Ocular lesions in cats diagnosed with systemic sporotrichosis.

OBJECTIVES: To describe the most common ocular lesions and demonstrate the frequency of ophthalmic involvement in a group of cats with systemic sporotrichosis. ANIMALS STUDIED: Two hundred seventy-four cats diagnosed with systemic sporotrichosis. The inclusion criteria included previous positive cytopathological examination, histopathological examination, or fungal culture. PROCEDURES: In a prospective case-control study, 274 cats diagnosed with systemic sporotrichosis underwent ophthalmic evaluation and received treatment for systemic sporotrichosis. Of these animals, 63 had ocular abnormalities which were recorded, and conjunctivitis was scored from 0 to 5. Diagnostic techniques utilized included fungal culture, as well as cytopathological (10 eyes; 10 cats), and histopathological examination of the palpebral conjunctiva and eyes (2 eyes). RESULTS: Cytopathological and histopathological examination of the conjunctiva, as well as fungal culture, proved to be important tests for the detection of Sporothrix sp. Five cats without the evidence of ophthalmic abnormalities also had a positive fungal culture. The identified ocular lesions in animals with systemic sporotrichosis included increased serous discharge (79 eyes; 53 cats), blepharoconjunctivitis (33 eyes; 25 cats), conjunctivitis (39 eyes, 20 cats), blepharitis (9 eyes; 8 cats), uveitis (5 eyes; 3 cats), and Florida keratopathy-like lesions (2 eyes; 1 cat). CONCLUSION: Sporotrichosis should be considered a differential diagnosis for conjunctivitis and blepharoconjunctivitis, especially in endemic areas. Fungal culture and cytopathology of ocular discharge and histopathological examinations of the conjunctiva are important for the diagnosis of ophthalmic sporotrichosis, although not all cats underwent laboratory testing in this study. Ocular discharge could be a source of contagion transmission.

Comparative analysis of antibody responses to outer surface protein (Osp)A and OspC in dogs vaccinated with Lyme disease vaccines.

Lyme disease (LD), the most common tick-borne disease of canines and humans in N. America, is caused by the spirochete Borreliella burgdorferi. Subunit and bacterin vaccines are available for the prevention of LD in dogs. LD bacterin vaccines, which are comprised of cell lysates of two strains of B. burgdorferi, contain over 1000 different proteins and cellular constituents. In contrast, subunit vaccines are defined in composition and consist of either outer surface protein (Osp)A or OspA and an OspC chimeritope. In this study, we comparatively assessed antibody responses to OspA and OspC induced by vaccination with all canine bacterin and subunit LD vaccines that are commercially available in North America. Dogs were administered a two-dose series of the vaccine to which they were assigned (3 weeks apart): Subunit-AC, Subunit-A, Bacterin-1, and Bacterin-2. Antibody titers to OspA and OspC were determined by ELISA and the ability of each vaccine to elicit antibodies that recognize diverse OspC proteins (referred to as OspC types) assessed by immunoblot. While all of the vaccines elicited similar OspA antibody responses, only Subunit-AC triggered a robust and broadly cross-reactive antibody response to divergent OspC proteins. The data presented within provide new information regarding vaccination-induced antibody responses to key tick and mammalian phase antigens by both subunit and bacterin LD canine vaccine formulations.

The Leptospiral General Secretory Protein D (GspD), a secretin, elicits complement-independent bactericidal antibody against diverse Leptospira species and serovars.

Leptospirosis, the most common zoonotic infection worldwide, is a multi-system disorder affecting the kidney, liver, and lungs. Infections can be asymptomatic, self-limiting or progress to multi-organ system failure and pulmonary hemorrhage. The incidence of canine and human leptospirosis is steadily increasing worldwide. At least sixty-four Leptospira species and several hundred lipopolysaccharide-based serovars have been defined. Preventive vaccines are available for use in veterinary medicine and limited use in humans in some countries. All commercially available vaccines are bacterin formulations that consist of a combination of laboratory cultivated strains of different lipopolysaccharide serotypes. The development of a broadly protective subunit vaccine would represent a significant step forward in efforts to combat leptospirosis in humans, livestock, and companion animals worldwide. Here we investigate the potential of General secretory protein D (GspD; LIC11570), a secretin, to serve as a possible antigen in a multi-valent vaccine formulation. GspD is conserved, expressed in vitro, antigenic during infection and elicits antibody with complement independent bactericidal activity. Importantly, antibody to GspD is bactericidal against diverse Leptospira species of the P1 subclade. Epitope mapping localized the bactericidal epitopes to the N-terminal N0 domain of GspD. The data within support further exploration of GspD as a candidate for inclusion in a next generation multi-protein subunit vaccine.

Structural and functional impacts of E5 genetic variants of human papillomavirus type 31.

Persistent infections caused by high-risk human papillomavirus (HR-HPV) are important, for the development of cervical lesions, but environmental and genetic factors are also related in the process of carcinogenesis. Among the genetic factors, the genetic variants of HR-HPV appear to be related to the risk of persistent infections. Therefore, the present study investigates variants of HPV31 E5 oncogene in cervical scraping samples from Brazilian women to assess their functional and structural effects, in order to identify possible repercussions of these variants on the infectious and carcinogenic process. Our results detected nucleotide changes previously described in the HPV31 E5 oncogene, which may play a critical role in the development of cancer due to its ability to promote cell proliferation and signal transmission. In our study, the interaction percentage of the 31E5 sequence generated by the Immune Epitope Server database and the Analysis Resource (IEDB) allowed us to include possible immunogenic epitopes with the MHC-I and MHC-II molecules, which may represent a possible relationship between protein suppression of the immune system. In the structural analysis of the HPV31 E5 oncoprotein, the N5D, I48 V, P56A, F80I and V64I polymorphisms can be found inserted within transmembrane regions. The P56A mutation has been predicted to be highly stabilizing and, therefore, can cause a change in protein function. Regarding the interaction of the E5 protein from HPV31 with the signaling of NF-kB pathway, we observed that in all variants of the E5 gene from HPV-31, the activity of the NF-kB pathway was increased compared to the prototype. Our study contributes to a more refined design of studies with the E5 gene from HPV31 and provides important data for a better understanding of how variants can be distinguished under their clinical consequences.

Antibody profiling of a Borreliella burgdorferi (Lyme disease) C6 antibody positive, symptomatic Rottweiler and her pups.

Lyme disease (LD) is a tick-transmitted disease caused by Borreliella burgdorferi (Bb). Temporal studies of maternal antibody (Ab) profiles in Bb infected pregnant dogs and their pups have not been conducted. In this study, Ab profiles of a client-owned Bb C6 Ab positive Rottweiler and her nine pups were assessed. The dam presented with lameness 12 days prior to parturition and was C6 Ab positive with a Quant C6 Ab concentration of 237U/mL. Treatment with amoxicillin was initiated and 11 days later nine pups were delivered. Screening of the sera from the dam and pups against Bb cell lysates and a panel of antigens revealed similar immunoreactivity profiles. While antigen-specific IgG and IgM reactivity persisted in the dam for at least 7 months, a rapid decline in IgG specific for BBA36, BBK53, BB0238, BBA73 and outer surface protein (Osp) E in the pups occurred between days 29 and 52 post-parturition. In contrast, Ab specific for DbpA and the diagnostic antigens VlsE (C6) and OspF, remained elevated in the pups. Sera from the dam displayed potent complement-dependent bactericidal activity against Bb. Sera from the pups was also bactericidal but primarily through a complement-independent mechanism. Lastly, single dose vaccination of the dam at day 51 post-parturition with a LD subunit vaccine consisting of OspA and an OspC chimeritope triggered a broad anti-OspC Ab response indicative of an anamnestic response. Although this study focused on a single case, these findings add to our knowledge of maternal Ab profiles and will aid the interpretation of serological assays in pups delivered by a Bb C6 Ab positive dog.

The PRIAMO study: active sexual life is associated with better motor and non-motor outcomes in men with early Parkinson's disease.

BACKGROUND AND PURPOSE: Data suggest a relationship between sexual dysfunction, mainly erectile dysfunction in men, and worse disease progression in Parkinson's disease (PD). There is scant evidence on the correlates of sexual activity in PD patients. By involving a subgroup of 355 patients from the PRIAMO (Parkinson Disease Non Motor Symptoms) study, the present 24-month longitudinal prospective analysis aims to demonstrate that the presence of active sexual life is associated with disease progression in early PD. METHODS AND RESULTS: Multivariable mixed-effect logistic regression models showed that gastrointestinal symptoms [odds ratio 0.56, 95% confidence interval (CI) 0.39-0.82, P = 0.003] and apathy (odds ratio 0.42, 95% CI 0.29-0.63, P < 0.001) were less likely to be associated with sexual activity in men. Analysis also demonstrated that sexual activity in men was associated with lower motor disability (coefficient -2.881, 95% CI -4.732 to -1.030, P = 0.002), better quality of life (coefficient -24.196, 95% CI -44.884 to -3.508, P = 0.022; coefficient 0.083, 95% CI 0.023-0.143, P = 0.006) and lower depression scores (coefficient -1.245, 95% CI -2.104 to -0.387, P = 0.004). No association was shown in women. CONCLUSIONS: This is the first prospective longitudinal study involving a large cohort of PD patients suggesting that sexual activity is associated with lower motor and non-motor disability as well as with better quality of life in men. These findings should prompt movement disorders specialists to periodically inquiry about their patients' sexual life.

Efficacy of hydrolyzed soy dog food and homemade food with original protein in the control of food-induced atopic dermatitis in dogs / Eficácia da ração de soja hidrolisada e da comida caseira com proteína original no controle da dermatite atópica induzida por alimentos em cães

Trophoallergens are specific components of food or its ingredients, able to precipitate the atopic eczema at 19.6% to 30% of the dogs with atopic dermatitis (AD). This study evaluated the efficacy of hydrolyzed soy dog food and homemade food with unusual protein in the control of chronic pruritus in dogs with AD. For this, twenty-eight dogs with AD were selected. AD diagnosis was based on Favrot's criteria. The animals were separated in two groups; one group consumed hydrolyzed soy dog food while the other group consumed homemade food with protein sources and original carbohydrates. They were evaluated every two weeks by the Rybnicek and CADLI scale over 60 days. Animals in the group that consumed hydrolyzed soy dog food presented a reduced score of pruritus (Rybnicek scale) on days +15, +30, +45 and +60 (P<0.01) compared to day 0. While the dogs in the homemade food group have not presented a significant difference (P>0.05) in 60 days of treatment. When evaluated by the Canine Atopic Dermatitis Lesion Index (CADLI), dogs treated with soy hydrolyzed dog food had a partial improvement on days +45 (P<0.05) and +60 (P<0.01) compared to day 0, while the dogs in the second group did not show improvements (P>0.05) in 60 days of treatment. In conclusion, soy hydrolyzed dog food has proved effective to partially control clinical signs of food-induced atopic dermatitis; however, it is not effective for the complete control of the disease.(AU)

Os trofoalérgenos são componentes específicos do alimento ou de seus ingredientes, capazes de precipitar o eczema atópico em 19,6% a 30% dos cães com dermatite atópica (DA). O presente estudo teve como objetivo avaliar a eficácia da ração de soja hidrolisada e da comida caseira com proteína não usual no controle do prurido crônico em cães com DA. Para isso foram utilizados vinte e oito cães com DA. O diagnóstico de DA foi baseado nos critérios de Favrot. Os animais foram separados em dois grupos, um grupo consumindo ração hidrolisada de soja e o outro grupo comida caseira com fontes de proteína e carboidratos originais. Estes foram avaliados quinzenalmente pela escala de Rybnicek e CADLI durante 60 dias. Os animais do grupo alimentado com ração hidrolisada de soja apresentaram uma minimização no escore de prurido (escala de Rybnicek) nos dias +15, +30, +45 e +60 (P<0,01) em relação ao dia 0. Já os cães do grupo alimentado com comida caseira não apresentaram diferença significativa (P>0,05) nos 60 dias de tratamento. Quando avaliados pelo índice de CADLl os cães tratados com ração hidrolisada de soja tiveram uma melhora parcial nos dias, +45 (P<0,05) e +60 (P<0,01) em relação ao dia 0, enquanto que os cães do segundo grupo não obtiveram melhora (P>0,05) nos 60 dias de tratamento. A ração hidrolisada de soja se mostrou efetiva para controlar parcialmente os sinais clínicos da dermatite atópica induzida por alimentos, no entanto, não é eficaz para o controle total da doença.(AU)

AARS2-related ovarioleukodystrophy: Clinical and neuroimaging features of three new cases.

INTRODUCTION: Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), previously known as hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) or pigmentary orthochromatic leukodystrophy (POLD), is the most frequent non-vascular adult-onset leukoencephalopathy. It is caused by autosomal dominant mutations in CSF1R gene. Recently, also autosomal recessive mutations in AARS2 gene were found to be the cause of an adult-onset leukodystrophy with axonal spheroids. Our aim was to achieve a genetic diagnosis in a cohort of CSF1R-negative patients, performing a sequence analysis of AARS2 gene. MATERIAL AND METHODS: AARS2 sequencing was performed in 38 CSF1R-negative patients with clinical and magnetic resonance imaging (MRI) findings of adult-onset leukoencephalopathy. RESULTS: Three patients carrying AARS2 compound heterozygous mutations have been found. All patients were female with ovarian failure and leukoencephalopathy. In 2 patients, MRI findings were consistent with previous reports while the third patient showed focal white matter (WM) lesions in the centrum semiovale and the corpus callosum in the absence of extensive involvement and rarefaction of the WM. MRI spectroscopy showed the presence of increased lactate in 2 patients, thus linking AARS2-related leukoencephalopathy with other mitochondrial leukoencephalopathies with high levels of cerebral lactate. CONCLUSION: We recommend screening for mutations in AARS2 gene in CSF1R-negative patients, also in the absence of a clear family history and peculiar MRI findings. Our results also suggest that findings of conventional MRI and MR spectroscopy may be useful in prompting the genetic screening.

Plasminogen binding and degradation by Treponema denticola: Identification of the plasminogen binding interface on the FhbB protein.

Treponema denticola is a proteolytic-anaerobic spirochete whose abundance in the subgingival crevice correlates with periodontal disease severity. Treponema denticola evades serum-mediated killing through the binding of factor H (FH), a negative regulator of the complement system. The T. denticolaFH receptor has been identified as FhbB, an 11.4kDa immunodominant lipoprotein. Three distinct subfamilies of FhbB proteins have been delineated and designated as FhbB1, FhbB2 and FhbB3. In this study we demonstrate that all FhbB variants bind human plasminogen (Plg). Competitive binding analyses revealed that FH and Plg do not compete for binding. Binding studies with FhbB135405 site-directed amino acid substitution mutants demonstrated that the interaction domains for FH and Plg on FhbB are separable. Inhibition of Plg-FhbB binding by ε-aminocaproic acid (a lysine analog) indicates that binding is mediated by electrostatic interactions that presumably occur with Lys binding sites contained within Plg "Kringle" domains 1, 2, 4 or 5. Similar to that demonstrated for FH, Plg can also serve as a substrate for the T. denticola protease, dentilisin. The in vivo consequences of dentilisin-mediated cleavage of Plg remained to be determined. The data presented demonstrate that FhbB is a multi-functional protein that may contribute to virulence through several mechanisms including immune evasion, manipulation of the host immune response, adherence or tissue invasion.

Eficácia da ciclosporina no controle da dermatite atópica em cães / Efficacy of cyclosporine in the control of atopic dermatitis in dogs

A dermatite atópica é uma dermatopatia inflamatória, pruriginosa, crônica, de origem genética, resultante da perda da função de barreira física da pele e da hiperreatividade à alérgenos ambientais, trofoalérgenos, alérgenos microbianos e a irritantes primários. Este estudo avaliou a eficácia da ciclosporina no controle do prurido e das lesões associadas à dermatite atópica em cães. Selecionaram-se 24 cães com diagnóstico de dermatite atópica baseados nos critérios de Favrot et al. (2010), os quais foram divididos em dois grupos de 12 cães, onde o Grupo 1, recebeu ciclosporina (5mg/kg/vo/24h), e o Grupo 2, foi tratado com prednisona (0,5mg/kg/vo/24h) em doses decrescentes, ambos por 60 dias. Os animais foram continuamente avaliados, e seus escores sintomato-lesionais, baseados na escala de CADESI-03, estabelecidos nos dias 0, 30 e 60. Em adição, os escores de prurido de cada animal, baseado nos critérios de Rybnicek, foram semanalmente avaliados, do dia 0 ao 63. Todos os dados coletados foram analisados pelo teste não paramétrico de Kruskal-Wallis, seguido do teste de Dunn´s e para as análises entre os grupos foi utilizado o teste t, considerado o nível de significância mínimo de 5%. A ciclosporina teve uma eficácia similar, no controle lesional, ao grupo que recebeu prednisona no dia (+30) (p<0,05) e no dia (+60) (p<0,001) do tratamento, em relação ao dia zero. Uma diferença significativa do escore do prurido foi observada nos dias +28, +35, +42, +49, +56 e +63 (p<0,001), e no dia +21 (p<0,01) em relação ao momento inicial do tratamento, porém sua eficácia foi inferior ao Grupo 2, a partir do 42º dia de avaliação, mantendo-se esta diferença nos dias +49, +56 e +63 (p>0,05). Apesar da ciclosporina ter sido menos eficaz no controle do prurido, este se manteve em níveis aceitáveis, e seu uso contínuo não foi associado a efeitos colaterais relevantes.(AU)

Atopic dermatitis is an itchy, chronic inflammatory skin disease of genetic origin, resulting from loss of the physical barrier function of the skin and hyper-reactivity to environmental allergens, trofoallergens, microbial allergens and to primary irritants. The efficacy of cyclosporine in the control of pruritus and lesions associated with atopic dermatitis in dogs was evaluated. Twenty-four dogs with atopic dermatitis were selected, based on Favrot et al.'s criteria (2010). They were divided into two groups of 12 dogs, where Group 1 received cyclosporine (5mg/kg/vo/24h), and Group 2 was treated with prednisone (0.5mg/kg/vo/24h) in decreasing doses, both for 60 days. The animals were continuously evaluated, and theirits lesional symptomatology scores were based on a Cadesi-03 scale, set on days 0, 30 and 60. Pruritus scores of each dog, based on Rybnicek´s criteria, were weekly evaluated, from day 0 to day 63. All collected data were analyzed by the nonparametric Kruskal-Wallis´ test, followed by Dunn's test, and for the analysis between the groups, considered the minimum significance level of 5%, t-test was used. Cyclosporin had similar efficacy in lesional control in the group which received prednisone on day (+30) (p<0.05) and on the day (+60) (p<0.001) of treatment, compared with day zero. A significant difference of the itching score was observed on days +28, +35, +42, +49, +56 and +63 (p<0.001), and on day +21 (p<0.01) when compared to initial treatment. However, its efficacy was lower than Group 2, from 42 days of evaluation on, keeping such difference on days +49, +56 and +63 (p>0.05). Although cyclosporin have been less effective in controlling itching, it remained at acceptable levels, and its continued use was not associated with significant side effects.(AU)

The PRIAMO study: urinary dysfunction as a marker of disease progression in early Parkinson's disease.

BACKGROUND AND PURPOSE: New venues are currently being explored to predict disease progression in Parkinson's disease (PD), such as non-motor subtypes and models merging motor and non-motor symptoms (NMS). By involving a subgroup of 585 patients from the PRIAMO (Parkinson Disease Non-motor Symptoms) study, the present 24-month longitudinal prospective analysis aimed to demonstrate that urinary dysfunction is an early marker of higher motor and non-motor burden as well as lower health-related quality of life. METHODS AND RESULTS: Multivariable mixed-effect logistic regression models controlling for demographic and clinical variables showed that the following NMS domains were associated with urinary dysfunction: gastrointestinal [odds ratio (OR) 2.57, 95% confidence interval (CI) 1.67-3.97, P < 0.001], cardiovascular (OR 2.22, 95% CI 1.18-4.17, P = 0.013), skin (OR 1.81, 95% CI 1.06-3.08, P = 0.029), sleep (OR 2.06, 95% CI 1.34-3.16, P = 0.001), pain (OR 1.85, 95% CI 1.21-2.83, P = 0.004), fatigue (OR 2.40, 95% CI 1.56-3.68, P < 0.001), apathy (OR 2.79, 95% CI 1.72-4.52, P < 0.001) and respiratory (OR 1.82, 95% CI 1.02-3.23, P = 0.039). Analysis also demonstrated that urinary dysfunction was associated with higher motor disability (coefficient 1.73, 95% CI 0.68-2.78, P = 0.001) and lower health-related quality of life (coefficient -0.05, 95% CI -0.08 to -0.02, P < 0.001, and coefficient -3.49, 95% CI -5.21 to -1.77, P < 0.001) but not with more severe cognitive disability (coefficient -0.34, 95% CI -0.92 to 0.24, P = 0.251). CONCLUSIONS: This is the first prospective longitudinal study involving a large cohort of PD patients demonstrating the relevance of urinary dysfunction as an early marker of higher motor and non-motor disability as well as lower health-related quality of life. These findings support a role for urinary dysfunction as an early marker of more severe disease progression.

Evaluation of the concentration of allergens from mites in fur and households dust of dogs with atopic dermatitis / Avaliação da concentração de alérgenos provenientes de ácaros na pelagem e na poeira de domicílios de cães com dermatite atópica

This study evaluated the concentration of Der p 1, Der f 1 and Blo t 5 in the fur and households of 20 dogs with atopic dermatitis (AD) and 20 healthy dogs. The diagnosis of AD was clinical based on Favrot's criteria. Dust samples were collected with a domestic vacuum cleaner. For each site, 1m2 was vacuumed for 2 min. The samples were collected in separate filters, transferred into plastic containers, sealed and kept frozen until ELISA analysis. In the fur of atopic dogs the average concentration of Der p 1 was 0.25µg/g compared to 0.03µg/g in healthy dogs. In households with atopic dogs the highest concentrations of Der p 1 were found in carpets (2.18µg/g), followed by couches (1.53µg/g), beds (1.14µg/g), dogs' bed linen (0.64µg/g) and floors (0.14µg/g). The concentrations of Der p 1 on carpets, couches and beds were significantly higher than in atopic dogs' fur (p<0.05). There was no statistical difference when comparing the concentrations of Der f 1 and Blo t 5 in different environments of atopic dogs (p>0.05). The concentrations of Der p 1, Der f 1 and Blo t 5 were equivalent in atopic and non-atopic dog's households. Among the allergens studied, Der p 1 was the most commonly found, predominantly in carpets and couches.(AU)

O presente estudo avaliou a concentração de Der p 1, Der f 1 e Blo t 5, na pelagem e no ambiente domiciliar de cães com dermatite atópica (DA). Para tal, foram selecionados 20 cães com DA e 20 cães saudáveis, e seus domicílios. O diagnóstico de DA foi baseado nos critérios de Favrot. As amostras de poeira foram colhidas com um aspirador de pó doméstico. Para cada local de colheita, foi aspirado 1m2 por dois minutos. As amostras foram recolhidas em filtros separadamente, transferidas para envelopes plásticos, seladas e mantidas congeladas até serem analisadas pelo método de ELISA. Na pelagem dos cães com DA, a concentração média de Der p 1 foi de 0,25µg/g de poeira e nos cães saudáveis foi de 0,03µg/g. No ambiente de cães com DA, o Der p 1 foi encontrado em maior concentração média no tapete (2,18 µg/g), seguido pelo sofá (1,53g/g), cama (1,14µg/g) e roupa de cama dos cães (0,64µg/g) e chão (0,14µg/g). As concentrações de Der p 1 no tapete, sofá e cama dos cães foram significativamente maiores que na pelagem de cães com dermatite atópica (p<0,05). Enquanto que, não houve diferença estatística quando comparadas as concentrações de Der f 1 e Blo t 5 nos diferentes ambientes avaliados (p>0,05). As concentrações de alérgenos Der p 1, Der f 1 e Blo t 5 se equivaleram em ambientes de cães com DA e saudáveis. Entre os alérgenos estudados, o Der p 1 foi o mais comumente encontrado, prevalecendo no tapete e no sofá.(AU)

Gender effect on non-motor symptoms in Parkinson's disease: are men more at risk?

INTRODUCTION: Several gender differences have been reported in Parkinson's Disease (PD). We evaluated the burden of non-motor symptoms (NMS) in PD and the possible gender differences in their occurrence. METHODS: The FRAGAMP study is a large multicenter case-control study. PD patients and controls underwent a face-to-face interview and a neurological examination performed by trained neurologists. Presence of NMS was investigated using a standardized questionnaire; cognitive impairment and depression were assessed using the Mini Mental State Examination and the Hamilton Depression Rating Scale respectively. RESULTS: 585 PD patients (59.5% men) and 481 controls (34.9% men) were enrolled in the study. All NMS were significantly more frequent among PD patients than controls. PD women showed a significantly higher frequency of depression and urinary disturbances than parkinsonian men; a close frequency among PD women and men was recorded for hallucination, cognitive impairment and sleep disorders. Nonetheless, with respect to the control population, according to logistic regression stratified by sex and adjusted by age, PD men showed a stronger positive significant association with almost all NMS compared to women, excepting for urinary disturbances. The strongest association among PD men was recorded for cognitive impairment (adjusted OR 5.44 for men and 2.82 for women) and depression (adjusted OR 30.88 for men and 12.72 for women). CONCLUSIONS: With respect to the general population, presence of NMS was stronger associated with male gender. Our data suggest that the presence of NMS among PD men is more strictly due to the neurodegenerative processes related to PD.

Testing and linearity calibration of films of phenol compounds exposed to thermal neutron field for EPR dosimetry.

This paper reports the preliminary results obtained by Electron Paramagnetic Resonance (EPR) measurements on films of IRGANOX® 1076 phenols with and without low content (5% by weight) of gadolinium oxide (Gd2O3) exposed in the thermal column of the Triga Mark II reactor of LENA (Laboratorio Energia Nucleare Applicata) of Pavia (Italy). Thanks to their size, the phenolic films here presented are good devices for the dosimetry of beams with high dose gradient and which require accurate knowledge of the precise dose delivered. The dependence of EPR signal as function of neutron dose was investigated in the fluence range between 10(11) cm(-2) and 10(14) cm(-2). Linearity of EPR response was found and the signal was compared with that of commercial alanine films. Our analysis showed that gadolinium oxide (5% by weight) can enhance the thermal neutron sensitivity more than 18 times. Irradiated dosimetric films of phenolic compound exhibited EPR signal fading of about 4% after 10 days from irradiation.

The Treponema denticola AtcR LytTR domain-containing response regulator interacts with three architecturally distinct promoter elements: implications for understanding the molecular signaling mechanisms that drive the progression of periodontal disease.

Treponema denticola is an oral spirochete and periopathogen that transitions from low abundance in healthy subgingival crevices to high abundance in periodontal pockets. The T. denticola response regulator AtcR harbors the relatively rare, LytTR DNA-binding domain. LytTR domain containing response regulators control critical transcriptional responses required for environmental adaptation. Using a multi-step bioinformatics approach, 26 strong lytTR recognition motifs were identified in the genome of T. denticola strain 35405. Electrophoretic mobility shift assays demonstrated that AtcR binds to these recognition motifs. High specificity-high affinity complexes formed with phosphorylated AtcR. The LytTR recognition sequences were found to exist in three distinct promoter architectures designated as LytTR1, LytTR2 and LytTR3 promoters. LytTR1 and LytTR2 promoters harbor σ(54) binding sites. The functional diversity of the proteins encoded by the putative AtcR regulon suggests that AtcR sits at the top of a regulatory cascade that plays a central role in facilitating T. denticola's ability to adapt to changing environmental conditions and thrive in periodontal pockets.

Analysis of the complement sensitivity of oral treponemes and the potential influence of FH binding, FH cleavage and dentilisin activity on the pathogenesis of periodontal disease.

Treponema denticola, a periopathogen, evades complement-mediated killing by binding the negative complement regulatory protein factor H (FH) to its surface via the FhbB protein. Paradoxically, bound FH is cleaved by T. denticola's dentilisin protease, a process hypothesized to trigger localized dysregulation of complement activation in periodontal pockets. The ability of other oral treponemes to evade complement-mediated killing and bind and cleave FH has not been assessed. In this report, we demonstrate that representative isolates of Treponema socranskii, Treponema medium, Treponema pectinovorum and Treponema maltophilum are also serum resistant, whereas Treponema vincentii and Treponema amylovorum are serum sensitive. Although T. denticola's ability to evade complement-mediated killing is strictly dependent on FH binding, other serum-resistant treponemal species lack FhbB and do not bind FH, indicating an FH-independent mechanism of complement evasion. To assess the influence of FhbB sequence variation on FH binding and cleavage by T. denticola, fhbB sequences were determined for 30 isolates. Three distinct phyletic types were identified. All T. denticola strains bound FH and were serum resistant, but differences in binding kinetics, dentilisin activity and FH cleavage ability were observed. Based on these analyses, we hypothesize that the composition of the T. denticola population is a determining factor that influences the progression and severity of periodontal disease.

Identification of Borrelia burgdorferi ospC genotypes in canine tissue following tick infestation: implications for Lyme disease vaccine and diagnostic assay design.

In endemic regions, Lyme disease is a potential health threat to dogs. Canine Lyme disease manifests with arthritis-induced lameness, anorexia, fever, lethargy, lymphadenopathy and, in some cases, fatal glomerulonephritis. A recent study revealed that the regional mean for the percentage of seropositive dogs in the north-east of the USA is 11.6%. The outer surface protein C (OspC) of Lyme disease spirochetes is an important virulence factor required for the establishment of infection in mammals. It is a leading candidate in human and canine Lyme disease vaccine development efforts. Over 30 distinct ospC phyletic types have been defined. It has been hypothesized that ospC genotype may influence mammalian host range. In this study, Ixodes scapularis ticks collected from the field in Rhode Island were assessed for infection with B. burgdorferi. Ticks were fed on purpose bred beagles to repletion and infection of the dogs was assessed through serology and PCR. Tissue biopsies (n=2) were collected from each dog 49 days post-tick infestation (dpi) and the ospC genotype of the infecting strains determined by direct PCR of DNA extracted from tissue or by PCR after cultivation of spirochetes from biopsy samples. The dominant ospC types associated with B. burgdorferi canine infections differed from those associated with human infection, indicating a relationship between ospC sequence and preferred host range. Knowledge of the most common ospC genotypes associated specifically with infection of dogs will facilitate the rational design of OspC-based canine Lyme disease vaccines and diagnostic assays.

Microbes bind complement inhibitor factor H via a common site.

To cause infections microbes need to evade host defense systems, one of these being the evolutionarily old and important arm of innate immunity, the alternative pathway of complement. It can attack all kinds of targets and is tightly controlled in plasma and on host cells by plasma complement regulator factor H (FH). FH binds simultaneously to host cell surface structures such as heparin or glycosaminoglycans via domain 20 and to the main complement opsonin C3b via domain 19. Many pathogenic microbes protect themselves from complement by recruiting host FH. We analyzed how and why different microbes bind FH via domains 19-20 (FH19-20). We used a selection of FH19-20 point mutants to reveal the binding sites of several microbial proteins and whole microbes (Haemophilus influenzae, Bordetella pertussis, Pseudomonas aeruginosa, Streptococcus pneumonia, Candida albicans, Borrelia burgdorferi, and Borrelia hermsii). We show that all studied microbes use the same binding region located on one side of domain 20. Binding of FH to the microbial proteins was inhibited with heparin showing that the common microbial binding site overlaps with the heparin site needed for efficient binding of FH to host cells. Surprisingly, the microbial proteins enhanced binding of FH19-20 to C3b and down-regulation of complement activation. We show that this is caused by formation of a tripartite complex between the microbial protein, FH, and C3b. In this study we reveal that seven microbes representing different phyla utilize a common binding site on the domain 20 of FH for complement evasion. Binding via this site not only mimics the glycosaminoglycans of the host cells, but also enhances function of FH on the microbial surfaces via the novel mechanism of tripartite complex formation. This is a unique example of convergent evolution resulting in enhanced immune evasion of important pathogens via utilization of a "superevasion site."