Wildmeat consumption and child health in Amazonia.

Consuming wildmeat may protect against iron-deficiency anemia, a serious public health problem globally. Contributing to debates on the linkages between wildmeat and the health of forest-proximate people, we investigate whether wildmeat consumption is associated with hemoglobin concentration in rural and urban children (< 5 years old) in central Brazilian Amazonia. Because dietary practices mediate the potential nutritional benefits of wildmeat, we also examined whether its introduction into children's diets is influenced by rural/urban location or household socio-economic characteristics. Sampling 610 children, we found that wildmeat consumption is associated with higher hemoglobin concentration among the rural children most vulnerable to poverty, but not in the least vulnerable rural, or urban children. Rural caregivers share wildmeat with children earlier-in-life than urban caregivers, potentially because of cultural differences, lower access to domesticated meat, and higher wildmeat consumption by rural households (four times the urban average). If wildmeat becomes unavailable through stricter regulations or over-harvesting, we predict a ~ 10% increased prevalence of anemia among extremely poor rural children. This modest protective effect indicates that ensuring wildmeat access is, alone, insufficient to control anemia. Sustainable wildlife management could enhance the nutritional benefits of wildlife for vulnerable Amazonians, but reducing multidimensional poverty and improving access to quality healthcare are paramount.

Assessment of fetal lung maturity using analysis of amniotic fluid from ewes that gave birth prematurely and at term / Avaliação da maturidade pulmonar fetal utilizando a análise de líquido amniótico de ovelhas que deram à luz prematuramente e a termo

The aim of this study was to evaluate the lung maturity of premature and full-term lambs by analyzing amniotic fluid using the following methods: Clements test, Nile blue cytology test, hematoxylin-Shorr stain, lamellar body count, and radiographic tests. The use of these methods is intended to identify high-risk newborns and provide immediate clinical intervention after birth. Altogether, 56 animals (24 ewes and 32 lambs) were included in the study and divided into 3 groups. Group I consisted of 8 ewes that were at approximately 145 days of gestation; this group delivered 10 lambs naturally. Group II consisted of 8 ewes that were at 138 days' gestation; this group delivered 11 lambs by cesarean section. Group III consisted of 8 ewes at 138 days' gestation; this group was administered intramuscular dexamethasone (16mg/animal) 36 hours prior to a cesarean section. Group III delivered11 lambs. Cytological tests were performed using a microscope with a maximum magnification of 1000x, while the Clements test was visually observed by one of the researchers. Amnioticfluid lamellar body counts were measured using transmission electron microscopy. Among the staining methods, hematoxylin-Shorr was reliable, and Group III had a greater number of orangeophilic cells when compared to Group II, probably due to corticoid administration. The Clements test showed pulmonary maturity in approximately 20% of Group I lambs and Group II showed 9.1% of bubbles; however, Group III had the highest pulmonary maturity percentage (36.4%). The lamellar bodies were measured, and all groups had sizes between 0.019 and 0.590μm. Radiographic evaluation revealed that the majority of lambs presented some level of pulmonary radiodensity, indicating an acinar pattern at birth. These results are in line with the expectations of each group. We found that the normal group showed greater pulmonary maturity, whereas Group II presented pulmonary immaturity, which is expected because this group comprised lambs born prematurely and Group III showed pulmonary maturity almost comparable to the normal delivery group (Group I). This is due to the fact that although these animals are premature, the use of dexamethasone helped in pulmonary maturation. Therefore, these pulmonary maturity tests are considered effective when more than one technique is used and can be used routinely in the care of a pregnant ewe in labor, where a simple collection of amniotic fluid can predict a high-risk pregnancy and alert the veterinarian if the newborn needs intensive supportive treatment.(AU)

O objetivo deste estudo foi avaliar a maturidade pulmonar de cordeiros prematuros e a termo por meio da análise do líquido amniótico utilizando os seguintes métodos: teste de Clements, teste de citologia do azul do Nilo, coloração de hematoxilina-Shorr, contagem de corpos lamelares e testes radiográficos. Um desses métodos tem por objetivo identificar recém-nascidos de alto risco e fornecer intervenção clínica imediata após o nascimento. Ao todo, 56 animais (24 ovelhas e 32 cordeiros) foram incluídos no estudo e divididos em 3 grupos. O grupo I foi composto por 8 ovelhas com aproximadamente 145 dias de gestação; este grupo deu à luz 10 cordeiros naturalmente. O Grupo II foi composto por 8 ovelhas com 138 dias de gestação; este grupo deu à luz 11 cordeiros por cesariana. Grupo III consistiu de 8 ovelhas com 138 dias de gestação; este grupo recebeu dexametasona intramuscular (16 mg / animal) 36 horas antes de uma cesariana. O Grupo III entregou 11 cordeiros. Os testes citológicos foram realizados em microscópio com aumento máximo de 1000x, enquanto o teste de Clements foi observado visualmente por um dos pesquisadores. A contagem de corpos lamelares de líquido amniótico foi medida usando microscopia eletrônica de transmissão. Dentre os métodos de coloração, o hematoxilina-Shorr foi confiável, sendo que o Grupo III apresentou maior número de células orangeofílicas quando comparado ao grupo II, provavelmente devido à administração de corticóide. O teste de Clements mostrou maturidade pulmonar em aproximadamente 20% dos cordeiros do Grupo I e o Grupo II apresentou 9,1% de bolhas; entretanto, o Grupo III apresentou o maior percentual de maturidade pulmonar (36,4%). Os corpos lamelares foram medidos e todos os grupos apresentaram tamanhos entre 0,019 e 0,590μm. A avaliação radiográfica revelou que a maioria dos cordeiros apresentava algum grau de radiodensidade pulmonar, indicando padrão acinar ao nascimento. Esses resultados estão alinhados com as expectativas de cada grupo. Verificamos que o grupo normal apresentou maior maturidade pulmonar, enquanto o Grupo II apresentou imaturidade pulmonar, o que é esperado por se tratar de cordeiros nascidos prematuramente e o Grupo III apresentou maturidade pulmonar quase comparável ao grupo de parto normal (Grupo I). Isso se deve ao fato de que, embora esses animais sejam prematuros, o uso da dexametasona auxiliou na maturação pulmonar. Portanto, esses testes de maturidade pulmonar são considerados eficazes quando mais de uma técnica são utilizadas e podem ser usadas rotineiramente no cuidado de uma ovelha gestante em trabalho de parto, onde uma simples coleta de líquido amniótico pode prever uma gravidez de alto risco e alertar o veterinário se o recém-nascido precisa de tratamento de suporte intensivo.(AU)

Effect of polyoma viremia on 3-year allograft kidney function.

BACKGROUND: Polyoma viremia is associated with damage to renal tubular and urothelial cells. This may imply that a certain level of viremia, even cleared thereafter, could be associated with long-term renal dysfunction. METHODS: We, retrospectively, analyzed 390 first renal transplants adult recipients (≥18 years) who were monitored for BK viremia in the first 12 months and evaluated estimated GFR (MDRD-4 equation) at 1 month and at the last follow-up (959 ± 392 days). RESULTS: One hundred and ninety-nine patients (51%) developed at least one positive viremia: 105 (53%) low viremia (<104  copies/mL), 36 (18%) high viremia (4 × 104  > viremia ≥ 104  copies/mL) and 58 (15%) viremia (≥4 × 104  copies/mL) consistent with polyoma virus associated nephropathy (PyVAN). Out of these 58 patients, 24 (6%) developed bx-proven (SV40+) PyVAN and 34(8.7%) presumptive PyVAN (SV40-). Baseline characteristics, immunosuppression, KDRI, rejection episodes, etc., did not differ among groups but there were more deceased donors and ATG induction therapy in the high viremia group. At last follow-up, all patients in the low, high viremia and presumptive PyVAN (except 2) had cleared BK viremia. Bx-proven PyVAN led to 14 graft losses, 10 due to PyVAN. In the presumptive PyVAN there was only one graft loss registered as due to PyVAN. eGFR, at 1 month after KTx, did not differ among groups (51 ± 22 vs 48 ± 24 vs 45 ± 27 vs 43 ± 18 vs 46 ± 22 mL/min/1.73 m2 ), for no, low and high viremia as well for presumptive PyVAN and bx-proven PyVAN groups, respectively. At the last follow-up, eGFR did not differ between the no, low, and high viremia compared to baseline and to each other but was statistically lower in the presumptive and bx-proven PyVAN (38 ± 15 and 17 ± 7 mL/min/1.73 m2 ) either compared to baseline or to the other groups. CONCLUSIONS: This study shows that low and high levels of BK viremia do not lead to GFR changes although very high viremia levels, compatible with presumptive or bx-proven PyVAN, even if cleared thereafter, lead to allograft damage and decreased GFR.

Variable sources of Bk virus in renal allograft recipients.

BK virus is the causative agent of polyomavirus-associated nephropathy, a major cause of kidney transplant failure affecting 1%-10% of recipients. Previous studies that investigated the viral source on the kidney recipient pointed that the donor is implicated in the origin of human polyomavirus BK (BKPyV) infection in recipients, but giving the low genetic variability of BKPyV this subject is still controversial. The aim of this study was to determine if BKPyV replicating in kidney recipients after transplantation is always originated from the donor. Urine and blood samples from 68 pairs of living donors and kidney recipients who underwent renal transplantation from August 2010-September 2011 were screened for BKPyV by real time polymerase chain reaction. Only three recipients presented viremia. When both donors and recipients were BKPyV positive, a larger fragment of VP1 region was obtained and sequenced to determine the level of similarity between them. A phylogenetic tree was built for the 12 pairs of sequences obtained from urine and high level of similarity among all sequences was observed, indicating that homology inferences for donor and recipient viruses must be cautiously interpreted. However, a close inspection on the donor-recipient pairs sequences revealed that 3 of 12 pairs presented considerably different viruses and 4 of 12 presented mixed infection, indicating that the source of BKPyV infection is not exclusively derived from the donor. We report that about 60% of the renal recipients shed BKPyV genetically distinct from the donor, confronting the accepted concept that the donor is the main source of recipients' infection.

BK virus salivary shedding and viremia in renal transplant recipients.

OBJECTIVES: This study aimed to verify the presence of polyomavirus BK (BKPyV) in the saliva of kidney transplant recipients and to correlate it with blood viremia. MATERIAL AND METHODS: We have conducted a cross-sectional study with a sample involving 126 renal transplant recipients. 126 samples of saliva and 52 samples of blood were collected from these patients. Detection and quantification of BKPyV were performed using a real-time PCR. To compare the presence of BKPyV in blood and saliva, the binomial proportion test was used. To verify associations between salivary shedding BKPyV and post-transplant periods (in months), the Mann-Whitney test was used. Spearman's correlation was used to correlate the viral load in the saliva with blood of kidney transplant recipients. RESULTS: The mean age of the study group was 51.11±12.45 years old, and 69 participants (54.8%) were female, with a mean post-transplantation time of 4.80±6.04 months. BKPyV was quantified in several samples of saliva and blood, with medians of 1,108 cp/mL and 1,255 cp/mL, respectively. Only 16/52 (30.8%) participants presented BKPyV in blood, and 59/126 (46.8%) excreted the virus in saliva (p=0.004). BKPyV shedding was found in patients at a shorter post-transplantation period (3.86±5.25, p=0.100). A weak correlation was observed between viral quantification in saliva and blood (Spearman's correlation coefficient=0.193). CONCLUSION: The results of this study suggested that, although saliva excretes more BKPyV than blood, there is no reliable correlation between salivary shedding and blood viremia, showing two independent compartments of viral replication.

Determination of viremia cut-off for risk to develop BKPyV-associated nephropathy among kidney transplant recipients.

BACKGROUND: BK polyomavirus (BKPyV)-associated nephropathy (BKPyVAN) is a consequence of BKPyV replication in the urinary tract in kidney transplant recipients (KTR). OBJECTIVES: The objectives were to determine the prevalence of BKPyV replication and BKPyVAN, risk factors associated to sustained viremia and BKPyVAN, and viremia cut-off that best predict the occurrence of sustained viremia and nephropathy in KTR of a single University Hospital Kidney Transplant Center. PATIENTS AND METHODS: All KTR undergoing transplantation from August 2010 to December 2011 were enrolled and monitored up to 2 years posttransplantation for BKPyV viruria by decoy cells shedding or polymerase chain reaction (PCR) and viremia by PCR. Kidney biopsy was indicated if sustained viremia (two or more viremia above 10 000 copies/mL) to confirm BKPyVAN diagnosis. RESULTS: In this study, 326 transplants were performed and 246 patients were included. Prevalence of viruria was 36.9%, viremia 22.3% and nephropathy 3.2%. Male gender was the only risk factor associated to sustained viremia or nephropathy. Cut-off value of viremia that best discriminates the progression to sustained viremia and to BKPyVAN was 37 488 and 44 956 copies/mL, respectively. CONCLUSIONS: Prevalence of viruria, viremia, and nephropathy were similar to those reported in literature but the cut-off value of viremia that best discriminates the risk of progression to nephropathy was greater than the value usually reported, which is 10 000 copies/mL.

Cerebellar degeneration and progressive ataxia associated with HIV-virus infection.

INTRODUCTION: The spectrum of neurologic disorders associated with HIV infection is very broad, resulting from direct virus invasion, opportunistic infections, malignancies and toxic effects of drugs. METHODS: Among a large cohort of ataxia patients (N = 1050) evaluated between 2008 and 2017, we detected four patients with HIV-infection who developed a pure progressive cerebellar ataxia syndrome combined with cerebellar atrophy. RESULTS: Adverse drug effects, opportunistic infections and malignancies as well as immune-reconstitution syndrome were ruled out based on history and laboratory data. The exact pathophysiological mechanisms of ataxia in HIV patients is not very clear, but seems to be immune-mediated or a direct neurotoxic virus effect leading to apoptosis of Purkinje and granular cells. CONCLUSION: HIV infection should be investigated in adult patients with undetermined sporadic progressive pure ataxia with cerebellar atrophy.

Matrixlysis, an improved sample preparation method for recovery of Mycobacteria from animal tissue material.

Mycobacterium caprae, a member of the Mycobacterium tuberculosis complex, is the main causative agent of bovine tuberculosis in alpine regions. Bacterial culture is the gold standard in bovine tuberculosis diagnostic but takes up to twelve weeks. This increases the time and costs for stocks affected with bovine tuberculosis. Hence this study focused on the implementation of a fast and precise mycobacterial detection method and compared it with currently used methods. Matrix lysis is a chemical lysis using high concentrations of urea to solubilize bovine and red deer tissue and was used to detect even smallest amounts or non-visible lesions of mycobacteria. A total of 64 samples collected from 44 animals (37 red deer and 7 cattle) were tested by Matrix lysis. Forty-three of these samples were used for Mycobacterium tuberculosis complex detection by quantitative PCR and other 21 for subtyping the genetically different variants of M. caprae. Furthermore, three Matrix lysis samples were used for Next Generation Sequencing. Our results confirm that Matrix lysis is a fast and precise method for detecting Mycobacterium tuberculosis complex in native tissue samples. However, at the moment it reaches its limits when the samples were analyzed by Next Generation Sequencing and RD4 subtyping.

Polyomavirus detection in multiple sclerosis patients under natalizumab therapy: Profile and frequency of urinary shedding

Patients undergoing Natalizumab (NTZ) therapy are at risk of progressive multifocal leukoencephalopathy (PML). Besides John Cunningham virus (JCV), BK polyomavirus might represent an additional concern for such patients since it can also infect CNS cells. Currently, data regarding the presence of anti-JCV antibodies added to previous immunosuppressive therapy and prolonged NTZ therapy has been used to classify patients at risk of developing PML. Here, we investigated the profile shedding of JCV and BKV in multiple sclerosis (MS) patients during treatment with NTZ. Serial blood and urine samples from 97 MS patients receiving either NTZ or ß-interferon were investigated for polyomavirus shedding. While all blood samples tested negative, 36% of the patients shed polyomavirus in the urine in at least one time point. From these, 21.7%, 9.3%, and 5.1% shed JCV, BKV, and both polyomavirus, respectively. No difference was observed between the rates of urinary shedding of patients treated with NTZ (38.9%) and patients treated with other drugs (34.5%), also no PML event was diagnosed during the follow-up. Therefore, urinary shedding might not be interfered by therapy condition. In our study, we also observed 14/27 (52%) of anti-JCV antibodies prevalence, and nearly half of them (42%) did not present any event of urinary shedding during the follow-up

Polyomavirus BK and JC in individuals with chronic kidney failure, kidney transplantation, and healthy controls.

BACKGROUND: New clinical approaches to diagnose and monitor individuals with systemic diseases have been employed through the use of oral fluids. Polyomavirus BK (BKPyV) and JC (JCPyV) infect asymptomatically around 80% of general population worldwide remaining latent in the body. In case of immunosuppression, a replication can occur, leading to diseases. OBJECTIVE: The aim of this study was to detect and quantify BKPyV and JCPyV in oral fluids of individuals with chronic kidney failure (CKF), kidney transplantation (KT) and controls compared with their detection in blood and urine, traditionally used for this test. STUDY DESIGN: Forty six subjects were included and distributed into 3 groups: 14 with CKF (Group 1), 12 with KT (Group 2) and 20 healthy individuals (Group 3). In a total, 315 samples were collected and analyzed through RT-PCR, being 151 of gingival crevicular fluid, 46 of saliva, 46 of mouthwash, 43 of blood and 29 of urine. RESULTS: All subjects from group 1 were positive for BKPyV in at least one collected samples and 14% were positive for JCPyV. In Group 2, 91.7% were positive for BKPyV and 51.7% for JCPyV. Among subjects of Group 3, 80% were positive for BKPyV and 45% for JCPyV. CONCLUSIONS: Oral fluids exhibited high prevalence of BKPyV and JCPyV and were equally efficient compared to urine and blood. The use of oral fluids to detect these polyomaviruses enhances positivity in screening, even in cases of absence of viremia and especially in individuals who are not able to urinate.

The effects of increased heme oxygenase-1 on the lymphoproliferative response in dogs with visceral leishmaniasis.

Canine visceral leishmaniasis (CVL) is known to affect the cellular immunity of infected dogs, through impairing lymphoproliferation and microbicidal mechanisms. This study examined heme oxygenase-1 (HO-1) and its metabolites, oxidative stress and IL-10 levels in CVL and investigated correlations between these parameters. Additionally, the effects of HO-1 inhibition on the lymphoproliferative response and cytokine production in lymph node cells (LNCs) from infected dogs were evaluated. Forty-four dogs, 24 controls and 20 dogs with CVL were selected. Plasma and splenic levels of HO-1, haptoglobin, soluble CD163 receptor, ferritin and IL-10 were determined using capture ELISA. The HO-1 levels and relative gene expression in peripheral blood and bone marrow mononuclear cells were also determined. LNCs proliferation was evaluated with an HO-1 activator and with an HO-1 inhibitor, in the presence of the Leishmania infantum soluble antigen (SAgL), using flow cytometry. HO-1, IL-2, IFN-gamma and IL-10 were also determined in these cultures using capture ELISA. Infected dogs presented oxidative stress and increased HO-1 levels and relative gene expression, with correlation between oxidative stress and HO-1. The substances from heme metabolism and IL-10 were also elevated in the plasma and spleens of infected dogs. IL-10 and HO-1 levels were positively correlated with one another. Inhibition of HO-1 increased LNCs proliferation and decreased IL-10 and IL-2 production in the presence of SAgL. The increased HO-1 metabolism observed in CVL is probably associated with oxidative stress and increased IL-10, which could be one of the mechanisms responsible for inhibition of the lymphoproliferative response in sick dogs.

Polyomavirus detection in multiple sclerosis patients under natalizumab therapy: Profile and frequency of urinary shedding.

Patients undergoing Natalizumab (NTZ) therapy are at risk of progressive multifocal leukoencephalopathy (PML). Besides John Cunningham virus (JCV), BK polyomavirus might represent an additional concern for such patients since it can also infect CNS cells. Currently, data regarding the presence of anti-JCV antibodies added to previous immunosuppressive therapy and prolonged NTZ therapy has been used to classify patients at risk of developing PML. Here, we investigated the profile shedding of JCV and BKV in multiple sclerosis (MS) patients during treatment with NTZ. Serial blood and urine samples from 97 MS patients receiving either NTZ or ß-interferon were investigated for polyomavirus shedding. While all blood samples tested negative, 36% of the patients shed polyomavirus in the urine in at least one time point. From these, 21.7%, 9.3%, and 5.1% shed JCV, BKV, and both polyomavirus, respectively. No difference was observed between the rates of urinary shedding of patients treated with NTZ (38.9%) and patients treated with other drugs (34.5%), also no PML event was diagnosed during the follow-up. Therefore, urinary shedding might not be interfered by therapy condition. In our study, we also observed 14/27 (52%) of anti-JCV antibodies prevalence, and nearly half of them (42%) did not present any event of urinary shedding during the follow-up. J. Med. Virol. 89:528-534, 2017. © 2016 Wiley Periodicals, Inc.

Occurrence, genotypic characterization, and patterns of shedding of human polyomavirus JCPyV and BKPyV in urine samples of healthy individuals in São Paulo, Brazil.

The objective of this study was to evaluate the prevalence, genotypic characterization, and determination of the patterns of shedding of human polyomavirus JC (JCPyV) and BK (BKPyV) in consecutive urine samples collected from healthy adults. Urine samples collected monthly over a 6 month period were screened by polymerase chain reaction (PCR) with two sets of primers complementary to the VP1 protein region specific for the JCPyV or BKPyV genome. The viral load of JCPyV and BKPyV in positive samples was determined by quantitative real time PCR. Seventy-one healthy individuals (ages between 18 and 65) were included in the study. Polyomavirus DNA urinary shedding was identified in 44 (62%) of the 71 individuals evaluated: BKPyV only in 16 (22.5%); JCPyV only in 19 (26.7%); and both in 9 (12.7%). Among the 28 individuals shedding JCPyV, the shedding was nearly continuous in 13 (46.4%) and sporadic in 15 (53.6%), whereas all BKPyV shedding was sporadic. A total of 45 (19 BKPyV and 26 JCPyV) strains were identified. Of the BKPyV strains, individuals were observed that excreted all genotypes except genotype 3 and the JCPyV strains, excretion of 5 different genotypes. Evaluating the age of individuals who excrete JCPyV and BKPyV, mostly are young adults, with a slight increase with increasing age and observing the viral load can not draw any parallel between the increase or decrease of age or excreted genotype as there was a wide variation both in the excretion of BKPyV and JCPyV. The high occurrence of isolated or simultaneous urinary shedding of JCPyV and BKPyV in healthy individuals merits further study.

Infecciones respiratorias agudas bajas y mortalidad posneonatal / Acute lower respiratory infections and post-neonatal mortality

La mortalidad por infecciones respiratorias agudas bajas (IRAB) en Argentina, constituye la tercera causa de muerte en menores de un año y es la primera causa si tomamos la mortalidad posneonatal. En este contexto, desde el año 2002, debido al lanzamiento del Programa Nacional IRAB, se lleva a cabo en el hospital en el período de Contingencia (1 de junio al 31 de agosto de cada año) el Centro de Prehospitalizacion,con el fin estratégico de disminuir la morbimortalidad de pacientes con enfermedad respiratoria aguda baja menores de 2 años. Durante 2012 realizamos un estudio descriptivo poblacional de cortetransversal, en el que se analizó el manejo de la Contingencia IRAB en el Hospital Luisa Cravenna de Gandulfo, contemplando la participación de todos los servicios involucrados. Entre los objetivos específicos se encuentran: obtener indicadores de morbimortalidad por IRAB y realizar contrarreferencia de pacientes IRAB atendidos en nuestro centro. Para la realización de este estudio se tuvieron en cuenta todos los niños menores de 2 años atendidos en nuestro hospital por IRAB. En el transcurso de la Contingencia,se atendió un 35% más de pacientes que en 2011, a expensas de esfuerzos propios y regionales.

Mortality for acute lower respiratory infections (ALRI) in Argentina is the third cause of death in infants less than one year old, and the first if we consider post-neonatal mortality. Against this backdrop, with the launch of the National ALRI Program, since 2002 the Pre-hospitalization Centre has been operat-ing in our hospital during the contingency period (July 1 to August 31 of each year), with the strategic aim of reducing the morbidity and mortality of infants aged less than two years old with acute lower respiratory pathology. In 2012, we carried out a cross-sectional, descriptive population study to analyze the way ALRI contingency was handled in the Luisa Cravenna de Gandulfo Hospital, considering the participation of all the medical services involved. The specific objectives included obtaining indicators of morbidity and mortality for ALRI and performing counter-references on ALRI patients treated in our health centre. In order to perform our study we included all infants aged less than two years old who were treated in our hospital for ALRI. During the contingency, due to self and regional efforts, we treated 35% more patients than in 2011.

Placebo-induced somatic sensations: a multi-modal study of three different placebo interventions.

Somatic sensations induced by placebos are a frequent phenomenon whose etiology and clinical relevance remains unknown. In this study, we have evaluated the quantitative, qualitative, spatial, and temporal characteristics of placebo-induced somatic sensations in response to three different placebo interventions: (1) placebo irritant solution, (2) placebo laser stimulation, and (3) imagined laser stimulation. The quality and intensity of evoked sensations were assessed using the McGill pain questionnaire and visual analogue scales (VAS), while subjects' sensation drawings processed by a geographic information system (GIS) were used to measure their spatial characteristics. We found that all three interventions are capable of producing robust sensations most frequently described as "tingling" and "warm" that can reach consider-able spatial extent (≤ 205 mm²) and intensity (≤ 80/100 VAS). Sensations from placebo stimulation were often referred to areas remote from the stimulation site and exhibit considerable similarity with referred pain. Interestingly, there was considerable similarity of qualitative features as well as spatial patterns across subjects and placebos. However, placebo laser stimulation elicited significantly stronger and more widespread sensations than placebo irritant solution. Finally, novelty seeking, a character trait assessed by the Temperament and Character Inventory and associated with basal dopaminergic activity, was less pronounced in subjects susceptible to report placebo-induced sensations. Our study has shown that placebo-induced sensations are frequent and can reach considerable intensity and extent. As multiple somatosensory subsystems are involved despite the lack of peripheral stimulus, we propose a central etiology for this phenomenon.

Red deer as maintenance host for bovine tuberculosis, Alpine region.

To estimate the prevalence of bovine tuberculosis in the Alpine region, we studied the epidemiology of Mycobacterium caprae in wildlife during the 2009-2012 hunting seasons. Free-ranging red deer (Cervus elaphus) were a maintenance host in a hot-spot area, mainly located in Austria.

Natalizumab treatment for multiple sclerosis: updates and considerations for safer treatment in JCV positive patients.

Natalizumab is currently one of the best options for treatment of patients with Multiple Sclerosis who have failed traditional prior therapies. However, prolonged use, prior immunosuppressive therapy and anti-JCV antibody status have been associated with increased risk of developing progressive multifocal leukoencephalopathy (PML). The evaluation of these conditions has been used to estimate risks of PML in these patients, and distinct (sometimes extreme) approaches are used to avoid the PML onset. At this time, the biggest issue facing the use of Natalizumab is how to get a balance between the risks and the benefits of the treatment. Hence, strategies for monitor JCV-positive patients undergoing Natalizumab treatment are deeply necessary. To illustrate it, we monitored JCV/DNA in blood and urine of a patient receiving Natalizumab for 12 months. We also bring to discussion the effectiveness of the current methods used for risk evaluation, and the real implications of viral reactivation.

Natalizumab treatment for multiple sclerosis: updates and considerations for safer treatment in JCV positive patients / Tratamento com Natalizumabe para esclerose múltipla: atualizações e considerações para um tratamento mais seguro em pacientes positivos para o VJC

Natalizumab is currently one of the best options for treatment of patients with Multiple Sclerosis who have failed traditional prior therapies. However, prolonged use, prior immunosuppressive therapy and anti-JCV antibody status have been associated with increased risk of developing progressive multifocal leukoencephalopathy (PML). The evaluation of these conditions has been used to estimate risks of PML in these patients, and distinct (sometimes extreme) approaches are used to avoid the PML onset. At this time, the biggest issue facing the use of Natalizumab is how to get a balance between the risks and the benefits of the treatment. Hence, strategies for monitor JCV-positive patients undergoing Natalizumab treatment are deeply necessary. To illustrate it, we monitored JCV/DNA in blood and urine of a patient receiving Natalizumab for 12 months. We also bring to discussion the effectiveness of the current methods used for risk evaluation, and the real implications of viral reactivation.

Natalizumabe é atualmente uma das melhores opções para o tratamento de pacientes com Esclerose Múltipla que não respondem aos tratamentos tradicionais. No entanto, o seu uso prolongado, o uso de terapia imunossupressora prévia e o status sorológico antivírus JC têm sido associados com o risco aumentado de desenvolvimento de Leucoencefalopatia Multifocal Progressiva (LEMP). A avaliação destas condições tem sido utilizada para estimar os riscos do desenvolvimento de LEMP nestes pacientes, e abordagens distintas (por vezes extremas) são empregadas para evitar o aparecimento dessa patologia. Atualmente, o grande desafio está em obter um equilíbrio entre os riscos e os benefícios do tratamento com Natalizumabe. Assim, é crucial desenvolver estratégias para monitorar pacientes portadores do vírus JC sob tratamento com Natalizumabe. A título de ilustração, pesquisamos o vírus no sangue e na urina de um paciente sob tratamento durante 12 meses. Também discutimos a eficácia dos métodos atualmente utilizados para avaliação de riscos e as implicações reais de reativação viral.

Multiple sclerosis and herpesvirus interaction.

Multiple sclerosis is the most common autoimmune inflammatory demyelinating disease of the central nervous system, and its etiology is believed to have both genetic and environmental components. Several viruses have already been implicated as triggers and there are several studies that implicate members of the Herpesviridae family in the pathogenesis of MS. The most important characteristic of these viruses is that they have periods of latency and exacerbations within their biological sanctuary, the central nervous system. The Epstein-Barr, cytomegalovirus, human herpesvirus 6 and human herpesvirus 7 viruses are the members that are most studied as being possible triggers of multiple sclerosis. According to evidence in the literature, the herpesvirus family is strongly involved in the pathogenesis of this disease, but it is unlikely that they are the only component responsible for its development. There are probably multiple triggers and more studies are necessary to investigate and define these interactions.