Granada Virus: a Natural Phlebovirus Reassortant of the Sandfly Fever Naples Serocomplex with Low Seroprevalence in Humans

A new member of the phlebovirus genus, tentatively named Granada virus, was detected in sandflies collected in Spain. By showing the presence of specific neutralizing antibodies in human serum collected in Granada, we show that Granada virus infects humans. The analysis of the complete genome of Granada virus revealed that this agent is likely to be a natural reassortant of the recently described Massilia virus (donor of the long and short segments) with ayet unidentified phlebovirus (donor of the medium segment)

Electroencephalogram changes during inhalation with nitric oxide in the pediatric intensive care patient--a preliminary report.

OBJECTIVES: Although endogenous nitric oxide (NO) is an excitatory mediator in the central nervous system, inhaled NO is not considered to cause neurologic side effects because of its short half-life. This study was motivated by a recent case report about neurologic symptoms and our own observation of severe electroencephalogram (EEG) abnormalities during NO inhalation. DESIGN: Blind, retrospective analyses of EEGs which were registered before, during, and after NO inhalation. EEG was classified in a 5-point rating system by an independent electroencephalographer who was blinded to the patients' clinical histories. Comparisons were made with the previous evaluation documented at recording. Other EEG-influencing parameters such as oxygen saturation, hemodynamics, electrolytes, and pH were evaluated. SETTING: Pediatric intensive care unit of a tertiary care university children's hospital. PATIENTS: Eleven ventilated, long-term paralyzed, sedated children (1 mo to 14 yrs) who had EEG or clinical assessment before NO treatment and EEG during NO inhalation. They were divided into two groups according to the NO-indication (e.g., congenital heart defect, acute respiratory distress syndrome). MEASUREMENTS AND MAIN RESULTS: All 11 patients had an abnormal EEG during NO inhalation. EEG-controls without NO showed remarkable improvement. EEG abnormalities were background slowing, low voltage, suppression burst (n = 2), and sharp waves (n = 2) independent of patients' age, NO-indication, and other EEG-influencing parameters. CONCLUSIONS: These preliminary data suggest the occurrence of EEG-abnormalities after application of inhaled NO in critically ill children. We found no correlation with other potential EEG-influencing parameters, although clinical state, medication, or hypoxemia might contribute. Comprehensive, prospective, clinical assessment regarding a causal relationship between NO-inhalation and EEG-abnormalities and their clinical importance is needed.

Association of Lutzomyia longipalpis (Diptera: Psychodidae) population density with climate variables in Montes Claros, an area of American visceral leishmaniasis transmission in the state of Minas Gerais, Brazil

In the present paper, we evaluate the relationship between climate variables and population density of Lutzomyia longipalpis in Montes Claros, an area of active transmission of American visceral leishmaniasis (AVL) in Brazil. Entomological captures were performed in 10 selected districts of the city, between September 2002-August 2003. A total of 773 specimens of L. longipalpiswere captured in the period and the population density could be associated with local climate variables (cumulative rainfall, average temperature and relative humidity) through a mathematical linear model with a determination coefficient (Rsqr) of 0.752. Although based on an oversimplified statistical analysis, as far as the vector is concerned, this approach showed to be potentially useful as a starting point to guide control measures for AVL in Montes Claros.

Potential contribution of 131I-labelled monoclonal anti-CEA antibodies in the treatment of liver metastases from colorectal carcinomas: pretherapeutic study with dose recovery in resected tissues.

20 patients with liver metastases from colorectal carcinoma undergoing laparotomy received 15-60 mg intravenously, either intact or fragments of, anti-carcinoembryonic antigen (anti-CEA) monoclonal antibodies labelled with 0.55-1.48 GBq (15-40 mCi) of 131I, 3-8 days prior to operation. The uptake measured per gram of metastases ranged from 0.33 to 6.6 x 10(-3%) of injected dose. Tumour to liver uptake ratios ranged from 2 to 33. The radiation dose, estimated in 6 patients (3 of each group), for an extrapolated dose of 3.7 GBq (100 mCi) of 131I ranged from 0.3 to 0.8 Gy in normal liver or spleen (an acceptable estimate for bone marrow radiation dose) and from 3.4 to 8.2 Gy to the hepatic metastases, indicating that probably other therapeutic modalities should be associated with radioimmunotherapy.

Factors related to transmission of and infection with Schistosoma mansoni in a village in the South-eastern Region of Brazil

In this transversal study, factors related to infection with and transmission of Schistosoma mansoni were explored. Based on stool examinations of two Kato-Katz smears of a single sample, the prevalences of schistosomiasis and geohelminths were established. In a multivariable analysis, sets of demographic, socio-economic and water contact pattern variables were tested for strength of relation with infection. Males presented a 3.39-times higher risk for infection than females. The age groups between 10-19 years and 20-30 years showed risks of infection 7.1- and 7.5-times higher, respectively, than the control age group between 0-10 years. Individuals practicing leisure activities had a 1.96-times higher risk than those without these activities. The malacological survey identified snails of the species Biomphalaria glabrata, Biomphalaria straminea and Biomphalaria tenagophila. Two exemplars of B. glabrata (0.53%) proved positive for S. mansoni. The socio-economic improvements observed in the locality suggest a protective and preventive effect towards infection with schistosomiasis, which requires further investigation with a longitudinal and more detailed study design. Considering our findings, a proposal for an integrated control program should be based on two pillars: one horizontal, which involves social empowerment and health education, and another more vertical, which delivers treatment and infrastructure improvements.

A nutritional intervention study with hydrolyzed collagen in pre-pubertal Spanish children: influence on bone modeling biomarkers

Aim: The aim of the study was to investigate the influence of dietary intake of commercial hydrolyzed collagen (Gelatine Royal ®) on bone remodeling in pre-pubertal children. Methods: A randomized double-blind study was carried out in 60 children (9.42 ± 1.31 years) divided into three groups according to the amount of partially hydrolyzed collagen taken daily for 4 months: placebo (G-I, n = 18), collagen (G-II, n = 20) and collagen + calcium (G-III, n = 22) groups. Analyses of the following biochemical markers were carried out: total and bone alkaline phosphatase (tALP and bALP), osteocalcin, tartrate-resistant acid phosphatase (TRAP), type I collagen carboxy terminal telopeptide, lipids, calcium, 25-hydroxyvitamin D, insulin-like growth factor 1 (IGF-1), thyroid-stimulating hormone, free thyroxin and intact parathormone. Results: There was a significantly greater increase in serum IGF-1 in G-III than in G II (p < 0.01) or G-I (p < 0.05) during the study period, and a significantly greater increase in plasma tALP in G-III than in G-I (p < 0.05). Serum bALP behavior significantly (p < 0.05) differed between G-II (increase) and G-I (decrease). Plasma TRAP behavior significantly differed between G-II and G-I (p < 0.01) and between G-III and G-II (p < 0.05). Conclusion: Daily dietary intake of hydrolyzed collagen seems to have a potential role in enhancing bone remodeling at key stages of growth and development.

Long-term efficacy and tolerability of flutamide combined with oral contraception in moderate to severe hirsutism: A 12-month, double-blind, parallel clinical trial

OBJECTIVE Our objective was to test the efficacy and tolerability of three doses of flutamide (125, 250, and 375 mg) combined with a triphasic oral contraceptive (ethynylestradiol/levonorgestrel) during 12 months to treat moderate to severe hirsutism in patients with polycystic ovary syndrome or idiopathic hirsutism. DESIGN We conducted a randomized, double-blind, placebo-controlled, parallel clinical trial. PATIENTS A total of 131 premenopausal women, suffering from moderate to severe hirsutism, were randomized to placebo or 125, 250, or 375 mg flutamide daily associated with a triphasic oral contraceptive pill. Hirsutism (Ferriman-Gallwey), acne and seborrhea (Cremoncini), and hormone serum levels were monitored at baseline and at 3 (except hormone serum levels), 6, and 12 months. Side effects and biochemical, hematological, and hepatic parameters were assessed. METHODS We used three-way ANOVA (subject, dose, and visit) with Scheffé adjustment for multiple comparisons or nonparametrical Friedman test and least-squares mean (paired data) and Kruskall-Wallis test for unpaired data analyses. We used chi(2) or Fisher's test for categorical data. RESULTS A total of 119 patients were included in the intention-to-treat analysis. All flutamide doses induced a significant decrease in hirsutism, acne, and seborrhea scores after 12 months compared with placebo without differences among dose levels. Similar related side effects were observed with placebo and 125 mg flutamide (12.5%), and slightly higher with 250 mg (17.3%) and 375 mg (21.2%). No statistically significant differences were observed either among doses or compared with placebo. CONCLUSIONS Flutamide at 125 mg daily during 12 months was the minimum effective dose to diminish hirsutism in patients with polycystic ovary syndrome or with idiopathic hirsutism.

Compositional evolution with mass transfer in closed systems

Evolution of compositions in time, space, temperature or other covariates is frequentin practice. For instance, the radioactive decomposition of a sample changes its composition with time. Some of the involved isotopes decompose into other isotopes of thesample, thus producing a transfer of mass from some components to other ones, butpreserving the total mass present in the system. This evolution is traditionally modelledas a system of ordinary di erential equations of the mass of each component. However,this kind of evolution can be decomposed into a compositional change, expressed interms of simplicial derivatives, and a mass evolution (constant in this example). A rst result is that the simplicial system of di erential equations is non-linear, despiteof some subcompositions behaving linearly.The goal is to study the characteristics of such simplicial systems of di erential equa-tions such as linearity and stability. This is performed extracting the compositional differential equations from the mass equations. Then, simplicial derivatives are expressedin coordinates of the simplex, thus reducing the problem to the standard theory ofsystems of di erential equations, including stability. The characterisation of stabilityof these non-linear systems relays on the linearisation of the system of di erential equations at the stationary point, if any. The eigenvelues of the linearised matrix and theassociated behaviour of the orbits are the main tools. For a three component system,these orbits can be plotted both in coordinates of the simplex or in a ternary diagram.A characterisation of processes with transfer of mass in closed systems in terms of stability is thus concluded. Two examples are presented for illustration, one of them is aradioactive decay

Detection of human bocavirus and human metapneumovirus by real-time PCR from patients with respiratory symptoms in Southern Brazil

The introduction of newer molecular methods has led to the discovery of new respiratory viruses, such as human metapneumovirus (hMPV) and human bocavirus (hBoV), in respiratory tract specimens. We have studied the occurrence of hMPV and hBoV in the Porto Alegre (PA) metropolitan area, one of the southernmost cities of Brazil, evaluating children with suspected lower respiratory tract infection from May 2007-June 2008. A real-time polymerase chain reaction method was used for amplification and detection of hMPV and hBoV and to evaluate coinfections with respiratory syncytial virus (RSV), influenza A and B, parainfluenza 1, 2 and 3, human rhinovirus and human adenovirus. Of the 455 nasopharyngeal aspirates tested, hMPV was detected in 14.5% of samples and hBoV in 13.2%. A unique causative viral agent was identified in 46.2% samples and the coinfection rate was 43.7%. For hBoV, 98.3% of all positive samples were from patients with mixed infections. Similarly, 84.8% of all hMPV-positive results were also observed in mixed infections. Both hBoV and hMPV usually appeared with RSV. In summary, this is the first confirmation that hMPV and hBoV circulate in PA; this provides evidence of frequent involvement of both viruses in children with clinical signs of acute viral respiratory tract infection, although they mainly appeared as coinfection agents.

Hippocampal sparing whole brain radiotherapy and simultaneously integrated boost with helical tomotherapy in patients with brain metastases

Materials/Methods: Four patients who underwent whole-brain radiotherapy (WBRT) and simultaneous integrated boost (SIB) between August 2010 and February 2011 were included to this study. Their age were 60, 61, 65, and 70 years. Primary diagnosis was infiltrative ductal breast cancer in two patients, sigmoid adenocarcinoma in one, and transitional bladder cancer in the other patient. All patients underwent cranial surgery but not all of the metastases were operated in 2 patients. All but one (five metastases) patient presented with single brain metastasis. In 2 of the 4 patients, hippocampus was spared contralaterally due to vicinity of the lesions to unilateral hippocampus. Planning irradiation dose was 30 Gy in 10 fractions for WBRT and 40 Gy in 10 fractions for SIB over two weeks in three patients. In one patient, WBRT and boost doses were 36Gy and 50.4 Gy in 18 fractions. Our maximum dose constraints for hippocampus and eyes were 10 and 20 Gy, respectively. All organs were contoured manually. Hippocampi were contoured according to published guidelines, and 5-mm margin expansion was used for hippocampal avoidance volume. All plans utilized a field width of 2.5 cm. Modulation factors ranged between 2 and 3.5. A pitch of 0,287 was used for all patients. All plans were evaluated according to conformity index (CI), homogeneity index (HI), target coverage (TC), and mean normalized total dose (NTDmean). An alpha/beta ratio of 2 was assumed for the hippocampus.Results: Median planning target volume (PTV) for metastases was 17.47 cc.Median hippocampal avoidance volume was 14.73 cc (range, 9.25-16.18 cc). Median average hippocampaldose was 11.84 Gy (range, 10.14-21.01 Gy). PTVs were fully covered with more than 95% of the prescribed dose for all patients. With a median follow-up time of 6 months (range, 3-9 months), all patients were alive without recurrent intracranial disease. To date, no neurocognitive decline reported in any of the patients.Conclusions: Preclinical evidence suggests that hippocampal sparing during cranial irradiation may mitigate neurocognitive decline. Using HT, we significantly reduced the mean dose to the hippocampus without jeopardizing coverage of metastases and whole brain.

Admissions of patients with alcohol intoxication in the Emergency Department: a growing phenomenon.

QUESTION UNDER STUDY: To investigate the change over time in the number of ED admissions with positive blood alcohol concentration (BAC) and to evaluate predictors of BAC level. METHODS: We conducted a single site retrospective study at the ED of a tertiary referral hospital (western part of Switzerland) and obtained all the BAC performed from 2002 to 2011. We determined the proportion of ED admissions with positive BAC (number of positive BAC/number of admissions). Regression models assessed trends in the proportion of admissions with positive BAC and the predictors of BAC level among patients with positive BAC. RESULTS: A total of 319,489 admissions were recorded and 20,021 BAC tests were performed, of which 14,359 were positive, divided 34.5% female and 65.5% male. The mean (SD) age was 41.7(16.8), and the mean BAC was 2.12(1.04) permille (g of ethanol/liter of blood). An increase in the number of positive BAC was observed, from 756 in 2002 to 1,819 in 2011. The total number of admissions also increased but less: 1.2 versus 2.4 times more admissions with positive BAC. Being male was independently associated with a higher (+0.19 permille) BAC, as was each passing year (+0.03). A significant quadratic association with age indicated a maximum BAC at age 53. CONCLUSION: We observed an increase in the percentage of admissions with positive BAC that was not limited to younger individuals. Given the potential consequences of alcohol intoxication, and the large burden imposed on ED teams, communities should be encouraged to take measures aimed at reducing alcohol intoxication.

Phase II study of temozolomide in combination with topotecan (TOTEM) in relapsed or refractory neuroblastoma: A European Innovative Therapies for Children with Cancer-SIOP-European Neuroblastoma study.

PURPOSE: To assess objective response rate (ORR) after two cycles of temozolomide in combination with topotecan (TOTEM) in children with refractory or relapsed neuroblastoma. PATIENTS AND METHODS: This multicenter, non-randomised, phase II study included children with neuroblastoma according to a two-stage Simon design. Eligibility criteria included relapsed or refractory, measurable or metaiodobenzylguanidine (mIBG) evaluable disease, no more than two lines of prior treatment. Temozolomide was administered orally at 150mg/m(2) followed by topotecan at 0.75mg/m(2) intravenously for five consecutive days every 28days. Tumour response was assessed every two cycles according to International Neuroblastoma Response Criteria (INRC), and reviewed independently. RESULTS: Thirty-eight patients were enroled and treated in 15 European centres with a median age of 5.4years. Partial tumour response after two cycles was observed in 7 out of 38 evaluable patients [ORR 18%, 95% confidence interval (CI) 8-34%]. The best ORR whatever the time of evaluation was 24% (95% CI, 11-40%) with a median response duration of 8.5months. Tumour control rate (complete response (CR)+partial response (PR)+mixed response (MR)+stable disease (SD)) was 68% (95% CI, 63-90%). The 12-months Progression-Free and Overall Survival were 42% and 58% respectively. Among 213 treatment cycles (median 4, range 1-12 per patient) the most common treatment-related toxicities were haematologic. Grade 3/4 neutropenia occurred in 62% of courses in 89% of patients, grade 3/4 thrombocytopenia in 47% of courses in 71% of patients; three patients (8%) had febrile neutropenia. CONCLUSION: Temozolomide-Topotecan combination results in very encouraging ORR and tumour control in children with heavily pretreated recurrent and refractory neuroblastoma with favourable toxicity profile.

Adherence to interferon β-1b treatment in patients with multiple sclerosis in Spain

BACKGROUND Adherence to interferon β-1b (INFβ-1b) therapy is essential to maximize the beneficial effects of treatment in multiple sclerosis (MS). For that reason, the main objectives of this study are to assess adherence to INFβ-1b in patients suffering from MS in Spain, and to identify the factors responsible for adherence in routine clinical practice. METHODOLOGY/PRINCIPAL FINDINGS This was an observational, retrospective, cross-sectional study including 120 Spanish patients with MS under INFβ-1b treatment. Therapeutic adherence was assessed with Morisky-Green test and with the percentage of doses received. The proportion of adherent patients assessed by Morisky-Green test was 68.3%, being indicative of poor adherence. Nevertheless, the percentage of doses received, which was based on the number of injected medication, was 94.3%. The main reason for missing INFβ-1b injections was forgetting some of the administrations (64%). Therefore, interventions that diminish forgetfulness might have a positive effect in the proportion of adherent patients and in the percentage of doses received. In addition, age and comorbidities had a significant effect in the number of doses injected per month, and should be considered in the management of adherence in MS patients. CONCLUSION/SIGNIFICANCE Among all the available methods for assessing adherence, the overall consumption of the intended dose has to be considered when addressing adherence.

Probing the interactions of NK cell receptors with ligand expressed in trans and cis.

Certain receptors on natural killer (NK) cells, which are specific for MHC class I (MHC-I) molecules, do not only interact with ligand expressed on opposing cell membranes (in trans) but also interact with those on the same cell membrane (in cis). Cis interactions have been demonstrated for only a small number of cell surface receptors. However, this has not been tested systematically, raising the possibility that additional receptors may be able to bind ligand expressed in cis. Here we describe a number of approaches to evaluate trans and cis binding of the Ly49A NK cell receptor to its H-2D(d) ligand. These procedures should facilitate the investigation of cis/trans interactions of other receptor-ligand pairs and simplify the analysis of NK cell receptor variants.

Habitat suitability of Anopheles vector species and association with human malaria in the Atlantic Forest in south-eastern Brazil

Every year, autochthonous cases of Plasmodium vivax malaria occur in low-endemicity areas of Vale do Ribeira in the south-eastern part of the Atlantic Forest, state of São Paulo, where Anopheles cruzii and Anopheles bellator are considered the primary vectors. However, other species in the subgenus Nyssorhynchus of Anopheles (e.g., Anopheles marajoara) are abundant and may participate in the dynamics of malarial transmission in that region. The objectives of the present study were to assess the spatial distribution of An. cruzii, An. bellator and An. marajoara and to associate the presence of these species with malaria cases in the municipalities of the Vale do Ribeira. Potential habitat suitability modelling was applied to determine both the spatial distribution of An. cruzii, An. bellator and An. marajoara and to establish the density of each species. Poisson regression was utilized to associate malaria cases with estimated vector densities. As a result, An. cruzii was correlated with the forested slopes of the Serra do Mar, An. bellator with the coastal plain and An. marajoara with the deforested areas. Moreover, both An. marajoara and An. cruzii were positively associated with malaria cases. Considering that An. marajoara was demonstrated to be a primary vector of human Plasmodium in the rural areas of the state of Amapá, more attention should be given to the species in the deforested areas of the Atlantic Forest, where it might be a secondary vector.