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We analyzed West Nile Virus (WNV) exposure from 1,222 blood donors during 2017-2018 from an area of south-central Spain. Results revealed WNV seroprevalence of 0.08% (95% CI 0.004%-0.4%) in this population. Our findings underscore the need for continued surveillance and research to manage WNV infection in this region.
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Anticorpos Antivirais , Doadores de Sangue , Febre do Nilo Ocidental , Vírus do Nilo Ocidental , Humanos , Espanha/epidemiologia , Febre do Nilo Ocidental/epidemiologia , Vírus do Nilo Ocidental/imunologia , Estudos Soroepidemiológicos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Anticorpos Antivirais/sangue , Adulto Jovem , Adolescente , IdosoRESUMO
Amyotrophic lateral sclerosis (ALS) is a complex disease characterized by the interplay of genetic and environmental factors for which, despite decades of intense research, diagnosis remains rather delayed, and most therapeutic options fail. Therefore, unravelling other potential pathogenetic mechanisms and searching for reliable markers are high priorities. In the present study, we employ the SOMAscan assay, an aptamer-based proteomic technology, to determine the circulating proteomic profile of ALS patients. The expression levels of ~1300 proteins were assessed in plasma, and 42 proteins with statistically significant differential expression between ALS patients and healthy controls were identified. Among these, four were upregulated proteins, Thymus- and activation-regulated chemokine, metalloproteinase inhibitor 3 and nidogen 1 and 2 were selected and validated by enzyme-linked immunosorbent assays in an overlapping cohort of patients. Following statistical analyses, different expression patterns of these proteins were observed in the familial and sporadic ALS patients. The proteins identified in this study might provide insight into ALS pathogenesis and represent potential candidates to develop novel targeted therapies.
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Esclerose Lateral Amiotrófica , Humanos , Esclerose Lateral Amiotrófica/metabolismo , Proteômica , Proteínas SanguíneasRESUMO
Amyotrophic Lateral Sclerosis (ALS) is a neural disorder gradually leading to paralysis of the whole body. Alterations in superoxide dismutase SOD1 gene have been linked with several variants of familial ALS. Here, we investigated a transgenic (Tg) cloned swine model expressing the human pathological hSOD1G93A allele. As in patients, these Tg pigs transmitted the disease to the progeny with an autosomal dominant trait and showed ALS onset from about 27â¯months of age. Post mortem analysis revealed motor neuron (MN) degeneration, gliosis and hSOD1 protein aggregates in brainstem and spinal cord. Severe skeletal muscle pathology including necrosis and inflammation was observed at the end stage, as well. Remarkably, as in human patients, these Tg pigs showed a quite long presymptomatic phase in which gradually increasing amounts of TDP-43 were detected in peripheral blood mononuclear cells. Thus, this transgenic swine model opens the unique opportunity to investigate ALS biomarkers even before disease onset other than testing novel drugs and possible medical devices.
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Esclerose Lateral Amiotrófica/patologia , Neurônios Motores/patologia , Doenças Musculares/genética , Degeneração Neural/genética , Superóxido Dismutase-1/genética , Proteinopatias TDP-43/genética , Esclerose Lateral Amiotrófica/genética , Animais , Animais Geneticamente Modificados , Modelos Animais de Doenças , Humanos , Doenças Musculares/patologia , Degeneração Neural/patologia , Suínos , Proteinopatias TDP-43/patologiaRESUMO
Plastic is a polymer extremely resistant to degradation that can remain for up to hundreds or thousands of years, leading to the accumulation of massive amounts of plastic waste throughout the planet's ecosystems. Due to exposure to various environmental factors, plastic breaks down into smaller particles named microplastics (1-5000 µm) and nanoplastics (<1 µm). Microplastics (MPs) are ubiquitous pollutants but, still, little is known about their effects on human and animal health. Herein, our aim is to investigate cytotoxicity, oxidative stress, inflammation and correlated gene modulation following exposure to polystyrene microplastics (PS-MPs) in HRT-18 and CMT-93 epithelial cell lines. After 6, 24 and 48 h PS-MPs treatment, cell viability (MTT) and oxidative stress (SOD) assays were performed; subsequently, expression changes and cytokines release were investigated by Real-Time PCR and Magnetic-beads panel Multiplex Assay, respectively. For each exposure time, a significantly increased cytotoxicity was observed in both cell lines, whereas SOD activity increased only in CMT-93 cells. Furthermore, Magnetic-beads Multiplex Assay revealed an increased release of IL-8 in HRT-18 cells' medium, also confirmed by gene expression analysis. Results obtained suggest the presence of a pro-inflammatory pattern induced by PS-MPs treatment that could be related to the observed increase in cytotoxicity.
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Antineoplásicos , Poluentes Químicos da Água , Humanos , Animais , Camundongos , Microplásticos/toxicidade , Poliestirenos/toxicidade , Plásticos , Ecossistema , Linhagem Celular , Poluentes Químicos da Água/toxicidadeRESUMO
Complete animal welfare evaluation in intensive farming is challenging. With this study, we investigate new biomarkers for animal physical and mental health by comparing plasma expression of biochemical indicators in dairy cows reared in three different systems: (A) semi-intensive free-stall, (B) non-intensive tie-stall, and (C) intensive free-stall. Additionally, protein levels of mature brain-derived neurotrophic factor (mBDNF) and its precursor form (proBDNF) and indoleamine 2,3-dioxygenase (IDO1) specific activity were evaluated in brain samples collected from 12 cattle culled between 73 and 138 months of age. Alterations in plasma lipid composition and in the kynurenine pathway of tryptophan metabolism were observed in the tie-stall-reared animals. The total plasma BDNF concentration was higher in tie-stall group compared to the two free-housing groups. Brain analysis of the tie-stall animals revealed a different mBDNF/proBDNF ratio, with a higher level of proBDNF (p < 0.001). Our data are similar to previous studies on animal models of depression, which reported that inhibition of the conversion of proBDNF in its mature form and/or elevated peripheral kynurenine pathway activation may underlie cerebral biochemical changes and induce depressive-like state behavior in animals.
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OBJECTIVE: The spread of bovine spongiform encephalopathy (BSE) agent to small ruminants is still a major issue in the surveillance of transmissible spongiform encephalopathies (TSEs). L-type bovine spongiform encephalopathy (L-BSE) is an atypical form of BSE with an unknown zoonotic potential that is transmissible to cattle and small ruminants. Our current knowledge of bovine atypical prion strains in sheep and goat relies only on experimental transmission studies by intracranial inoculation. To assess oral susceptibility of goats to L-BSE, we orally inoculated five goats with cattle L-BSE brain homogenates and investigated pathogenic prion protein (PrPsc) distribution by an ultrasensitive in vitro conversion assay known as Real-Time Quaking Induced Conversion (RT-QuIC). RESULTS: Despite a prolonged observation period of 80 months, all these animals and the uninfected controls did not develop clinical signs referable to TSEs and tested negative by standard diagnostics. Otherwise, RT-QuIC analysis showed seeding activity in five out of five examined brain samples. PrPsc accumulation was also detected in spinal cord and lymphoreticular system. These results indicate that caprine species are susceptible to L-BSE by oral transmission and that ultrasensitive prion tests deserve consideration to improve the potential of current surveillance systems against otherwise undetectable forms of animal prion infections.
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Encefalopatia Espongiforme Bovina , Doenças Priônicas , Príons , Animais , Encéfalo/metabolismo , Bovinos , Encefalopatia Espongiforme Bovina/diagnóstico , Cabras , Doenças Priônicas/diagnóstico , Doenças Priônicas/veterinária , Proteínas Priônicas/metabolismo , OvinosRESUMO
The olfactory system (OS) is involved in many infectious and neurodegenerative diseases, both human and animal, and it has recently been investigated in regard to transmissible spongiform encephalopathies. Previous assessments of nasal mucosa infection by prions following intracerebral challenge suggested a potential centrifugal spread along the olfactory nerve fibers of the pathological prion protein (PrP(Sc)). Whether the nasal cavity may be a route for centripetal prion infection to the brain has also been experimentally studied. With the present study, we wanted to determine whether prion deposition in the OS occurs also under field conditions and what type of anatomical localization PrP(Sc) might display there. We report here on detection by different techniques of PrP(Sc) in the nasal mucosa and in the OS-related brain areas of sheep affected by natural scrapie. PrP(Sc) was detected in the perineurium of the olfactory nerve bundles in the medial nasal concha and in nasal-associated lymphoid tissue. Olfactory receptor neurons did not show PrP(Sc) immunostaining. PrP(Sc) deposition was found in the brain areas of olfactory fiber projection, chiefly in the olfactory bulb and the olfactory cortex. The prevalent PrP(Sc) deposition patterns were subependymal, perivascular, and submeningeal. This finding, together with the discovery of an intense PrP(Sc) immunostaining in the meningeal layer of the olfactory nerve perineurium, at the border with the subdural space extension surrounding the nerve rootlets, strongly suggests a probable role of cerebrospinal fluid in conveying prion infectivity to the nasal submucosa.
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Mucosa Nasal/química , Nervo Olfatório/química , Condutos Olfatórios/química , Proteínas PrPSc/análise , Scrapie/patologia , Animais , Mucosa Nasal/patologia , Bulbo Olfatório/química , Bulbo Olfatório/patologia , Nervo Olfatório/patologia , Condutos Olfatórios/patologia , Neurônios Receptores Olfatórios/química , Neurônios Receptores Olfatórios/patologia , Nervos Periféricos/química , OvinosRESUMO
OBJECTIVE: To compare the incidence of severe hepatitis in HIV-infected patients receiving rifampicin plus pyrazinamide (RZ) for antituberculosis prophylaxis with that of patients receiving a conventional isoniazid-based regime for 6 to 12 months (6-12H). METHODS: Meta-analysis of randomized controlled trials, in which RZ was compared with 6-12H, the standard regimen for latent tuberculosis infection in HIV-infected patients. A systematic search of studies published between 1986 and 2007 was carried out, and 5 randomized clinical trials conducted in Spain (2), the USA (1), Haiti (1), and Zambia (1) were identified. The absence or presence of severe hepatoxicity, which was defined as toxicity causing the death of the patient or requiring treatment withdrawal, was assessed as a binary response, and the outcome measure was the difference in the risk of hepatotoxicity between patients receiving RZ and those receiving 6-12H (controls). RESULTS: Among the 5 trials retrieved, 1 was excluded from the final analysis because of incomplete data on the development of hepatotoxicity. A final total of 2657 patients were included (1324 patients receiving RZ and 1333 receiving 6-12H). The development of severe hepatotoxicity was lower in the RZ group than in the 6-12H group (1.208% vs. 2.851%; P=0.0042, 95% CI: -0.028 to -0.005). The meta-analysis showed no statistical evidence of heterogeneity between the studies or publication bias. The difference in the risk of severe hepatotoxicity favored the RZ regimen in both the fixed effects model (-0.0119, 95% CI: -0.0206 to -0.0033) and random effects model (-0.0147, 95% CI: -0.0289 to -0.0006). CONCLUSIONS: The meta-analysis did not demonstrate an increased risk of severe hepatoxicity in HIV-infected patients receiving tuberculosis prophylaxis with the rifampicin/pyrazinamide combination compared to the conventional 6- or 12-month isoniazid-based regimen.
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Antibioticoprofilaxia , Antituberculosos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Infecções por HIV/complicações , Pirazinamida/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Tuberculose/prevenção & controle , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Antituberculosos/administração & dosagem , Antituberculosos/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Sinergismo Farmacológico , Quimioterapia Combinada , Infecções por HIV/tratamento farmacológico , Humanos , Isoniazida/administração & dosagem , Isoniazida/efeitos adversos , Isoniazida/uso terapêutico , Pirazinamida/administração & dosagem , Pirazinamida/uso terapêutico , RiscoRESUMO
BACKGROUND: Infections caused by KPC-producing Klebsiella pneumoniae (KPC-Kp) are not well represented in pivotal trials with ceftazidime-avibactam (CAZ-AVI). This study aimed to investigate its efficacy in a single-centre cohort of patients infected with KPC-Kp. METHODS: A retrospective observational study was conducted of consecutive patients treated for > 72 hours with CAZ-AVI for KPC-Kp infections. Fourteen-day clinical response was considered when none of these criteria were present: i) the patient died before day 14, ii) treatment with CAZ-AVI at day 14 for persistence of symptoms or signs of infection, iii) recurrence. A multivariate logistic regression model was used to identify factors predictive of 14-day clinical failure. A propensity score to receive targeted initial treatment with CAZ-AVI was used as a covariate of the analysis. RESULTS: Forty-seven patients were included. The median age was 70 years and the median Charlson index was 4. The most frequent sources of infection were intraabdominal (n = 18; 38.3%) followed by pneumonia (n = 14; 29.8%). Twenty-five patients (53.2%) had septic shock. CAZ-AVI was used as monotherapy in 34 (72.3%) of the cases. CAZ-AVI resistance was detected after CAZ-AVI therapy in six of 47 (12.7%) patients. Thirty-day crude mortality was 23.4% (n = 11). The 14-day clinical response rate was 59.6% (n = 28). Pneumonia (OR 7.57; 95% CI 1.45-39.43; P = 0.01), and INCREMENT-CPE score > 7 points (OR 6.73; 95% CI 1.39-34.94; P = 0.02) were associated with 14-day clinical failure. CONCLUSIONS: CAZ-AVI offers an advance for the treatment of KPC-Kp infections. In patients with pneumonia or an INCREMENT-CPE score > 7 points it may be reasonable to use CAZ-AVI in combination.
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Compostos Azabicíclicos/uso terapêutico , Proteínas de Bactérias/metabolismo , Ceftazidima/uso terapêutico , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , beta-Lactamases/metabolismo , Idoso , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Combinação de Medicamentos , Farmacorresistência Bacteriana/fisiologia , Feminino , Humanos , Infecções por Klebsiella/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Espanha , Resultado do TratamentoRESUMO
Since 2005, two cases of natural bovine spongiform encephalopathies (BSE) have been reported in goats. Furthermore, experimental transmissions of classical (C-BSE) and atypical (L-BSE) forms of BSE in goats were also reported. To minimize further spreading of prion diseases in small ruminants the development of a highly sensitive and specific test for ante-mortem detection of infected animals would be of great value. Recent studies reported high diagnostic value of a second generation of cerebrospinal fluid (CSF) Real-Time Quaking-Induced Conversion (RT-QuIC) assay across a wide spectrum of human prions. Here, we applied this improved QuIC (IQ-CSF) for highly efficient detection of TSEs prion protein in goat cerebrospinal fluid. IQ-CSF sensitivity and specificity were evaluated on CSF samples collected at disease endpoint from goats naturally and experimentally infected with scrapie or bovine isolates of C-BSE and L-BSE, respectively. Next, CSF samples collected from L-BSE infected goats during pre-symptomatic stage were also analysed. PrPL-BSE associated seeding activity was detected at early time points after experimental inoculation, with an average time of 439 days before clinical symptoms appeared. Taken together these data are indicative of the great potential of this in vitro prion amplification assay as ante-mortem TSE test for live and asymptomatic small ruminants.
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Encefalopatia Espongiforme Bovina/líquido cefalorraquidiano , Doenças das Cabras/líquido cefalorraquidiano , Cabras/líquido cefalorraquidiano , Príons/isolamento & purificação , Animais , Encéfalo/patologia , Bovinos , Encefalopatia Espongiforme Bovina/diagnóstico , Doenças das Cabras/diagnóstico , Humanos , Proteínas PrPSc/isolamento & purificaçãoRESUMO
INTRODUCTION: Total hip and knee arthroplasty (THA/TKA) are surgical procedures with proven benefits. Although the literature reports outcomes of fusion of the lumbar spine comparable to those of THA/TKA in general health-related quality-of-life (HRQoL) questionnaires, functional assessment is nevertheless needed for these results to be of use in clinical practice and management. Aim of our study was to prove that lumbar spinal fusion has similar if not better outcomes than THA/TKA using intervention-specific HRQoL questionnaires and functional assessment questionnaires. MATERIALS AND METHODS: Observational, ambispective, multicentre study of three cohorts undergoing lumbar spinal fusion (n = 115), THA (n = 119) and TKA (n = 253). Patients were evaluated using the Short-Form-12 (SF-12), Harris-Hip-Score, Hospital for Special Surgery Scale (HSS) and Oswestry Low Back Pain Disability questionnaires. A minimum follow-up of two years was conducted. RESULTS: The SF-12 showed significant improvement in all groups. The SF-12 physical component summary score indicated a more severe pre-operative status (p = 0.031) in the THA cohort. The mental component summary score indicated a less severe pre-operative status in the TKA cohort (p = 0.008) and greater post-operative improvement in the TKA and THA cohorts across follow-up (six months p = 0.021; one year p = 0.012; two years p = 0.042). Functional assessment indicated greater pre-operative disability in the THA group. At two years of follow-up, functional improvement according to the Harris, HSS and Oswestry questionnaires were 152.01%, 50.07% and 41.14% respectively. CONCLUSIONS: This study demonstrates that lumbar spinal fusion and total knee and hip arthroplasty are comparable in terms of functional improvement when thoroughly studied with health, quality-of-life and functional assessment questionnaires.
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Monitoring of small ruminants for transmissible spongiform encephalopathies (TSEs) has recently become more relevant after two natural scrapie suspected cases of goats were found to be positive for classical BSE (C-BSE). C-BSE probably established itself in this species unrecognized, undermining disease control measures. This opens the possibility that TSEs in goats may remain an animal source for human prion diseases. Currently, there are no data regarding the natural presence of the atypical BSE in caprines. Here we report that C-BSE and L-type atypical BSE (L-BSE) isolates from bovine species are intracerebrally transmissible to goats, with a 100% attack rate and a significantly shorter incubation period and survival time after C-BSE than after L-BSE experimental infection, suggesting a lower species barrier for classical agentin goat. All animals showed nearly the same clinical features of disease characterized by skin lesions, including broken hair and alopecia, and abnormal mental status. Histology and immunohistochemistry showed several differences between C-BSE and L-BSE infection, allowing discrimination between the two different strains. The lymphoreticular involvement we observed in the C-BSE positive goats argues in favour of a peripheral distribution of PrPSc similar to classical scrapie. Western blot and other currently approved screening tests detected both strains in the goats and were able to classify negative control animals. These data demonstrate that active surveillance of small ruminants, as applied to fallen stock and/or healthy slaughter populations in European countries, is able to correctly identify and classify classical and L-BSE and ultimately protect public health.
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Encéfalo/patologia , Encefalopatia Espongiforme Bovina/patologia , Doenças das Cabras/patologia , Proteínas PrPSc/metabolismo , Scrapie/patologia , Animais , Encéfalo/metabolismo , Bovinos , Encefalopatia Espongiforme Bovina/metabolismo , Encefalopatia Espongiforme Bovina/transmissão , Doenças das Cabras/metabolismo , Doenças das Cabras/transmissão , Cabras , Patologia Clínica , Scrapie/metabolismo , Scrapie/transmissãoRESUMO
Amyloid-ß (Aß) deposits are seen in aged individuals of many mammalian species that possess the same aminoacid sequence as humans. This study describes Aß deposition in 102 clinically characterized cattle brains from animals aged 0 to 20 years. Extracellular and intracellular Aß deposition was detected with 4G8 antibody in the cortex, hippocampus, and cerebellum. X-34 staining failed to stain Aß deposits, indicating the non ß-pleated nature of these deposits. Western blot analysis and surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry revealed in Tris, Triton, and formic acid fractions the presence of different Aß peptides, characterized mainly by C-terminally truncated forms. Exploration of the genetic variability of APOE, PSEN1, and PSEN2 genes involved in Alzheimer's disease pathogenesis revealed several previously unreported polymorphisms. This study demonstrates certain similarities between Aß deposition patterns exhibited in cattle brains and those in the human brain in early stages of aging. Furthermore, the identification of the same Aß peptides reported in humans, but unable to form aggregates, supports the hypothesis that cattle may be protected against amyloid plaque formation.
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Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Envelhecimento/metabolismo , Envelhecimento/patologia , Animais , Apolipoproteínas E/genética , Western Blotting , Encéfalo/crescimento & desenvolvimento , Encéfalo/patologia , Bovinos , Espaço Extracelular/metabolismo , Frequência do Gene , Técnicas de Genotipagem , Proteína Glial Fibrilar Ácida/metabolismo , Imuno-Histoquímica , Espaço Intracelular/metabolismo , Neuroglia/metabolismo , Neuroglia/patologia , Neurônios/metabolismo , Neurônios/patologia , Polimorfismo Genético , Presenilina-1/genética , Presenilina-2/genética , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
Strongyloides stercoralis has a unique ability to replicate in the human host and lead to chronic infection that can persist for several decades. Thirty-three patients (10 travellers and 23 immigrants) with imported S. stercoralis infection were studied and clinical and epidemiological characteristics described. Only 16 patients (48.5%) reported symptoms, mainly of the gastrointestinal tract. Eosinophilia was present in 21 (63.6%) patients. Seven patients (21.2%) had an immunocompromising condition. Patients were classified into chronic asymptomatic infection (17/33, 51.5%), chronic symptomatic infection (11/33, 33.3%) and hyperinfection (5/33, 15.2%). Four of the latter (80%) had an immunocompromising condition. Strongyloides stercoralis infection should be considered in immigrants and travellers with eosinophilia or compatible symptoms coming from endemic areas. Diagnosis should always be sought in immunocompromised hosts.