM) components, in addition to digesting fibrin, facilitating bacterial invasion and dissemination. Pla generation triggers the induction of matrix metalloproteases (MMPs) in a cascade of events that enhances the proteolytic capacity of the spirochetes. These activities in concert with the interference exerted by the Plg/Pla on the complement system - helping the bacteria to evade the immune system - should illuminate our understanding of the mechanisms involved in host infection. PMID:25914944

  14. Efficacy of a multifactorial intervention on therapeutic adherence in patients with chronic obstructive pulmonary disease (COPD): a randomized controlled trial

    PubMed Central

    2014-01-01

    Background Therapeutic adherence of patients with chronic obstructive pulmonary disease (COPD) is poor. This study evaluated the effectiveness of a multifactorial intervention on improving the therapeutic adherence in chronic obstructive pulmonary disease (COPD) patients with scheduled inhalation therapy. Methods The study design consisted of a randomised controlled trial in a primary care setting. 146 patients diagnosed with COPD were randomly allocated into two groups using the block randomisation technique. One-year follow-ups with three visits were performed. The intervention consisted of motivational aspects related to adherence (beliefs and behaviour) in the form of group and individual interviews, cognitive aspects in the form of information about the illness and skills in the form of training in inhalation techniques. Cognitive-emotional aspects and training in inhalation techniques were reinforced during all visits of the intervention group. The main outcome measure was adherence to the medication regimen. Therapeutic adherence was determined by the percentage of patients classified as good adherent as evaluated by dose or pill count. Results Of the 146 participants (mean age 69.8 years, 91.8% males), 41.1% reported adherence (41.9% of the control group and 40.3% of the intervention group). When multifactorial intervention was applied, the reported adherence was 32.4% for the control group and 48.6% for the intervention group, which showed a statistically significant difference (p = 0.046). Number needed to treat is 6.37. In the intervention group, cognitive aspects increased by 23.7% and skilled performance of inhalation techniques increased by 66.4%. The factors related to adherence when multifactorial intervention was applied were the number of exacerbations (OR = 0.66), visits to health centre (OR = 0.93) and devices (OR = 2.4); illness severity (OR = 0.67), beta-2-adrenergic (OR = 0.16) and xantine (OR = 0.19) treatment

  15. Diet and Exercise Adherence and Practices among Medically Underserved Patients with Chronic Disease: Variation across Four Ethnic Groups

    ERIC Educational Resources Information Center

    Orzech, Kathryn M.; Vivian, James; Huebner Torres, Cristina; Armin, Julie; Shaw, Susan J.

    2013-01-01

    Many factors interact to create barriers to dietary and exercise plan adherence among medically underserved patients with chronic disease, but aspects related to culture and ethnicity are underexamined in the literature. Using both qualitative ("n" = 71) and quantitative ("n" = 297) data collected in a 4-year, multimethod study among patients with…

  16. Comparison of the genome of the oral pathogen Treponema denticola with other spirochete genomes.

    PubMed

    Seshadri, Rekha; Myers, Garry S A; Tettelin, Hervé; Eisen, Jonathan A; Heidelberg, John F; Dodson, Robert J; Davidsen, Tanja M; DeBoy, Robert T; Fouts, Derrick E; Haft, Dan H; Selengut, Jeremy; Ren, Qinghu; Brinkac, Lauren M; Madupu, Ramana; Kolonay, Jamie; Durkin, Scott A; Daugherty, Sean C; Shetty, Jyoti; Shvartsbeyn, Alla; Gebregeorgis, Elizabeth; Geer, Keita; Tsegaye, Getahun; Malek, Joel; Ayodeji, Bola; Shatsman, Sofiya; McLeod, Michael P; Smajs, David; Howell, Jerrilyn K; Pal, Sangita; Amin, Anita; Vashisth, Pankaj; McNeill, Thomas Z; Xiang, Qin; Sodergren, Erica; Baca, Ernesto; Weinstock, George M; Norris, Steven J; Fraser, Claire M; Paulsen, Ian T

    2004-04-13

    We present the complete 2,843,201-bp genome sequence of Treponema denticola (ATCC 35405) an oral spirochete associated with periodontal disease. Analysis of the T. denticola genome reveals factors mediating coaggregation, cell signaling, stress protection, and other competitive and cooperative measures, consistent with its pathogenic nature and lifestyle within the mixed-species environment of subgingival dental plaque. Comparisons with previously sequenced spirochete genomes revealed specific factors contributing to differences and similarities in spirochete physiology as well as pathogenic potential. The T. denticola genome is considerably larger in size than the genome of the related syphilis-causing spirochete Treponema pallidum. The differences in gene content appear to be attributable to a combination of three phenomena: genome reduction, lineage-specific expansions, and horizontal gene transfer. Genes lost due to reductive evolution appear to be largely involved in metabolism and transport, whereas some of the genes that have arisen due to lineage-specific expansions are implicated in various pathogenic interactions, and genes acquired via horizontal gene transfer are largely phage-related or of unknown function. PMID:15064399

  17. Diet and Exercise Adherence and Practices Among Medically Underserved Patients With Chronic Disease: Variation Across Four Ethnic Groups

    PubMed Central

    Orzech, Kathryn M.; Vivian, James; Torres, Cristina Huebner; Armin, Julie; Shaw, Susan J.

    2013-01-01

    Many factors interact to create barriers to dietary and exercise plan adherence among medically underserved patients with chronic disease, but aspects related to culture and ethnicity are underexamined in the literature. Using both qualitative (n = 71) and quantitative (n = 297) data collected in a 4-year, multimethod study among patients with hypertension and/ or diabetes, the authors explored differences in self-reported adherence to diet and exercise plans and self-reported daily diet and exercise practices across four ethnic groups—Whites, Blacks, Vietnamese, and Latinos—at a primary health care center in Massachusetts. Adherence to diet and exercise plans differed across ethnic groups even after controlling for key sociodemographic variables, with Vietnamese participants reporting the highest adherence. Food and exercise options were shaped by economic constraints as well as ethnic and cultural familiarity with certain foods and types of activity. These findings indicate that health care providers should consider ethnicity and economic status together to increase effectiveness in encouraging diverse populations with chronic disease to make healthy lifestyle changes. PMID:22505574

  18. Reviewing molecular adaptations of Lyme borreliosis spirochetes in the context of reproductive fitness in natural transmission cycles.

    PubMed

    Tsao, Jean I

    2009-01-01

    Lyme borreliosis (LB) is caused by a group of pathogenic spirochetes - most often Borrelia burgdorferi, B. afzelii, and B. garinii - that are vectored by hard ticks in the Ixodes ricinus-persulcatus complex, which feed on a variety of mammals, birds, and lizards. Although LB is one of the best-studied vector-borne zoonoses, the annual incidence in North America and Europe leads other vector-borne diseases and continues to increase. What factors make the LB system so successful, and how can researchers hope to reduce disease risk - either through vaccinating humans or reducing the risk of contacting infected ticks in nature? Discoveries of molecular interactions involved in the transmission of LB spirochetes have accelerated recently, revealing complex interactions among the spirochete-tick-vertebrate triad. These interactions involve multiple, and often redundant, pathways that reflect the evolution of general and specific mechanisms by which the spirochetes survive and reproduce. Previous reviews have focused on the molecular interactions or population biology of the system. Here molecular interactions among the LB spirochete, its vector, and vertebrate hosts are reviewed in the context of natural maintenance cycles, which represent the ecological and evolutionary contexts that shape these interactions. This holistic system approach may help researchers develop additional testable hypotheses about transmission processes, interpret laboratory results, and guide development of future LB control measures and management. PMID:19368764

  19. Reviewing molecular adaptations of Lyme borreliosis spirochetes in the context of reproductive fitness in natural transmission cycles

    PubMed Central

    Tsao, Jean I.

    2009-01-01

    Lyme borreliosis (LB) is caused by a group of pathogenic spirochetes – most often Borrelia burgdorferi, B. afzelii, and B. garinii – that are vectored by hard ticks in the Ixodes ricinus-persulcatus complex, which feed on a variety of mammals, birds, and lizards. Although LB is one of the best-studied vector-borne zoonoses, the annual incidence in North America and Europe leads other vector-borne diseases and continues to increase. What factors make the LB system so successful, and how can researchers hope to reduce disease risk – either through vaccinating humans or reducing the risk of contacting infected ticks in nature? Discoveries of molecular interactions involved in the transmission of LB spirochetes have accelerated recently, revealing complex interactions among the spirochete-tick-vertebrate triad. These interactions involve multiple, and often redundant, pathways that reflect the evolution of general and specific mechanisms by which the spirochetes survive and reproduce. Previous reviews have focused on the molecular interactions or population biology of the system. Here molecular interactions among the LB spirochete, its vector, and vertebrate hosts are reviewed in the context of natural maintenance cycles, which represent the ecological and evolutionary contexts that shape these interactions. This holistic system approach may help researchers develop additional testable hypotheses about transmission processes, interpret laboratory results, and guide development of future LB control measures and management. PMID:19368764

  20. Factors associated with early adherence to tiotropium in chronic obstructive pulmonary disease.

    PubMed

    Laforest, Laurent; Licaj, Idlir; Devouassoux, Gilles; Hartwig, Susanne; Marvalin, Serge; Van Ganse, Eric

    2013-02-01

    Tiotropium is an innovative intervention in chronic obstructive pulmonary disease (COPD). Early adherence to tiotropium remains inadequately explored, notably time from initiation to discontinuation (persistence). In patients with COPD, the factors associated with the risk of discontinuing the treatment with tiotropium within 12 months following initiation were identified (12-month persistence). Claim databases from the French Social Security were used. A random sample of patients (aged 50-80 years) who initiated tiotropium soon after launch was selected. Factors associated with the persistence were investigated (Log-rank test and multivariate Cox model). Of the 1147 newly treated patients (mean age 68 years, 33% women), 64% remained in the treatment of tiotropium for over a period of 12 months following initiation. More than 10% of the patients interrupted therapy after a single dispensing, most often those with mild COPD. Lower risks of discontinuing tiotropium within 12 months following initiation were observed when it was initiated by a private sector specialist (hazard ratio (HR) = 0.65, 95% confidence interval (CI) = (0.52-0.82)), by hospital-based physician (HR = 0.58, 95% CI = (0.42-0.78)), when ≥ 2 other respiratory drugs were associated (HR = 0.74, 95% CI = (0.58-0.95)) and in case of long-term disease status (HR = 0.78, 95% CI = (0.63-0.97)). Conversely, no clear effect appeared according to age or gender. In this population of patients with COPD, fewer early discontinuations of tiotropium were observed in patients having a severe condition. PMID:23149384

  1. Periplasmal Physics: The Rotational Dynamics of Spirochetal Flagella

    NASA Astrophysics Data System (ADS)

    Huber, Greg

    2012-02-01

    Spirochetes are distinguished by the location of their flagella, which reside within the periplasm: the tiny space between the bacterial cell wall and the outer membrane. In Borrelia burgdorferi/ (the causative agent of Lyme Disease), rotation of the flagella leads to cellular undulations that drive swimming. Exactly how these shape changes arise due to the forces and torques acting between the flagella and the cell body is unknown. By applying low-Reynolds number hydrodynamic theory to the motion of an elastic flagellum rotating in the periplasm, we show that the flagella are most likely separated from the bacterial cell wall by a lubricating layer of fluid. We obtain analytical solutions for the force and torque on the rotating flagellum through lubrication analysis, as well as through scaling analysis, and find results are in close agreement numerical simulations. (Joint work with J. Yang and C.W. Wolgemuth.)

  2. Effect of an Educational Program on Adherence to Therapeutic Regimen among Chronic Kidney Disease Stage5 (CKD5) Patients under Maintenance Hemodialysis

    ERIC Educational Resources Information Center

    Deif, Hala I. Abo; Elsawi, Khiria; Selim, Mohga; NasrAllah, Mohamed M.

    2015-01-01

    The burden of chronic disease on health care services worldwide is growing and the increased development of educational interventions which help patients to better manage their conditions is evident internationally. It has been recognized that poor adherence can be a serious risk to the health and wellbeing of patients. Adherence to fluid…

  3. Health and Nutrition Literacy and Adherence to Treatment in Children, Adolescents, and Young Adults With Chronic Kidney Disease and Hypertension, North Carolina, 2015

    PubMed Central

    Ferris, Maria; Rak, Eniko

    2016-01-01

    Introduction Adherence to treatment and dietary restrictions is important for health outcomes of patients with chronic/end-stage kidney disease and hypertension. The relationship of adherence with nutritional and health literacy in children, adolescents, and young adults is not well understood. The current study examined the relationship of health literacy, nutrition knowledge, nutrition knowledge–behavior concordance, and medication adherence in a sample of children and young people with chronic/end-stage kidney disease and hypertension. Methods We enrolled 74 patients (aged 7–29 y) with a diagnosis of chronic/end-stage kidney disease and hypertension from the University of North Carolina Kidney Center. Participants completed instruments of nutrition literacy (Disease-Specific Nutrition Knowledge Test), health literacy (Newest Vital Sign), nutrition behavior (Nutrition Knowledge–Behavior Concordance Scale), and medication adherence (Morisky Medication Adherence Scale). Linear and binary logistic regressions were used to test the associations. Results In univariate comparisons, nutrition knowledge was significantly higher in people with adequate health literacy. Medication adherence was related to nutrition knowledge and nutrition knowledge–behavior concordance. Multivariate regression models demonstrated that knowledge of disease-specific nutrition restrictions did not significantly predict nutrition knowledge–behavior concordance scores. In logistic regression, knowledge of nutrition restrictions did not significantly predict medication adherence. Lastly, health literacy and nutrition knowledge–behavior concordance were significant predictors of medication adherence. Conclusion Nutrition knowledge and health literacy skills are positively associated. Nutrition knowledge, health literacy, and nutrition knowledge–behavior concordance are positively related to medication adherence. Future research should focus on additional factors that may predict

  4. Strategies to promote adherence to nutritional advice in patients with chronic kidney disease: a narrative review and commentary

    PubMed Central

    Beto, Judith A; Schury, Katherine A; Bansal, Vinod K

    2016-01-01

    Chronic kidney disease (CKD) requires extensive changes to food and lifestyle. Poor adherence to diet, medications, and treatments has been estimated to vary between 20% and 70%, which in turn can contribute to increased mortality and morbidity. Delivering effective nutritional advice in patients with CKD coordinates multiple diet components including calories, protein, sodium, potassium, calcium, phosphorus, and fluid. Dietary intake studies have shown difficulty in adhering to the scope and complexity of the CKD diet parameters. No single educational or clinical strategy has been shown to be consistently effective across CKD populations. Highest adherence has been observed when both diet and education efforts are individualized to each patient and adapted over time to changing lifestyle and CKD variables. This narrative review and commentary summarizes nutrition education literature and published strategies for providing nutritional advice in CKD. A cohort of practical and effective strategies for increasing dietary adherence to nutritional advice are provided that include communicating with “talking control” principles, integrating patient-owned technology, acknowledging the typical food pattern may be snacking rather than formal meals, focusing on a single goal rather than multiple goals, creating active learning and coping strategies (frozen sandwiches, visual hands-on activities, planting herb gardens), and involving the total patient food environment. PMID:26893578

  5. Adherence to a home-based exercise program and incidence of cardiovascular disease in type 2 diabetes patients.

    PubMed

    Shinji, S; Shigeru, M; Ryusei, U; Mitsuru, M; Shigehiro, K

    2007-10-01

    The aim of this study was to examine the association between adherence to a home-based exercise program and the incidence of cardiovascular disease (CVD) in patients with type 2 diabetes. We investigated 102 patients with type 2 diabetes aged 35 to 75 years, and followed them prospectively for 17.2 months. Before enrollment, all patients received a traditional exercise prescription. The exercise program consisted of a daily walking exercise at home for 20 - 30 minutes. Self-reported adherence to the exercise program and the incidence of CVD were confirmed by information obtained from telephone interviews. There were 38 dropouts among the patients in the exercise program. Dropouts were significantly younger than completers. The rate of obesity was significantly higher among the dropouts than among the completers. No differences were observed between the two groups for gender, history of CVD and other clinical characteristics. During the follow-up, we documented 8 new cases of CVD. The incidence of CVD during the follow-up was 1.56 percent among the program completers and 18.4 percent among the dropouts. Adherence to the home-based exercise was inversely related to the incidence of CVD (p < 0.01). These associations persisted after adjustment for age and other covariates. In conclusion, adherence to an exercise program is associated with a reduced incidence of CVD among patients with type 2 diabetes. PMID:17436204

  6. Genome Sequence of the Pathogenic Intestinal Spirochete Brachyspira hyodysenteriae Reveals Adaptations to Its Lifestyle in the Porcine Large Intestine

    PubMed Central

    La, Tom; Ryan, Karon; Moolhuijzen, Paula; Albertyn, Zayed; Shaban, Babak; Motro, Yair; Dunn, David S.; Schibeci, David; Hunter, Adam; Barrero, Roberto; Phillips, Nyree D.; Hampson, David J.

    2009-01-01

    Brachyspira hyodysenteriae is an anaerobic intestinal spirochete that colonizes the large intestine of pigs and causes swine dysentery, a disease of significant economic importance. The genome sequence of B. hyodysenteriae strain WA1 was determined, making it the first representative of the genus Brachyspira to be sequenced, and the seventeenth spirochete genome to be reported. The genome consisted of a circular 3,000,694 base pair (bp) chromosome, and a 35,940 bp circular plasmid that has not previously been described. The spirochete had 2,122 protein-coding sequences. Of the predicted proteins, more had similarities to proteins of the enteric Escherichia coli and Clostridium species than they did to proteins of other spirochetes. Many of these genes were associated with transport and metabolism, and they may have been gradually acquired through horizontal gene transfer in the environment of the large intestine. A reconstruction of central metabolic pathways identified a complete set of coding sequences for glycolysis, gluconeogenesis, a non-oxidative pentose phosphate pathway, nucleotide metabolism, lipooligosaccharide biosynthesis, and a respiratory electron transport chain. A notable finding was the presence on the plasmid of the genes involved in rhamnose biosynthesis. Potential virulence genes included those for 15 proteases and six hemolysins. Other adaptations to an enteric lifestyle included the presence of large numbers of genes associated with chemotaxis and motility. B. hyodysenteriae has diverged from other spirochetes in the process of accommodating to its habitat in the porcine large intestine. PMID:19262690

  7. Sensitive multiplex PCR assay to differentiate Lyme spirochetes and emerging pathogens Anaplasma phagocytophilum and Babesia microti

    PubMed Central

    2013-01-01

    Background The infection with Borrelia burgdorferi can result in acute to chronic Lyme disease. In addition, coinfection with tick-borne pathogens, Babesia species and Anaplasma phagocytophilum has been increasing in endemic regions of the USA and Europe. The currently used serological diagnostic tests are often difficult to interpret and, moreover, antibodies against the pathogens persist for a long time making it difficult to confirm the cure of the disease. In addition, these tests cannot be used for diagnosis of early disease state before the adaptive immune response is established. Since nucleic acids of the pathogens do not persist after the cure, DNA-based diagnostic tests are becoming highly useful for detecting infectious diseases. Results In this study, we describe a real-time multiplex PCR assay to detect the presence of B. burgdorferi, B. microti and A. phagocytophilum simultaneously even when they are present in very low copy numbers. Interestingly, this quantitative PCR technique is also able to differentiate all three major Lyme spirochete species, B. burgdorferi, B. afzelii, and B. garinii by utilizing a post-PCR denaturation profile analysis and a single molecular beacon probe. This could be very useful for diagnosis and discrimination of various Lyme spirochetes in European countries where all three Lyme spirochete species are prevalent. As proof of the principle for patient samples, we detected the presence of low number of Lyme spirochetes spiked in the human blood using our assay. Finally, our multiplex assay can detect all three tick-borne pathogens in a sensitive and specific manner irrespective of the level of each pathogen present in the sample. We anticipate that this novel diagnostic method will be able to simultaneously diagnose early to chronic stages of Lyme disease, babesiosis and anaplasmosis using the patients’ blood samples. Conclusion Real-time quantitative PCR using specific primers and molecular beacon probes for the selected

  8. Escherichia coli isolated from a Crohn's disease patient adheres, invades, and induces inflammatory responses in polarized intestinal epithelial cells.

    PubMed

    Eaves-Pyles, Tonyia; Allen, Christopher A; Taormina, Joanna; Swidsinski, Alexander; Tutt, Christopher B; Jezek, G Eric; Islas-Islas, Martha; Torres, Alfredo G

    2008-07-01

    Inflammatory diseases of the intestinal tract are a major health concern both in the United States and around the world. Evidence now suggests that a new category of Escherichia coli, designated Adherent Invasive E. coli (AIEC) is highly prevalent in Crohn's Disease (CD) patients. AIEC strains have been shown to colonize and adhere to intestinal epithelial cells (IEC). However, the role AIEC strains play in the induction of an inflammatory response is not known. Therefore, we examined several E. coli strains (designated LF82, O83:H1, 6604 and 6655) that were isolated from CD patients for their ability to induce inflammation in two IEC, Caco-2BBe and T-84 cells. Results showed that each strain had varying abilities to adhere to and invade IEC as well as induced cytokine secretion from polarized IEC. However, E. coli O83:H1 displayed the best characteristics of AIEC strains as compared to the prototype AIEC strain LF82, inducing cytokine secretion from IEC and promoting immune cell migration through IEC. Upon further analysis, E. coli O83:H1 did not harbor virulence genes present in known pathogenic intestinal organisms. Further characterization of E. coli O83:H1 virulence determinants showed that a non-flagellated O83:H1 strain significantly decreased the organism's ability to adhere to and invade both IEC and elicit IEC cytokine secretion compared to the wild type and complemented strains. These findings demonstrate that E. coli O83:H1 possesses the characteristics of the AIEC LF82 strain that may contribute to the low-grade, chronic inflammation observed in Crohn's disease. PMID:17900983

  9. Targeting Medication Non-Adherence Behavior in Selected Autoimmune Diseases: A Systematic Approach to Digital Health Program Development

    PubMed Central

    van Mierlo, Trevor; Fournier, Rachel; Ingham, Michael

    2015-01-01

    Background 29 autoimmune diseases, including Rheumatoid Arthritis, gout, Crohn’s Disease, and Systematic Lupus Erythematosus affect 7.6-9.4% of the population. While effective therapy is available, many patients do not follow treatment or use medications as directed. Digital health and Web 2.0 interventions have demonstrated much promise in increasing medication and treatment adherence, but to date many Internet tools have proven disappointing. In fact, most digital interventions continue to suffer from high attrition in patient populations, are burdensome for healthcare professionals, and have relatively short life spans. Objective Digital health tools have traditionally centered on the transformation of existing interventions (such as diaries, trackers, stage-based or cognitive behavioral therapy programs, coupons, or symptom checklists) to electronic format. Advanced digital interventions have also incorporated attributes of Web 2.0 such as social networking, text messaging, and the use of video. Despite these efforts, there has not been little measurable impact in non-adherence for illnesses that require medical interventions, and research must look to other strategies or development methodologies. As a first step in investigating the feasibility of developing such a tool, the objective of the current study is to systematically rate factors of non-adherence that have been reported in past research studies. Methods Grounded Theory, recognized as a rigorous method that facilitates the emergence of new themes through systematic analysis, data collection and coding, was used to analyze quantitative, qualitative and mixed method studies addressing the following autoimmune diseases: Rheumatoid Arthritis, gout, Crohn’s Disease, Systematic Lupus Erythematosus, and inflammatory bowel disease. Studies were only included if they contained primary data addressing the relationship with non-adherence. Results Out of the 27 studies, four non-modifiable and 11 modifiable

  10. Diversity of Spirochetes in Endodontic Infections ▿

    PubMed Central

    Sakamoto, Mitsuo; Siqueira, José F.; Rôças, Isabela N.; Benno, Yoshimi

    2009-01-01

    The diversity of spirochetes in primary endodontic infections of teeth with chronic apical periodontitis or acute apical abscesses was investigated using 16S rRNA gene clone library analysis. The prevalences of three common cultivable oral Treponema species were also determined using species-specific nested PCR. All detected spirochetes belonged to the genus Treponema. Overall, 28 different taxa were identified from the 431 clones sequenced: 9 cultivable and validly named species, 1 cultivable as-yet-uncharacterized strain, and 18 as-yet-uncultivated phylotypes, 17 of which were novel. The large majority of clones (94%) were from cultivable named species. The numbers of Treponema species/phylotypes per selected positive sample ranged from 2 to 12. Species-specific nested PCR detected T. denticola, T. socranskii, and T. maltophilum in 59 (66%), 33 (37%), and 26 (29%) of the 90 cases of primary endodontic infections, respectively. Clone library analysis revealed diverse Treponema species/phylotypes as part of the microbiota associated with asymptomatic and symptomatic (abscess) endodontic infections. Although several as-yet-uncultivated Treponema phylotypes were disclosed, including novel taxa, cultivable named species were more abundant and frequently detected. PMID:19261792

  11. Diversity of spirochetes in endodontic infections.

    PubMed

    Sakamoto, Mitsuo; Siqueira, José F; Rôças, Isabela N; Benno, Yoshimi

    2009-05-01

    The diversity of spirochetes in primary endodontic infections of teeth with chronic apical periodontitis or acute apical abscesses was investigated using 16S rRNA gene clone library analysis. The prevalences of three common cultivable oral Treponema species were also determined using species-specific nested PCR. All detected spirochetes belonged to the genus Treponema. Overall, 28 different taxa were identified from the 431 clones sequenced: 9 cultivable and validly named species, 1 cultivable as-yet-uncharacterized strain, and 18 as-yet-uncultivated phylotypes, 17 of which were novel. The large majority of clones (94%) were from cultivable named species. The numbers of Treponema species/phylotypes per selected positive sample ranged from 2 to 12. Species-specific nested PCR detected T. denticola, T. socranskii, and T. maltophilum in 59 (66%), 33 (37%), and 26 (29%) of the 90 cases of primary endodontic infections, respectively. Clone library analysis revealed diverse Treponema species/phylotypes as part of the microbiota associated with asymptomatic and symptomatic (abscess) endodontic infections. Although several as-yet-uncultivated Treponema phylotypes were disclosed, including novel taxa, cultivable named species were more abundant and frequently detected. PMID:19261792

  12. Medication adherence and tolerability of Alzheimer’s disease medications: study protocol for a randomized controlled trial

    PubMed Central

    2013-01-01

    Background The class of acetylcholinesterase inhibitors (ChEI), including donepezil, rivastigmine, and galantamine, have similar efficacy profiles in patients with mild to moderate Alzheimer’s disease (AD). However, few studies have evaluated adherence to these agents. We sought to prospectively capture the rates and reasons for nonadherence to ChEI and determine factors influencing tolerability and adherence. Methods/design We designed a pragmatic randomized clinical trial to evaluate the adherence to ChEIs among older adults with AD. Participants include AD patients receiving care within memory care practices in the greater Indianapolis area. Participants will be followed at 6-week intervals up to 18 weeks to measure the primary outcome of ChEI discontinuation and adherence rates and secondary outcomes of behavioral and psychological symptoms of dementia. The primary outcome will be assessed through two methods, a telephone interview of an informal caregiver and electronic medical record data captured from each healthcare system through a regional health information exchange. The secondary outcome will be measured by the Healthy Aging Brain Care Monitor and the Neuropsychiatric Inventory. In addition, the trial will conduct an exploratory evaluation of the pharmacogenomic signatures for the efficacy and the adverse effect responses to ChEIs. We hypothesized that patient-specific factors, including pharmacogenomics and pharmacokinetic characteristics, may influence the study outcomes. Discussion This pragmatic trial will engage a diverse population from multiple memory care practices to evaluate the adherence to and tolerability of ChEIs in a real world setting. Engaging participants from multiple healthcare systems connected through a health information exchange will capture valuable clinical and non-clinical influences on the patterns of utilization and tolerability of a class of medications with a high rate of discontinuation. Trial Registration

  13. Impact of adherence to WHO infant feeding recommendations on later risk of obesity and non-communicable diseases: systematic review.

    PubMed

    Martin, Anne; Bland, Ruth M; Connelly, Andrew; Reilly, John J

    2016-07-01

    Adherence to WHO infant feeding recommendations has short-term benefits and may also help in the prevention of non-communicable diseases (NCDs). This study reviewed the evidence on whether adherence to all elements of the WHO infant feeding recommendations (comparison group those exclusively breastfed to 6 months, introduced to appropriate complementary feeding from 6 months, with continued breastfeeding to at least 24 months; exposure group characterised by non-adherence to any of the three recommendations) is associated with reduced risk of later obesity or cardiometabolic disease. The population of interest was children not classified as very low weight (weight-for-age z-score >-3.0). MEDLINE, EMBASE, Global Health, CINAHL plus, ProQuest Dissertations and Thesis were systematically searched from 2001 to July 2014, manual reference searching of a birth cohort register (http://www.birthcohorts.net/) as well as papers identified in the search and selected journals was carried out. The database search yielded 9050 records, 275 English-language full-text articles were screened, but no studies were eligible, failing to meet the following criteria: comparison (213); exposure (14); population (3); relevant outcome (5); outcome before 24 months (9); insufficient information provided (30); plus one study was qualitative. Eight studies met the inclusion criterion of exclusive breastfeeding to 6 months, but did not meet the other inclusion criteria. The present study has revealed an important gap in the evidence on NCD prevention, and suggestions for addressing this evidence gap are provided. PMID:26259927

  14. What's in a name? Concordance is better than adherence for promoting partnership and self-management of chronic disease.

    PubMed

    Randall, Sue; Neubeck, Lis

    2016-01-01

    The choice of language health professionals use to discuss self-management of chronic disease is important and influences patients' self-management. The words compliance, adherence and concordance are used to discuss patients' agreement with prescribed treatment plans, but have different tone and meanings. Models of care linked to the words compliance and adherence are underpinned by interactions between patients and healthcare providers that merely reinforce instructions about treatments. The 'patient-professional partnership' is introduced as a model by Bodenheimer et al. (2002, p. 2469) whereby true partnership working should be an opportunity to pool the expertise of both parties to arrive at mutually agreed goals in concordance. The impact these words might have on partnership working is important in defining the patient-health professional relationship, and for the patients' healthcare outcomes and the potential effect on healthcare utilisation. PMID:27150465

  15. Mobilifilum chasei: morphology and ecology of a spirochete from an intertidal stratified microbial mat community

    NASA Technical Reports Server (NTRS)

    Margulis, L.; Hinkle, G.; Stolz, J.; Craft, F.; Esteve, I.; Guerrero, R.

    1990-01-01

    Spirochetes were found in the lower anoxiphototrophic layer of a stratified microbial mat (North Pond, Laguna Figueroa, Baja California, Mexico). Ultra-structural analysis of thin sections of field samples revealed spirochetes approximately 0.25 micrometer in diameter with 10 or more periplasmic flagella, leading to the interpretation that these spirochetes bear 10 flagellar insertions on each end. Morphometric study showed these free-living spirochetes greatly resemble certain symbiotic ones, i.e., Borrelia and certain termite spirochetes, the transverse sections of which are presented here. The ultrastructure of this spirochete also resembles Hollandina and Diplocalyx (spirochetes symbiotic in arthropods) more than it does Spirochaeta, the well known genus of mud-dwelling spirochetes. The new spirochete was detected in mat material collected both in 1985 and in 1987. Unique morphology (i.e., conspicuous outer coat of inner membrane, large number of periplasmic flagella) and ecology prompt us to name a new free-living spirochete.

  16. Forces and Torques on Rotating Spirochete Flagella

    PubMed Central

    Yang, Jing; Huber, Greg; Wolgemuth, Charles W.

    2012-01-01

    Spirochetes are a unique group of motile bacteria that are distinguished by their helical or flat-wave shapes and the location of their flagella, which reside within the tiny space between the bacterial cell wall and the outer membrane (the periplasm). In Borrelia burgdorferi, rotation of the flagella produces cellular undulations that drive swimming. How these shape changes arise due to the forces and torques that act between the flagella and the cell body is unknown. It is possible that resistive forces come from friction or from fluid drag, depending on whether or not the flagella are in contact with the cell wall. Here, we consider both of these cases. By analyzing the motion of an elastic flagellum rotating in the periplasmic space, we show that the flagella are most likely separated from the bacterial cell wall by a lubricating layer of fluid. This analysis then provides drag coefficients for rotation and sliding of a flagellum within the periplasm. PMID:22243185

  17. Forces and torques on rotating spirochete flagella.

    PubMed

    Yang, Jing; Huber, Greg; Wolgemuth, Charles W

    2011-12-23

    Spirochetes are a unique group of motile bacteria that are distinguished by their helical or flat-wave shapes and the location of their flagella, which reside within the tiny space between the bacterial cell wall and the outer membrane (the periplasm). In Borrelia burgdorferi, rotation of the flagella produces cellular undulations that drive swimming. How these shape changes arise due to the forces and torques that act between the flagella and the cell body is unknown. It is possible that resistive forces come from friction or from fluid drag, depending on whether or not the flagella are in contact with the cell wall. Here, we consider both of these cases. By analyzing the motion of an elastic flagellum rotating in the periplasmic space, we show that the flagella are most likely separated from the bacterial cell wall by a lubricating layer of fluid. This analysis then provides drag coefficients for rotation and sliding of a flagellum within the periplasm. PMID:22243185

  18. Forces and Torques on Rotating Spirochete Flagella

    NASA Astrophysics Data System (ADS)

    Yang, Jing; Huber, Greg; Wolgemuth, Charles W.

    2011-12-01

    Spirochetes are a unique group of motile bacteria that are distinguished by their helical or flat-wave shapes and the location of their flagella, which reside within the tiny space between the bacterial cell wall and the outer membrane (the periplasm). In Borrelia burgdorferi, rotation of the flagella produces cellular undulations that drive swimming. How these shape changes arise due to the forces and torques that act between the flagella and the cell body is unknown. It is possible that resistive forces come from friction or from fluid drag, depending on whether or not the flagella are in contact with the cell wall. Here, we consider both of these cases. By analyzing the motion of an elastic flagellum rotating in the periplasmic space, we show that the flagella are most likely separated from the bacterial cell wall by a lubricating layer of fluid. This analysis then provides drag coefficients for rotation and sliding of a flagellum within the periplasm.

  19. Development and Cultural Adaptation Of the Spanish Version of the End Stage Renal Disease Adherence Questionnaire (SESRD-AQ)

    PubMed Central

    Kim, Youngmee; Evangelista, Lorraine S.

    2015-01-01

    We previously developed and validated the End-Stage Renal Disease Adherence Questionnaire (ESRD-AQ) to measure adherence behaviors (e.g., hemodialysis attendance, medication use, fluid restrictions, and diet) of patients on maintenance hemodialysis. To determine whether the ESRD-AQ can be used to measure adherence behaviors in non- English-speaking patients, we translated and adapted the ESRD-AQ into Spanish (SESRD-AQ) using forward and backward translation and cultural adaptation of the content. Validity and reliability were measured using item-level content validity indexes, intraclass correlation coefficients, and known-group analysis. All validity indices were within an acceptable range; strong test-retest stability existed across all items, with intraclass correlation coefficients ranging from 0.82 to 1.00. The developed SESRD-AQ is a valid assessment tool for use among Spanish-speaking patients on maintenance hemodialysis. This instrument refinement and validation process can be replicated with other maintenance hemodialysis population groups. PMID:24579396

  20. Better Adherence to the Mediterranean Diet Could Mitigate the Adverse Consequences of Obesity on Cardiovascular Disease: The SUN Prospective Cohort

    PubMed Central

    Eguaras, Sonia; Toledo, Estefanía; Hernández-Hernández, Aitor; Cervantes, Sebastián; Martínez-González, Miguel A.

    2015-01-01

    Strong observational evidence supports the association between obesity and cardiovascular events. In elderly high-risk subjects, the Mediterranean diet (MedDiet) was reported to counteract the adverse cardiovascular effects of adiposity. Whether this same attenuation is also present in younger subjects is not known. We prospectively examined the association between obesity and cardiovascular clinical events (myocardial infarction, stroke or cardiovascular death) after 10.9 years follow-up in 19,065 middle-aged men and women (average age 38 year) according to their adherence to the MedDiet (<6 points or ≥6 points in the Trichopoulou’s Mediterranean Diet Score). We observed 152 incident cases of cardiovascular disease (CVD). An increased risk of CVD across categories of body mass index (BMI) was apparent if adherence to the MedDiet was low, with multivariable-adjusted hazard ratios (HRs): 1.44 (95% confidence interval: 0.93–2.25) for ≥25 – <30 kg/m2 of BMI and 2.00 (1.04–3.83) for ≥30 kg/m2 of BMI, compared to a BMI < 25 kg/m2. In contrast, these estimates were 0.77 (0.35–1.67) and 1.15 (0.39–3.43) with good adherence to MedDiet. Better adherence to the MedDiet was associated with reduced CVD events (p for trend = 0.029). Our results suggest that the MedDiet could mitigate the harmful cardiovascular effect of overweight/obesity. PMID:26556370

  1. Better Adherence to the Mediterranean Diet Could Mitigate the Adverse Consequences of Obesity on Cardiovascular Disease: The SUN Prospective Cohort.

    PubMed

    Eguaras, Sonia; Toledo, Estefanía; Hernández-Hernández, Aitor; Cervantes, Sebastián; Martínez-González, Miguel A

    2015-11-01

    Strong observational evidence supports the association between obesity and cardiovascular events. In elderly high-risk subjects, the Mediterranean diet (MedDiet) was reported to counteract the adverse cardiovascular effects of adiposity. Whether this same attenuation is also present in younger subjects is not known. We prospectively examined the association between obesity and cardiovascular clinical events (myocardial infarction, stroke or cardiovascular death) after 10.9 years follow-up in 19,065 middle-aged men and women (average age 38 year) according to their adherence to the MedDiet (<6 points or ≥6 points in the Trichopoulou's Mediterranean Diet Score). We observed 152 incident cases of cardiovascular disease (CVD). An increased risk of CVD across categories of body mass index (BMI) was apparent if adherence to the MedDiet was low, with multivariable-adjusted hazard ratios (HRs): 1.44 (95% confidence interval: 0.93-2.25) for ≥25 - <30 kg/m² of BMI and 2.00 (1.04-3.83) for ≥30 kg/m² of BMI, compared to a BMI < 25 kg/m². In contrast, these estimates were 0.77 (0.35-1.67) and 1.15 (0.39-3.43) with good adherence to MedDiet. Better adherence to the MedDiet was associated with reduced CVD events (p for trend = 0.029). Our results suggest that the MedDiet could mitigate the harmful cardiovascular effect of overweight/obesity. PMID:26556370

  2. Efficacy and safety of a multifactor intervention to improve therapeutic adherence in patients with chronic obstructive pulmonary disease (COPD): protocol for the ICEPOC study

    PubMed Central

    2011-01-01

    Background Low therapeutic adherence to medication is very common. Clinical effectiveness is related to dose rate and route of administration and so poor therapeutic adherence can reduce the clinical benefit of treatment. The therapeutic adherence of patients with chronic obstructive pulmonary disease (COPD) is extremely poor according to most studies. The research about COPD adherence has mainly focussed on quantifying its effect, and few studies have researched factors that affect non-adherence. Our study will evaluate the effectiveness of a multifactor intervention to improve the therapeutic adherence of COPD patients. Methods/Design A randomized controlled clinical trial with 140 COPD diagnosed patients selected by a non-probabilistic method of sampling. Subjects will be randomly allocated into two groups, using the block randomization technique. Every patient in each group will be visited four times during the year of the study. Intervention: Motivational aspects related to adherence (beliefs and behaviour): group and individual interviews; cognitive aspects: information about illness; skills: inhaled technique training. Reinforcement of the cognitive-emotional aspects and inhaled technique training will be carried out in all visits of the intervention group. Discussion Adherence to a prescribed treatment involves a behavioural change. Cognitive, emotional and motivational aspects influence this change and so we consider the best intervention procedure to improve adherence would be a cognitive and emotional strategy which could be applied in daily clinical practice. Our hypothesis is that the application of a multifactor intervention (COPD information, dose reminders and reinforcing audiovisual material, motivational aspects and inhalation technique training) to COPD patients taking inhaled treatment will give a 25% increase in the number of patients showing therapeutic adherence in this group compared to the control group. We will evaluate the effectiveness

  3. Medication Adherence Patterns after Hospitalization for Coronary Heart Disease. A Population-Based Study Using Electronic Records and Group-Based Trajectory Models

    PubMed Central

    Librero, Julián; Sanfélix-Gimeno, Gabriel; Peiró, Salvador

    2016-01-01

    Objective To identify adherence patterns over time and their predictors for evidence-based medications used after hospitalization for coronary heart disease (CHD). Patients and Methods We built a population-based retrospective cohort of all patients discharged after hospitalization for CHD from public hospitals in the Valencia region (Spain) during 2008 (n = 7462). From this initial cohort, we created 4 subcohorts with at least one prescription (filled or not) from each therapeutic group (antiplatelet, beta-blockers, ACEI/ARB, statins) within the first 3 months after discharge. Monthly adherence was defined as having ≥24 days covered out of 30, leading to a repeated binary outcome measure. We assessed the membership to trajectory groups of adherence using group-based trajectory models. We also analyzed predictors of the different adherence patterns using multinomial logistic regression. Results We identified a maximum of 5 different adherence patterns: 1) Nearly-always adherent patients; 2) An early gap in adherence with a later recovery; 3) Brief gaps in medication use or occasional users; 4) A slow decline in adherence; and 5) A fast decline. These patterns represented variable proportions of patients, the descending trajectories being more frequent for the beta-blocker and ACEI/ARB cohorts (16% and 17%, respectively) than the antiplatelet and statin cohorts (10% and 8%, respectively). Predictors of poor or intermediate adherence patterns were having a main diagnosis of unstable angina or other forms of CHD vs. AMI in the index hospitalization, being born outside Spain, requiring copayment or being older. Conclusion Distinct adherence patterns over time and their predictors were identified. This may be a useful approach for targeting improvement interventions in patients with poor adherence patterns. PMID:27551748

  4. Guideline Adherence in Outpatient Clinics for Chronic Obstructive Pulmonary Disease: Results from a Clinical Audit

    PubMed Central

    López-Campos, Jose L.; Abad Arranz, Maria; Calero-Acuña, Carmen; Romero-Valero, Fernando; Ayerbe-García, Ruth; Hidalgo-Molina, Antonio; Aguilar-Pérez-Grovas, Ricardo I.; García-Gil, Francisco; Casas-Maldonado, Francisco; Caballero-Ballesteros, Laura; Sánchez-Palop, María; Pérez-Tejero, Dolores; Segado, Alejandro; Calvo-Bonachera, Jose; Hernández-Sierra, Bárbara; Doménech, Adolfo; Arroyo-Varela, Macarena; González-Vargas, Francisco; Cruz-Rueda, Juan J.

    2016-01-01

    Objectives Previous clinical audits of COPD have provided relevant information about medical intervention in exacerbation admissions. The present study aims to evaluate adherence to current guidelines in COPD through a clinical audit. Methods This is a pilot clinical audit performed in hospital outpatient respiratory clinics in Andalusia, Spain (eight provinces with more than 8 million inhabitants), including 9 centers (20% of the public centers in the area) between 2013 and 2014. Cases with an established diagnosis of COPD based on risk factors, clinical symptoms, and a post-bronchodilator FEV1/FVC ratio of less than 0.70 were deemed eligible. The performance of the outpatient clinics was benchmarked against three guidance documents available at the time of the audit. The appropriateness of the performance was categorized as excellent (>80%), good (60−80%), adequate (40−59%), inadequate (20−39%), and highly inadequate (<20%). Results During the audit, 621 clinical records were audited. Adherence to the different guidelines presented a considerable variability among the different participating hospitals, with an excellent or good adherence for symptom recording, MRC or CAT use, smoking status evaluation, spirometry, or bronchodilation therapy. The most outstanding areas for improvement were the use of the BODE index, the monitoring of treatments, the determination of alpha1-antitrypsin, the performance of exercise testing, and vaccination recommendations. Conclusions The present study reflects the situation of clinical care for COPD patients in specialized secondary care outpatient clinics. Adherence to clinical guidelines shows considerable variability in outpatient clinics managing COPD patients, and some aspects of the clinical care can clearly be improved. PMID:26985822

  5. Phylogeny of not-yet-cultured spirochetes from termite guts.

    PubMed Central

    Paster, B J; Dewhirst, F E; Cooke, S M; Fussing, V; Poulsen, L K; Breznak, J A

    1996-01-01

    Comparisons of 16S rDNA sequences were used to determine the phylogeny of not-yet-cultured spirochetes from hindguts of the African higher termite, Nasutitermes lujae (Wasmann). The 16S rRNA genes were amplified directly from spirochete-rich hindguts by using universal primers, and the amplified products were cloned into Escherichia coli. Clones were screened with a spirochete-specific DNA probe. Analysis of 1,410 base positions of the 16S rDNA insert from one spirochete clone, designated NL1, supported its assignment to the genus Treponema, with average interspecies similarities of ca. 85%. The sequence of NL1 was most closely related (ca. 87 to 88% similarity) to sequences of Spirochaeta stenostrepta and Spirochaeta caldaria and to a previously published sequence (ca. 87% similarity) of spirochetal clone MDS1 from the Australian lower termite, Mastotermes darwiniensis (Froggatt). On the basis of 16S rRNA sequence comparisons and individual base signatures, clones NL1 and MDS1 clearly represent two novel species of Treponema, although specific epithets have not yet been proposed. The gross morphology of NL1 was determined from in situ hybridization experiments with an NL1-specific, fluorescently labeled oligonucleotide probe. Cells were approximately 0.3 to 0.4 by 30 microns in size, with a wavelength and amplitude of about 10 microns and 0.8 to 1.6 micron, respectively. Moreover, electron microscopy of various undulate cells present in gut contents confirmed that they possessed ultrastructural features typical of spirochetes, i.e., a wavy protoplasmic cylinder, periplasmic flagella, and an outer sheath. The sequence data suggest that termite gut spirochetes may represent a separate line of descent from other treponemes and that they constitute a significant reservoir of previously unrecognized spirochetal biodiversity. PMID:8593040

  6. Interaction of spirochetes with the host.

    PubMed

    Hindersson, P; Thomas, D; Stamm, L; Penn, C; Norris, S; Joens, L A

    1992-01-01

    The success of an invading organism must depend on several cytoplasmic, surface-associated and secreted factors. The technical difficulties in handling pathogenic spirochetes like Treponema pallidum and Borrelia burgdorferi have made it difficult to define specific factors involved in entry and long-term survival. The problem of defining virulence factors has been attacked by several strategies: T. pallidum secretes a number of immunogenic low molecular mass proteins. The most predominant are of molecular weight 15.5 and 22 kDa. Preliminary data suggest that antibodies against these proteins induce protective immunity in rabbits experimentally infected with T. pallidum. Many potentially important surface-associated antigens of T. pallidum have now been cloned and characterized. Two of these, TpD and TpE, are lipoproteins which exhibit characteristic size heterogeneity. The apparent molecular weight of TpE from T. pallidum and T. pertenue are different. The clinical symptoms in syphilis and yaws are very different, but sequence analysis of TpE has shown that the TpE proteins are indeed very similar in the two strains. This observation makes it unlikely that heterogeneity of TpE can account for the different clinical symptoms of syphilis and yaws. Sequence data for another newly sequenced surface-associated antigen of T. pallidum (molecular weight 41 kDa) indicate that this protein is involved in glucose transport and chemotaxis/motility. Intracellular factors like the molecular chaperonin GroEL have been documented both in treponemes and borreliae. This stress protein is involved in cellular repair processes and folding/assembly of protein subunits. Indirect evidence suggests that GroEL affects the ability of spirochetes to survive in the stressful environment of the infected host. Several lines of evidence suggest that the Osp proteins of Borrelia are important for host/parasite interaction. Further support for this idea has come from studies of a series of

  7. Global ecology and epidemiology of Borrelia garinii spirochetes

    PubMed Central

    Comstedt, Pär; Jakobsson, Tobias; Bergström, Sven

    2011-01-01

    Lyme borreliosis (LB) is a tick-transmitted infectious disease caused by Borrelia burgdorferi sensu lato (s. l.). In Europe, three different Borrelia species are the main causative agents of LB: B. burgdorferi sensu stricto (s.s.), Borrelia afzelii, and Borrelia garinii. The latter depends heavily on birds as its main reservoir hosts. In fact, birds can act both as biological carriers of Borrelia and transporters of infected ticks. The seasonal migration of many bird species not only aid in the spread of B. garinii to new foci but also influence the high level of diversity found within this species. B. garinii have been isolated not only from terrestrial birds in Europe, but also from seabirds worldwide, and homology between isolates in these two different infection cycles suggests an overlap and exchange of strains. In addition, it has been shown that birds can maintain and spread B. garinii genotypes associated with LB in humans. This review article discusses the importance of birds in the ecology and epidemiology of B. garinii spirochetes. PMID:22957111

  8. Crohn's disease-associated adherent-invasive E. coli are selectively favoured by impaired autophagy to replicate intracellularly.

    PubMed

    Lapaquette, Pierre; Glasser, Anne-Lise; Huett, Alan; Xavier, Ramnik J; Darfeuille-Michaud, Arlette

    2010-01-01

    Ileal lesions in Crohn's disease (CD) patients are colonized by pathogenic adherent-invasive Escherichia coli (AIEC) able to invade and to replicate within intestinal epithelial cells. Recent genome-wide association studies have highlighted the autophagy pathway as being associated with CD risk. In the present study we investigated whether defects in autophagy enhance replication of commensal and pathogenic Escherichia coli and CD-associated AIEC. We show that functional autophagy limits intracellular AIEC replication and that a subpopulation of the intracellular bacteria is located within LC3-positive autophagosomes. In IRGM and ATG16L1 deficient cells intracellular AIEC LF82 bacteria have enhanced replication. Surprisingly autophagy deficiency did not interfere with the ability of intracellular bacteria to survive and/or replicate for any other E. coli strains tested, including non-pathogenic, environmental, commensal, or pathogenic strains involved in gastro enteritis. Together these findings demonstrate a central role for autophagy restraining Adherent-Invasive E. coli strains associated with ileal CD. AIEC infection in patients with polymorphisms in autophagy genes may have a significant impact on the outcome of intestinal inflammation. PMID:19747213

  9. Mealtime-related dosing directions for proton-pump inhibitors in gastroesophageal reflux disease: physician knowledge, patient adherence.

    PubMed

    Solem, Caitlyn; Mody, Reema; Stephens, Jennifer; Macahilig, Cynthia; Gao, Xin

    2014-01-01

    OBJECTIVE To describe physicians' knowledge, patients' adherence, and perceptions of both regarding mealtime-related dosing directions for proton-pump inhibitors (PPIs). DESIGN Chart review and survey of patients and physicians. SETTING United States, with data collected between January and July 2011. PARTICIPANTS Patients being treated for gastroesophageal reflux disease (GERD) with PPIs and their prescribing physicians. MAIN OUTCOME MEASURES Patient- and physician-reported perception of PPI mealtime-related directions as important/inconvenient (seven-point Likert scale; 7 = very important/very inconvenient); physician-reported knowledge of PPI mealtime-related dosing directions based on whether the agent is labeled to be taken 30-60 minutes before eating (DIR-esomeprazole magnesium [Nexium-AstraZeneca], lansoprazole, and omeprazole) or labeled to be taken regardless of meals (NoDIR-dexlansoprazole [Dexilant-Takeda], rabeprazole, and pantoprazole); and patient-reported PPI mealtime-related directions received and adherence to directions. RESULTS Physicians (n = 262) recruited 501 patients who had been prescribed PPIs (262 DIR/239 NoDIR; mean age 51 years, 37% men, 56% nonerosive GERD [29% undocumented]). Across PPIs, physicians frequently reported incorrect directions or "did not know directions" (29% for esomeprazole to 69% for pantoprazole). While 98% of patients reported receiving directions from their physicians and 55% from their pharmacists, only 65% of DIR patients and 18% of NoDIR received directions consistent with product labeling. Physicians perceived greater inconvenience than patients (4.4 vs. 1.6, P < 0.001) and greater importance (5.2 vs. 4.5, P < 0.001) of mealtime-related directions. Overall, 81% of patients reported taking their PPI as directed. CONCLUSION While this patient cohort was adherent to directions given, physicians' directions were often inconsistent with product labeling. Understanding physician and patient knowledge gaps may be

  10. Endemic Foci of the Tick-Borne Relapsing Fever Spirochete Borrelia crocidurae in Mali, West Africa, and the Potential for Human Infection

    PubMed Central

    Schwan, Tom G.; Anderson, Jennifer M.; Lopez, Job E.; Fischer, Robert J.; Raffel, Sandra J.; McCoy, Brandi N.; Safronetz, David; Sogoba, Nafomon; Maïga, Ousmane; Traoré, Sékou F.

    2012-01-01

    Background Tick-borne relapsing fever spirochetes are maintained in endemic foci that involve a diversity of small mammals and argasid ticks in the genus Ornithodoros. Most epidemiological studies of tick-borne relapsing fever in West Africa caused by Borrelia crocidurae have been conducted in Senegal. The risk for humans to acquire relapsing fever in Mali is uncertain, as only a few human cases have been identified. Given the high incidence of malaria in Mali, and the potential to confuse the clinical diagnosis of these two diseases, we initiated studies to determine if there were endemic foci of relapsing fever spirochetes that could pose a risk for human infection. Methodology/Principal Findings We investigated 20 villages across southern Mali for the presence of relapsing fever spirochetes. Small mammals were captured, thin blood smears were examined microscopically for spirochetes, and serum samples were tested for antibodies to relapsing fever spirochetes. Ornithodoros sonrai ticks were collected and examined for spirochetal infection. In total, 11.0% of the 663 rodents and 14.3% of the 63 shrews tested were seropositive and 2.2% of the animals had active spirochete infections when captured. In the Bandiagara region, the prevalence of infection was higher with 35% of the animals seropositive and 10% infected. Here also Ornithodoros sonrai were abundant and 17.3% of 278 individual ticks tested were infected with Borrelia crocidurae. Fifteen isolates of B. crocidurae were established and characterized by multi-locus sequence typing. Conclusions/Significance The potential for human tick-borne relapsing fever exists in many areas of southern Mali. PMID:23209863

  11. Inactivation of genes for antigenic variation in the relapsing fever spirochete Borrelia hermsii reduces infectivity in mice and transmission by ticks.

    PubMed

    Raffel, Sandra J; Battisti, James M; Fischer, Robert J; Schwan, Tom G

    2014-04-01

    Borrelia hermsii, a causative agent of relapsing fever of humans in western North America, is maintained in enzootic cycles that include small mammals and the tick vector Ornithodoros hermsi. In mammals, the spirochetes repeatedly evade the host's acquired immune response by undergoing antigenic variation of the variable major proteins (Vmps) produced on their outer surface. This mechanism prolongs spirochete circulation in blood, which increases the potential for acquisition by fast-feeding ticks and therefore perpetuation of the spirochete in nature. Antigenic variation also underlies the relapsing disease observed when humans are infected. However, most spirochetes switch off the bloodstream Vmp and produce a different outer surface protein, the variable tick protein (Vtp), during persistent infection in the tick salivary glands. Thus the production of Vmps in mammalian blood versus Vtp in ticks is a dominant feature of the spirochete's alternating life cycle. We constructed two mutants, one which was unable to produce a Vmp and the other was unable to produce Vtp. The mutant lacking a Vmp constitutively produced Vtp, was attenuated in mice, produced lower cell densities in blood, and was unable to relapse in animals after its initial spirochetemia. This mutant also colonized ticks and was infectious by tick-bite, but remained attenuated compared to wild-type and reconstituted spirochetes. The mutant lacking Vtp also colonized ticks but produced neither Vtp nor a Vmp in tick salivary glands, which rendered the spirochete noninfectious by tick bite. Thus the ability of B. hermsii to produce Vmps prolonged its survival in blood, while the synthesis of Vtp was essential for mammalian infection by the bite of its tick vector. PMID:24699793

  12. Influence of patients’ disease knowledge and beliefs about medicines on medication adherence: findings from a cross-sectional survey among patients with type 2 diabetes mellitus in Palestine

    PubMed Central

    2014-01-01

    Background Diabetes mellitus (DM) is a common serious health problem. Medication adherence is a key determinant of therapeutic success in patients with diabetes mellitus. The purpose of this study was to assess medication adherence and its potential association with beliefs and diabetes – related knowledge in patients with type II DM. Methods This study was carried out at Al-Makhfia governmental diabetes primary healthcare clinic in Nablus, Palestine. Main outcome of interest in the study was medication adherence. The Beliefs about Medicines Questionnaire (BMQ) was used to assess beliefs. Morisky Medication Adherence Scale (MMSA-8©) was used to assess medication adherence. The Michigan diabetes knowledge test (MDKT) was used to assess diabetes – related knowledge. Univariate and multivariate analysis were carried out using Statistical Package for Social Sciences (SPSS 20). Results Four hundred and five patients were interviewed. The mean ± SD age of the participants was 58.3 ± 10.4 (range = 28 – 90) years. More than half (53.3%) of the participants were females. Approximately 42.7% of the study sample were considered non-adherent (MMAS-8© score of < 6). Multivariate analysis showed that the following variables were significantly associated with non-adherence: disease-related knowledge, beliefs about necessity of anti-diabetic medications, concerns about adverse consequences of anti-diabetic medications and beliefs that medicines in general are essentially harmful. Diabetic patients with high knowledge score and those with strong beliefs in the necessity of their anti-diabetic medications were less likely to be non-adherent ([O.R = 0.87, 95% CI of 0.78 – 0.97] and [O.R = 0.93, 95% of 0.88 – 0.99] respectively). However, diabetic patients with high concerns about adverse consequences of anti-diabetic medications and those with high belief that all medicines are harmful were more likely to be non-adherent ([O.R = 1.09; 95% C

  13. Variable Tick Protein in Two Genomic Groups of the Relapsing Fever Spirochete Borrelia hermsii in Western North America

    PubMed Central

    Porcella, Stephen F.; Raffel, Sandra J.; Anderson, Donald E.; Gilk, Stacey D.; Bono, James L.; Schrumpf, Merry E.; Schwan, Tom G.

    2005-01-01

    Borrelia hermsii is the primary cause of tick-borne relapsing fever in North America. When its tick vector, Ornithodoros hermsi, acquires these spirochetes from the blood of an infected mammal, the bacteria switch their outer surface from one of many bloodstream variable major proteins (Vmps) to a unique protein, Vtp (Vsp33). Vtp may be critical for successful tick transmission of B. hermsii; however, the gene encoding this protein has been described previously in only one isolate. Here we identified and sequenced the vtp gene in 31 isolates of B. hermsii collected over 40 years from localities throughout much of its known geographic distribution. Seven major Vtp types were found. Little or no sequence variation existed within types, but between them significant variation was observed, similar to the pattern of diversity described for the outer surface protein C (OspC) gene in Lyme disease spirochetes. The pattern of sequence relatedness among the Vtp types was incongruent in two branches compared to two genomic groups identified among the isolates by multilocus sequence typing of the 16S rRNA, flaB, gyrB, and glpQ genes. Therefore, both horizontal transfer and recombination within and between the two genomic groups were responsible for some of the variation observed in the vtp gene. O. hermsi ticks were capable of transmitting spirochetes in the newly identified genomic group. Therefore, given the longevity of the tick vector and persistent infection of spirochetes in ticks, these arthropods rather than mammals may be the likely host where the exchange of spirochetal DNA occurs. PMID:16177341

  14. Enhancing adherence through education.

    PubMed

    Smrtka, Jennifer; Caon, Christina; Saunders, Carol; Becker, Brenda L; Baxter, Nancy

    2010-10-01

    The treatment of multiple sclerosis (MS) has advanced greatly since the introduction of disease-modifying therapies (DMTs) in the early 1990s. Although the DMTs have exhibited significant efficacy in relapsing-remitting MS and other forms of the disease, the degree of benefit depends heavily on patient adherence to recommended regimens. This article addresses some of the most pressing areas of unmet need in educating advanced-practice nurses, neurologists, patients, and support care partners regarding strategies that can overcome obstacles to adherence. The observations presented here are based on clinical experience with real-life cognitive, psychosocial, and cultural impediments to adherence. The article also explores the ways in which adherence may be affected by emerging therapies for MS (such as oral agents) as well as the educational needs that will arise with the further evolution of MS care. PMID:21049830

  15. Rethinking adherence.

    PubMed

    Steiner, John F

    2012-10-16

    In 2012, the Centers for Medicare & Medicaid Services (CMS) will introduce measures of adherence to oral hypoglycemic, antihypertensive, and cholesterol-lowering drugs into its Medicare Advantage quality program. To meet these quality goals, delivery systems will need to develop and disseminate strategies to improve adherence. The design of adherence interventions has too often been guided by the mistaken assumptions that adherence is a single behavior that can be predicted from readily available patient characteristics and that individual clinicians alone can improve adherence at the population level.Effective interventions require recognition that adherence is a set of interacting behaviors influenced by individual, social, and environmental forces; adherence interventions must be broadly based, rather than targeted to specific population subgroups; and counseling with a trusted clinician needs to be complemented by outreach interventions and removal of structural and organizational barriers. To achieve the adherence goals set by CMS, front-line clinicians, interdisciplinary teams, organizational leaders, and policymakers will need to coordinate efforts in ways that exemplify the underlying principles of health care reform. PMID:23070491

  16. Tick Surveillance for Relapsing Fever Spirochete Borrelia miyamotoi in Hokkaido, Japan

    PubMed Central

    Konnai, Satoru; Ohashi, Kazuhiko; Nakao, Minoru; Ito, Takuya; Andoh, Masako; Maeda, Ken; Watarai, Masahisa; Sato, Kozue; Kawabata, Hiroki

    2014-01-01

    During 2012–2013, a total of 4325 host-seeking adult ticks belonging to the genus Ixodes were collected from various localities of Hokkaido, the northernmost island of Japan. Tick lysates were subjected to real-time PCR assay to detect borrelial infection. The assay was designed for specific detection of the Relapsing fever spirochete Borrelia miyamotoi and for unspecific detection of Lyme disease-related spirochetes. Overall prevalence of B. miyamotoi was 2% (71/3532) in Ixodes persulcatus, 4.3% (5/117) in Ixodes pavlovskyi and 0.1% (1/676) in Ixodes ovatus. The prevalence in I. persulcatus and I. pavlovskyi ticks were significantly higher than in I. ovatus. Co-infections with Lyme disease-related spirochetes were found in all of the tick species. During this investigation, we obtained 6 isolates of B. miyamotoi from I. persulcatus and I. pavlovskyi by culture in BSK-M medium. Phylogenetic trees of B. miyamotoi inferred from each of 3 housekeeping genes (glpQ, 16S rDNA, and flaB) demonstrated that the Hokkaido isolates were clustered with Russian B. miyamotoi, but were distinguishable from North American and European B. miyamotoi. A multilocus sequence analysis using 8 genes (clpA, clpX, nifS, pepX, pyrG, recG, rplB, and uvrA) suggested that all Japanese B. miyamotoi isolates, including past isolates, were genetically clonal, although these were isolated from different tick and vertebrate sources. From these results, B. miyamotoi-infected ticks are widely distributed throughout Hokkaido. Female I. persulcatus are responsible for most human tick-bites, thereby I. persulcatus is likely the most important vector of indigenous relapsing fever from tick bites in Hokkaido. PMID:25111141

  17. Adherent invasive Escherichia coli strains from patients with Crohn's disease survive and replicate within macrophages without inducing host cell death.

    PubMed

    Glasser, A L; Boudeau, J; Barnich, N; Perruchot, M H; Colombel, J F; Darfeuille-Michaud, A

    2001-09-01

    Escherichia coli strains recovered from Crohn's disease (CD) lesions are able to adhere to and invade cultured intestinal epithelial cells. We analyzed the behavior within macrophages of adherent invasive E. coli (AIEC) strains isolated from patients with CD. All the 15 AIEC strains tested were able to replicate extensively within J774-A1 cells: the numbers of intracellular bacteria increased 2.2- to 74.2-fold at 48 h over that at 1 h postinfection. By use of murine peritoneal macrophages and human monocyte-derived-macrophages, the reference AIEC strain LF82 was confirmed to be able to survive intracellularly. Transmission electron micrographs of AIEC LF82-infected macrophages showed that at 24 h postinfection, infected cells harbored large vacuoles containing numerous bacteria, as a result of the fusion of several vacuoles occurring after 8 h postinfection. No lactate dehydrogenase (LDH) release, no sign of DNA fragmentation or degradation, and no binding to fluorescein isothlocyanate-labeled annexin V were observed with LF82-infected J774-A1 cells, even after 24 h postinfection. LF82-infected J774-A1 cells secreted 2.7-fold more tumor necrosis factor alpha (TNF-alpha) than cells stimulated with 1 microg of lipopolysaccharide (LPS)/ml. No release of interleukin-1beta was observed with LPS-prestimulated J774-A1 cells infected with AIEC LF82. These findings showed that (i) AIEC strains are able to survive and to replicate within macrophages, (ii) AIEC LF82 replication does not induce any cell death of the infected cells, and (iii) LF82-infected J774-A1 cells release high levels of TNF-alpha. These properties could be related to some features of CD and particularly to granuloma formation, one of the hallmarks of CD lesions. PMID:11500426

  18. Medication possession ratio: implications of using fixed and variable observation periods in assessing adherence with disease-modifying drugs in patients with multiple sclerosis

    PubMed Central

    Kozma, Chris M; Dickson, Michael; Phillips, Amy L; Meletiche, Dennis M

    2013-01-01

    Background The purpose of this study was to compare two methods of adherence calculation using administrative data for patients with multiple sclerosis (MS) who are prescribed disease-modifying drugs. Methods Pharmacy-billed disease-modifying drug prescription claims were selected from the 2007–2008 LifeLink™ Health Plan Claims Database. The index date was the first disease-modifying drug prescription claim. Two cohorts were created: all patients with a disease-modifying drug claim in 2007 and a subset with continuous eligibility for 12 months post-index. Adherence was calculated across all disease-modifying drugs for 12 months post-index. Medication possession ratios (MPRs) with variable (start to end of therapy) and fixed (365 days) duration denominators were calculated. Variable MPR was calculated by summing days supply from the first to the last prescription (inclusive) divided by time between the last prescription date plus days supply and the first prescription date. Variable MPR was evaluated for all patients and the continuously eligible cohort. Fixed MPR used the same numerator but divided by 365 days of follow-up and evaluated only for the continuously eligible cohort. Results There were 3405 patients with MS and a disease-modifying drug claim in 2007 and 2145 in the continuously eligible cohort. Means for variable MPR ranged from 87.5% ± 16.6% for the continuously eligible cohort to 90.5% ± 16.0% for the 2007 cohort. The comparable value for fixed MPR was 78.0% ± 28.2% for the continuously eligible cohort. Fixed MPR gave a consistently lower rate of adherence than variable MPR at an 80% adherence threshold. Conclusion Different adherence measures can yield different outcomes, especially when using different eligibility criteria. These results demonstrate the importance of full disclosure of methods used for calculations and specification of the study population. PMID:23807840

  19. Adherence to the 2006 American Heart Association Diet and Lifestyle Recommendations for cardiovascular disease risk reduction is associated with bone health in older Puerto Ricans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cardiovascular disease (CVD) and osteoporosis are 2 major public health problems that share common pathophysiological mechanisms. It is possible that strategies to reduce CVD risk may also benefit bone health. We tested the hypothesis that adherence to the 2006 American Heart Association Diet and Li...

  20. Adherence index based on the American Heart Association 2006 diet and lifestyle recommendations: associations with cardiovascular disease risk factors in the Boston Puerto Rican health study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In 2006, the AHA released diet and lifestyle recommendations (AHA-DLR) for cardiovascular disease (CVD) risk reduction. The effect of adherence to these recommendations on CVD risk is unknown. Our objective was to develop a unique diet and lifestyle score based on the AHA-DLR and to evaluate this sc...

  1. Study protocol for a randomized controlled trial to assess the feasibility of an open label intervention to improve hydroxyurea adherence in youth with sickle cell disease

    PubMed Central

    Smaldone, Arlene; Findley, Sally; Bakken, Suzanne; Matiz, L. Adriana; Rosenthal, Susan L.; Jia, Haomiao; Matos, Sergio; Manwani, Deepa; Green, Nancy S.

    2016-01-01

    Background Community health workers (CHW) are increasingly recognized as a strategy to improve health outcomes for the underserved with chronic diseases but has not been formally explored in adolescents with sickle cell disease (SCD). SCD primarily affects African American, Hispanic and other traditionally underserved populations. Hydroxyurea (HU), an oral, once-daily medication, is the only approved therapeutic drug for sickle cell disease and markedly reduces symptoms, morbidity and mortality and improves quality of life largely by increasing hemoglobin F blood levels. This paper presents the rationale, study design and protocol for an open label randomized controlled trial to improve parent-youth partnerships in self-management and medication adherence to HU in adolescents with SCD. Methods/Design A CHW intervention augmented by text messaging was designed for adolescents with SCD ages 10–18 years and their parents to improve daily HU adherence. Thirty adolescent parent dyads will be randomized with 2:1 intervention group allocation. Intervention dyads will establish a relationship with a culturally aligned CHW to identify barriers to HU use, identify cues to build a habit, and develop a dyad partnership to improve daily HU adherence and achieve their individualized “personal best” hemoglobin F target. Intervention feasibility, acceptability and efficacy will be assessed via a 2-site trial. Outcomes of interest are HU adherence, dyad self-management communication, quality of life, and resource use. Discussion Despite known benefits, poor HU adherence is common. If feasible and acceptable, the proposed intervention may improve health of underserved adolescents with SCD by enhancing long-term HU adherence. PMID:27327779

  2. Predictors of Long-Term Adherence to Continuous Positive Airway Pressure Therapy in Patients with Obstructive Sleep Apnea and Cardiovascular Disease in the SAVE Study

    PubMed Central

    Chai-Coetzer, Ching Li; Luo, Yuan-Ming; Antic, Nick A.; Zhang, Xi-Long; Chen, Bao-Yuan; He, Quan-Ying; Heeley, Emma; Huang, Shao-Guang; Anderson, Craig; Zhong, Nan-Shan; McEvoy, R. Doug

    2013-01-01

    Study Objectives: To determine the clinical variables that best predict long- term continuous positive airway pressure (CPAP) adherence among patients with cardiovascular disease who have obstructive sleep apnea (OSA). Design: 12-mo prospective within-trial observational study. Setting: Centers in China, Australia, and New Zealand participating in the Sleep Apnea cardioVascular Endpoints (SAVE) study. Patients: There were 275 patients age 45-70 y with cardiovascular disease (i.e., previously documented transient ischemic attack, stroke, or coronary artery disease) and OSA (4% oxygen desaturation index (ODI) > 12) who were randomized into the CPAP arm of the SAVE trial prior to July 1, 2010. Methods: Age, sex, country of residence, type of cardiovascular disease, baseline ODI, severity of sleepiness, and Hospital Anxiety and Depression Scale (HADS) scores plus CPAP side effects and adherence at 1 mo were entered in univariate analyses in an attempt to identify factors predictive of CPAP adherence at 12 mo. Variables with P < 0.2 were then included in a multivariate analysis using a linear mixed model with sites as a random effect and 12-mo CPAP use as the dependent outcome variable. Measurements and Results: CPAP adherence at 1, 6, and 12 mo was (mean ± standard deviation) 4.4 ± 2.0, 3.8 ± 2.3, and 3.3 ± 2.4 h/night, respectively. CPAP use at 1 mo (effect estimate ± standard error, 0.65 ± 0.07 per h increase, P < 0.001) and side effects at 1 mo (-0.24 ± 0.092 per additional side effect, P = 0.009) were the only independent predictors of 12- mo CPAP adherence. Conclusion: Continuous positive airway pressure use in patients with coexisting cardiovascular disease and moderate to severe obstructive sleep apnea decreases significantly over 12 months. This decline can be predicted by early patient experiences with continuous positive airway pressure (i.e., adherence and side effects at 1 month), raising the possibility that intensive early interventions could

  3. Minimal ecosystems: spirochetes populations as an example of functional stability

    NASA Astrophysics Data System (ADS)

    Berlanga, M.; Guerrero, R.

    2005-09-01

    Microbial mats are an extant paradigm of the earliest ecosystems. Defining the minimal ecosystem requirements necessary for the survival and proliferation of organisms is crucial in the search for extraterrestrial life and for establishing Earth-like ecosystems beyond our planet. Microbial mats are multilayered biofilms that operate as almost closed systems with persistent oxidation-reduction gradients and restricted vertical flows. Under the driving force of light the components interact and feedback flows become established. The community is the highest biological unit in an ecological hierarchy. The knowledge of the community composition is essential to understand the microbial mats dynamics. Understanding the factors that determine ecosystem stability has been one of the main challenges for ecologists. It has been pointed that both major and minor populations are important for maintaining ecosystem stability. Spirochetes represent one of the minor heterotrophic groups (ca. 1% total population) in microbial mats. However, when samples were examined with primers specific for the spirochete group, highly diverse collections of spirochete 16S rDNA were uncovered. Spirochetes may constitute a ubiquitous component of microbial mats that are linked to other microbial communities by robust trophic interactions.

  4. Adherence to hydroxyurea medication by children with sickle cell disease (SCD) using an electronic device: a feasibility study.

    PubMed

    Inoue, Susumu; Kodjebacheva, Gergana; Scherrer, Tammy; Rice, Gary; Grigorian, Matthew; Blankenship, Jeremy; Onwuzurike, Nkechi

    2016-08-01

    Adherence to hydroxyurea (HU) is a significant modifying factor in sickle cell vaso-occlusive pain. We conducted a study using an electronic medication container-monitor-reminder device (GlowCap™) to track adherence and determine whether use of this device affected rates of HU adherence. Subjects were regular attendees to our clinic. They were given a 37-item questionnaire and were asked to use a GlowCap containing HU. When the device cap is opened, it makes a remote "medication taken" record. The device also provides usage reminder in the form of lights and alarm sounds if the cap opening is delayed. Nineteen subjects participated in the survey, and 17 in the intervention phase. Of the 17, 12 had reliable adherence data. Seventeen caregivers of patients and two patients completed the survey. Two most common barriers to adherence identified were lack of reminders and absence of medicine home delivery. The intervention component of this study, which used both the electronic (GlowCap) method and medication possession ratio showed that the median adherence rate for the 12 patients evaluated was 85 %. The GlowCap device accurately kept a record of adherence rates. This device may be an effective tool for increasing HU medication adherence. PMID:27225236

  5. Detection of a Borrelia miyamotoi sensu lato relapsing-fever group spirochete from Ixodes pacificus in California.

    PubMed

    Mun, Jeomhee; Eisen, Rebecca J; Eisen, Lars; Lane, Robert S

    2006-01-01

    We investigated whether host-seeking nymphs and adults of the western blacklegged tick, Ixodes pacificus Cooley & Kohls, the primary vector of Lyme disease spirochetes in far-western North America, are infected naturally with relapsing-fever group spirochetes in Mendocino County, California. Relapsing-fever group borreliae were detected in four (1.7%) of 234 nymphal and two (0.7%) of 282 adult host-seeking I. pacificus ticks by polymerase chain reaction and sequence analysis of the 16S rRNA and flagellin genes, respectively, exhibiting 99 and 98.5% sequence homology to Borrelia miyamotoi Fukunaga. Phylogenetic analysis based on these two genes revealed that the borreliae detected in these ticks belong to the relapsing-fever group and that these are closely related to, if not identical with, B. miyamotoi. PMID:16506458

  6. Inactivation of Genes for Antigenic Variation in the Relapsing Fever Spirochete Borrelia hermsii Reduces Infectivity in Mice and Transmission by Ticks

    PubMed Central

    Raffel, Sandra J.; Battisti, James M.; Fischer, Robert J.; Schwan, Tom G.

    2014-01-01

    Borrelia hermsii, a causative agent of relapsing fever of humans in western North America, is maintained in enzootic cycles that include small mammals and the tick vector Ornithodoros hermsi. In mammals, the spirochetes repeatedly evade the host’s acquired immune response by undergoing antigenic variation of the variable major proteins (Vmps) produced on their outer surface. This mechanism prolongs spirochete circulation in blood, which increases the potential for acquisition by fast-feeding ticks and therefore perpetuation of the spirochete in nature. Antigenic variation also underlies the relapsing disease observed when humans are infected. However, most spirochetes switch off the bloodstream Vmp and produce a different outer surface protein, the variable tick protein (Vtp), during persistent infection in the tick salivary glands. Thus the production of Vmps in mammalian blood versus Vtp in ticks is a dominant feature of the spirochete’s alternating life cycle. We constructed two mutants, one which was unable to produce a Vmp and the other was unable to produce Vtp. The mutant lacking a Vmp constitutively produced Vtp, was attenuated in mice, produced lower cell densities in blood, and was unable to relapse in animals after its initial spirochetemia. This mutant also colonized ticks and was infectious by tick-bite, but remained attenuated compared to wild-type and reconstituted spirochetes. The mutant lacking Vtp also colonized ticks but produced neither Vtp nor a Vmp in tick salivary glands, which rendered the spirochete noninfectious by tick bite. Thus the ability of B. hermsii to produce Vmps prolonged its survival in blood, while the synthesis of Vtp was essential for mammalian infection by the bite of its tick vector. PMID:24699793

  7. [Treatment adherence: a key element].

    PubMed

    Bastida, Guillermo; Sánchez Montes, Cristina; Aguas, Mariam

    2011-12-01

    A substantial percentage of patients fail to follow health professionals' recommendations, which affects the management of chronic diseases, reducing the effectiveness of therapeutic interventions and increasing the costs of the disease. Lack of adherence is a multidimensional phenomenon and is influenced by numerous factors that should be identified. A multiplicity of measures is available to improve adherence, such as simplifying treatment administration, but none of these measures is effective when used alone. One way of tackling lack of adherence is by identifying patients' barriers to medication and involving them in decision making. Ulcerative colitis (UC) poses a risk for lack of treatment adherence. In this disease, poor adherence correlates with poor disease control (drug effectiveness) and with higher costs. As in other chronic diseases, the causes associated with poor adherence are multiple, including psychosocial factors, the physician-patient relationship and patients' prejudices toward medication. A single dose of aminosalycylates (5-ASA) should be recommended, as this dose is as safe and effective as other regimens. However, by itself, this recommendation does not seem to improve adherence. Identifying the scale of the problem and developing strategies to involve the patient in decision making is crucial to improve treatment adherence. PMID:25443221

  8. A Call to Order at the Spirochetal Host-Pathogen Interface

    PubMed Central

    Zückert, Wolfram R.

    2013-01-01

    Summary As the Lyme disease spirochete Borrelia burgdorferi shuttles back and forth between arthropod vector and vertebrate host, it encounters vastly different and hostile environments. Major mechanisms contributing to the success of this pathogen throughout this complex transmission cycle are phase and antigenic variation of abundant and serotype-defining surface lipoproteins. These peripherally membrane-anchored virulence factors mediate niche-specific interactions with vector/host factors and protect the spirochete from the perils of the mammalian immune response. In this issue of Molecular Microbiology, Tilly, Bestor and Rosa redefine the roles of two lipoproteins, OspC and VlsE, during mammalian infection. Using a variety of promoter fusions in combination with a sensitive in vivo “use it or lose it” gene complementation assay, the authors demonstrate that proper sequential expression of OspC followed by VlsE indeed matters. A previously suggested general functional redundancy between these and other lipoproteins is shown to be limited and dependent on an immunodeficient experimental setting that is arguably of diminished ecological relevance. These data reinforce the notion that OspC plays a unique role during initial infection while the antigenically variant VlsE proteins allow for persistence in the mammalian host. PMID:23750784

  9. Biologic Influences on Exercise Adherence.

    ERIC Educational Resources Information Center

    Dishman, Rod K.

    1981-01-01

    Diagnostic profiles of 362 male participants in an exercise program were analyzed to determine the biological variables between exercise adherence and symptoms of coronary disease. Findings indicated that individuals with lower metabolic capacity tended to adhere longer, to be less fit, were leaner, and began with more symptoms related to coronary…

  10. New infectious spirochete isolated from short-tailed shrews and white-footed mice.

    PubMed

    Anderson, J F; Johnson, R C; Magnarelli, L A; Hyde, F W; Andreadis, T G

    1987-08-01

    A spirochete with two periplasmic flagella was isolated from the blood or tissues of spleens and kidneys from short-tailed shrews (Blarina brevicauda) and white-footed mice (Peromyscus leucopus) in Connecticut and Minnesota. After inoculation, the shrew-mouse spirochete infected Swiss mice and Syrian hamsters. This spirochete is morphologically and serologically distinct from the species of Treponema, Borrelia, Leptospira, and Spirochaeta examined. PMID:3305565

  11. Spirochetes in ticks and antibodies to Borrelia burgdorferi in white-tailed deer from Connecticut, New York State, and North Carolina.

    PubMed

    Magnarelli, L A; Anderson, J F; Apperson, C S; Fish, D; Johnson, R C; Chappell, W A

    1986-04-01

    Ticks were screened for spirochetes and serum samples from white-tailed deer (Odocoileus virginianus) were assayed for antibodies to Borrelia burgdorferi during 1983-1984. Using fluorescein isothiocyanate-labeled rabbit antibodies produced to B. burgdorferi, the etiologic agent of Lyme disease, spirochetes were detected in Ixodes dammini (10.5% of 1,193) and Dermacentor albipictus (0.6% of 157) adults from Connecticut, I. dammini nymphs (49.1% of 108) and adults (64.7% of 99) from Armonk, New York, and in I. scapularis (0.4% of 531) and Amblyomma americanum (3.5% of 173) adults from North Carolina. Infected ticks were either seeking hosts or feeding on deer during the summer and fall. Direct fluorescent antibody staining also revealed spirochetes in two larvae of I. scapularis that emerged from eggs deposited by separate females in the laboratory. Using indirect immunofluorescence tests, antibodies to B. burgdorferi were identified in white-tailed deer living in tick-infested areas of all three states. Aside from minor cross-reactivity, there was no serologic evidence of Treponema or Leptospira infections. Ixodes dammini is a primary vector of B. burgdorferi in northeastern United States, but in North Carolina, other ixodid ticks may transmit this spirochete to humans and wildlife. PMID:3520030

  12. Treatment acceptance and adherence in HIV disease: patient identity and the perceived impact of physician-patient communication.

    PubMed

    Laws, M Barton; Rose, Gary S; Bezreh, Tanya; Beach, Mary Catherine; Taubin, Tatiana; Kogelman, Laura; Gethers, Marcia; Wilson, Ira B

    2012-01-01

    Studies have found that physician-patient relationships and communication quality are related to medication adherence and outcomes in HIV care. Few qualitative studies exist of how people living with HIV experience clinical communication about their self-care behavior. Eight focus groups with people living with HIV in two US cities were conducted. Participants responded to a detailed discussion guide and to reenactments of actual physician-patient dialogue about antiretroviral adherence. The 82 participants were diverse in age, sex, and ethnicity. Most had been living with HIV for many years and had stable relationships with providers. They appreciated providers who knew and cared about their personal lives, who were clear and direct about instructions, and who were accessible. Most had struggled to overcome addiction, emotional turmoil, and/or denial before gaining control over their lives and becoming adherent to medications. They made little or no causal attribution for their transformation to any outside agency, including their providers. They generally saw medication adherence as a function of autonomous motivation. Successful coping with HIV with its prevalent behavioral comorbidities, stigma, and other challenges requires a transformation of identity and internalization of motivation to maintain health. Effective methods for clinicians to support such development are needed. PMID:23271898

  13. HIV Medication Adherence

    MedlinePlus

    HIV Treatment HIV Medication Adherence (Last updated 3/1/2016; last reviewed 3/1/2016) Key Points Medication adherence means sticking ... exactly as prescribed. Why is adherence to an HIV regimen important? Adherence to an HIV regimen gives ...

  14. Optimizing adherence to antiretroviral therapy

    PubMed Central

    Sahay, Seema; Reddy, K. Srikanth; Dhayarkar, Sampada

    2011-01-01

    HIV has now become a manageable chronic disease. However, the treatment outcomes may get hampered by suboptimal adherence to ART. Adherence optimization is a concrete reality in the wake of ‘universal access’ and it is imperative to learn lessons from various studies and programmes. This review examines current literature on ART scale up, treatment outcomes of the large scale programmes and the role of adherence therein. Social, behavioural, biological and programme related factors arise in the context of ART adherence optimization. While emphasis is laid on adherence, retention of patients under the care umbrella emerges as a major challenge. An in-depth understanding of patients’ health seeking behaviour and health care delivery system may be useful in improving adherence and retention of patients in care continuum and programme. A theoretical framework to address the barriers and facilitators has been articulated to identify problematic areas in order to intervene with specific strategies. Empirically tested objective adherence measurement tools and approaches to assess adherence in clinical/ programme settings are required. Strengthening of ART programmes would include appropriate policies for manpower and task sharing, integrating traditional health sector, innovations in counselling and community support. Implications for the use of theoretical model to guide research, clinical practice, community involvement and policy as part of a human rights approach to HIV disease is suggested. PMID:22310817

  15. Construction of a three-dimensional model of cardiovascular disease and deployment of a new method of fostering patient adherence to instruction

    PubMed Central

    Nakano, Masuyo; Shirotake, Shoichi

    2013-01-01

    Background For the patient-oriented medical services, it is important to assist the patient in understanding the management of cardiovascular diseases. The strategy of medication instruction is particularly important to enhance medication adherence. Objective and methods The original model was newly constructed and covers multiple factors, including those related to renin–angiotensin, metabolism of glucose and lipids, blood coagulation, and the organic basis of the disease. The four factors of cardiovascular diseases and their relationship with the disease state are expressed in the form of a tetrahedral model. Results and discussion This disease model illustrates in points, lines, surfaces, and spaces that the factors combine with each other and result in a pathological condition, as determined by the degree of involvement of each factor in a discontinuous manner. The model helps cardiovascular patients to understand visually that there is more than one pathological condition. Our model allowed patients to quickly comprehend the complex pharmacotherapy of cardiovascular diseases by presenting the information in the form of a three-dimensional structure. Lifestyle-related diseases, including cardiovascular diseases, involve complicated factors and require careful pharmacotherapy which is tailored to individual patient needs. In this regard, the development of instructional tools is particularly effective. Conclusion The three-dimensional model shows optimum treatment by correctly considering both the quantity and quality of the four pathological factors associated with cardiovascular diseases. Appropriate patient compliance instruction based on life guidance is thought to be essential in the treatment of cardiovascular diseases. PMID:23836964

  16. A structured exercise programme during haemodialysis for patients with chronic kidney disease: clinical benefit and long-term adherence

    PubMed Central

    Anding, Kirsten; Bär, Thomas; Trojniak-Hennig, Joanna; Kuchinke, Simone; Krause, Rolfdieter; Rost, Jan M; Halle, Martin

    2015-01-01

    Objective Long-term studies regarding the effect of a structured physical exercise programme (SPEP) during haemodialysis (HD) assessing compliance and clinical benefit are scarce. Study design A single-centre clinical trial, non-randomised, investigating 46 patients with HD (63.2±16.3 years, male/female 24/22, dialysis vintage 4.4 years) performing an SPEP over 5 years. The SPEP (twice/week for 60 min during haemodialysis) consisted of a combined resistance (8 muscle groups) and endurance (supine bicycle ergometry) training. Exercise intensity was continuously adjusted to improvements of performance testing. Changes in endurance and resistance capacity, physical functioning and quality of life (QoL) were analysed over 1 year in addition to long-term adherence and economics of the programme over 5 years. Average power per training session, maximal strength tests (maximal exercise repetitions/min), three performance-based tests for physical function, SF36 for QoL were assessed in the beginning and every 6 months thereafter. Results 78% of the patients completed the programme after 1 year and 43% after 5 years. Participants were divided—according to adherence to the programme—into three groups: (1) high adherence group (HA, >80% of 104 training sessions within 12 months), (2) moderate adherence (MA, 60–80%), and 3. Low adherence group (LA, <60%)) with HA and MA evaluated quantitatively. One-year follow-up data revealed significant (p<0.05) improvement for both groups in all measured parameters: exercise capacity (HA: 55%, MA: 45%), strength (HA: >120%, MA: 40–50%), QoL in three scores of SF36 subscales and physical function in the three tests taken between 11% and 31%. Moreover, a quantitative correlation analysis revealed a close association (r=0.8) between large improvement of endurance capacity and weak physical condition (HA). Conclusions The exercise programme described improves physical function significantly and can be integrated

  17. 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…

  18. Point Mutations in FimH Adhesin of Crohn's Disease-Associated Adherent-Invasive Escherichia coli Enhance Intestinal Inflammatory Response

    PubMed Central

    Dreux, Nicolas; Denizot, Jérémy; Martinez-Medina, Margarita; Mellmann, Alexander; Billig, Maria; Kisiela, Dagmara; Chattopadhyay, Sujay; Sokurenko, Evgeni; Neut, Christel; Gower-Rousseau, Corinne; Colombel, Jean-Frédéric; Bonnet, Richard; Darfeuille-Michaud, Arlette; Barnich, Nicolas

    2013-01-01

    Adherent-invasive Escherichia coli (AIEC) are abnormally predominant on Crohn's disease (CD) ileal mucosa. AIEC reference strain LF82 adheres to ileal enterocytes via the common type 1 pili adhesin FimH and recognizes CEACAM6 receptors abnormally expressed on CD ileal epithelial cells. The fimH genes of 45 AIEC and 47 non-AIEC strains were sequenced. The phylogenetic tree based on fimH DNA sequences indicated that AIEC strains predominantly express FimH with amino acid mutations of a recent evolutionary origin - a typical signature of pathoadaptive changes of bacterial pathogens. Point mutations in FimH, some of a unique AIEC-associated nature, confer AIEC bacteria a significantly higher ability to adhere to CEACAM-expressing T84 intestinal epithelial cells. Moreover, in the LF82 strain, the replacement of fimHLF82 (expressing FimH with an AIEC-associated mutation) with fimHK12 (expressing FimH of commensal E. coli K12) decreased the ability of bacteria to persist and to induce severe colitis and gut inflammation in infected CEABAC10 transgenic mice expressing human CEACAM receptors. Our results highlight a mechanism of AIEC virulence evolution that involves selection of amino acid mutations in the common bacterial traits, such as FimH protein, and leads to the development of chronic inflammatory bowel disease (IBD) in a genetically susceptible host. The analysis of fimH SNPs may be a useful method to predict the potential virulence of E. coli isolated from IBD patients for diagnostic or epidemiological studies and to identify new strategies for therapeutic intervention to block the interaction between AIEC and gut mucosa in the early stages of IBD. PMID:23358328

  19. Improving physician's adherence to completing vaccination schedules for patients with type 2 diabetes attending non-communicable diseases clinics in West Bay Health Center, Qatar

    PubMed Central

    Tawfik, Hassan; Bashwar, Zelaikha; Al-Ali, Amal; Salem, Mohamed; Abdelbagi, Isameldin

    2015-01-01

    Incomplete vaccination for patients with type 2 diabetes attending non-communicable diseases (NCD) clinics is an issue that could affect patient's health and wellness negatively and puts patients at high risk of serious diseases. We aimed to improve physicians adherence to complete vaccination schedule for patients with type 2 diabetes attending NCD clinics in west bay health center according to American Diabetes Association (ADA) recommendation by 25% by January 2015. In the pre-intervention phase: the quality improvement team designed a checklist to collect the percentage of physician's adherence of prescription of the recommended vaccination for patients with type 2 diabetes. The percentage of complete vaccination in patients with diabetes attending NCD clinic in West Bay Health Center was 20% . In the intervention phase the intervention was in the form of: the creation a vaccination form and attached to the (NCD) progress note; to distribute and remind the physicians about the ADA guidelines vaccination recommendations; a summary of the vaccination schedule developed and attached to (NCD) form; development of vaccination reminder posters and posters in the waiting area, nurse station, and physician clinics and education and orientation sessions for NCD clinic staff. In the post-intervention phase the average percentage of complete vaccination in patients with diabetes attending NCD clinic in West Bay Health Center increased to 69%. PMID:26732463

  20. Understanding the Impact of Hazardous and Harmful Use of Alcohol and/or Other Drugs on ARV Adherence and Disease Progression

    PubMed Central

    Kader, Rehana; Govender, Rajen; Seedat, Soraya; Koch, John Randy; Parry, Charles

    2015-01-01

    The objective of this study was to understand the impact of hazardous and harmful use of alcohol and/or other drugs on ARV adherence and disease progression among HIV patients. A cross-sectional study design was used. A total of 1503 patients attending HIV clinics in Cape Town, South Africa were screened for problematic substance use. A sub-sample of 607 patients (303 patients who screened positive for problematic substance use and 304 who did not) participated in this study. Hazardous or harmful alcohol use and problematic drug use predicted missing and stopping ARVs which, in turn, was associated with a decrease in CD4 counts and more rapid HIV-disease progression and poorer health outcomes in people living with HIV/AIDS (PLWHA). The findings of this study underscore the need for an integrated approach to managing substance-use disorders in PLWHA. PMID:25933422

  1. Characterization and evolution of dermal filaments from patients with Morgellons disease.

    PubMed

    Middelveen, Marianne J; Mayne, Peter J; Kahn, Douglas G; Stricker, Raphael B

    2013-01-01

    Morgellons disease is an emerging skin disease characterized by formation of dermal filaments associated with multisystemic symptoms and tick-borne illness. Some clinicians hypothesize that these often colorful dermal filaments are textile fibers, either self-implanted by patients or accidentally adhering to lesions, and conclude that patients with this disease have delusions of infestation. We present histological observations and electron microscopic imaging from representative Morgellons disease samples revealing that dermal filaments in these cases are keratin and collagen in composition and result from proliferation and activation of keratinocytes and fibroblasts in the epidermis. Spirochetes were detected in the dermatological specimens from our study patients, providing evidence that Morgellons disease is associated with an infectious process. PMID:23326202

  2. Characterization and evolution of dermal filaments from patients with Morgellons disease

    PubMed Central

    Middelveen, Marianne J; Mayne, Peter J; Kahn, Douglas G; Stricker, Raphael B

    2013-01-01

    Morgellons disease is an emerging skin disease characterized by formation of dermal filaments associated with multisystemic symptoms and tick-borne illness. Some clinicians hypothesize that these often colorful dermal filaments are textile fibers, either self-implanted by patients or accidentally adhering to lesions, and conclude that patients with this disease have delusions of infestation. We present histological observations and electron microscopic imaging from representative Morgellons disease samples revealing that dermal filaments in these cases are keratin and collagen in composition and result from proliferation and activation of keratinocytes and fibroblasts in the epidermis. Spirochetes were detected in the dermatological specimens from our study patients, providing evidence that Morgellons disease is associated with an infectious process. PMID:23326202

  3. Borrelia burgdorferi Sensu Lato Spirochetes in Wild Birds in Northwestern California: Associations with Ecological Factors, Bird Behavior and Tick Infestation

    PubMed Central

    Newman, Erica A.; Eisen, Lars; Eisen, Rebecca J.; Fedorova, Natalia; Hasty, Jeomhee M.; Vaughn, Charles; Lane, Robert S.

    2015-01-01

    Although Borrelia burgdorferi sensu lato (s.l.) are found in a great diversity of vertebrates, most studies in North America have focused on the role of mammals as spirochete reservoir hosts. We investigated the roles of birds as hosts for subadult Ixodes pacificus ticks and potential reservoirs of the Lyme disease spirochete B. burgdorferi sensu stricto (s.s.) in northwestern California. Overall, 623 birds representing 53 species yielded 284 I. pacificus larvae and nymphs. We used generalized linear models and zero-inflated negative binomial models to determine associations of bird behaviors, taxonomic relationships and infestation by I. pacificus with borrelial infection in the birds. Infection status in birds was best explained by taxonomic order, number of infesting nymphs, sampling year, and log-transformed average body weight. Presence and counts of larvae and nymphs could be predicted by ground- or bark-foraging behavior and contact with dense oak woodland. Molecular analysis yielded the first reported detection of Borrelia bissettii in birds. Moreover, our data suggest that the Golden-crowned Sparrow (Zonotrichia atricapilla), a non-resident species, could be an important reservoir for B. burgdorferi s.s. Of 12 individual birds (9 species) that carried B. burgdorferi s.l.-infected larvae, no birds carried the same genospecies of B. burgdorferi s.l. in their blood as were present in the infected larvae removed from them. Possible reasons for this discrepancy are discussed. Our study is the first to explicitly incorporate both taxonomic relationships and behaviors as predictor variables to identify putative avian reservoirs of B. burgdorferi s.l. Our findings underscore the importance of bird behavior to explain local tick infestation and Borrelia infection in these animals, and suggest the potential for bird-mediated geographic spread of vector ticks and spirochetes in the far-western United States. PMID:25714376

  4. Spirosymplokos deltaeiberi nov. gen., nov. sp.: variable-diameter composite spirochete from microbial mats

    NASA Technical Reports Server (NTRS)

    Guerrero, R.; Ashen, J.; Sole, M.; Margulis, L.

    1993-01-01

    Large (up to 100 micrometers long), loosely coiled, free-living spirochetes with variable diameters (from 0.4 to 3 micrometers in the same cell) were seen at least 40 times between August 1990 and January 1993. These spirochetes were observed in mud water and enrichment media from highly specific habitats in intertidal evaporite flats at three disjunct localities, one in Spain and two in Mexico. All three are sites of commercial saltworks. Associated with Microcoleus chthonoplastes the large spirochetes from Spain display phototaxis and a composite organization. Shorter and smaller-diameter spirochetes are seen inside both healthy and spent periplasm of larger ones. Small spirochetes attached to large ones have been observed live. From two to twelve spirochete protoplasmic cylinders were seen inside a single common outer membrane. A distinctive granulated cytoplasm in which the granules are of similar diameter (20-32 nanometers) to that of the flagella (26 nanometers) was present. Granule diameters were measured in thin section and in negatively-stained whole-mount preparations. Based on their ultrastructure, large size, variable diameter, number of flagella (3 to 6), and phototactic behavior these unique spirochetes are formally named Spirosymplokos deltaeiberi. Under anoxic (or low oxygen) conditions they formed blooms in mixed culture in media selective for spirochetes. Cellobiose was the major carbon source in 80% seawater, the antibiotic rifampicin was added, mat from the original field site was present and tubes were incubated in the light at from 18-31 degrees C. Within 1-2 weeks populations of the large spirochete developed at 25 degrees C but they could not be transferred to fresh medium.

  5. Lyme Disease Frequently Asked Questions (FAQ)

    MedlinePlus

    ... of the Lyme disease spirochete, Borrelia burgdorferi , in Syrian hamsters. J Parasitol 85: 426-30. Moody KD, ... that enables public health officials to look for trends and take actions to reduce disease and improve ...

  6. Adherence to Methotrexate therapy in Rheumatoid Arthritis

    PubMed Central

    Arshad, Nasim; Ahmad, Nighat Mir; Saeed, Muhammad Ahmed; Khan, Saira; Batool, Shabnam; Farman, Sumaira

    2016-01-01

    Objective: To determine adherence to methotrexate (MTX) therapy in patients with Rheumatoid Arthritis (RA) and to identify factors that promote either adherence or non adherence. Methods: One hundred Rheumatoid Arthritis patients on MTX for at least two months were enrolled. Questionnaire was completed by direct interview. Details recorded were, demographics (age, sex, education, monthly income), disease duration, duration on MTX and current dose. Disease Activity Score on 28 joint counts (DAS 28) at the current visit, concomitant drugs taken and number of doses of MTX missed in the previous 8 weeks were noted. Non adherence was defined as omission of any three or more prescribed doses of MTX in previous 8 week. Patients were asked for the factors that motivated their adherence to MTX as well as factors for non adherence. Presence of side effects due to MTX was also recorded. Result: Non adherence was found among 23% of cases. Patients of low socioeconomic group (p <0.0001) and on MTX for longer duration (p <0.001) had higher non adherence. Non adherent patients had significantly higher disease activity as measured by DAS 28 (p<0.001). Good counseling and education by the doctor was a strong predictor of adherence (p <0.001). Lack of affordability (p <0.001); lack of availability at local pharmacy (p <0.001); lack of family support (p <0.001) and lack of awareness regarding need and importance of MTX (p < 0.001were found as significant factors for non adherence. Conclusion: MTX non adherence in RA is noted in about one fourth of study group. Various economical and social issues lead to non adherence but good patient education and counseling by doctor could promote adherence in this study group. PMID:27182251

  7. Usefulness of recombinant γ-gliadin 1 for identifying patients with celiac disease and monitoring adherence to a gluten-free diet

    PubMed Central

    Srinivasan, Bharani; Focke-Tejkl, Margarete; Weber, Milena; Pahr, Sandra; Baar, Alexandra; Atreya, Raja; Neurath, Markus F.; Vogelsang, Harald; Huber, Wolf-Dietrich; Valenta, Rudolf

    2015-01-01

    Background Celiac disease (CD) is an inflammatory disease of the small intestine caused by an immunologic hypersensitivity reaction to dietary wheat gluten. Objectives We sought to clone, express, and perform IgA epitope mapping of a CD-specific wheat antigen and to study its usefulness for identifying patients with CD and monitoring adherence to a gluten-free diet. Methods A synthetic gene coding for γ-gliadin 1 (GG1) was expressed in Escherichia coli. Recombinant γ-gliadin 1 (rGG1) was purified and characterized biochemically, structurally, and immunologically by using sera from patients with CD and control subjects. Overlapping GG1 peptides were synthesized for IgA and IgG epitope mapping. GG1 and peptide-specific antibodies were raised for tracing GG1 in cereals and dietary wheat products and to study its resistance to digestion. Results rGG1 was expressed and purified. rGG1-based IgA ELISAs performed in populations of patients with CD and control subjects showed a specificity of 92.9%, which was higher than that of gliadin extract (e). Furthermore, it allowed monitoring of adherence to a gluten-free diet in patients. A 26-amino-acid peptide from the proline-glutamine–rich repetitive N-terminal region was identified as the immunodominant IgA epitope. GG1-related antigens were found in rye, barley, and spelt but not in oat, rice, or maize. GG1 was detected in dietary wheat products after baking, and in particular, the major IgA epitope–containing region was resistant against digestion. Conclusions rGG1 and its epitope might be useful for identifying patients with CD, monitoring treatment, and studying the pathomechanisms of CD and development of preventive and therapeutic strategies. PMID:26078104

  8. A novel flagellar sheath protein, FcpA, determines filament coiling, translational motility and virulence for the Leptospira spirochete.

    PubMed

    Wunder, Elsio A; Figueira, Cláudio P; Benaroudj, Nadia; Hu, Bo; Tong, Brian A; Trajtenberg, Felipe; Liu, Jun; Reis, Mitermayer G; Charon, Nyles W; Buschiazzo, Alejandro; Picardeau, Mathieu; Ko, Albert I

    2016-08-01

    Leptospira are unique among bacteria based on their helical cell morphology with hook-shaped ends and the presence of periplasmic flagella (PF) with pronounced spontaneous supercoiling. The factors that provoke such supercoiling, as well as the role that PF coiling plays in generating the characteristic hook-end cell morphology and motility, have not been elucidated. We have now identified an abundant protein from the pathogen L. interrogans, exposed on the PF surface, and named it Flagellar-coiling protein A (FcpA). The gene encoding FcpA is highly conserved among Leptospira and was not found in other bacteria. fcpA(-) mutants, obtained from clinical isolates or by allelic exchange, had relatively straight, smaller-diameter PF, and were not able to produce translational motility. These mutants lost their ability to cause disease in the standard hamster model of leptospirosis. Complementation of fcpA restored the wild-type morphology, motility and virulence phenotypes. In summary, we identified a novel Leptospira 36-kDa protein, the main component of the spirochete's PF sheath, and a key determinant of the flagella's coiled structure. FcpA is essential for bacterial translational motility and to enable the spirochete to penetrate the host, traverse tissue barriers, disseminate to cause systemic infection and reach target organs. PMID:27113476

  9. Comparative Genome Analysis of the Pathogenic Spirochetes Borrelia burgdorferi and Treponema pallidum

    PubMed Central

    Subramanian, G.; Koonin, Eugene V.; Aravind, L.

    2000-01-01

    A comparative analysis of the predicted protein sequences encoded in the complete genomes of Borrelia burgdorferi and Treponema pallidum provides a number of insights into evolutionary trends and adaptive strategies of the two spirochetes. A measure of orthologous relationships between gene sets, termed the orthology coefficient (OC), was developed. The overall OC value for the gene sets of the two spirochetes is about 0.43, which means that less than one-half of the genes show readily detectable orthologous relationships. This emphasizes significant divergence between the two spirochetes, apparently driven by different biological niches. Different functional categories of proteins as well as different protein families show a broad distribution of OC values, from near 1 (a perfect, one-to-one correspondence) to near 0. The proteins involved in core biological functions, such as genome replication and expression, typically show high OC values. In contrast, marked variability is seen among proteins that are involved in specific processes, such as nutrient transport, metabolism, gene-specific transcription regulation, signal transduction, and host response. Differences in the gene complements encoded in the two spirochete genomes suggest active adaptive evolution for their distinct niches. Comparative analysis of the spirochete genomes produced evidence of gene exchanges with other bacteria, archaea, and eukaryotic hosts that seem to have occurred at different points in the evolution of the spirochetes. Examples are presented of the use of sequence profile analysis to predict proteins that are likely to play a role in pathogenesis, including secreted proteins that contain specific protein-protein interaction domains, such as von Willebrand A, YWTD, TPR, and PR1, some of which hitherto have been reported only in eukaryotes. We tentatively reconstruct the likely evolutionary process that has led to the divergence of the two spirochete lineages; this reconstruction seems

  10. Bisphosphonates adherence for treatment of osteoporosis

    PubMed Central

    2013-01-01

    Background Osteoporosis is a disease of bone metabolism in which bisphosphonates (BPS) are the most common medications used in its treatment, whose main objective is to reduce the risk of fractures. The aim of this study was to conduct a systematic review on BPs adherence for treatment of osteoporosis. Methods Systematic review of articles on BPs adherence for treatment of osteoporosis, indexed on MEDLINE (via PubMed) databases, from inception of databases until January 2013. Search terms were “Adherence, Medication” (MeSH term), “Bisphosphonates” (MeSH term), and “Osteoporosis” (MeSH term). Results Of the 78 identified studies, 27 met the eligibility criteria. Identified studies covered a wide range of aspects regarding adherence and associated factors, adherence and fracture, adherence and BPs dosage. The studies are mostly observational, conducted with women over 45 years old, showing low rates of adherence to treatment. Several factors may influence adherence: socio-economic and cultural, participation of physicians when guidance is given to the patient, the use of bone turnover markers, and use of generic drugs. The monthly dosage is associated with greater adherence compared to weekly dosage. Conclusions Considering the methodological differences between the studies, the results converge to show that adherence to treatment of osteoporosis with BPs is still inadequate. Further experimental studies are needed to evaluate the adherence and suggest new treatment options. PMID:23705998

  11. Cotransmission of Divergent Relapsing Fever Spirochetes by Artificially Infected Ornithodoros hermsi▿†

    PubMed Central

    Policastro, Paul F.; Raffel, Sandra J.; Schwan, Tom G.

    2011-01-01

    The soft tick Ornithodoros hermsi, which ranges in specific arboreal zones of western North America, acts as a vector for the relapsing fever spirochete Borrelia hermsii. Two genomic groups (genomic group I [GGI] and GGII) of B. hermsii are differentiated by multilocus sequence typing yet are codistributed in much of the vector's range. To test whether the tick vector can be infected via immersion, noninfected, colony-derived O. hermsi larvae were exposed to reduced-humidity conditions before immersion in culture suspensions of several GGI and GGII isolates. We tested for spirochetes in ticks by immunofluorescence microscopy and in mouse blood by quantitative PCR of the vtp locus to differentiate spirochete genotypes. The immersed larval ticks were capable of spirochete transmission to mice at the first nymphal feeding. Tick infection with mixed cultures of isolates DAH (vtp-6) (GGI) and MTW-2 (vtp-5) (GGII) resulted in ticks that caused spirochetemias in mice consisting of MTW-2 or both DAH and MTW-2. These findings show that this soft tick species can acquire B. hermsii by immersion in spirochete suspensions, that GGI and GGII isolates can coinfect the tick vector by this method, and that these spirochetes can be cotransmitted to a rodent host. PMID:21965393

  12. Cosmopolitan distribution of the large composite microbial mat spirochete, Spirosymplokos deltaeiberi

    NASA Technical Reports Server (NTRS)

    Margulis, L.; Navarrete, A.; Sole, M.

    1998-01-01

    Inocula from organic-rich black muds immediately underlying intertidal laminated microbial mats dominated by Microcoleus chthonoplastes yielded large, variable diameter spirochetes. These unusual spirochetes, previously reported only from the Alfacs Peninsula at the delta of the Ebro river in northeast Spain, contain striking arrays of cytoplasmic granules packed into their protoplasmic cylinders. On several occasions, both in summer and winter, the huge spirochetes were recognized in samples from mats growing in the Sippewissett salt marsh at Woods Hole Massachusetts. They were also seen in similar samples from microbial mats at North Pond, Laguna Figueroa, Baja California Norte, Mexico. The identity of these spirochetes was confirmed by electron microscopy: number and disposition of flagella, composite structure, measurements of their distinctive cytoplasmic granules. The granules, larger, more conspicuous and present in addition to ribosomes, are hypothesized to contain ATPases. As culture conditions worsen, these spirochetes retract into membrane-bounded round bodies in which they form refractile inclusions. From morphology and behavior we conclude the North American spirochetes from both Atlantic and Pacific intertidal microbial mats are indistinguishable from those at the delta of the Ebro river. We conclude a cosmopolitan distribution for Spirosymplokos deltaeiberi.

  13. Intravital Imaging of Vascular Transmigration by the Lyme Spirochete: Requirement for the Integrin Binding Residues of the B. burgdorferi P66 Protein

    PubMed Central

    Kumar, Devender; Ristow, Laura C.; Shi, Meiqing; Mukherjee, Priyanka; Caine, Jennifer A.; Lee, Woo-Yong; Kubes, Paul; Coburn, Jenifer; Chaconas, George

    2015-01-01

    Vascular extravasation, a key step in systemic infection by hematogenous microbial pathogens, is poorly understood, but has been postulated to encompass features similar to vascular transmigration by leukocytes. The Lyme disease spirochete can cause a variety of clinical manifestations, including arthritis, upon hematogenous dissemination. This pathogen encodes numerous surface adhesive proteins (adhesins) that may promote extravasation, but none have yet been implicated in this process. In this work we report the novel use of intravital microscopy of the peripheral knee vasculature to study transmigration of the Lyme spirochete in living Cd1d-/-mice. In the absence of iNKT cells, major immune modulators in the mouse joint, spirochetes that have extravasated into joint-proximal tissue remain in the local milieu and can be enumerated accurately. We show that BBK32, a fibronectin and glycosaminoglycan adhesin of B. burgdorferi involved in early steps of endothelial adhesion, is not required for extravasation from the peripheral knee vasculature. In contrast, almost no transmigration occurs in the absence of P66, an outer membrane protein that has porin and integrin adhesin functions. Importantly, P66 mutants specifically defective in integrin binding were incapable of promoting extravasation. P66 itself does not promote detectable microvascular interactions, suggesting that vascular adhesion of B. burgdorferi mediated by other adhesins, sets the stage for P66-integrin interactions leading to transmigration. Although integrin-binding proteins with diverse functions are encoded by a variety of bacterial pathogens, P66 is the first to have a documented and direct role in vascular transmigration. The emerging picture of vascular escape by the Lyme spirochete shows similarities, but distinct differences from leukocyte transmigration. PMID:26684456

  14. Intravital Imaging of Vascular Transmigration by the Lyme Spirochete: Requirement for the Integrin Binding Residues of the B. burgdorferi P66 Protein.

    PubMed

    Kumar, Devender; Ristow, Laura C; Shi, Meiqing; Mukherjee, Priyanka; Caine, Jennifer A; Lee, Woo-Yong; Kubes, Paul; Coburn, Jenifer; Chaconas, George

    2015-12-01

    Vascular extravasation, a key step in systemic infection by hematogenous microbial pathogens, is poorly understood, but has been postulated to encompass features similar to vascular transmigration by leukocytes. The Lyme disease spirochete can cause a variety of clinical manifestations, including arthritis, upon hematogenous dissemination. This pathogen encodes numerous surface adhesive proteins (adhesins) that may promote extravasation, but none have yet been implicated in this process. In this work we report the novel use of intravital microscopy of the peripheral knee vasculature to study transmigration of the Lyme spirochete in living Cd1d-/-mice. In the absence of iNKT cells, major immune modulators in the mouse joint, spirochetes that have extravasated into joint-proximal tissue remain in the local milieu and can be enumerated accurately. We show that BBK32, a fibronectin and glycosaminoglycan adhesin of B. burgdorferi involved in early steps of endothelial adhesion, is not required for extravasation from the peripheral knee vasculature. In contrast, almost no transmigration occurs in the absence of P66, an outer membrane protein that has porin and integrin adhesin functions. Importantly, P66 mutants specifically defective in integrin binding were incapable of promoting extravasation. P66 itself does not promote detectable microvascular interactions, suggesting that vascular adhesion of B. burgdorferi mediated by other adhesins, sets the stage for P66-integrin interactions leading to transmigration. Although integrin-binding proteins with diverse functions are encoded by a variety of bacterial pathogens, P66 is the first to have a documented and direct role in vascular transmigration. The emerging picture of vascular escape by the Lyme spirochete shows similarities, but distinct differences from leukocyte transmigration. PMID:26684456

  15. Medication Adherence Measures: An Overview.

    PubMed

    Lam, Wai Yin; Fresco, Paula

    2015-01-01

    WHO reported that adherence among patients with chronic diseases averages only 50% in developed countries. This is recognized as a significant public health issue, since medication nonadherence leads to poor health outcomes and increased healthcare costs. Improving medication adherence is, therefore, crucial and revealed on many studies, suggesting interventions can improve medication adherence. One significant aspect of the strategies to improve medication adherence is to understand its magnitude. However, there is a lack of general guidance for researchers and healthcare professionals to choose the appropriate tools that can explore the extent of medication adherence and the reasons behind this problem in order to orchestrate subsequent interventions. This paper reviews both subjective and objective medication adherence measures, including direct measures, those involving secondary database analysis, electronic medication packaging (EMP) devices, pill count, and clinician assessments and self-report. Subjective measures generally provide explanations for patient's nonadherence whereas objective measures contribute to a more precise record of patient's medication-taking behavior. While choosing a suitable approach, researchers and healthcare professionals should balance the reliability and practicality, especially cost effectiveness, for their purpose. Meanwhile, because a perfect measure does not exist, a multimeasure approach seems to be the best solution currently. PMID:26539470

  16. Medication Adherence Measures: An Overview

    PubMed Central

    Lam, Wai Yin; Fresco, Paula

    2015-01-01

    WHO reported that adherence among patients with chronic diseases averages only 50% in developed countries. This is recognized as a significant public health issue, since medication nonadherence leads to poor health outcomes and increased healthcare costs. Improving medication adherence is, therefore, crucial and revealed on many studies, suggesting interventions can improve medication adherence. One significant aspect of the strategies to improve medication adherence is to understand its magnitude. However, there is a lack of general guidance for researchers and healthcare professionals to choose the appropriate tools that can explore the extent of medication adherence and the reasons behind this problem in order to orchestrate subsequent interventions. This paper reviews both subjective and objective medication adherence measures, including direct measures, those involving secondary database analysis, electronic medication packaging (EMP) devices, pill count, and clinician assessments and self-report. Subjective measures generally provide explanations for patient's nonadherence whereas objective measures contribute to a more precise record of patient's medication-taking behavior. While choosing a suitable approach, researchers and healthcare professionals should balance the reliability and practicality, especially cost effectiveness, for their purpose. Meanwhile, because a perfect measure does not exist, a multimeasure approach seems to be the best solution currently. PMID:26539470

  17. Self-reported adherence to a home-based exercise program among patients affected by psoriatic arthritis with minimal disease activity.

    PubMed

    Chimenti, Maria Sole; Triggianese, Paola; Conigliaro, Paola; Santoro, Matteo; Lucchetti, Ramona; Perricone, Roberto

    2014-11-01

    More than half of all patients with psoriatic arthritis (PsA) exhibit progressive erosive arthritis, associated with severe functional impairment and psychosocial disability. Biologics have been suggested to be more effective in inducing minimal disease activity" (MDA) than disease-modifying antirheumatic drugs (DMARDs). Behavioral patient education appears to be more effective in encouraging patients to increase their physical activity (PA) levels. The aim of the study was to evaluate the benefits of home-based exercises program on disease activity and quality of life in MDA-PsA patients treated with an anti-tumor necrosis factor (TNF) and DMARD therapy. We observed a self-reported adherence rate to home-based exercise of 76.6% and data showed the impact of the exercise program on self-reported health and mental assessment. A positive relationship between patient and therapist is crucial, influencing the quality of the performance, the emotional support, and increasing motivation in PsA patients. PMID:25381979

  18. Patient Characteristics Associated with Medication Adherence

    PubMed Central

    Rolnick, Sharon J; Pawloski, Pamala A.; Hedblom, Brita D.; Asche, Stephen E.; Bruzek, Richard J.

    2013-01-01

    Objective Despite evidence indicating therapeutic benefit for adhering to a prescribed regimen, many patients do not take their medications as prescribed. Non-adherence often leads to morbidity and to higher health care costs. The objective of the study was to assess patient characteristics associated with medication adherence across eight diseases. Design Retrospective data from a repository within an integrated health system was used to identify patients ≥18 years of age with ICD-9-CM codes for primary or secondary diagnoses for any of eight conditions (depression, hypertension, hyperlipidemia, diabetes, asthma or chronic obstructive pulmonary disease, multiple sclerosis, cancer, or osteoporosis). Electronic pharmacy data was then obtained for 128 medications used for treatment. Methods Medication possession ratios (MPR) were calculated for those with one condition and one drug (n=15,334) and then for the total population having any of the eight diseases (n=31,636). The proportion of patients adherent (MPR ≥80%) was summarized by patient and living-area (census) characteristics. Bivariate associations between drug adherence and patient characteristics (age, sex, race, education, and comorbidity) were tested using contingency tables and chi-square tests. Logistic regression analysis examined predictors of adherence from patient and living area characteristics. Results Medication adherence for those with one condition was higher in males, Caucasians, older patients, and those living in areas with higher education rates and higher income. In the total population, adherence increased with lower comorbidity and increased number of medications. Substantial variation in adherence was found by condition with the lowest adherence for diabetes (51%) and asthma (33%). Conclusions The expectation of high adherence due to a covered pharmacy benefit, and to enhanced medication access did not hold. Differences in medication adherence were found across condition and by

  19. Influence of exercise adherence level on modifiable coronary heart disease risk factors and functional-fitness levels in middle-aged men.

    PubMed Central

    Wallace, E S; White, J A; Downie, A; Dalzell, G; Doran, D

    1993-01-01

    The study investigated the potential health benefits of two levels of short-term exercise intervention, compared with non-intervention, on selected modifiable coronary heart disease (CHD) risk factors and functional fitness states in middle-aged men. All subjects underwent medical screening and signed informed consent before carrying out a standardized graded treadmill walk which required exercise up to 85% of age-predicted maximal heart rate. The results of the test were used together with musculoskeletal fitness assessments, for the prescription of a personalized exercise programme lasting 14 weeks. In all, 55 subjects were classified by adherence into high (HA, n = 20), low (LA, n = 19), or non-adherence (NA, n = 16) groups according to the degree of documented participation in the programme based on standard criteria (American College of Sports Medicine 1978, 1990). In addition, the respective groups of subjects were classified according to other modifiable and non-modifiable CHD risk factors and compared by self-reported levels of activity and sport involvement as well as perceived body weight classification. The results indicated that there were more comprehensive improvements in functional fitness including significant gains in aerobic endurance capacity, muscular endurance and flexibility in the HA group compared with the LA and NA groups. However, there was little or no change in the modifiable CHD risk factors in any of the respective groups, although anthropometric indices of weight, body mass index (BMI), skinfolds and waist:hips ratio tended to decrease in the HA and LA groups but increased marginally in the NA group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8358578

  20. Development of Heptylmannoside-Based Glycoconjugate Antiadhesive Compounds against Adherent-Invasive Escherichia coli Bacteria Associated with Crohn’s Disease

    PubMed Central

    Sivignon, Adeline; Yan, Xibo; Alvarez Dorta, Dimitri; Bonnet, Richard; Bouckaert, Julie; Fleury, Etienne; Bernard, Julien; Gouin, Sébastien G.; Darfeuille-Michaud, Arlette

    2015-01-01

    ABSTRACT The ileal lesions of Crohn’s disease (CD) patients are colonized by adherent-invasive Escherichia coli (AIEC) bacteria. These bacteria adhere to mannose residues expressed by CEACAM6 on host cells in a type 1 pilus-dependent manner. In this study, we investigated different antagonists of FimH, the adhesin of type 1 pili, for their ability to block AIEC adhesion to intestinal epithelial cells (IEC). Monovalent and multivalent derivatives of n-heptyl α-d-mannoside (HM), a nanomolar antagonist of FimH, were tested in vitro in IEC infected with the AIEC LF82 strain and in vivo by oral administration to CEACAM6-expressing mice infected with LF82 bacteria. In vitro, multivalent derivatives were more potent than the monovalent derivatives, with a gain of efficacy superior to their valencies, probably owing to their ability to form bacterial aggregates. Of note, HM and the multi-HM glycoconjugates exhibited lower efficacy in vivo in decreasing LF82 gut colonization. Interestingly, HM analogues functionalized with an isopropylamide (1A-HM) or β-cyclodextrin pharmacophore at the end of the heptyl tail (1CD-HM) exerted beneficial effects in vivo. These two compounds strongly decreased the amount of LF82 bacteria in the feces of mice and that of bacteria associated with the gut mucosa when administered orally at a dose of 10 mg/kg of body weight after infection. Importantly, signs of colitis and intestinal inflammation induced by LF82 infection were also prevented. These results highlight the potential of the antiadhesive compounds to treat CD patients abnormally colonized by AIEC bacteria and point to an alternative to the current approach focusing on blocking proinflammatory mediators. PMID:26578673

  1. Risk factor control and adherence to treatment in patients with coronary heart disease in the Republic of Srpska, Bosnia and Herzegovina in 2005–2006

    PubMed Central

    Loncar, Sasa; Krneta, Milenko; Skrbic, Ranko; Lazarevic, Aleksandar; Lee, Brian T.; Lopez, Victor A.; Wong, Nathan D.

    2010-01-01

    Introduction European treatment guidelines in persons with known coronary heart disease (CHD) focus on adherence to antiplatelet therapy, β-blockers, ACE/ARBs, and lipid-lowering agents, with goals for blood pressure (BP) of < 140/90 mm Hg and LDL cholesterol of < 3.0 mmol/l. Data on adherence to these measures in Eastern Europe are limited. Material and methods The Third Republic of Srpska, Bosnia and Herzegovina, Coronary Prevention Study (ROSCOPS III) was conducted in 2005–2006 at 10 primary heath care centres in 601 patients (36% female, mean age 55 years) with CHD including acute myocardial infarction or ischaemia, coronary artery bypass graft, or angioplasty who were examined and interviewed at least 6 months after the event. We examined the proportion of subjects on recommended treatments and at goal for BP, LDL-C, and non-smoking. Results The proportion of subjects on recommended treatments included 61% for β-blockers, 79% for ACE/ARBs, 63% for lipid-lowering agents and 74% for antiplatelet therapy. Only 30% of subjects were on all four of these treatments. 59% of subjects had BP at goal of < 140/90 mm Hg and 33% were controlled to < 130/80 mm Hg, 41% for LDL-C, and 88% were non-smokers. Improvements were seen in lipid-lowering and ACE/ARB drug use and non-smoking status from an earlier survey (ROSCOPS II) in 2002–2003. Conclusions Our data show, despite improvement over recent years, that many persons with CHD in the Republic of Srpska, Bosnia and Herzegovina are neither on recommended treatments nor at target for BP and/or LDL-C. Improved efforts targeted at both physicians and patients to address these issues are needed. PMID:22371744

  2. Confirmation of Borrelia burgdorferi spirochetes by polymerase chain reaction in placentas of women with reactive serology for Lyme antibodies.

    PubMed

    Figueroa, R; Bracero, L A; Aguero-Rosenfeld, M; Beneck, D; Coleman, J; Schwartz, I

    1996-01-01

    The purpose of our study was to determine whether Borrelia burgdorferi spirochetes were present in placentas of asymptomatic women with reactive Lyme serology using a silver stain, and to confirm the identity of the spirochetes by polymerase chain reaction (PCR). Sixty placentas of asymptomatic women with ELISA-positive or-equivocal serology for Lyme antibodies during pregnancy were examined for spirochetes using a silver stain. The results of the ELISA serology were confirmed by Western blot analysis. PCR amplification for B. burgdorferi was performed on placentas identified to have spirochetes and on a group of placentas negative for spirochetes. Spirochetes were identified by silver staining in 3 (5%) of the 60 placentas. PCR confirmed B. burgdorferi nucleotide sequences in 2 of the placentas. The 5 women had equivocal Lyme ELISA and negative syphilis serology. The results of the Western blot analysis were negative in 2 cases and indeterminate in 1 case. Six controls were negative for spirochetes by silver staining and PCR. A normal perinatal outcome was observed in all cases. Spirochetes identified in placental tissue of pregnancies with reactive Lyme serology were confirmed by PCR to be B. burgdorferi. There was no relationship between the presence of placental spirochetes and the results of Lyme serology or the pregnancy outcome. PMID:8793493

  3. The Riboswitch Regulates a Thiamine Pyrophosphate ABC Transporter of the Oral Spirochete Treponema denticola ▿ †

    PubMed Central

    Bian, Jiang; Shen, Hongwu; Tu, Youbin; Yu, Aiming; Li, Chunhao

    2011-01-01

    Thiamine pyrophosphate (TPP), a biologically active form of thiamine (vitamin B1), is an essential cofactor in all living systems. Microorganisms either synthesize TPP via de novo biosynthesis pathways or uptake exogenous thiamine from the environment via specific transporters. The oral spirochete Treponema denticola is an important pathogen that is associated with human periodontal diseases. It lacks a de novo TPP biosynthesis pathway and needs exogenous TPP for growth, suggesting that it may obtain exogenous TPP via a thiamine transporter. In this study, we identified a gene cluster that encodes a TPP ABC transporter which consists of a TPP-binding protein (TDE0143), a transmembrane permease (TDE0144), and a cytosolic ATPase (TDE0145). Transcriptional and translational analyses showed that the genes encoding these three proteins are cotranscribed and form an operon (tbpABCTd) that is initiated by a σ70-like promoter. The expression level of this operon is negatively regulated by exogenous TPP and is mediated by a TPP-sensing riboswitch (Tdthi-box). Genetic and biochemical studies revealed that the TDE0143 deletion mutant (T. denticola ΔtbpA) had a decreased ability to transport exogenous TPP, and the mutant failed to grow when exogenous TPP was insufficient. These results taken together indicate that the tbpABCTd operon encodes an ABC transporter that is required for the uptake of exogenous TPP and that the expression of this operon is regulated by a TPP-binding riboswitch via a feedback inhibition mechanism. PMID:21622748

  4. Contributions of NanI Sialidase to Caco-2 Cell Adherence by Clostridium perfringens Type A and C Strains Causing Human Intestinal Disease

    PubMed Central

    Li, Jihong

    2014-01-01

    Previous studies showed that Clostridium perfringens type D animal disease strain CN3718 uses NanI sialidase for adhering to enterocyte-like Caco-2 cells. The current study analyzed whether NanI is similarly important when type A and C human intestinal disease strains attach to Caco-2 cells. A PCR survey determined that the nanI gene was absent from typical type A food poisoning (FP) strains carrying a chromosomal enterotoxin (CPE) gene or the genetically related type C Darmbrand (Db) strains. However, the nanI gene was present in type A strains from healthy humans, type A strains causing CPE-associated antibiotic-associated diarrhea (AAD) or sporadic diarrhea (SD), and type C Pig-Bel strains. Consistent with NanI sialidase being the major C. perfringens sialidase when produced, FP and Db strains had little supernatant sialidase activity compared to other type A or C human intestinal strains. All type A and C human intestinal strains bound to Caco-2 cells, but NanI-producing strains had higher attachment levels. When produced, NanI can contribute to host cell attachment of human intestinal disease strains, since a nanI null mutant constructed in type A SD strain F4969 had lower Caco-2 cell adhesion than wild-type F4969 or a complemented strain. Further supporting a role for NanI in host cell attachment, sialidase inhibitors reduced F4969 adhesion to Caco-2 cells. Collectively, these results suggest that NanI may contribute to the intestinal attachment and colonization needed for the chronic diarrhea of CPE-associated AAD and SD, but this sialidase appears to be dispensable for the acute pathogenesis of type A FP or type C enteritis necroticans. PMID:25135687

  5. The challenge of patient adherence.

    PubMed

    Martin, Leslie R; Williams, Summer L; Haskard, Kelly B; Dimatteo, M Robin

    2005-09-01

    Quality healthcare outcomes depend upon patients' adherence to recommended treatment regimens. Patient nonadherence can be a pervasive threat to health and wellbeing and carry an appreciable economic burden as well. In some disease conditions, more than 40% of patients sustain significant risks by misunderstanding, forgetting, or ignoring healthcare advice. While no single intervention strategy can improve the adherence of all patients, decades of research studies agree that successful attempts to improve patient adherence depend upon a set of key factors. These include realistic assessment of patients' knowledge and understanding of the regimen, clear and effective communication between health professionals and their patients, and the nurturance of trust in the therapeutic relationship. Patients must be given the opportunity to tell the story of their unique illness experiences. Knowing the patient as a person allows the health professional to understand elements that are crucial to the patient's adherence: beliefs, attitudes, subjective norms, cultural context, social supports, and emotional health challenges, particularly depression. Physician-patient partnerships are essential when choosing amongst various therapeutic options to maximize adherence. Mutual collaboration fosters greater patient satisfaction, reduces the risks of nonadherence, and improves patients' healthcare outcomes. PMID:18360559

  6. Free-living spirochetes from Cape Cod microbial mats detected by electron microscopy

    NASA Technical Reports Server (NTRS)

    Teal, T. H.; Chapman, M.; Guillemette, T.; Margulis, L.

    1996-01-01

    Spirochetes from microbial mats and anaerobic mud samples collected in salt marshes were studied by light microscopy, whole mount and thin section transmission electron microscopy. Enriched in cellobiose-rifampin medium, selective for Spirochaeta bajacaliforniensis, seven distinguishable spirochete morphotypes were observed. Their diameters ranged from 0.17 micron to > 0.45 micron. Six of these morphotypes came from southwest Cape Cod, Massachusetts: five from Microcoleus-dominated mat samples collected at Sippewissett salt marsh and one from anoxic mud collected at School Street salt marsh (on the east side of Eel Pond). The seventh morphotype was enriched from anoxic mud sampled from the north central Cape Cod, at the Sandy Neck salt marsh. Five of these morphotypes are similar or identical to previously described spirochetes (Leptospira, Spirochaeta halophila, Spirochaeta bajacaliforniensis, Spirosymplokos deltaeiberi and Treponema), whereas the other two have unique features that suggest they have not been previously described. One of the morphotypes resembles Spirosymplokos deltaeiberi (the largest free-living spirochete described), in its large variable diameter (0.4-3.0 microns), cytoplasmic granules, and spherical (round) bodies with composite structure. This resemblance permits its tentative identification as a Sippewissett strain of Spirosymplokos deltaeiberi. Microbial mats samples collected in sterile Petri dishes and stored dry for more than four years yielded many organisms upon rewetting, including small unidentified spirochetes in at least 4 out of 100 enrichments.

  7. Quality of Reporting and Adherence to ARRIVE Guidelines in Animal Studies for Chagas Disease Preclinical Drug Research: A Systematic Review

    PubMed Central

    Gulin, Julián Ernesto Nicolás; Rocco, Daniela Marisa; García-Bournissen, Facundo

    2015-01-01

    Publication of accurate and detailed descriptions of methods in research articles involving animals is essential for health scientists to accurately interpret published data, evaluate results and replicate findings. Inadequate reporting of key aspects of experimental design may reduce the impact of studies and could act as a barrier to translation of research findings. Reporting of animal use must be as comprehensive as possible in order to take advantage of every study and every animal used. Animal models are essential to understanding and assessing new chemotherapy candidates for Chagas disease pathology, a widespread parasitic disease with few treatment options currently available. A systematic review was carried out to compare ARRIVE guidelines recommendations with information provided in publications of preclinical studies for new anti-Trypanosoma cruzi compounds. A total of 83 publications were reviewed. Before ARRIVE guidelines, 69% of publications failed to report any macroenvironment information, compared to 57% after ARRIVE publication. Similar proportions were observed when evaluating reporting of microenvironmental information (56% vs. 61%). Also, before ARRIVE guidelines publication, only 13% of papers described animal gender, only 18% specified microbiological status and 13% reported randomized treatment assignment, among other essential information missing or incomplete. Unfortunately, publication of ARRIVE guidelines did not seem to enhance reporting quality, compared to papers appeared before ARRIVE publication. Our results suggest that there is a strong need for the scientific community to improve animal use description, animal models employed, transparent reporting and experiment design to facilitate its transfer and application to the affected human population. Full compliance with ARRIVE guidelines, or similar animal research reporting guidelines, would be an excellent start in this direction. PMID:26587586

  8. Quality of Reporting and Adherence to ARRIVE Guidelines in Animal Studies for Chagas Disease Preclinical Drug Research: A Systematic Review.

    PubMed

    Gulin, Julián Ernesto Nicolás; Rocco, Daniela Marisa; García-Bournissen, Facundo

    2015-11-01

    Publication of accurate and detailed descriptions of methods in research articles involving animals is essential for health scientists to accurately interpret published data, evaluate results and replicate findings. Inadequate reporting of key aspects of experimental design may reduce the impact of studies and could act as a barrier to translation of research findings. Reporting of animal use must be as comprehensive as possible in order to take advantage of every study and every animal used. Animal models are essential to understanding and assessing new chemotherapy candidates for Chagas disease pathology, a widespread parasitic disease with few treatment options currently available. A systematic review was carried out to compare ARRIVE guidelines recommendations with information provided in publications of preclinical studies for new anti-Trypanosoma cruzi compounds. A total of 83 publications were reviewed. Before ARRIVE guidelines, 69% of publications failed to report any macroenvironment information, compared to 57% after ARRIVE publication. Similar proportions were observed when evaluating reporting of microenvironmental information (56% vs. 61%). Also, before ARRIVE guidelines publication, only 13% of papers described animal gender, only 18% specified microbiological status and 13% reported randomized treatment assignment, among other essential information missing or incomplete. Unfortunately, publication of ARRIVE guidelines did not seem to enhance reporting quality, compared to papers appeared before ARRIVE publication. Our results suggest that there is a strong need for the scientific community to improve animal use description, animal models employed, transparent reporting and experiment design to facilitate its transfer and application to the affected human population. Full compliance with ARRIVE guidelines, or similar animal research reporting guidelines, would be an excellent start in this direction. PMID:26587586

  9. Direct Measurement of Helical Cell Motion of the Spirochete Leptospira

    PubMed Central

    Nakamura, Shuichi; Leshansky, Alexander; Magariyama, Yukio; Namba, Keiichi; Kudo, Seishi

    2014-01-01

    Leptospira are spirochete bacteria distinguished by a short-pitch coiled body and intracellular flagella. Leptospira cells swim in liquid with an asymmetric morphology of the cell body; the anterior end has a long-pitch spiral shape (S-end) and the posterior end is hook-shaped (H-end). Although the S-end and the coiled cell body called the protoplasmic cylinder are thought to be responsible for propulsion together, most observations on the motion mechanism have remained qualitative. In this study, we analyzed the swimming speed and rotation rate of the S-end, protoplasmic cylinder, and H-end of individual Leptospira cells by one-sided dark-field microscopy. At various viscosities of media containing different concentrations of Ficoll, the rotation rate of the S-end and protoplasmic cylinder showed a clear correlation with the swimming speed, suggesting that these two helical parts play a central role in the motion of Leptospira. In contrast, the H-end rotation rate was unstable and showed much less correlation with the swimming speed. Forces produced by the rotation of the S-end and protoplasmic cylinder showed that these two helical parts contribute to propulsion at nearly equal magnitude. Torque generated by each part, also obtained from experimental motion parameters, indicated that the flagellar motor can generate torque >4000 pN nm, twice as large as that of Escherichia coli. Furthermore, the S-end torque was found to show a markedly larger fluctuation than the protoplasmic cylinder torque, suggesting that the unstable H-end rotation might be mechanically related to changes in the S-end rotation rate for torque balance of the entire cell. Variations in torque at the anterior and posterior ends of the Leptospira cell body could be transmitted from one end to the other through the cell body to coordinate the morphological transformations of the two ends for a rapid change in the swimming direction. PMID:24411236

  10. Benefit and Adherence of the Disease Management Program “Diabetes 2”: A Comparison of Turkish Immigrants and German Natives with Diabetes

    PubMed Central

    Makowski, Anna Christin; Kofahl, Christopher

    2014-01-01

    There is an ongoing debate about equity and equality in health care, and whether immigrants benefit equally from services as the non-immigrant population. The study focuses on benefits from and adherence to the diabetes mellitus type 2 (DM 2) disease management program (DMP) among Turkish immigrants in Germany. So far, it has not been researched whether this group benefits from enrollment in the DMP as well as diabetics from the non-immigrant population. Data on the non-immigrant sample (N = 702) stem from a survey among members of a German health insurance, the Turkish immigrant sample (N = 102) was recruited in the area of Hamburg. Identical questions in both surveys enable comparing major components. Regarding process quality, Turkish diabetics do not differ from the non-immigrant sample; moreover, they have significantly more often received documentation and diabetes training. In terms of outcome quality however, results display a greater benefit on behalf of the non-immigrant sample (e.g., blood parameters and body mass index), and they also met more of the DMP criteria. This underlines the need of diabetics with Turkish background for further education and information in order to become the empowered patient as is intended by the DMP as well as to prevent comorbidities. PMID:25233016

  11. The Crohn's disease-associated adherent-invasive Escherichia coli strain LF82 replicates in mature phagolysosomes within J774 macrophages.

    PubMed

    Bringer, Marie-Agnès; Glasser, Anne-Lise; Tung, Ching-Hsuan; Méresse, Stéphane; Darfeuille-Michaud, Arlette

    2006-03-01

    Adherent-invasive Escherichia coli (AIEC) bacteria isolated from Crohn's disease patients are able to extensively replicate within macrophages in large vacuoles. The mechanism by which AIEC bacteria survive within phagocytic cells is unknown. This report describes the maturation of AIEC LF82-containing phagosomes within J774 macrophages. LF82-containing phagosomes traffic through the endocytic pathway as shown by the sequential acquisition and loss of EEA1 and Rab7 and by accumulation of Lamp-1, Lamp-2 and cathepsin D. We demonstrated that AIEC LF82-containing phagosomes mature into active phagolysosomes where bacteria are exposed to low pH and to the degradative activity of cathepsin D. Finally, we showed that an acidic environment is necessary for replication of AIEC LF82 bacteria within J774 macrophages. Thus, evidence is provided that AIEC LF82 bacteria do not escape from the endocytic pathway but undergo normal interaction with host endomembrane organelles and replicate within acidic and cathepsin D-positive vacuolar phagolysosomes. PMID:16469058

  12. HtrA stress protein is involved in intramacrophagic replication of adherent and invasive Escherichia coli strain LF82 isolated from a patient with Crohn's disease.

    PubMed

    Bringer, Marie-Agnès; Barnich, Nicolas; Glasser, Anne-Lise; Bardot, Olivier; Darfeuille-Michaud, Arlette

    2005-02-01

    Adherent and invasive Escherichia coli (AIEC) bacteria isolated from Crohn's disease patients are able to greatly replicate within macrophages without escaping from the phagosome and without inducing macrophage death. In the present study, evidence is provided that in AIEC strain LF82 the htrA gene encoding the stress protein HtrA is essential for intracellular replication within J774-A1 macrophages. Deletion of the htrA gene in strain LF82 induced increased sensitivity of the isogenic mutant to oxidative stress caused by hydrogen peroxide and a reduced rate of growth in an acid and nutrient-poor medium partly reproducing the microenvironment of the phagosome. In vitro experiments using an LF82 htrA gene promoter fusion with the lacZ gene revealed a 38-fold activation of the promoter in AIEC LF82 intramacrophagic bacteria. The CpxRA two-component signaling pathway was not involved in this activation. In addition, the activation of the LF82 htrA gene promoter was not observed in the nonpathogenic E. coli K-12 intramacrophagic bacteria, indicating that the AIEC LF82 genetic background is crucial for induction of htrA gene transcription during phagocytosis. PMID:15664909

  13. Adherence to Cardiovascular Medications: Lessons Learned and Future Directions

    PubMed Central

    Kronish, Ian M; Ye, Siqin

    2013-01-01

    Approximately 50% of patients with cardiovascular disease and/or its major risk factors have poor adherence to their prescribed medications. Finding novel methods to help patients improve their adherence to existing evidence-based cardiovascular drug therapies has enormous potential to improve health outcomes while potentially reducing health care costs. The goal of this report is to provide a review of the current understanding of adherence to cardiovascular medications from the point of view of prescribing clinicians and cardiovascular researchers. Key topics addressed include: 1) definitions of medication adherence; 2) prevalence and impact of non-adherence; 3) methods for assessing medication adherence; 4) reasons for poor adherence; and 5) approaches to improving adherence to cardiovascular medications. For each of these topics, the report seeks to identify important gaps in knowledge and opportunities for advancing the field of cardiovascular adherence research. PMID:23621969

  14. Adherence to monthly online self-assessments for short-term monitoring: a 1-year study in relapsing-remitting multiple sclerosis patients after start of disease modifying treatment

    PubMed Central

    Jongen, Peter Joseph; Sanders, Evert; Zwanikken, Cees; Koeman, Jan; Visser, Leo H; Koopmans, Petra; Lehnick, Dirk

    2013-01-01

    Background The participation of neurologists and patients in studies on the effectiveness and safety of newly authorized drugs in multiple sclerosis (MS) is insufficient. Monthly online self-assessments using patient-reported outcomes may help in short-term monitoring of neurological changes and side effects. Objective Investigate in relapsing-remitting (RR) MS patients the adherence to monthly online self-assessments after the start of disease modifying treatment. Methods Observational study in 39 neurological departments in The Netherlands. Patients starting glatiramer acetate treatment were instructed to complete online the Modified Fatigue Impact Scale 5-item version and the 8-item Leeds Multiple Sclerosis Quality of Life scale every month during 1 year (T0 toT12). Results Sixty-three investigators included 163 analyzable patients. At T3, 148 (90.8%) patients had completed all questionnaires; at T6, 142 (87.1%); at T9, 133 (81.6%); and at T12, 123 (75.5%). Eight (4.9%) patients did not complete any questionnaire. Median values for inter-assessment intervals ranged from 32 to 34 days (first quartile [Q1] 30 days, third quartile [Q3] 41 days), and the final assessment was at 417 days (median: Q1 385 days, Q3 480 days). Forty-three (26.3%) patients completed the questionnaires at all time points (completion adherent) with their final assessment within 30 days after the scheduled T12 (interval adherent). Eighty (49.1%) patients were completion adherent, but not interval adherent. Forty (24.5%) patients were not completion adherent, as they discontinued assessments prematurely. Men were more interval adherent than women (47.5% vs 20.0%; P = 0.001). Conclusion The observation that three out of four (75.5%) RRMS patients completed two short questionnaires at all monthly time points during 1 year after the start of disease modifying treatment suggests that intensive online monitoring in this patient group is feasible. As only one in five (19.6%) patients adhered to the

  15. Immune Evasion and Recognition of the Syphilis Spirochete in Blood and Skin of Secondary Syphilis Patients: Two Immunologically Distinct Compartments

    PubMed Central

    Cruz, Adriana R.; Ramirez, Lady G.; Zuluaga, Ana V.; Pillay, Allan; Abreu, Christine; Valencia, Carlos A.; La Vake, Carson; Cervantes, Jorge L.; Dunham-Ems, Star; Cartun, Richard; Mavilio, Domenico; Radolf, Justin D.; Salazar, Juan C.

    2012-01-01

    Background The clinical syndrome associated with secondary syphilis (SS) reflects the propensity of Treponema pallidum (Tp) to escape immune recognition while simultaneously inducing inflammation. Methods To better understand the duality of immune evasion and immune recognition in human syphilis, herein we used a combination of flow cytometry, immunohistochemistry (IHC), and transcriptional profiling to study the immune response in the blood and skin of 27 HIV(-) SS patients in relation to spirochetal burdens. Ex vivo opsonophagocytosis assays using human syphilitic sera (HSS) were performed to model spirochete-monocyte/macrophage interactions in vivo. Results Despite the presence of low-level spirochetemia, as well as immunophenotypic changes suggestive of monocyte activation, we did not detect systemic cytokine production. SS subjects had substantial decreases in circulating DCs and in IFNγ-producing and cytotoxic NK-cells, along with an emergent CD56−/CD16+ NK-cell subset in blood. Skin lesions, which had visible Tp by IHC and substantial amounts of Tp-DNA, had large numbers of macrophages (CD68+), a relative increase in CD8+ T-cells over CD4+ T-cells and were enriched for CD56+ NK-cells. Skin lesions contained transcripts for cytokines (IFN-γ, TNF-α), chemokines (CCL2, CXCL10), macrophage and DC activation markers (CD40, CD86), Fc-mediated phagocytosis receptors (FcγRI, FcγR3), IFN-β and effector molecules associated with CD8 and NK-cell cytotoxic responses. While HSS promoted uptake of Tp in conjunction with monocyte activation, most spirochetes were not internalized. Conclusions Our findings support the importance of macrophage driven opsonophagocytosis and cell mediated immunity in treponemal clearance, while suggesting that the balance between phagocytic uptake and evasion is influenced by the relative burdens of bacteria in blood and skin and the presence of Tp subpopulations with differential capacities for binding opsonic antibodies. They also

  16. Carrageenan Gum and Adherent Invasive Escherichia coli in a Piglet Model of Inflammatory Bowel Disease: Impact on Intestinal Mucosa-associated Microbiota.

    PubMed

    Munyaka, Peris M; Sepehri, Shadi; Ghia, Jean-Eric; Khafipour, Ehsan

    2016-01-01

    Inflammatory bowel diseases (IBD) including Crohn's disease (CD), and ulcerative colitis (UC), are chronic conditions characterized by chronic intestinal inflammation. Adherent invasive Escherichia coli (AIEC) pathotype has been increasingly implicated in the etiopathogenesis of IBD. In a 21-day study, we investigated the effects of AIEC strain UM146 inoculation on microbiota profile of the ileal, cecal, ascending and descending colon in a pig model of experimental colitis. Carrageenan gum (CG) was used to induce colitis in weaner piglets whereas AIEC strain UM146 previously isolated from a CD patient was included to investigate a cause or consequence effect in IBD. Treatments were: (1) control; (2) CG; (3) AIEC strain UM146; and (4) CG+UM146. Pigs in groups 2 and 4 received 1% CG in drinking water from day 1 of the study while pigs in groups 3 and 4 were inoculated with UM146 on day 8. Following euthanization on day 21, tissue mucosal scrapings were collected and used for DNA extraction. The V4 region of bacterial 16S rRNA gene was then subjected to Illumina sequencing. Microbial diversity, composition, and the predicted functional metagenome were determined in addition to short chain fatty acids profiles in the digesta and inflammatory cytokines in the intestinal tissue. CG-induced colitis decreased bacterial species richness and shifted community composition. At the phylum level, an increase in Proteobacteria and Deferribacteres and a decrease in Firmicutes, Actinobacteria, and Bacteroidetes were observed in CG and CGUM146 compared to control and UM146. The metabolic capacity of the microbiome was also altered in CG and CGUM146 compared to UM146 and control in the colon. We demonstrated that CG resulted in bacterial dysbiosis and shifted community composition similar to what has been previously observed in IBD patients. However, AIEC strain UM146 alone did not cause any clear changes compared to CG or control in our experimental IBD pig model. PMID:27092122

  17. Carrageenan Gum and Adherent Invasive Escherichia coli in a Piglet Model of Inflammatory Bowel Disease: Impact on Intestinal Mucosa-associated Microbiota

    PubMed Central

    Munyaka, Peris M.; Sepehri, Shadi; Ghia, Jean-Eric; Khafipour, Ehsan

    2016-01-01

    Inflammatory bowel diseases (IBD) including Crohn's disease (CD), and ulcerative colitis (UC), are chronic conditions characterized by chronic intestinal inflammation. Adherent invasive Escherichia coli (AIEC) pathotype has been increasingly implicated in the etiopathogenesis of IBD. In a 21-day study, we investigated the effects of AIEC strain UM146 inoculation on microbiota profile of the ileal, cecal, ascending and descending colon in a pig model of experimental colitis. Carrageenan gum (CG) was used to induce colitis in weaner piglets whereas AIEC strain UM146 previously isolated from a CD patient was included to investigate a cause or consequence effect in IBD. Treatments were: (1) control; (2) CG; (3) AIEC strain UM146; and (4) CG+UM146. Pigs in groups 2 and 4 received 1% CG in drinking water from day 1 of the study while pigs in groups 3 and 4 were inoculated with UM146 on day 8. Following euthanization on day 21, tissue mucosal scrapings were collected and used for DNA extraction. The V4 region of bacterial 16S rRNA gene was then subjected to Illumina sequencing. Microbial diversity, composition, and the predicted functional metagenome were determined in addition to short chain fatty acids profiles in the digesta and inflammatory cytokines in the intestinal tissue. CG-induced colitis decreased bacterial species richness and shifted community composition. At the phylum level, an increase in Proteobacteria and Deferribacteres and a decrease in Firmicutes, Actinobacteria, and Bacteroidetes were observed in CG and CGUM146 compared to control and UM146. The metabolic capacity of the microbiome was also altered in CG and CGUM146 compared to UM146 and control in the colon. We demonstrated that CG resulted in bacterial dysbiosis and shifted community composition similar to what has been previously observed in IBD patients. However, AIEC strain UM146 alone did not cause any clear changes compared to CG or control in our experimental IBD pig model. PMID:27092122

  18. CARD15 variants determine a disturbed early response of monocytes to adherent-invasive Escherichia coli strain LF82 in Crohn's disease.

    PubMed

    Peeters, H; Bogaert, S; Laukens, D; Rottiers, P; De Keyser, Filip; Darfeuille-Michaud, A; Glasser, A-L; Elewaut, D; De Vos, M

    2007-06-01

    Caspase activation and recruitment domain 15 (CARD15) and Toll-like receptor 4 (TLR4) are respectively intracellular and membrane-bound receptors for bacterial cell wall components [respectively muramyl dipeptide (MDP) and lipopolysaccharide (LPS)]. Polymorphisms in CARD15 and TLR4 have been linked with Crohn's disease (CD). Adherent-invasive Escherichia coli (AIEC) strains with particular adhesion and invasion characteristics have been specifically associated with CD ileal mucosa. The aim of this study was to investigate the functional impact of these polymorphisms on monocytes in patients with CD, in response to MDP, LPS and AIEC strain LF82. Monocytes were isolated from 40 patients with CD using magnetic cell sorting, stimulated with LPS or MDP or infected with AIEC. IL-1beta, IL-6, IL-8, IL-10, IL-12 and tumour necrosis factor alpha induction was assessed using quantitative real time-polymerase chain reaction, Cytometric Bead Array and ELISA. Bacterial intracellular survival and replication was assessed using a gentamicin protection assay. Results were linked with the presence of CARD15 and TLR4 polymorphisms. Monocytes of patients with CARD15 polymorphisms showed an early reduced cytokine response (IL-1beta, IL-6 and IL-10) to infection with AIEC, which was restored after 20 h. A gene-dose effect was seen, comparing wild-types, heterozygotes and homozygotes. We found no differences in intracellular survival and replication of AIEC. Heterozygous carriage of TLR4 polymorphisms did not influence monocyte response. In conclusion, patients with CD carrying CARD15 polymorphisms show a disturbed early inflammatory monocyte response after infection with AIEC strain LF82. For the first time, a functional defect was detected in single heterozygous carriers. These findings reflect the potential role of a genetically altered host response to disease-related bacteria in the pathogenesis of CD. PMID:17504508

  19. Evidence for an ABC-Type Riboflavin Transporter System in Pathogenic Spirochetes

    PubMed Central

    Deka, Ranjit K.; Brautigam, Chad A.; Biddy, Brent A.; Liu, Wei Z.; Norgard, Michael V.

    2013-01-01

    ABSTRACT Bacterial transporter proteins are involved in the translocation of many essential nutrients and metabolites. However, many of these key bacterial transport systems remain to be identified, including those involved in the transport of riboflavin (vitamin B2). Pathogenic spirochetes lack riboflavin biosynthetic pathways, implying reliance on obtaining riboflavin from their hosts. Using structural and functional characterizations of possible ligand-binding components, we have identified an ABC-type riboflavin transport system within pathogenic spirochetes. The putative lipoprotein ligand-binding components of these systems from three different spirochetes were cloned, hyperexpressed in Escherichia coli, and purified to homogeneity. Solutions of all three of the purified recombinant proteins were bright yellow. UV-visible spectra demonstrated that these proteins were likely flavoproteins; electrospray ionization mass spectrometry and thin-layer chromatography confirmed that they contained riboflavin. A 1.3-Å crystal structure of the protein (TP0298) encoded by Treponema pallidum, the syphilis spirochete, demonstrated that the protein’s fold is similar to the ligand-binding components of ABC-type transporters. The structure also revealed other salient details of the riboflavin binding site. Comparative bioinformatics analyses of spirochetal genomes, coupled with experimental validation, facilitated the discovery of this new ABC-type riboflavin transport system(s). We denote the ligand-binding component as riboflavin uptake transporter A (RfuA). Taken together, it appears that pathogenic spirochetes have evolved an ABC-type transport system (RfuABCD) for survival in their host environments, particularly that of the human host. PMID:23404400

  20. Impact of patient-selected care buddies on adherence to HIV care, disease progression and conduct of daily life among pre-antiretroviral HIV-infected patients in Rakai, Uganda: a randomized controlled trial

    PubMed Central

    Nakigozi, Gertrude; Makumbi, Fredrick E.; Bwanika, John Baptist; Atuyambe, Lynn; Reynolds, Steven J.; Kigozi, Godfrey; Nalugoda, Fred; Chang, Larry W.; Kiggundu, Valerian; Serwadda, David; Wawer, Maria J.; Gray, Ronald H.; Kamya, Moses R.

    2015-01-01

    Background Data are limited on effects of household or community support persons (“care buddies”) on enrolment into and adherence to pre-antiretroviral HIV care. We assessed the impact of care buddies on adherence to HIV clinic appointments, HIV progression and conduct of daily life among pre-ART HIV-infected individuals in Rakai, Uganda. Methods 1209 HIV infected pre-ART patients aged ≥15 years were randomized to standard of care (SOC) (n = 604) or patient-selected care buddy (PSCB) (n= 605) and followed at 6 and 12 months. Outcomes were adherence to clinic visits; HIV disease progression and self-reported conduct of daily life. Incidence and prevalence rate ratios and 95% confidence intervals (95%CI) were used to assess outcomes in the intent-to-treat and as-treated analyses. Results Baseline characteristics were comparable. In the ITT analysis both arms were comparable with respect to adherence to CD4 monitoring visits (adjPRR 0.98, 95%CI 0.93-1.04, p=0.529) and HIV progression (adjPRR=1.00, 95%CI 0.77-1.31, p=0.946). Good conduct of daily life was significantly higher in the PSCB than the SOC arm (adjPRR 1.08, 95%CI 1.03-1.13, p=0.001). More men (61%) compared to women (30%) selected spouses/partners as buddies (p<0.0001.) 22% of PSCB arm participants discontinued use of buddies. Conclusion In pre-ART persons, having care buddies improved the conduct of daily life of the HIV infected patients but had no effect on HIV disease progression and only limited effect on clinic appointment adherence. PMID:26039929

  1. Certain canine weakly beta-hemolytic intestinal spirochetes are phenotypically and genotypically related to spirochetes associated with human and porcine intestinal spirochetosis.

    PubMed Central

    Duhamel, G E; Muniappa, N; Mathiesen, M R; Johnson, J L; Toth, J; Elder, R O; Doster, A R

    1995-01-01

    Four canine weakly beta-hemolytic intestinal spirochetes associated with intestinal spirochetosis (IS-associated WBHIS) were compared with IS-associated human and porcine WBHIS and the type species for Serpulina hyodysenteriae and S. innocens by using phenotypic and genotypic parameters. The IS-associated canine, human, and porcine WBHIS belonged to a phyletic group distinct from but related to previously described Serpulina type species. PMID:7559984

  2. A current and historical perspective on disparities in US childhood pneumococcal conjugate vaccine adherence and in rates of invasive pneumococcal disease: Considerations for the routinely-recommended, pediatric PCV dosing schedule in the United States.

    PubMed

    McLaughlin, John M; Utt, Eric A; Hill, Nina M; Welch, Verna L; Power, Edward; Sylvester, Gregg C

    2016-01-01

    Previous research has suggested that reducing the US 4-dose PCV13 schedule to a 3-dose schedule may provide cost savings, despite more childhood pneumococcal disease. The study also stressed that dose reduction should be coupled with improved PCV adherence, however, US PCV uptake has leveled-off since 2008. An estimated 24-36% of US children aged 5-19 months are already receiving a reduced PCV schedule (i.e., missing ≥1 dose). This raises a practical concern that, under a reduced, 3-dose schedule, a similar proportion of children may receive ≤2 doses. It is also unknown if a reduced, 3-dose PCV schedule in the United States will afford the same disease protection as 3-dose schedules used elsewhere, given lower US PCV adherence. Finally, more assurance is needed that, under a reduced schedule, racial, socioeconomic, and geographic disparities in PCV adherence will not correspond with disproportionately higher rates of pneumococcal disease among poor or minority children. PMID:26376039

  3. TLR1/TLR2 heterodimers play an important role in the recognition of Borrelia spirochetes.

    PubMed

    Oosting, Marije; Ter Hofstede, Hadewych; Sturm, Patrick; Adema, Gosse J; Kullberg, Bart-Jan; van der Meer, Jos W M; Netea, Mihai G; Joosten, Leo A B

    2011-01-01

    After infection with Borrelia species, the risk for developing Lyme disease varies significantly between individuals. Recognition of Borrelia by the immune system is mediated by pattern recognition receptors (PRRs), such as TLRs. While TLR2 is the main recognition receptor for Borrelia spp., little is known about the role of TLR1 and TLR6, which both can form functionally active heterodimers with TLR2. Here we investigated the recognition of Borrelia by both murine and human TLR1 and TLR6. Peritoneal macrophages from TLR1- and TLR6- gene deficient mice were isolated and exposed to Borrelia. Human PBMCs were stimulated with Borrelia with or without specific TLR1 and TLR6 blocking using specific antibodies. Finally, the functional consequences of TLR polymorphisms on Borrelia-induced cytokine production were assessed. Splenocytes isolated from both TLR1-/- and TLR6-/- mice displayed a distorted Th1/Th2 cytokine balance after stimulation with B.burgdorferi, while no differences in pro-inflammatory cytokine production were observed. In contrast, blockade of TLR1 with specific neutralizing antibodies led to decreased cytokine production by human PBMCs after exposure to B.burgdorferi. Blockade of human TLR6 did not lead to suppression of cytokine production. When PBMCs from healthy individuals bearing polymorphisms in TLR1 were exposed to B.burgdorferi, a remarkably decreased in vitro cytokine production was observed in comparison to wild-type controls. TLR6 polymorphisms lead to a minor modified cytokine production. This study indicates a dominant role for TLR1/TLR2 heterodimers in the induction of the early inflammatory response by Borrelia spirochetes in humans. PMID:21998742

  4. Antigenic Targets of the Bovine Humoral Response to PDD-associated Spirochetes Change with Subsequent Exposure

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Papillomatous digital dermatitis (PDD), also known as hairy heel wart, is a major cause of lameness of cows in the U.S. dairy industry. Cattle are known to mount a humoral response to spirochetes isolated from PDD lesions. This study was undertaken to evaluate the progression of the bovine humoral i...

  5. Papillomatous Digital Dermatitis Spirochetes Suppress the Bovine Macrophage Innate Immune Response

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Papillomatous digital dermatitis (PDD) is a polymicrobial infection in soft tissue adjacent to the hoof and is the leading cause of lameness in dairy cattle. Treponema phagedenis-like (TPL) spirochetes are a constant feature of PDD lesions and are localized deep in infected tissue. Host-cell respon...

  6. Evaluation of medication adherence in Lebanese hypertensive patients.

    PubMed

    Yassine, Mohammad; Al-Hajje, Amal; Awada, Sanaa; Rachidi, Samar; Zein, Salam; Bawab, Wafa; Bou Zeid, Mayssam; El Hajj, Maya; Salameh, Pascale

    2016-09-01

    Controlling hypertension is essential in cardiovascular diseases. Poor medication adherence is associated with poor disease outcomes, waste of healthcare resources, and contributes to reduced blood pressure control. This study evaluates treatment adherence to antihypertensive therapy in Lebanese hypertensive patients by estimating the proportion of adherent hypertensive patients using a validated tool and investigates what factors predict this behavior. A questionnaire-based cross-sectional study was conducted on a random sample of 210 hypertensive outpatients selected from clinics located in tertiary-care hospitals and from private cardiology clinics located in Beirut. Adherence level was measured using a validated 8-item Modified Morisky Medication Adherence Scale (MMMAS). Among 210 patients, 50.5% showed high adherence, 27.1% medium adherence, and 22.4% low adherence to medication. Mean MMMAS score was 6.59±2.0. In bivariate analyses, having controlled blood pressure (p=0.003) and taking a combination drug (p=0.023) were predictors of high adherence. Forgetfulness (p<0.01), complicated drug regimen (p=0.001), and side effects (p=0.006) were predictors of low adherence after multiple liner regression. Logistic regression results showed that calcium channel blockers (p=0.030) were associated with increased adherence levels. In conclusion, developing multidisciplinary intervention programs to address the factors identified, in addition to educational strategies targeting healthcare providers, are necessary to enhance patient adherence. PMID:26232704

  7. Managing treatment for end-stage renal disease--a qualitative study exploring cultural perspectives on facilitators and barriers to treatment adherence.

    PubMed

    Griva, K; Ng, H J; Loei, J; Mooppil, N; McBain, H; Newman, S P

    2013-01-01

    Although adherence to hemodialysis (HD) regimes is important to maximise good clinical outcomes, it remains suboptimal and not well understood, particularly for those in non-Western settings and patients from Asian cultures. This qualitative study sought to explore cultural perspectives on facilitators and barriers to treatment adherence in HD patients. A descriptive exploratory design was used for the study, incorporating individual semi-structured interviews (n = 17) and three focus groups (n = 20). Each interview/focus group was audio-taped and transcribed verbatim, and coding was conducted by two coders using an iterative process. Study participants identified personal and social/contextual factors as major barriers or facilitators of treatment adherence. Barriers include time consumption, forgetfulness, concerns about safety, poor knowledge/understanding, poor communication and lack of control/social pressure. Participants also identified facilitators, both internal (self-initiated) and external (initiated by family, health care professional and peers) to ensure treatment adherence. These included support from family members and social obligation towards others, risk perception, establishment of routines and peer support. Internal and external factors can hinder or facilitate adherence to diet, fluid and medications in the context of dialysis. Several of these barriers/facilitators can be effectively addressed in the context of interventions and psycho-educational programmes. PMID:22780853

  8. Serum Concentrations of Insulin, Ghrelin, Adiponectin, Leptin, Leptin Receptor and Lipocalin-2 in Children with Celiac Disease Who Do and Do Not Adhere to a Gluten-Free Diet

    PubMed Central

    Janas, Roman M.; Rybak, Anna; Wierzbicka-Rucińska, Aldona; Socha, Piotr; Śnitko, Rafał; Szaflarska-Popławska, Anna; Stolarczyk, Anna; Oralewska, Beata; Cytra-Jarocka, Elżbieta; Iwańczak, Barbara; Grzybowska-Chlebowczyk, Urszula; Cichy, Wojciech; Czaja-Bulsa, Grażyna; Socha, Jerzy

    2016-01-01

    Background/Aims The roles of the many bioactive peptides in the pathogenesis of celiac disease remain unclear. To evaluate the serum concentrations of insulin, ghrelin, adiponectin, leptin, leptin receptor, and lipocalin-2 in children with celiac disease who do and do not adhere to a gluten-free diet (GFD, intermittent adherence). Methods Prepubertal, pubertal, and adolescent celiac children were included in this study (74 girls and 53 boys on a GFD and 80 girls and 40 boys off of a GFD). Results Insulin levels in prepubertal (9.01±4.43 μIU/mL), pubertal (10.3±3.62 μIU/mL), and adolescent (10.8±4.73 μIU/mL) girls were higher than those in boys (5.88±2.02, 8.81±2.88, and 8.81±2.26 μIU/mL, respectively) and were neither age-dependent nor influenced by a GFD. Prepubertal children off of a GFD exhibited higher ghrelin levels than prepubertal children on a GFD. Adiponectin levels were not age-, sex- nor GFD-dependent. Adherence to a GFD had no effect on the expression of leptin, leptin receptor, and lipocalin-2. Conclusions Adherence to a GFD had no influence on the adiponectin, leptin, leptin receptor, and lipocalin-2 concentrations in celiac children, but a GFD decreased highly elevated ghrelin levels in prepubertal children. Further studies are required to determine whether increased insulin concentrations in girls with celiac disease is suggestive of an increased risk for hyperinsulinemia. PMID:27074817

  9. Review of evidence for immune evasion and persistent infection in Lyme disease

    PubMed Central

    Berndtson, Keith

    2013-01-01

    Is chronic illness in patients with Lyme disease caused by persistent infection? Three decades of basic and clinical research have yet to produce a definitive answer to this question. This review describes known and suspected mechanisms by which spirochetes of the Borrelia genus evade host immune defenses and survive antibiotic challenge. Accumulating evidence indicates that Lyme disease spirochetes are adapted to persist in immune competent hosts, and that they are able to remain infective despite aggressive antibiotic challenge. Advancing understanding of the survival mechanisms of the Lyme disease spirochete carry noteworthy implications for ongoing research and clinical practice. PMID:23637552

  10. Adherence index based on the AHA 2006 diet and lifestyle recommendations is associated with select cardiovascular disease risk factors in older Puerto Ricans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: The effect of adherence to the American Heart Association (AHA) 2006 Diet and Lifestyle recommendations is unknown. Objective: To develop a unique diet and lifestyle score based on the AHA 2006 Diet and Lifestyle (AHA DL) recommendations. We evaluated this score in relation to available ...