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Based on statistical analyses applied to official data from the Digital Atlas of Disasters in Brazil over the last 25 years, we evidenced a consistent intensification in the annual occurrence of natural disasters in the state of Pará, located in the eastern Brazilian Amazon. The quantitative comparison between the averages of the most intense period of disasters (2017 to 2023) and the earlier years (1999 to 2016) revealed a remarkable percentage increase of 473%. Approximately 81% of the state’s municipalities were affected, as indicated by disaster mapping. A clear seasonal pattern was observed, with Hydrological disasters (Inundations, Flash floods, and Heavy rainfall) peaking between February and May, while Climatological disasters (Droughts and Forest fires) were most frequent from August to October. The catastrophic impacts on people and the economy were documented, showing a significant rise in the number of homeless individuals and those directly affected, alongside considerable material damage and economic losses for both the public and private sectors. Furthermore, we conducted a comprehensive composite analysis on the tropical ocean–atmosphere dynamic structure that elucidated the various triggering mechanisms of disasters arising from Inundations, Droughts, and Forest fires (on seasonal scale), and Flash floods and Heavy rainfall (on sub-monthly scale) in Pará. The detailed characterization of disasters on a municipal scale is relevant in terms of the scientific contribution applied to the strategic decision-making, planning, and implementation of public policies aimed at early risk management (rather than post-disaster response), which is critical for safeguarding human well-being and strengthening the resilience of Amazonian communities vulnerable to climate change.

Based on statistical analyses applied to official data from the Digital Atlas of Disasters in Brazil over the last 25 years, we evidenced a consistent intensification in the annual occurrence of natural disasters in the state of Pará, located in the eastern Brazilian Amazon. The quantitative comparison between the averages of the most intense period of disasters (2017 to 2023) and the earlier years (1999 to 2016) revealed a remarkable percentage increase of 473%. Approximately 81% of the state's municipalities were affected, as indicated by disaster mapping. A clear seasonal pattern was observed, with Hydrological disasters (Inundations, Flash floods, and Heavy rainfall) peaking between February and May, while Climatological disasters (Droughts and Forest fires) were most frequent from August to October. The catastrophic impacts on people and the economy were documented, showing a significant rise in the number of homeless individuals and those directly affected, alongside considerable material damage and economic losses for both the public and private sectors. Furthermore, we conducted a comprehensive composite analysis on the tropical ocean–atmosphere dynamic structure that elucidated the various triggering mechanisms of disasters arising from Inundations, Droughts, and Forest fires (on seasonal scale), and Flash floods and Heavy rainfall (on sub-monthly scale) in Pará. The detailed characterization of disasters on a municipal scale is relevant in terms of the scientific contribution applied to the strategic decision-making, planning, and implementation of public policies aimed at early risk management (rather than post-disaster response), which is critical for safeguarding human well-being and strengthening the resilience of Amazonian communities vulnerable to climate change. [ABSTRACT FROM AUTHOR]

Precision medicine has revolutionized the field of neuroimmunology, with innovative approaches that characterize diseases based on their biology, deeper understanding of the factors leading to heterogeneity within the same disease, development of targeted therapies, and strategies to tailor therapies to each patient. This review explores the impact of precision medicine on various neuroimmunological conditions, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), optic neuritis, autoimmune encephalitis, and immune-mediated neuropathies. We discuss advances in disease subtyping, recognition of novel entities, promising biomarkers, and the development of more selective monoclonal antibodies and cutting-edge synthetic cell-based immunotherapies in neuroimmunological disorders. In addition, we analyze the challenges related to affordability and equity in the implementation of these emerging technologies, especially in situations with limited resources.

This research aimed to analyze the relationship between deforestation (DFT) and climatic variables during the rainy (CHU+) and less-rainy (CHU−) seasons in the Tapajós River basin. Data were sourced from multiple institutions, including the Climatic Research Unit (CRU), Center for Weather Forecasts and Climate Studies (CPTEC), PRODES Program (Monitoring of Brazilian Amazon Deforestation Project), National Water Agency (ANA) and National Centers for Environmental Prediction/National Oceanic and Atmospheric Administration (NCEP/NOAA). The study assessed anomalies (ANOM) in maximum temperature (TMAX), minimum temperature (TMIN) and precipitation (PREC) over three years without the occurrence of the El Niño–Southern Oscillation (ENSO) atmospheric–oceanic phenomenon. It also examined areas with higher DFT density using the Kernel methodology and analyzed the correlation between DFT and climatic variables. Additionally, it assessed trends using the Mann–Kendall technique for both climatic and environmental data. The results revealed significant ANOM in TEMP and PREC. In PREC, the highest values of ANOM were negative in CHU+. Regarding temperature, the most significant values were positive ANOM in the south, southwest and northwestern regions of the basin. Concerning DFT density, data showed that the highest concentration was of medium density, primarily along the highways. The most significant correlations were found between DFT and TEMP during the CHU− season in the Middle and Lower Tapajós sub-basins, regions where the forest still exhibits more preserved characteristics. Furthermore, the study identified a positive trend in TEMP and a negative trend in PREC.

The great current challenge for the conservation and use of natural resources refers to global climate change, because of its impacts felt in different intensities at global, regional, and local spatial scales. Within the system of environmental protection areas in Brazil, the extractive reserves ensure the sustainable use of natural resources by traditional populations, thus maintaining the cultural and biological aspects of a region. Such populations, being in close management of the surrounding environments, tend to perceive changes in ecological processes that many need for their livelihoods. The use of this perception of local populations in conjunction with academic research evidence has a high potential to allow a whole and systemic view of possible changes in natural phenomena. This study developed an integrated analysis of scientific evidence and local perceptions to understand the variation of precipitation in a community inserted in an extractive reserve in the eastern Amazon. We used 30 years of precipitation data from the Brazilian National Institute of Meteorology - INMET, the Southern Oscillation Index - SOI, and the Atlantic Meridional Mode Index - AMM. Furthermore, we applied a form to measure the population's perception of possible changes in rainfall cycles in the region. The meteorological data indicate that the region of the community has been presenting a rainfall reduction; however, people in the community do not perceive this trend. Although it is public knowledge that the global climate is undergoing changes, a fact noted after the integrating analysis of scientific evidence with local knowledge in Resexmar Soure is that the perceptions of traditional populations often focus on smaller temporal and spatial scale visions.

ABSTRACT The Scientific Department of Neuroimmunology of the Brazilian Academy of Neurology (DCNI/ABN) and Brazilian Committee for Treatment and Research in Multiple Sclerosis and Neuroimmunological Diseases (BCTRIMS) provide recommendations in this document for vaccination of the population with demyelinating diseases of the central nervous system (CNS) against infections in general and against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19. We emphasize the seriousness of the current situation in view of the spread of COVID-19 in our country. Therefore, reference guides on vaccination for clinicians, patients, and public health authorities are particularly important to prevent some infectious diseases. The DCNI/ABN and BCTRIMS recommend that patients with CNS demyelinating diseases (e.g., MS and NMOSD) be continually monitored for updates to their vaccination schedule, especially at the beginning or before a change in treatment with a disease modifying drug (DMD). It is also important to note that vaccines are safe, and physicians should encourage their use in all patients. Clearly, special care should be taken when live attenuated viruses are involved. Finally, it is important for physicians to verify which DMD the patient is receiving and when the last dose was taken, as each drug may affect the induction of immune response differently.

ABSTRACT Background: To improve the comparability of multiple sclerosis (MS) prevalence across Brazilian regions, the Brazilian Committee for Treatment and Research in MS has implemented a standardized approach to assess the prevalence of the disease in five key cities, which were deemed representative of their regions in terms of socio-geographical features and where in-person revision of each case was feasible. Objective: To report the point-prevalence of MS in Passo Fundo, one of the key cities in Southern Brazil. Methods: We sought to identify all MS patients who were living in Passo Fundo on July 1st, 2015. The primary source for case ascertainment was records from the offices of neurologists and neurosurgeons practicing in the city. Multiple secondary sources were used to maximize identification of cases. All patients underwent in-person review of the diagnosis by a panel of neurologists with experience in MS. Results: We identified 52 MS patients living in Passo Fundo on July 1st, 2015. The point-prevalence rate for MS was 26.4/100,000 population (95% confidence interval, 19.7 to 34.6/100,000). Among the MS cases, 42 (80.8%) were female, for a sex ratio of 4.2:1. Forty-six cases (88.5%) were categorized as relapsing-remitting MS, and the remaining 6 cases, as secondary progressive MS (11.5%). Other epidemiological and clinical features were comparable to national and international MS populations. Conclusions: The prevalence of MS in Passo Fundo is one of the highest reported in Brazil so far. Studies in other key Brazilian cities, using the same methodology, are currently being carried out.

Abstract Improvements in assays for detecting serum antibodies against myelin oligodendrocyte glycoprotein (MOG) have led to the appreciation of MOG‐antibody‐associated disease (MOGAD) as a novel disorder. However, much remains unknown about its etiology. We performed human leukocyte antigen (HLA) analysis in 82 MOGAD patients of European ancestry in the UK population. No HLA class II associations were observed, thus questioning the mechanism of anti‐MOG antibody generation. A weak protective association of HLA‐C*03:04 was observed (OR = 0.26, 95% CI = 0.10‐0.71, pc = 0.013), suggesting a need for continued efforts to better understand MOGAD genetics and pathophysiology.

Rubia Carla Formighieri Giordani,1 Suely Ruiz Giolo,2 Camila Muhl,3 Arune João Estavela,4 Janete Ismael Mabuie Gove4 1Department of Nutrition, Federal University of Parana, Curitiba, Parana, Brazil; 2Department of Statistics, Federal University of Parana, Curitiba, Parana, Brazil; 3Department of Psychology, FAE University, Curitiba, Parana, Brazil; 4High Institute of Health Sciences, Maputo, MozambiqueCorrespondence: Rubia Carla Formighieri GiordaniDepartment of Nutrition, Federal University of Parana, Curitiba, Parana, 80210-170, BrazilTel +55 41 3360 4056Email rubia@ufpr.brPurpose: This study aimed to validate the Portuguese version of the Fear of COVID-19 Scale (FCV-19S) and investigate its association with sociodemographic and pandemic-related variables in the population of Mozambique.Participants and Methods: A cross-sectional online survey recruited 387 Mozambicans aged 18 to 70 years. The psychometric properties of the Portuguese version of the FCV-19S were evaluated using confirmatory factor analysis and Rash analysis. Additionally, the association of the FCV-19S with sociodemographic and pandemic-related variables was investigated using the two-sample t-test, one-way analysis of variance, and logistic regression.Results: The unidimensional factor structure of the Portuguese version of the FCV-19S was confirmed, and the scale showed good internal consistency reliability. The FCV-19S properties tested from the Rasch analysis were satisfactory. Women and those with lower education levels had higher scores of fear. Moreover, significantly higher levels of fear were observed among those being in an at-risk group for COVID-19, having family members or friends diagnosed or with death confirmed by COVID-19, and not being confident that they would receive adequate care from the public health services in case of COVID-19 infection.Conclusion: The Portuguese version of FCV-19S has strong psychometric properties and can be used to assess the fear of COVID-19 in the Portuguese-speaking population of Mozambique. As the adverse impacts of the COVID-19 pandemic on mental health represents a challenge to clinical psychiatry, and information on mental health in African countries is still scarce, our findings may assist in the planning of public mental health policies, aimed mainly at specific segments of the population, such as women and people in extreme poverty.Keywords: mental health, fear scale, infection, pandemic, psychometrics

Abstract Objective Fatigue is a common and disabling symptom amongst people with multiple sclerosis, however it has not been compared across the central nervous system (CNS) inflammatory diseases associated with aquaporin‐4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) antibodies (Ab). We explored the factors associated with fatigue within and across the two diseases, and compared fatigue levels between them. Methods We performed a cross‐sectional study of 90 AQP4‐Ab and 44 MOG‐Ab patients. Fatigue was assessed using the Modified Fatigue Impact Scale (MFIS). Clinical, demographic, and psychometric (anxiety, depression, pain) data were used as independent variables. Multivariable linear regression was used to identify significant independent variables associated with fatigue within and across the two diseases. Results Within AQP4‐Ab patients, age (P = 0.002), disease duration (P = 0.004), number of clinical attacks (P = 0.001), disability (P = 0.007), pain interference (P

O sensoriamento remoto e o índice de risco de fogo são as formas de detecção e previsão de queimadas utilizadas pelo Instituto Nacional de Pesquisas Espaciais para monitorar a frequência de queimadas no Brasil, no entanto observa-se que a ocorrência de uma queimada nem sempre é prevista pelo índice do risco de fogo, particularmente na região da Amazônia oriental. Assim, esta pesquisa foi motivada pelo objetivo de analisar o padrão espaçotemporal das queimadas detectadas via satélite e a eficiência dos alertas de previsão de queimadas gerados pelo cálculo do risco de fogo, considerando a variabilidade dos fenômenos meteorológicos que podem influenciar o regime pluviométrico e alterar a ocorrência de focos de queimada na região da Amazônia oriental. As análises desta investigação consideraram as alterações das condições meteorológicas moduladas pela variabilidade interanual do fenômeno El Niño Oscilação Sul ocorridas entres os anos de 2000 e 2017. Os resultados mostraram que, em anos menos chuvosos, os focos de queimada apresentaram maior frequência ao longo do ano. Já nos mais chuvosos, tenderam a concentrar-se no segundo semestre em proporção superior à observada nos anos mais secos. A maior parte dos focos de queimada (80%) ocorreu em áreas alteradas pela atividade humana, resultado não captado pelo índice de risco de fogo, indicando que, por este levar em conta somente variáveis ambientais e não incluir a ação do homem como parâmetro, a eficiência em antecipar a ocorrência de uma queimada se torna limitada.

Antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) have been found in some cases diagnosed as seronegative neuromyelitis optica spectrum disorder (NMOSD). MOG-IgG allowed the identification of a subgroup with a clinical course distinct from that of NMOSD patients who are seropositive for aquaporin-4-IgG antibodies. MOG-IgG is associated with a wider clinical phenotype, not limited to NMOSD, with the majority of cases presenting with optic neuritis (ON), encephalitis with brain demyelinating lesions, and/or myelitis. Therefore, we propose the term MOG-IgG-associated Optic Neuritis, Encephalitis, and Myelitis (MONEM). Depending on the clinical characteristics, these patients may currently be diagnosed with NMOSD, acute disseminated encephalomyelitis, pediatric multiple sclerosis, transverse myelitis, or ON. With specific cell-based assays, MOG-IgG is emerging as a potential biomarker of inflammatory disorders of the central nervous system. We review the growing body of evidence on MONEM, focusing on its clinical aspects.

Introduction: Studies indicate that war-affected and displaced groups, compared to local non-refugee populations, suffer variable but generally higher rates of stress-related somatic symptoms. The relation between traumatic events and somatization is poorly explored. Objectives: To assess the impact of trauma on somatic symptoms in forced migrants recently hosted in Italy. Methods: First generation asylum seekers/refugees of age over 18 referred to Umberto I Hospital, Rome, for a routine infectivologic screening were consecutively enrolled. The following tools were administered: Somatic Symptom Scale 8 (SSS-8), Life Events Check List (LEC-5), and Stress-related Vulnerability Scale (SVS). Results: Eighty-five subjects participated to the study (males=80 (94.1%); mean age= 28.3 SD=7.4). Fifty-eight (68%) participants reported at least one clinically significant somatic symptom and all reported at least one severe traumatic event in the LEC-5. Pearson Correlation Coefficients of SSS-8 total score with respect to LEC-5 and SVS lack of Social Support Subscale score were r=0,327 (p=0.003), r=0.529 (p=0.0001). A stepwise linear regression confirmed that LEC-5 total score (Beta standardized correlation coefficient = 0.151; p = 0.027) and SVS lack of Social Support Subscale (Beta standardized correlation coefficient = -0.309; p = 0.010) were significant predictors of SSS-8 total score. Conclusions: High levels of somatization were associated to the number of lifetime traumatic events and to perceived lack of social support in forced migrants. It is important to correctly recognize somatic symptoms in traumatized forced migrants. [ABSTRACT FROM AUTHOR]

Several animal and human studies have implicated CD4+ T helper 17 (Th17) cells and their downstream pathways in the pathogenesis of central nervous system (CNS) autoimmunity in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), challenging the traditional Th1-Th2 paradigm. Th17 cells can efficiently cross the blood-brain barrier using alternate ways from Th1 cells, promote its disruption, and induce the activation of other inflammatory cells in the CNS. A number of environmental factors modulate the activity of Th17 pathways, so changes in the diet, exposure to infections, and other environmental factors can potentially change the risk of development of autoimmunity. Currently, new drugs targeting specific points of the Th17 pathways are already being tested in clinical trials and provide basis for the development of biomarkers to monitor disease activity. Herein, we review the key findings supporting the relevance of the Th17 pathways in the pathogenesis of MS and NMOSD, as well as their potential role as therapeutic targets in the treatment of immune-mediated CNS disorders.

A região de Carajás (constituída principalmente das cidades de Marabá, Parauapebas, Curionópolis, Canaã dos Carajás e Eldorado dos Carajás) no estado do Pará e a região de São Luís no estado do Maranhão são os polos mais importantes para a companhia Vale do Rio Doce. Assim, nesta pesquisa foi realizada uma análise das variáveis meteorológicas, temperatura (máxima, mínima e amplitude térmica) e precipitação para essas duas localidades. Foi calculada a correlação entre o gradiente térmico continental e o marítimo com a variabilidade pluviométrica sazonal da Amazônia oriental objetivando identificar o principal modulador da precipitação da região de estudo. Observou-se que a variabilidade climática da temperatura, tanto do ar como do oceano, nas duas regiões estudadas, apresentam um padrão semelhante de crescimento, resultado que produz resultados diferentes sobre a precipitação de cada localidade. Foi identificado que a intensidade da anomalia térmica no Nino 4, localizado a 5N-5S, 160E-150W no oceano atlântico, interfere diretamente sobre as variáveis meteorológicas no sudeste da Amazônia oriental e que a anomalia de TSM do oceano Pacífico possui maior correlação com a variabilidade pluviométrica da cidade de São Luís. .

This article presents the development of a system used by the Brazilian Network of Legal Metrology and Quality – INMETRO and its delegated public bodies to increase the coverage of mandatory periodic verification on measuring instruments in Brazil, especially non automatic weighing instruments. Based on a governmental database of active establishments that allowed the choice of an specific economic activity, the system provides a list of establishments where measuring instruments are used to commercial transitions and, therefore, subject to periodic mandatory verification. As a result, the use of system increased the number of measuring instruments controlled in Brazil, revealed areas for improvement and provided references to set goals.

ABSTRACT Autoantibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) have been reported in patients with inflammatory central nervous system disorders including isolated optic neuritis (ON). We compared our MOG-IgG ON patients with multiple sclerosis (MS) patients presenting with ON. Methods and results: Among the total of 38 patients with optic neuropathies, six patients with isolated ON were MOG-IgG positive and eight patients with ON fulfilled the diagnostic criteria for MS. All MS patients were negative for MOG-IgG using a cell-based assay. When compared with the MS group, the MOG-IgG patients were older (mean 47 years), more frequently male (ratio 2:1) and had a higher frequency of bilateral and/or recurrent ON. The brain magnetic resonance imaging of all MOG-IgG positive patients was normal or had only unspecific white matter T2 lesions. Conclusion: These findings suggest that MOG-IgG is a biomarker of an inflammatory demyelinating CNS disease distinct from MS.

ABSTRACT The expanding therapeutic arsenal in multiple sclerosis (MS) has allowed for more effective and personalized treatment, but the choice and management of disease-modifying therapies (DMTs) is becoming increasingly complex. In this context, experts from the Brazilian Committee on Treatment and Research in Multiple Sclerosis and the Neuroimmunology Scientific Department of the Brazilian Academy of Neurology have convened to establish this Brazilian Consensus for the Treatment of MS, based on their understanding that neurologists should be able to prescribe MS DMTs according to what is better for each patient, based on up-to-date evidence and practice. We herein propose practical recommendations for the treatment of MS, with the main focus on the choice and management of DMTs, as well as present a review of the scientific rationale supporting therapeutic strategies in MS.

ABSTRACT Familial cases of early-onset prominent frontal lobe dysfunction associated with epilepsy have not been reported to date. We report a mother and her only daughter with incapacitating behavioral manifestations of frontal lobe dysfunction and epilepsy of variable severity. The possibility of a hitherto undescribed genetic condition is discussed.

Resumo: A dinâmica de transmissão da dengue é multifatorial e envolve aspectos socioeconômicos, ecológicos e ambientais, sendo este último intimamente relacionado às condições climáticas locais que interferem no ciclo reprodutivo dos vetores da doença. Por sua vez, o clima é dependente dos mecanismos oceânicos tropicais, a exemplo das fases de El Niño/La Niña sobre o Pacífico. O presente trabalho contribui com esta temática e reporta as correlações entre o índice MEI (Multivariate ENOS Index) do Pacífico e o número de casos notificados de dengue em sete capitais da Amazônia brasileira, no período de 2001 a 2012. Além disso, investiga-se o padrão de sazonalidade (médias trimestrais) dos casos de dengue ao longo da região. As evidências de que o fenômeno El Niño/La Niña provoca redução/aumento no padrão pluviométrico local é consistente com o número menor/maior de casos notificados de dengue na maior parte das capitais amazônicas, cujo resultado foi comprovado pelas correlações negativas estatisticamente significantes encontradas para Manaus (Amazonas), São Luís (Maranhão), Belém (Pará) e Palmas (Tocantins). As médias dos 12 anos (2001/2012) revelaram a presença de sazonalidade pronunciada na incidência de dengue na maioria das capitais, com picos acentuados de janeiro a março [Rio Branco (Acre), Manaus, Belém e Palmas] e de abril a junho (São Luís), correspondendo em torno de 50% a 70% do total anual. As localidades mais ao norte [Boa Vista (Roraima) e Macapá (Amapá)] revelaram registro da dengue ao longo de todos os trimestres do ano, não apresentando sazonalidade acentuada.

Orthpoxvirus infection can spread more easily in a population with a waning immunity with the subsequent emergence/re-emergence of the viruses pertaining to this genus. In the last two decades, several cases of Orthopoxvirus, and in particular Cowpoxvirus infections in humans were reported in different parts of the world, possibly due to the suspension of smallpox vaccinations. To date, in Italy, few investigations were conducted on the presence of these infections, and because of this a serosurvey was carried out to evaluate Cowpoxvirus infection in feline colonies situated in the province of Rome, since these are also susceptible to other zoonotic viruses belonging to Orthopoxvirus, and from which humans may contract the infection. The sample design was set at an expected minimum seroprevalence of 7.5%, a 5% standard error and 95% confidence level. In parallel, a serological investigation was conducted using convenience sampling in domestic, exotic and wild susceptible animals of the Latium and Tuscany Regions, which are areas in the jurisdiction of the Istituto Zooprofilattico Sperimentale del Lazio e della Toscana, coordinating this study. The serological methods employed were indirect immunofluorescence for 36 sera of nonhuman primate and virus neutralization for 1198 sera of different species. All the 1234 sera examined were negative for the presence of antibodies against Cowpoxvirus, indicating its limited circulation in the areas of investigation. The methodology applied for the serosurveillance could be adopted in the case of outbreaks of this infection and for the evaluation of the spread of this infection in the area of interest, to obtain essential information crucial for animal and public health policies according to the One Health concept.

Nowadays, leptospirosis is a re‑emerging widespread infectious disease often underestimate worldwide. The National Reference Centre for Leptospirosis (NRCL), at the Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna, Brescia (Italy), with the cooperation of all the other Istituti Zooprofilattici Sperimentali (IIZZSS), evaluated the distribution of such important zoonosis in Italy. Serological data obtained between 2010‑2011 by each laboratory were collected by the NRCL and discussed. Serum samples collected from 43,935 animal specimens were analysed by the Microscopic Agglutination Test (MAT), using a panel of 8 serogroups as antigens (Australis, Ballum, Canicola, Grippotyphosa, Icterohaemorrhagiae, Pomona, Sejroe, Tarassovi). A MAT cut‑off of 1:100 was used to identify the serological positivities, 6,279 sera showed positive titers. Bovine (46.9%), swine (27.5%), ovine and goat (7.4%), dog (6.9%), and wild boar (4.5%) samples were delivered to the Laboratories more frequently than equine and other species sera. Data analysis showed that the most common serogroups in Italy are: Australis present in dogs, wild boars, horses, hares, swine, foxes, and rodents; Sejroe detected in cattle, sheep, goats, and buffaloes; Icterohaemorrhagiae present in dogs, goats, and foxes; Pomona detected in swine, cattle, and wild species; Grippotyphosa reported in hares.

In order to clarify the role of cytochrome in nitrate reductase we have performed spectrophotometric and stopped-flow kinetic studies of reduction and oxidation of the cytochrome hemes with analogues of physiological quinones, using menadione as an analogue of menaquinone and duroquinone as an analogue of ubiquinone, and comparing the results with those obtained with dithionite. The spectrophotometric studies indicate that reduction of the cytochrome hemes varies according to the analogue of quinone used, and in no cases is it complete. Stopped-flow kinetics of heme oxidation by potassium nitrate indicates that there are two distinct reactions, depending on whether the hemes were previously reduced by menadiol or by duroquinol. These results, and those of spectrophotometric studies of a mutant lacking the highest-potential [Fe-S] cluster, allow us to propose a two-pathway electron transfer model for nitrate reductase A from Escherichia coli.

Aims: The aim of this study was to assess the effects of a single infusion of the bisphosphonate neridronate (N) on parameters of inflammation and bone resorption in rheumatoid arthritis (RA)., Methods: Forty-five patients with active RA were randomly allocated on a double blind basis to receive a single intravenous infusion of either N 25 mg (15 patients), N 50 mg (15 patients), or placebo (15 patients). At baseline and after 7 and 21 days, we assessed the following: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and Ritchie's articular index as indices of disease activity; and urinary free deoxypyridinoline (DPyr), N-telopeptide of type I collagen (NTx) and hydroxyproline (OHP) as indices of bone resorption., Results: At day 7, N 25 mg significantly decreased ESR compared to N 50 mg (p=0.002), and CRP compared to placebo (p=0.036). With regard to bone resorption markers, at day 7, both N 25 mg and 50 mg compared to placebo significantly decreased NTx (p<0.0005 and p=0.003, respectively) and OHP (p=0.001 and p=0.004, respectively). At day 21, N 50 mg significantly decreased OHP compared to placebo (p=0.017). DPyr levels remained unchanged in the three groups., Conclusions: N 25 mg and 50 mg exerted different effects on RA activity parameters, since only the lower dose significantly decreased ESR and CRP. Both doses of N inhibited bone resorption, with a transient, significant reduction in urinary NTx and OHP, but without any effect on DPyr.

The trimethylamine N-oxide (TMAO) reductase of Escherichia coli is a molybdoenzyme that catalyses the reduction of the TMAO to trimethylamine (TMA) with a redox potential of +130 mV. We have successfully substituted the molybdenum with tungsten and obtained an active tungsto-TMAO reductase. Kinetic studies revealed that the catalytic efficiency of the tungsto-substituted TMAO reductase (W-TorA) was increased significantly (twofold), although a decrease of about 50% in its kcat was found compared with the molybdo-TMAO reductase (Mo-TorA). W-TorA is more sensitive to high pH, is less sensitive to high NaCl concentration and is more heat resistant than Mo-TorA. Most importantly, the W-TorA becomes capable of reducing sulphoxides and supports the anaerobic growth of a bacterial host on these substrates. The evolutionary implication and mechanistic significance of the tungsten substitution are discussed.

We have compared the steady-state kinetics of wild-type nitrate reductase A and two mutant forms with altered beta subunits. To mimic conditions in vivo as closely as possible, we used analogues of the physiological quinols as electron donors and membranes with overexpressed nitrate reductase A in preference to a purified alpha beta gamma complex. With the wild-type enzyme both menadiol and duroquinol supply their electrons for the reduction of nitrate at rates that depend on the square of the quinol concentration, menadiol having the higher catalytic constant. The results as a whole are consistent with a substituted-enzyme mechanism for the reduction of nitrate by the quinols. Kinetic experiments suggest that duroquinol and menadiol deliver their electrons at different sites on nitrate reductase, with cross-inhibition. Menadiol inhibits the duroquinol reaction strongly, suggesting that menaquinol may be the preferred substrate in vivo. To examine whether electron transfer from menadiol and duroquinol for nitrate reduction requires the presence of all of the Fe-S centres, we have studied the steady-state kinetics of mutants with beta subunits that lack an Fe-S centre. The loss of the highest-potential Fe-S centre results in an enzyme without menadiol activity, but retaining duroquinol activity; the kinetic parameters are within a factor of two of those of the wild-type enzyme, indicating that this centre is not required for the duroquinol activity. The loss of a low-potential Fe-S centre affects the activity with both quinols: the enzyme is still active but the catalytic constants for both quinols are decreased by about 75%, indicating that this centre is important but not essential for the activity. The existence of a specific site of reaction on nitrate reductase for each quinol, together with the differences in the effects on the two quinols produced by the loss of the Fe-S centre of +80 mV, suggests that the pathways for transfer of electrons from duroquinol and menadiol are not identical.

gamma-Glutamyltranspeptidase (gamma GT) appears in serum in multiple forms; their significance and clinical utility in hepatobiliary and pancreatic diseases are still a matter of controversy. Electrophoretic separation of the multiple forms of gamma GT on agarose gel was performed in 20 alcoholic patients (six with cirrhosis and 14 with fatty liver) and the results compared with those obtained in 50 healthy volunteers, 43 patients affected with chronic hepatitis C, 36 patients with posthepatitic cirrhosis and in 52 epileptic patients on long-term anti-epileptic medication. Multiple forms of gamma GT were separated into several bands (up to 11), labelled 0a, 0b, 1a, 1b, 2a, 2b, 2c, 3a, 3b, 4a, 4b. In the alcoholic patients nine fractions were detected, and the electrophoretic pattern observed was significantly different from that observed in healthy volunteers and in patients with chronic hepatitis C or posthepatitic cirrhosis. No differences were observed in the electrophoretic patterns in the alcohol abusers and epileptic patients. In alcoholic patients significant differences were observed in the electrophoretic patterns in relation to the degree of liver injury; the electrophoretic patterns in patients with alcohol-related cirrhosis and posthepatitic cirrhosis differed significantly. The separation of multiple forms of gamma GT has high sensitivity and good reproducibility. It may be proposed as a complementary test in the diagnosis of alcoholic liver disease.

A soluble alpha beta complex of nitrate reductase can be obtained from a strain of Escherichia coli that lacks the narI gene and expresses only the alpha and beta subunits. The beta subunit contains four Fe-S centres and the alpha subunit contains the molybdenum cofactor, which is the site at which nitrate is reduced. Despite the lack of the gamma subunit of the complete enzyme, this complex can still catalyse the reduction of nitrate with artificial electron donors such as benzyl viologen, so that it is suitable for studying the transfer of electrons between these two types of redox centre. To examine whether the electrons from reduced benzyl viologen are initially delivered to the Fe-S centres, or directly to the molybdenum cofactor, or both, we have studied the steady-state kinetics and the binding of benzyl viologen to the alpha beta complex and mutants alpha beta* with altered beta subunits. Reduction of the enzyme by reduced benzyl viologen in the absence of nitrate showed that all four Fe-S centres and the molybdenum cofactor could be reduced. Two classes of site with different equilibrium constants could be distinguished. The kinetic results suggest that benzyl viologen supplies its electrons directly to the molybdenum cofactor, at a rate showing a hyperbolic dependence on the square of the concentration of the electron donor. A reaction mechanism is proposed for the reduction of nitrate catalysed by the alpha beta complex of nitrate reductase with artificial electron donors.

Eight hundred broilers were examined to define the reference values of nine blood constituents (total proteins, albumin, total and free cholesterol, triglycerides, aspartate aminotransferase (AST), alkaline phosphatase (ALP), calcium, and phosphorus). The broilers, coming from 20 different commercial poultry operations, were equally divided into different groups according to age (21 and 45 days), strain (Arbor Acres and Hybro), sex, and sampling season (summer or winter). Age and sampling season were the variation sources that most influenced the values of the hematochemical variables examined. The interaction of age with strain influenced total proteins total and free cholesterol, triglycerides, and ALP. The interaction of age with sampling season influenced all hematochemical constituents except triglycerides. Reference limits defined by .975 and .025 fractiles were computed for each blood constituent according to the significance of different variation sources and their combinations. Reference limits defined herein could be used as indicators of metabolic and health conditions of a poultry farm.

When fixed charges and enzyme molecules are not homogeneously distributed in a matrix, the degree of organization of charges, of enzyme molecules and of charges with respect to enzyme molecules modulate the enzyme reaction rate. The overall reaction velocity of the bound enzyme system may be expressed in terms of monovariate moments of the charge density distribution and of the bivariate moments of the charge and enzyme density distributions. With respect to the situation where fixed charges and enzyme molecules are randomly distributed in the matrix, the molecular organization, as expressed by the monovariate and bivariate moments results in an increase or a decrease, of the overall reaction rate, as well as in the appearance of a kinetic cooperativity. The degree of spatial organization of objects may be expressed quantitatively through the concept of minimal spanning tree. This concept may thus be applied to the quantification of the degree of order that may exist in the bidimensional distribution of enzyme molecules in a charged matrix. Primary walls of isolated plant cells in sterile culture behave as a polyanion and contain different enzymes. The spatial distribution in sycamore cell walls of an acid phosphatase has been studied through the concept of minimal spanning tree and shown to be non-randomly distributed in the polyanionic matrix, but clustered in that matrix. This spatial organization results in a modulation of the reaction rate of the cell-wall-bound phosphatase reaction. Both the theoretical and experimental results presented in this study leave little doubt as to the validity of the idea that in situ the organization of fixed charges and enzyme molecules modulate the overall dynamics of enzyme reactions.

A beta-fucosidase located in the latex serum of Lactuca sativa has been isolated and purified to homogeneity. This enzyme greatly differs from the other fucosidases already known in that it is strictly specific for the fucosyl residue and for the anomeric beta carbon. It is the first time that such an enzyme is shown to exist. The enzyme is a monomer and its molecular mass is close to 37 kDa. Its sedimentation constant is equal to 2.8 S. It is very stable at pH 5.5 in citrate/phosphate buffer but extensive denaturation occurs up to pH 7.5. Kinetic studies have shown that two ionization steps probably control the rate of the enzymatic hydrolysis. No precise information could be obtained about the possible in vivo role of this beta-fucosidase. However, the pure enzyme can release fucose from the cell walls obtained from hypocotyls of L. sativa. This result may be taken as evidence for the presence of beta-fucosidic links in these walls so that the enzyme could be involved in the differentiation of articulated laticifers.