Migraine and the risk of all-cause dementia, Alzheimer's disease, and vascular dementia: A prospective cohort study in community-dwelling older adults.

OBJECTIVES: Dementia is the most common neurological disease in older adults; headaches, including migraines, are the most common neurological disorder across all ages. The objective of this study was to explore the relationship between migraines and dementia, including Alzheimer's disease (AD) and vascular dementia (VaD). METHODS: Analyses were based on 679 community-dwelling participants 65+ years from the Manitoba Study of Health and Aging, a population-based, prospective cohort study. Participants screened as cognitively intact at baseline had complete data on migraine history and all covariates at baseline and were assessed for cognitive outcomes (all-cause dementia, AD, and VaD) 5 years later. The association of exposure (lifetime history of migraines), confounding (age, gender, education, and depression), and intervening variables (hypertension, myocardial infarction, other heart conditions, stroke, and diabetes) with all-cause dementia and dementia subtypes (AD and VaD) was assessed using multiple logistic regression models. RESULTS: A history of migraines was significantly associated with both all-cause dementia (odds ratio [OR]=2.97; 95% confidence interval [CI]=1.25-6.61) and AD (OR=4.22; 95% CI=1.59-10.42), even after adjustment for confounding and intervening variables. Migraines were not significantly associated with VaD either before (OR=1.83; 95% CI=0.39-8.52) or after (OR=1.52; 95% CI=0.20-7.23) such adjustment. CONCLUSIONS: Migraines were a significant risk factor for AD and all-cause dementia. Despite the vascular mechanisms involved in migraine physiology, migraines were not significantly associated with VaD in this study. Recognition of the long-term detrimental consequences of migraines for AD and dementia has implications for migraine management, as well as for our understanding of AD etiology.

Lumbar multifidus muscle thickness does not predict patients with low back pain who improve with trunk stabilization exercises.

OBJECTIVE: To understand lumbar multifidus (LM) muscle activation as a clinical feature to predict patients with low back pain (LBP) who are likely to benefit from stabilization (STB) exercises. DESIGN: Prospective, cohort study. SETTING: Outpatient physical therapy clinics. PARTICIPANTS: Persons with LBP were recruited for this study. Subjects (N=25) were classified as either eligible to receive STB exercises or ineligible on the basis of current clinical prediction rules. INTERVENTIONS: Six weeks of STB treatment. MAIN OUTCOME MEASURES: Before and after treatment, subjects underwent rehabilitative ultrasound imaging to quantify LM-muscle activation and completed disability and pain questionnaires. Analyses were performed to examine the (1) relation between LM-muscle activation and current clinical features used to predict patients with LBP likely to benefit from STB exercises, (2) LM-muscle activation between the STB-eligible and STB-ineligible groups before and after STB treatment, and (3) relation between LM-muscle activation before STB treatment and (a) disability and (b) pain outcomes after treatment for both groups. RESULTS: No relation was found between LM-muscle activation and the number of clinical features. Before STB treatment, LM-muscle activation between the STB-eligible and STB-ineligible groups did not differ. After STB treatment, LM-muscle activation differed between the groups; however, this interaction was because the LM-muscle activation for the STB-eligible group decreased after treatment while that for the STB-ineligible group increased after treatment. Finally, only the STB-eligible group had a significant reduction in disability following treatment; however, no relation was found between LM-muscle activation before treatment and (a) disability or (b) pain outcomes after treatment in the STB-eligible group. CONCLUSIONS: LM-muscle activation does not appear to be a clinical feature that predicts patients with LBP likely to benefit from STB exercises.

Epitope-specific anti-prion antibodies upregulate apolipoprotein E and disrupt membrane cholesterol homeostasis.

The mechanisms of neuronal degeneration induced by the transformation of normal cellular prion protein (PrP(C)) into disease-associated PrP(Sc) are not fully understood. Previous reports have demonstrated that cross-linking cellular prion protein by anti-PrP(C) antibodies can promote neuronal apoptosis. In this report, we now show that treatment of neuronal cells with anti-prion antibodies leads to sequestration of free cholesterol in cell membranes, significant overexpression of apolipoprotein E, and to cytoplasmic phospholipase A2 activation as well as to production of prostaglandin. These results confirm the in vivo toxic effects and indicate that anti-prion antibody treatment of neurons lead to deleterious effects. Finally, great caution should be exerted when adopting antibody-based therapy for prion diseases.

Ecology of Tularemia in Central US Endemic Region.

Tularemia is a zoonotic disease that occurs in the Northern Hemisphere caused by the gammabacterium Francisella tularensis. The most severe form of human tularemia occurs in the central USA and involves a rabbit enzootic cycle, ixodid tick vectors, and F. tularensis subspecies tularensis genotype A1. Enzootic tularemia is thought to have a spring-summer seasonality corresponding to the questing activity of its primary tick vectors. Domestic cats, another common incidental host, acquire the infection by preying on infected rabbits. The seasonality of tularemia in cats, which demonstrate a bimodal seasonal incidence curve with peaks in the spring and late summer-fall, may serve as a surrogate for the seasonality of the disease in its enzootic host. Human tularemia shows a unimodal late spring, early summer peak, which correlates to the seasonal questing activity of tick vectors of human tularemia. This difference in seasonality suggests that different tick species or tick life stages are involved in maintenance of the enzootic rabbit-tick cycle.

Comparison of sampler filling times among selected arterial blood samplers.

BACKGROUND: True arterial blood samples are essential in making clinical decisions for respiratory patients. Previous studies using only the Portex Pro-Vent arterial sampler have shown a significant difference between arterial and venous filling times. The goal of this study was to determine whether there is a statistically significant difference between sampler filling times measured at a normal mean arterial pressure among multiple arterial samplers with plungers and to determine whether there is a statistically significant difference in filling times between venous and normal mean arterial pressures for a sampler without a plunger. METHODS: We assembled an extracorporeal laboratory model to circulate a synthetic compound composed of 0.9% sodium chloride solution and Life/form artificial blood, and we used hemostats to create pressures within the circuit. We randomly selected samplers and measured the filling times of 4 arterial samplers with plungers at a normal mean arterial pressure (93 ± 1 mm Hg). We also measured the filling time of one arterial sampler without a plunger at a normal mean arterial pressure and at a simulated venous pressure (9 ± 2 mm Hg). We used the Kruskal-Wallis one-way analysis of variance to compare arterial filling times in samplers, and we used a t test for independent samples to compare venous and arterial filling times in the sampler without a plunger. RESULTS: There was a statistically significant difference between sampler filling times among the 4 arterial samplers with a plunger (P < .001). There was a statistically significant difference between arterial and venous pressure filling times for the sampler without a plunger (P < .001). CONCLUSIONS: Although there was a statistically significant difference between arterial filling times among various samplers with plungers, the difference was < 1 s and was not deemed clinically important. Regardless of the sampler brand being used, respiratory therapists and other clinicians performing arterial punctures can use sampler filling time to identify a successful arterial puncture while drawing blood.

Evaluation of the tensile strengths of four monofilament absorbable suture materials after immersion in canine urine with or without bacteria.

OBJECTIVE: To evaluate the tensile strength, elongation, and degradation of 4 monofilament absorbable suture materials that undergo degradation by hydrolysis in specimens of canine urine with various physical characteristics. SAMPLE POPULATION: 4 monofilament absorbable sutures (polydioxanone, poliglecaprone 25, polyglyconate, and glycomer 631). PROCEDURE: Voided urine was collected from 6 healthy dogs, pooled, filter-sterilized, and prepared to provide 5 media: sterile neutral (pH, 7.0), sterile acidic (pH, 6.2), sterile basic (pH, 8.8), Escherichia coli-inoculated, and Proteus mirabilis-inoculated urine. Ten strands of each suture material were immersed in each of the media for 0 to 28 days. Tensile strength and elongation of each suture material were evaluated by use of a texture analyzer on days 0, 1, 3, 7, 10, 14, 21, and 28. RESULTS: Reduction in tensile strength was detected for all materials in all urine specimens over time. Polyglyconate and polydioxanone had superior tensile strengths in sterile neutral and E. coli-inoculated urine, and polydioxanone retained the greatest tensile strength throughout the study period. All suture materials disintegrated before day 7 in P. mirabilis-inoculated urine. CONCLUSIONS AND CLINICAL RELEVANCE: Polydioxanone, polyglyconate, and glycomer 631 may be acceptable for urinary bladder closure in the presence of sterile neutral and E. coli-contaminated urine. Tensile strength of poliglecaprone 25 in urine may be unacceptable by the critical healing time for bladder tissue (14 to 21 days). During bladder surgery, exposure of suture material that degrades via hydrolysis to urine containing Proteus spp should be minimized.

Naturally occurring tularemia in a dog.

A 4-year-old spayed female Irish Setter was examined because of acute onset of lethargy, anorexia, and weakness. The dog had eaten an adult rabbit 36 hours earlier. Tularemia was suspected because of the rabbit exposure; however, other common diseases characterized by fever, malaise, and lymphadenopathy of acute onset were also considered (ie, ehrlichiosis and Rocky Mountain spotted fever). The dog was treated with doxycycline (5 mg/kg [2.3 mg/lb], PO, q 24 h) for 14 days as well as supportive treatment with a balanced electrolyte solution (lactated Ringer's solution [200 mL, SC]). The diagnosis was first established by results of bacteriologic cultures of fine-needle aspirates obtained from lymph nodes and confirmed by results of ELISA and a polymerase chain reaction assay Successful and timely antemortem diagnosis of tularemia in dogs can be accomplished through lymph node aspiration and bacteriologic culture.

Outcomes are not different for patient-matched versus nonmatched treatment in subjects with chronic recurrent low back pain: a randomized clinical trial.

BACKGROUND CONTEXT: Classification schemas for low back pain (LBP), such as the Treatment-Based Classification and the Movement System Impairment, use common clinical features to subgroup patients with LBP and are purported to improve treatment outcomes. PURPOSE: To assess if providing matched treatments based on patient-specific clinical features led to superior treatment outcomes compared with an unmatched treatment for subjects with chronic recurrent LBP. STUDY DESIGN: This study is a randomized controlled trial. PATIENT SAMPLE: Subjects (n=124) with LBP (≥12 months) with or without recurrences underwent a standardized clinical examination to group them into one of two strata: ineligible or eligible for stabilization exercises based on the Treatment-Based Classification schema. Subjects underwent additional clinical tests to assign them to one of the five possible Movement System Impairment categories. OUTCOME MEASURES: Questionnaires were collected electronically at Week 0 (before treatment), Week 7 (after the 6-week 1-hour treatment sessions), and 12 months. Using the Oswestry disability index (0-100) and the Numeric Pain Rating Scale (0-10), the primary analysis was performed using the intention-to-treat principle. Secondary outcomes included fear-avoidance beliefs and psychosocial work-related and general health status. METHODS: After subjects were categorized based on their particular clinical features using both the Treatment-Based Classification and Movement System Impairment schemas, they were randomized into one of two treatments using a 3:1 ratio for matched or unmatched treatments. The treatments were trunk stabilization exercise or Movement System Impairment-directed exercises. RESULTS: Of the patients allocated to treatment for this study, 76 received a matched treatment and 25 received an unmatched treatment. After treatment, both groups showed a statistically significant improvement in the primary outcome measures and almost all the secondary measures; however, the matched treatment group did not demonstrate superior outcomes at Week 7 or 12 months, except on one of the secondary measures (Graded Chronic Pain Scale [Disability Scale]) (p=.01). CONCLUSIONS: Providing a matched treatment based on either the Treatment-Based Classification or the Movement System Impairment classification schema did not improve treatment outcomes compared with an unmatched treatment for patients with chronic LBP, except on one secondary disability measure.

Biology of Francisella tularensis subspecies holarctica live vaccine strain in the tick vector Dermacentor variabilis.

BACKGROUND: The γ-proteobacterium Francisella tularensis is the etiologic agent of seasonal tick-transmitted tularemia epizootics in rodents and rabbits and of incidental infections in humans. The biology of F. tularensis in its tick vectors has not been fully described, particularly with respect to its quanta and duration of colonization, tissue dissemination, and transovarial transmission. A systematic study of the colonization of Dermacentor variabilis by the F. tularensis subsp. holarctica live vaccine strain (LVS) was undertaken to better understand whether D. variabilis may serve as an inter-epizootic reservoir for F. tularensis. METHODOLOGY/PRINCIPAL FINDINGS: Colony-reared larva, nymph, and adult D. variabilis were artificially fed LVS via glass capillary tubes fitted over the tick mouthparts, and the level of colonization determined by microbial culture. Larvae and nymphs were initially colonized with 8.8 ± 0.8 × 10(1) and 1.1 ± 0.03 × 10(3) CFU/tick, respectively. Post-molting, a significant increase in colonization of both molted nymphs and adults occurred, and LVS persisted in 42% of molted adult ticks at 126 days post-capillary tube feeding. In adult ticks, LVS initially colonized the gut, disseminated to hemolymph and salivary glands by 21 days, and persisted up to 165 days. LVS was detected in the salivary secretions of adult ticks after four days post intra-hemocoelic inoculation, and LVS recovered from salivary gland was infectious to mice with an infectious dose 50% of 3 CFU. LVS in gravid female ticks colonized via the intra-hemocoelic route disseminated to the ovaries and then to the oocytes, but the pathogen was not recovered from the subsequently-hatched larvae. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that D. variabilis can be efficiently colonized with F. tularensis using artificial methods. The persistence of F. tularensis in D. variabilis suggests that this tick species may be involved in the maintenance of enzootic foci of tularemia in the central United States.

Chromosome rearrangement and diversification of Francisella tularensis revealed by the type B (OSU18) genome sequence.

The gamma-proteobacterium Francisella tularensis is one of the most infectious human pathogens, and the highly virulent organism F. tularensis subsp. tularensis (type A) and less virulent organism F. tularensis subsp. holarctica (type B) are most commonly associated with significant disease in humans and animals. Here we report the complete genome sequence and annotation for a low-passage type B strain (OSU18) isolated from a dead beaver found near Red Rock, Okla., in 1978. A comparison of the F. tularensis subsp. holarctica sequence with that of F. tularensis subsp. tularensis strain Schu4 (P. Larsson et al., Nat. Genet. 37:153-159, 2005) highlighted genetic differences that may underlie different pathogenicity phenotypes and the evolutionary relationship between type A and type B strains. Despite extensive DNA sequence identity, the most significant difference between type A and type B isolates is the striking amount of genomic rearrangement that exists between the strains. All but two rearrangements can be attributed to homologous recombination occurring between two prominent insertion elements, ISFtu1 and ISFtu2. Numerous pseudogenes have been found in the genomes and are likely contributors to the difference in virulence between the strains. In contrast, no rearrangements have been observed between the OSU18 genome and the genome of the type B live vaccine strain (LVS), and only 448 polymorphisms have been found within non-transposase-coding sequences whose homologs are intact in OSU18. Nonconservative differences between the two strains likely include the LVS attenuating mutation(s).

Ocular penetration of oral doxycycline in the horse.

OBJECTIVE: To investigate intraocular penetration of orally administered doxycycline in the normal equine eye and to compare intraocular and serum doxycycline concentrations. Procedures Six mares were administered doxycycline at 10 mg/kg every 12 h by nasogastric tube for 5 days. Blood, aqueous, and vitreous samples were collected on days 1 and 5. All samples were assayed for doxycycline concentrations. Aqueous and vitreous samples were also assayed for protein quantitation. RESULTS: Doxycycline was rapidly absorbed after the first dose (T(max) value of 1.42 +/- 1.28 h); and elimination of doxycycline occurred slowly (median t(1/2) = 10.88 h). Doxycycline could not be detected in the aqueous on days 1 and 5, nor could it be detected in the vitreous on day 1. On day 5, the mean vitreous doxycycline concentration was 0.17 +/- 0.04 microg/mL at 2 h after drug administration. CONCLUSIONS: Repeated oral administration of doxycycline in the horse resulted in steady state serum concentrations of < 1 microg/mL; however, it did not result in appreciable concentrations of drug in the aqueous and vitreous in normal eyes.