Primary care doctors' attitude towards drug allergy in Portugal: a questionnaire.

Summary: Background. The aim of the study was to learn about perception of drug allergy by general practitioners (GP) from continental Portugal, identify difficulties and educational needs for its management. Methods. A total of 372 answers were obtained. A questionnaire was addressed to GPs. Results. The most commonly identified drugs were antibiotics for 65.3% of the GPs and skin was the most commonly affected organ for 65.8%. Drug allergy was considered as very important in clinical practice by 73.7%, but difficulties in recognizing it were stated by 70.2%. Further education in this field wouldbe welcome by 97.8% of the doctors. The collaboration of Immunoallergology centers was considered non satisfactory by 39.8% of GPs and 45.7% of them stated that two-thirds of the suspected reactions were not investigated. Conclusions. These points deserve consideration in future health educational and organizational strategies.

Genome-wide scan reveals genomic regions and candidate genes underlying direct and maternal effects of preweaning calf mortality in Nellore cattle.

We conducted analysis to estimate genetic parameters and to identify genomic regions and candidate genes affecting direct and maternal effects of preweaning calf mortality (PWM) in Nellore cattle. Phenotypic records of 67,196 animals, and 8443 genotypes for 410,936 SNPs were used. Analysis were performed through the weighted single-step GBLUP approach and considering a threshold animal model via Bayesian Inference. Direct and maternal heritability estimates were of 0.2143 ± 0.0348 and 0.0137 ± 0.0066, respectively. The top 10 genomic regions accounted for 13.61 and 14.23% of the direct and maternal additive genetic variances and harbored a total of 63 and 91 positional candidate genes, respectively. Two overlapping regions on BTA2 were identified for both direct and maternal effects. Candidate genes are involved in biological mechanisms i.e. embryogenesis, immune response, feto-maternal communication, circadian rhythm, hormone alterations, myometrium adaptation, and milk secretion, which are critical for the successful calf growth and survival during preweaning period.

Production of arachidonic acid by Mortierella alpina using wastes from potato chips industry.

AIMS: This research aimed to determine the potential use of wastes from the potato chips industry as a carbon source to develop an economical culture medium for the production of biomass, lipids and arachidonic acid (ARA) by Mortierella alpina. METHODS AND RESULTS: A synthetic culture medium was optimized using a Plackett-Burman and central composite rotatable design, and used as a base to evaluate and characterize the potential use of wastes from the potato chips industry as carbon sources for the production of biomass, lipids and ARA by M. alpina. The waste was selected among other solid and liquid hydrolysed residues/by-products, and local low-cost alternatives for nitrogen sources were also evaluated. After 6 days of fermentation, the biomass concentration reached 20 g l-1 with 40% of total lipids, and a 35% ARA content in the lipids fraction. Savings in production were calculated using a sensitivity analysis for the alternative culture medium in different scenarios. CONCLUSIONS: This study showed a 7% savings in culture media expenses in the production of ARA-enriched biomass of M. alpina, compared to the conventional synthetic culture medium, when waste from the potato chips industry was used as an alternative source of carbon and macro/microelements, supplemented with a low-cost yeast extract alternative. SIGNIFICANCE AND IMPACT OF THE STUDY: The demonstration of the use of potato chips wastes as a low-cost carbon source for the biomass, lipids and ARA production, suggesting an eco-friendly alternative for the use of agri-food wastes for valuable metabolites production.

Intramolecular Hydrogen Bonds in Tip-Functionalized Single-Walled Carbon Nanotubes as pH-Sensitive Gates.

Since their discovery, carbon nanotubes and other related nanomaterials are in the spotlight due to their unique molecular structures and properties, having a wide range of applications. The cage-like structure of carbon nanotubes is especially appealing as a route to confine molecules, isolating them from the solvent medium. This study aims to explore and characterize, through density functional theory (DFT) calculations, covalent tip-functionalization of single-walled carbon nanotubes (SWCNTS) with carboxymethyl moieties that establish pH sensitive molecular gates. The response of the molecular gate to pH fluctuations arises from variations in the noncovalent interactions between functionalized groups, which depend on the extent of protonation, leading to conformational changes. Overall, the hydrogen bonds present in the molecular models under study, as evaluated through topological analysis and pKa calculations, suggest that functionalized SWCNTs may be suitable for the design of drug delivery systems to enhance the efficiency of some pharmacological treatments, or even in the area of catalysis and separation processes, through their incorporation in nanocomposites.

Genomic reaction norm models exploiting genotype × environment interaction on sexual precocity indicator traits in Nellore cattle.

Brazilian beef cattle are raised predominantly on pasture in a wide range of environments. In this scenario, genotype by environment (G×E) interaction is an important source of phenotypic variation in the reproductive traits. Hence, the evaluation of G×E interactions for heifer's early pregnancy (HP) and scrotal circumference (SC) traits in Nellore cattle, belonging to three breeding programs, was carried out to determine the animal's sensitivity to the environmental conditions (EC). The dataset consisted of 85 874 records for HP and 151 553 records for SC, from which 1800 heifers and 3343 young bulls were genotyped with the BovineHD BeadChip. Genotypic information for 826 sires was also used in the analyses. EC levels were based on the contemporary group solutions for yearling body weight. Linear reaction norm models (RNM), using pedigree information (RNM_A) or pedigree and genomic information (RNM_H), were used to infer G×E interactions. Two validation schemes were used to assess the predictive ability, with the following training populations: (a) forward scheme-dataset was split based on year of birth from 2008 for HP and from 2011 for SC; and (b) environment-specific scheme-low EC (-3.0 and -1.5) and high EC (1.5 and 3.0). The inclusion of the H matrix in RNM increased the genetic variance of the intercept and slope by 18.55 and 23.00% on average respectively, and provided genetic parameter estimates that were more accurate than those considering pedigree only. The same trend was observed for heritability estimates, which were 0.28-0.56 for SC and 0.26-0.49 for HP, using RNM_H, and 0.26-0.52 for SC and 0.22-0.45 for HP, using RNM_A. The lowest correlation observed between unfavorable (-3.0) and favorable (3.0) EC levels were 0.30 for HP and -0.12 for SC, indicating the presence of G×E interaction. The G×E interaction effect implied differences in animals' genetic merit and re-ranking of animals on different environmental conditions. SNP marker-environment interaction was detected for Nellore sexual precocity indicator traits with changes in effect and variance across EC levels. The RNM_H captured G×E interaction effects better than RNM_A and improved the predictive ability by around 14.04% for SC and 21.31% for HP. Using the forward scheme increased the overall predictive ability for SC (20.55%) and HP (11.06%) compared with the environment-specific scheme. The results suggest that the inclusion of genomic information combined with the pedigree to assess the G×E interaction leads to more accurate variance components and genetic parameter estimates.

Spectrum of Field-Ionized Triplet Gerade Rydberg States of H2 and Comparison to Multichannel Quantum-Defect Theory.

A spectrum of field-ionized triplet Rydberg states of gerade symmetry H2 has been measured, excited from the υ″ = 0, N″ = 1-3 rovibrational levels of the metastable c3Πu-2pπ state in a 6 keV fast molecular beam. The field-ionized spectrum is kinetic energy labeled in order to separate it from the well-studied υ+ ≥ 1 autoionization spectrum. The spectrum consists of both ns and nd Rydberg series with n between 10 and 28 converging to the υ+ = 0, N+ = 1-3 levels of the X+ 2Σg+ ground state of H2+. Transitions with changes in vibration and/or rotation are also identified. The spectral positions of 59 transitions in the field ionization spectrum are identified and assigned quantum numbers using the predictions of multichannel quantum-defect theory (MQDT). The transition energies and subsequent effective quantum defects are compared between the experiment and theory. Most of the observed transitions, within the experimental uncertainty of 0.2 cm-1, agree with the energies predicted by MQDT.

Effect of Bioactive Composites on Microhardness of Enamel Exposed to Carious Challenge.

This study verified if experimental composites containing calcium phosphate nanoparticles exert a protective effect against enamel demineralization. Three experimental resin-based composites containing 60 vol% of fillers were manipulated. Filler phase was constituted by silanized barium glass and 0%, 10% or 20% (by volume) of dicalcium phosphate dihydrate (DPCD) nanoparticles functionalized with the monomer triethylene glycol dimethacrylate (TEGDMA). Cavities (10 x 2 x 2 mm) were prepared in bovine enamel and restored using one of the experimental materials (n=10). Specimens were exposed to pH cycling (demineralizing solution: pH 5.0/4h, remineralizing solution: pH 7.0/20h, 14 days). Enamel Knoop microhardness (100g/10s) was measured on the surface (SH) and after transversal sectioning up to 90 µm depth (cross-sectional microhardness, CSH). Microhardness values and the percent of microhardness loss were analyzed ANOVA/Tukey test and Student's paired t-test (alpha: 5%). The materials did not differ in respect to SH. Enamel adjacent to DCPD-containing composite restorations showed smaller reductions in CSH (-1.2% to -3.5%) than the enamel from control group (-12.5%), while CSH of enamel restored with resin-modified glass ionomer was similar to the other groups (-4.5%). DCPD-containing composites reduced enamel demineralization in comparison to a conventional composite.

Mutations associated with drug resistance and prevalence of vaccine escape mutations in patients with chronic hepatitis B infection.

The Brazilian public health system (SUS) has provided antiviral drugs for chronic hepatitis B treatment for over 10 years, but a system for monitoring for drug-related resistance mutations is not available. Determine the presence of HBV mutations associated with resistance to nucleos(t)ide analogs among 81 patients with chronic HBV infection in Salvador-BA-Brazil. HBV-DNA was PCR amplified with primers deduced from the rt domain at the HBV P gene, the sequence extended 1032 bp (from amino acid 1 to 344-rt domain). Those sequences were submitted to the HBV drug resistance database to retrieve each mutation according to the genotype. HBV genotype A1 (85.2%) was the most prevalent, followed by genotype A2 (4.9%), F (6.2%), and C1, D2, and D4 (1.2% each). Six patients (7%) exhibited resistance mutations to LAM, ETV, and TDF: two with patterns L180M + M204V and four with other different patterns: L80I + L180M + M204I; L80V + L180M + M204V; M204I; A194T. All of these mutations were present in patients with genotype A (four A1 and two A2). In addition, four mutations in gene S (three cases with the sI195M mutation and one with the W196L mutation), were detected, corresponding to a rate of 6% of vaccine escape mutations. Althougth the small sample size, an association was found between the occurrence of HBV resistance mutations and HBeAg positivity, co-infection with HIV and a history of treatment for HBV and/or HIV.

A water quality index for recreation in Brazilian freshwaters.

Use of water for leisure activities has long been prevalent in human societies, especially where the climate is favorable. Water resources with appealing conditions for primary contact recreational activities include rivers, waterfall plunge pools, dams and lakes, as well as sea coasts. Recreational use has specific demands for water quality, particularly as regards risks to human health such as exposure to pathogenic organisms, toxic substances, and submerged hazards. In Brazil, there is insufficient monitoring of bathing water conditions and currently used methodology has some limitations particularly the lack of guidance on interpretation of variables other than faecal bacterial indicators. The objectives of this study were: (1) to establish variables contributing to assessment of freshwater bathing conditions in Brazil; (2) to develop an integrated index of suitability-for-use for bathing in Brazil; and (3) to improve the methodology for assessing bathing water quality in Brazil. Based on a metadata analysis and consultation with Brazilian water professionals, a water quality index was developed incorporating the variables: Escherichia coli, cyanobacterial density, turbidity (visual clarity) and pH. This index should advance the management of recreational waters in Brazil, by improving the evaluation of freshwater bathing conditions and protecting the health of frequent users.

In situ Effect of Chewing Gum with and without CPP-ACP on Enamel Surface Hardness Subsequent to ex vivo Acid Challenge.

The erosion-protective effect of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) is controversial. This study aimed to investigate the ability of CPP-ACP chewing gum to prevent a single event of erosive demineralization in situ. Bovine enamel blocks (n = 120) were randomly assigned to 3 phases according to the baseline surface hardness: phase I (PI) - chewing gum with CPP-ACP, phase II (PII) - chewing gum without CPP-ACP, and control phase (PIII) - salivary effect without stimulation (no gum). Nineteen volunteers participated in this study during 3 crossover phases of 2 h. In PI and PII, the volunteers wore intraoral palatal appliances for 120 min and chewed a unit of the corresponding chewing gum for the final 30 min. In the control phase the volunteers wore the appliance for 2 h, without chewing gum. Immediately after intraoral use, the appliances were extraorally immersed in a cola drink for 5 min to promote erosive demineralization. The percentage of surface hardness loss was calculated. The data were analyzed by ANOVA models and Tukey's test. Lower enamel hardness loss was found after the use of chewing gum with CPP-ACP (PI: 32.7%) and without CPP-ACP (PII: 33.5%) compared to the salivary effect without stimulation (PIII: 39.8%) (p < 0.05). There was no difference between PI and PII (p > 0.05). The results suggest that the use of chewing gum immediately before an erosive demineralization can diminish enamel hardness loss. However, the presence of CPP-ACP in the chewing gum cannot enhance this protective effect.

The Kite Latissimus Dorsi Flap for Breast Reconstruction: An Attempt to Reduce Lateral Chest Wall Deformity and Axillary Bulking.

UNLABELLED: The latissimus dorsi flap is a commonly used tissue transfer for volume replacement in partial or total breast reconstruction. In this era of cosmetic awareness and oncoplastic breast surgery, two main defects are related to the conventional technique: the back scar and the bulkiness on the lateral chest wall, under the axilla. Axillary bulking, a disturbing defect for the majority of patients, is a persistent consequence, independent of the technique used, even when the proximal tendon is cut. We describe a new approach, the kite latissimus dorsi flap, consisting of harvesting the flap, partially or totally, with pedicle dissection from the muscle, extending dissection, perforator style if needed, until the external border of the breast (anterior axillary line) is reached. The muscle is then cut at that level, leaving no unnecessary volume under the axilla, which would cause bulkiness and chest wall deformity. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Control of White Spot Lesions with Use of Fluoride Varnish or Chlorhexidine Gel During Orthodontic Treatment A Randomized Clinical Trial.

OBJECTIVE: To compare the effectiveness of fluoride varnish and 2% chlorhexidine gel for controlling active white spot lesions (WSLs) adjacent to orthodontic brackets. STUDY DESIGN: Thirty-five orthodontic patients (17.2 ± 2.3 years old) presenting 60 WSLs adjacent to orthodontic brackets were enrolled in this randomized, blind, 3-armed and controlled clinical trial. The patients were randomly allocated to 1 of 3 arms: (1) two applications of 5% NaF varnish- F, with one-week interval, (2) two applications of 2% chlorhexidine gel-CHX, with one-week interval and (3) usual home care-control (CO). The WSLs were scored by using a DIAGNOdent pen. An independent examiner scored the surfaces using Nyvad criteria for caries assessment. RESULTS: A total of thirty patients presenting 51 lesions completed the study. All treatments reduced the fluorescence values during the experimental period; however, F induced faster remineralization than CHX. After 3 months, 70.58 % were inactive considering all groups. DIAGNOdent pen and Nyvad presented a significant correlation. CONCLUSION: After 3 months of treatment, F, CHX and CO were capable of controlling the WSLs adjacent to the orthodontic brackets. However, the treatment with F was capable of controlling the progression of the WSLs in a shorter period of time.

Genetic association of growth traits with carcass and meat traits in Nellore cattle.

The aim of this study was to estimate genetic and phenotypic associations of growth traits with carcass and meat traits in Nellore cattle. Data from male and female animals were used for weaning weight (WW; N = 241,416), yearling weight (YW, N = 126,596), weight gain from weaning to yearling (GWY, N = 78,687), and yearling hip height (YHH, N = 90,720), respectively; 877 male animals were used for hot carcass weight (HCW) and 884 for longissimus muscle area (LMA), backfat thickness (BT), marbling score (MS), and shear force (SF). The variance components were estimated by the restricted maximum likelihood method using three-trait animal models that included WW. The model for WW included direct and maternal additive genetic, maternal permanent environmental, and residual effects as random effects; contemporary group as fixed effects; and age of dam at calving and age of animal as covariates (linear and quadratic effects). For the other traits, maternal effects and the effect of age of dam at calving were excluded from the model. Heritability ranged from 0.10 ± 0.12 (LMA) to 0.44 ± 0.007 (YW). Genetic correlations ranged from -0.40 ± 0.38 (WW x LMA) to 0.55 ± 0.10 (HCW x YW). Growth, carcass, and meat traits have sufficient genetic variability to be included as selection criteria in animal breeding programs.

Levels of mannose-binding lectin in individuals with visceral leishmaniasis in the northeast region of Brazil.

Visceral leishmaniasis (VL) is one of the seven priority endemic diseases in the world. The clinical outcome of many infections is not only dependent on the pathogenic organism, but also on the genetic variability of the host susceptibility to infection. Mannose-binding lectin (MBL) is a protein that plays an important role in the innate immune system. The aim of this study was to compare the serum levels of MBL between healthy controls and carriers of VL. The VL cases were recruited randomly from the main hospitals and referral outpatient clinics for VL in São Luís, and from home visits. Determination of MBL protein levels was performed by enzyme-linked immunosorbent assay. Of the 161 patients with VL and the 161 healthy controls, 60.9 and 67.1% had high levels of MBL, respectively. There was no significant difference in MBL levels between cases and controls. Low socioeconomic status and living conditions are conducive to the occurrence of VL. Owing to the small number of existing studies, it is extremely important to conduct further studies on MBL levels and susceptibility to VL, especially in regions where the disease is endemic, such as Maranhão, Brazil.

Prevalence of subclinical infectious agents in a blood donor population tested on every donation.

OBJECTIVES: This study aimed to assess the prevalence of blood-borne infectious agents in healthy, client-owned dogs from a blood donor population in Portugal and Spain, and to address the importance of a screening protocol on every donation. MATERIALS AND METHODS: Client-owned healthy dogs were tested before each donation on a veterinary blood bank. Blood samples from new potential donors, and from regular donors, were tested by real-time polymerase chain reaction for Leishmania species, Ehrlichia species, Brucella species, Babesia species and Anaplasma species Serological tests were also performed for Leishmania species, Ehrlichia species and Dirofilaria immitis. All donors were tested for every infectious agent in each donation. RESULTS: The study found that out of a total of 8036 donors and 35,120 samples tested, 3.9% of blood donors tested positive for at least one of the agents, with the most prevalent being Anaplasma species (2.1%). Serological tests also revealed positive results in 14.0% of donors, with the highest percentage for Leishmania species (7.7%). Moreover, the study found that 28.2% of positive results were from dogs with negative results in donations performed 3 to 12 months before, and 18.0% of positive results were recent infections. CLINICAL SIGNIFICANCE: These findings indicate a high prevalence of infectious agents in seemingly healthy, selected dogs eligible to become blood donors in the Iberian Peninsula, highlighting the importance of regular testing on every donation. This study emphasises the importance of a regular screening protocol for every donation instead of annual testing, as is commonly performed in veterinary medicine.

Different protocols to produce artificial dentine carious lesions in vitro and in situ: hardness and mineral content correlation.

This study compared dentine demineralization induced by in vitro and in situ models, and correlated dentine surface hardness (SH), cross-sectional hardness (CSH) and mineral content by transverse microradiography (TMR). Bovine dentine specimens (n = 15/group) were demineralized in vitro with the following: MC gel (6% carboxymethylcellulose gel and 0.1 M lactic acid, pH 5.0, 14 days); buffer I (0.05 M acetic acid solution with calcium, phosphate and fluoride, pH 4.5, 7 days); buffer II (0.05 M acetic acid solution with calcium and phosphate, pH 5.0, 7 days), and TEMDP (0.05 M lactic acid with calcium, phosphate and tetraethyl methyl diphosphonate, pH 5.0, 7 days). In an in situ study, 11 volunteers wore palatal appliances containing 2 bovine dentine specimens, protected with a plastic mesh to allow biofilm development. The volunteers dripped a 20% sucrose solution on each specimen 4 times a day for 14 days. In vitro and in situ lesions were analyzed using TMR and statistically compared by ANOVA. TMR and CSH/SH were submitted to regression and correlation analysis (p < 0.05). The in situ model produced a deep lesion with a high R value, but with a thin surface layer. Regarding the in vitro models, MC gel produced only a shallow lesion, while buffers I and II as well as TEMDP induced a pronounced subsurface lesion with deep demineralization. The relationship between CSH and TMR was weak and not linear. The artificial dentine carious lesions induced by the different models differed significantly, which in turn might influence further de- and remineralization processes. Hardness analysis should not be interpreted with respect to dentine mineral loss.

Beyond behavioural observations: a deeper view through the sensory reactions of children with profound intellectual and multiple disabilities.

BACKGROUND: The present study was aimed at assessing the behavioural and physiological responsiveness of three children with profound intellectual and multiple disabilities to a set of sensory stimuli. METHODS: Eighteen items, 'believed' by clinicians to be appropriate for routine interventions, were presented to the participants and responsiveness was assessed in terms of: (i) consistent behavioural and electrodermal reactions and (ii) biphasic changes in heart rate. RESULTS: Results were twofold. First, all participants showed frequent consistent physiological reactions but rare consistent behavioural ones. Second, all participants showed biphasic changes in heart rate, pointing to the possibility of different appraisals (novelty and pleasantness) of most of the presented items. CONCLUSIONS: Data here presented may have implications for the development and the emotional well-being of individuals with profound intellectual and multiple disabilities in that it suggests that reactions to, and potential appraisals of, sensory stimuli may occur despite the lack of consistent observable behaviours.

Wealth dynamics in a market with information asymmetries.

Financial markets are usually investigated through time series such as prices and volumes that describe the behavior of the system as a whole. Such observables emerge from microeconomic interactions between market participants. Agent-based models have been utilized to shed light on this process. The model's ability to produce statistics frequently found in empirical data is evidence of some correspondence with real markets. Here, an agent-based market model is proposed. Different trader profiles with short- and long-term motivations are considered, and limitations on the agents' skills to manipulate information are inserted into the model. According to their profile and limitations, agents are rational. A differential equation approximation is employed to find the value to which the price converges and the timescale of this process. The relationship between agents' attributes and the evolution of their wealth is explored in different scenarios. Agent's average wealth was not significantly affected by information processing accuracy, but the standard deviation was. The increased risk is the main consequence of low accuracy. The model yielded price series with multifractal behavior and heavy-tailed return distributions, which are nontrivial statistics frequently observed in empirical series.