Managing systemic reactions and venom immunotherapy in vespid-venom allergy: observations from a retrospective study of Portuguese patients.

Summary: Background. Vespula spp. and Polistes spp. are relevant species in South Europe, with Vespa velutina nigrithorax (VVN) being considered a public health problem. We aimed to characterize a cohort of Portuguese patients referred for large local reaction (LLR) and/or systemic reaction (SR) to vespids. In patients treated with venom immunotherapy (VIT), induction protocol and frequency of adverse reactions were evaluated. Methods. Retrospective study including patients with LLR and SR to vespids referred to our Immunoallergology Department (2008-2022). Results. A total of 129 patients were evaluated, the majority were male adults (n = 77, 59.7%), from rural areas. From these, 51 patients had SR (Mueller classification: 7.8% grade I, 19.6% grade II, 37.3% grade III, 35.3% grade IV). We found no differences regarding the levels of total serum IgE, basal serum tryptase value, sIgE levels to the eliciting venom or their molecular components, regarding the severity of the SR that motivated the referral to our clinic. In the SR group, previous LLR Hymenoptera sting were reported in 15.7%. Thirty-eight patients (74.5%) initiated VIT: 22 with wasp venom, 14 with paper wasp venom and 2 with Vespa velutina venom. There was one mild systemic reaction, not requiring adrenaline and 4 LLR. Re-stings after VIT occurred in 16 patients, without any systemic or local reactions. Currently, eleven patients remain under VIT. Conclusions. Most vespid-venom allergic patients are male adults from rural areas. Sensitization to wasp venom was present in 52.9%, paper wasp in 33.3% and Vespa velutina in 13.7%. The frequency of adverse reactions during both induction and maintenance phases appears to be low. Despite a reduced sample size, our experience with VVN VIT, suggests its safety.

Eating behaviour patterns are associated with excessive weight gain after liver transplantation.

BACKGROUND: Weight gain and obesity are important issues in liver transplant (LTx) recipients. Although dietary habits are probably related to excessive weight gain after LTx, some studies have failed to demonstrate these associations. The present study aimed to assess eating behaviour and verify its association with weight gain and excessive weight among LTx recipients. METHODS: The investigation comprised a cross-sectional study. Post-LTx patients, aged >18 years were evaluated about their eating behaviour [Three Factor Eating Questionnaire-R21 (TFEQ-R21)]. The scores of the TFEQ-R21 [uncontrolled eating (UE), cognitive restraint (CR) and emotional eating (EE)] were determined. Excessive weight was classified as body mass index ≥25 kg/m² and obesity ≥30 kg/m². RESULTS: In total, 270 patients (age 58.0 years; range 20.0-77.0 years; 64.1% men) were assessed. Average weight gain was 8.0 kg (range -16.0 to 41.0 kg). Of the patients, 64.1% (n = 173) had excessive weight and 23.3% (n = 63) were obese. Post-LTx weight gain was significantly correlated with UE (r = 0.311, P < 0.001) and EE (r = 0.287, P < 0.001). Patients with excessive weight had significantly higher scores than others: CR (61.0; range 0-122.0 versus 44.0; range 0-116.0) (P = 0.003) and EE (11.0; range 0-100.0 versus 0.0; range 0-100.0) (P = 0.030). Patients with obesity had higher scores than non-obese UE (22.0; range 0-77.0 versus 14.0; range 0-85.0; P = 0.028), CR (55.0; range 11.0-116.0 versus 50.0; range 0-122.0) (P = 0.017) and EE (16.0; range 0-100.0 versus 5.0; range 0-100.0) individuals (P < 0.001). The greatest quartiles of weight gain had higher scores on the eating behaviours of UE and EE, especially those with weight gain ≥14 kg. UE was associated with weight gain. CR was associated with being overweight. EE was associated with obesity. CONCLUSIONS: Uncontrolled eating is associated with weight gain, CR was associated with excessive weight and EE was associated with obesity after LTx.

Climatic variables drive temporal patterns of α and ß diversities of dung beetles.

Understanding the mechanisms underpinning spatiotemporal diversity patterns of biological communities is a major goal of ecology. We aimed to test two ecological hypotheses: (i) temporal patterns of ß-diversity will mostly be driven by nestedness, with a loss of species from summer to winter, and (ii) nestedness values will correlate with climatic variables instead of turnover values, indicating either a loss of species during winter or a gain of species during summer. We sampled dung beetles using standardized sampling protocols along a year in four Atlantic forest sites: two at the northwest and two at the central region of Rio Grande do Sul state, southern Brazil. We partitioned temporal patterns of ß-diversity into turnover and nestedness in order to investigate if community changes are driven by species substitution or gain/loss across time. Our results highlighted five main findings: (i) dung beetle composition varied more with sites than site geographic position; (ii) there was almost one and a half 'true' dung beetle assemblages regarding the spatial distribution of species weighed by abundance; (iii) we found a positive influence of mean temperature and a negative influence of relative humidity on both species richness and abundance; (iv) both spatial and temporal dissimilarity among sites were dominated by species replacement, while the relative importance of nestedness was higher in temporal than spatial patterns; (v) there was an effect of precipitation and relative humidity on temporal patterns of ß-diversity components, but these effects were site-dependent. Contrary to our expectations, the ß-diversity component of turnover dominated both spatial and temporal patterns in dung beetle dissimilarity among sites and months. Distinct climatic variables affected differently the α-diversity and ß-diversity components of dung beetle assemblages. Partitioning ß-diversity into temporal components is a promising approach to unveil patterns of the community dynamics and to produce insights on mechanisms underlying such patterns.

Detection of bacterial contamination in platelet concentrates from Brazilian donors by molecular amplification of the ribosomal 16S gene.

OBJECTIVE: The aim of our work was to establish a semi-automated high-throughput DNA amplification method for the universal screening of bacteria in platelet concentrates (PCs). BACKGROUND: Among cases of transfusion transmission of infectious agents, bacterial contamination ranks first in the number of events, morbidity and mortality. Transmission occurs mainly by transfused PCs. Automated culture is adopted by some blood banks for screening of bacterial contamination, but this procedure is expensive and has a relatively long turnaround time. METHODS: PCs were spiked with suspensions of five different bacterial species in a final concentration of 1 and 10 colony-forming units (CFU) per millilitre. After incubation, the presence of bacteria was investigated by real-time polymerase chain reaction (PCR) and by the Enhanced Bacterial Detection System (eBDS, Pall) assay as a reference method. Real-time PCR amplification was performed with a set of universal primers and probes targeting the 16S rRNA gene. Co-amplification of human mitochondrial DNA served as an internal control. RESULTS: Using the real-time PCR method, it was possible to detect the presence of all bacterial species tested with an initial concentration of 10 CFU mL-1 24 h after contamination, except for Staphylococcus hominis. The PCR assay also detected, at 24 h, the presence of Serratia marcescens and Enterobacter cloacae with an initial concentration of 1 CFU mL-1 . CONCLUSIONS: The real-time PCR assay may be a reliable alternative to conventional culture methods in the screening of bacterial contamination of PCs, enabling bacterial detection even with a low initial concentration of microorganisms.

Universality of fluctuations in the Kardar-Parisi-Zhang class in high dimensions and its upper critical dimension.

We show that the theoretical machinery developed for the Kardar-Parisi-Zhang (KPZ) class in low dimensions is obeyed by the restricted solid-on-solid model for substrates with dimensions up to d=6. Analyzing different restriction conditions, we show that the height distributions of the interface are universal for all investigated dimensions. It means that fluctuations are not negligible and, consequently, the system is still below the upper critical dimension at d=6. The extrapolation of the data to dimensions d≥7 predicts that the upper critical dimension of the KPZ class is infinite.

Prevalence of Treponema pallidum DNA among blood donors with two different serologic tests profiles for syphilis in São Paulo, Brazil.

The presence of Treponema pallidum DNA was assessed by real-time PCR in samples of blood donors with reactive serologic tests for syphilis. Treponema pallidum DNA was detected in two (1·02%) of 197 samples of VDRL>8, EIA+ and FTA-ABS+ donors, and in no sample from 80 VDRL−, EIA+ and FTA-ABS+ donors. Donors VDRL−, EIA+ and FTA-ABS+ lack demonstrable T. pallidum DNA in their blood and are unlike to transmit syphilis. Donors VDRL>8, EIA+ and FTA-ABS+ carry the risk of syphilis infectivity even in concomitance to antibodies detection. Serologic screening for syphilis may still play a role to prevent its transfusion transmission.

Demographic, risk factors and motivations among blood donors with reactive serologic tests for syphilis in São Paulo, Brazil.

OBJECTIVE: To identify the demographic characteristics, risk factors and motivations for donating among blood donors with reactive serologic tests for syphilis. BACKGROUND: Post-donation interviews with syphilis seropositive blood donors improve recruitment and screening strategies. METHODS: This case-control study compares 75 Venereal Disease Research Laboratory (VDRL) > 8, EIA+ (enzyme immunoassay) and FTA-ABS+ (fluorescent treponemal antibody); 80 VDRL-, EIA+ and FTA-ABS+; and 34 VDRL- and EIA- donors between 2004 and 2009. Donors were assessed by their demographic characteristics, sexual behaviour, history of alcohol and illicit drugs use, and motivations to donate. RESULTS: Donors with VDRL > 8 were more likely to be divorced [AOR = 12·53; 95% confidence interval (CI) 1·30-120·81], to have had more than six sexual partners (AOR=7·1; 95% CI 1·12-44·62) and to report male-male-sex in the past 12 months (AOR=8·18; 95% CI 1·78-37·60). Donors with VDRL-, EIA+ and FTA-ABS+ were less likely to be female (AOR=0·26; 95% CI 0·07-0·96), more likely to be older (AOR=10·2; 95% CI 2·45-42·58 ≥ 39 and <60 years old) and to have had more than six sexual partners in the past 12 months (AOR = 8·37; 95% CI 1·49-46·91). There was no significant difference among groups regarding illicit drugs use; 30·7% (VDRL > 8) and 12·5% (VDRL-, EIA+ and FTA-ABS+) of donors reported that they had been at risk for HIV infection (P = 0·004). One-third of donors came to the blood bank to help a friend or a relative who needed blood. CONCLUSION: Although donors exposed to syphilis reported and recognised some high risk behaviour, most were motivated by direct appeal to donate blood. Monitoring the risk profile of blood donors can benefit public health and improve blood safety.

Salivary pellicle composition and multispecies biofilm developed on titanium nitrided by cold plasma.

OBJECTIVE: The aim of this study was to evaluate the composition of the salivary pellicle (SP) and multispecies biofilm developed on titanium nitrided by cold plasma. METHODS: Titanium discs were allocated into a control group (Ti) and an experimental group (TiN - titanium-nitrided by cold plasma). The disc surface topography was characterized by scanning electron microscopy (SEM) and atomic force microscopy (AFM). The chemical composition of the disc surface was determined by X-ray photoelectron spectroscopy (XPS). Stimulated, clarified, and filtered saliva was used to form pellicles on the discs. Proteome analysis of the adsorbed SP proteins was performed by liquid chromatography-mass spectrometry (LC-MS). The surface free energy (SFE) was evaluated before and after SP formation. A multispecies biofilm composed of Actinomyces naeslundii, Streptococcus oralis, Streptococcus mutans, Fusobacterium nucleatum, Veillonella dispar, and Candida albicans was developed on the SP-coated discs. Viable microorganism counts were determined. The biomass and average thickness of biofilms were analyzed by confocal laser-scanning microscopy (CLSM) with COMSTAT software. The biofilm organization was visualized by SEM. RESULTS: The surface topography was similar in both groups. The SFE of the TiN group did not differ from that of the Ti group (p>0.05), although the adsorption of pellicle proteins increased the SFE in both pellicle-coated groups (p<0.001). Different proteins were identified on the Ti and TiN surfaces. The amount of biofilm was similar for both groups (p=0.416), but the counts of F. nucleatum and S. oralis were higher in the TiN group (p<0.001). Similar biofilms were characterized by the COMSTAT data, CLSM images, and SEM images. CONCLUSION: The titanium nitrided by cold plasma exhibited differences in SP composition and multispecies microbial biofilm population compared to the control titanium surface.

Kardar-Parisi-Zhang universality class in (2+1) dimensions: universal geometry-dependent distributions and finite-time corrections.

The dynamical regimes of models belonging to the Kardar-Parisi-Zhang (KPZ) universality class are investigated in d=2+1 by extensive simulations considering flat and curved geometries. Geometry-dependent universal distributions, different from their Tracy-Widom counterpart in one dimension, were found. Distributions exhibit finite-time corrections hallmarked by a shift in the mean decaying as t(-ß), where ß is the growth exponent. Our results support a generalization of the ansatz h=v(∞)t+(Γt)(ß)χ+η+ζt(-ß) to higher dimensions, where v(∞), Γ, ζ, and η are nonuniversal quantities whereas ß and χ are universal and the last one depends on the surface geometry. Generalized Gumbel distributions provide very good fits of the distributions in at least four orders of magnitude around the peak, which can be used for comparisons with experiments. Our numerical results call for analytical approaches and experimental realizations of the KPZ class in two-dimensional systems.

The 14bp-deletion allele in the HLA-G gene confers susceptibility to the development of hepatocellular carcinoma in the Brazilian population.

Human leukocyte antigen-G (HLA-G) is a nonclassical HLA class I molecule involved in tumor escape mechanisms. Considering that the HLA-G 14bp insertion/deletion polymorphism is located at the 3' untranslated region (3'UTR) in exon 8, and since it has been associated with the magnitude of HLA-G production, we studied the association of 14bp insertion/deletion polymorphism with the risk of developing hepatocellular carcinoma (HCC). A total of 109 HCC patients followed at the University Hospital, Faculty of Medicine of Ribeirão Preto, São Paulo, Brazil, and 202 healthy controls from the same geographic area were genotyped for the 14bp insertion/deletion polymorphism using polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis. Compared to controls, the frequency of the 14bp deletion allele was overrepresented in HCC patients (65% versus 56%, respectively, P = 0.0326). The 14bp deletion conferred an odds ratio (OR) of 1.46 [95% confidence interval (CI): 1.04-2.05]. Similarly, the deletion/deletion genotype was marginally overrepresented in HCC patients (45% versus 35% in controls, P = 0.0871), conferring an OR of 1.54 (95% CI: 0.96-2.48). The frequencies of the deletion/insertion or insertion/insertion genotypes observed in patients were not statistically different from those observed in controls (P > 0.05). Our results suggest that the 14bp-deletion allele in HLA-G gene is associated with HCC susceptibility in a Brazilian population.

Universal fluctuations in Kardar-Parisi-Zhang growth on one-dimensional flat substrates.

We present a numerical study of the evolution of height distributions (HDs) obtained in interface growth models belonging to the Kardar-Parisi-Zhang (KPZ) universality class. The growth is done on an initially flat substrate. The HDs obtained for all investigated models are very well fitted by the theoretically predicted Gaussian orthogonal ensemble (GOE) distribution. The first cumulant has a shift that vanishes as t(-1/3), while the cumulants of order 2≤n≤4 converge to GOE as t(-2/3) or faster, behaviors previously observed in other KPZ systems. These results yield evidences for the universality of the GOE distribution in KPZ growth on flat substrates. Finally, we further show that the surfaces are described by the Airy(1) process.

Questing for an optimal, universal viral agent for oncolytic virotherapy.

One of the most promising strategies to treat cancer is attacking it with viruses designed to exploit specific altered pathways. Here, the effects of oncolytic virotherapy on tumors having compact, papillary, and disconnected morphologies are investigated through computer simulations of a multiscale model coupling macroscopic reaction-diffusion equations for the nutrients with microscopic stochastic rules for the actions of individual cells and viruses. The interaction among viruses and tumor cells involves cell infection, intracellular virus replication, and the release of new viruses in the tissue after cell lysis. The evolution over time of both the viral load and cancer cell population, as well as the probabilities for tumor eradication, were evaluated for a range of multiplicities of infection, viral entries, and burst sizes. It was found that in immunosuppressed hosts, the antitumor efficacy of a virus is primarily determined by its entry efficiency, its replicative capacity within the tumor, and its ability to spread over the tissue. However, the optimal traits for oncolytic viruses depend critically on the tumor growth dynamics and do not necessarily include rapid replication, cytolysis, or spreading, currently assumed as necessary conditions for a successful therapeutic outcome. Our findings have potential implications on the design of new vectors for the viral therapy of cancer.

Modelling of epitaxial film growth with an Ehrlich-Schwoebel barrier dependent on the step height.

The formation of mounded surfaces in epitaxial growth is attributed to the presence of barriers against interlayer diffusion in the terrace edges, known as Ehrlich-Schwoebel (ES) barriers. We investigate a model for epitaxial growth using an ES barrier explicitly dependent on the step height. Our model has an intrinsic topological step barrier even in the absence of an explicit ES barrier. We show that mounded morphologies can be obtained even for a small barrier while a self-affine growth, consistent with the Villain-Lai-Das Sarma equation, is observed in the absence of an explicit step barrier. The mounded surfaces are described by a super-roughness dynamical scaling characterized by locally smooth (facetted) surfaces and a global roughness exponent α > 1. The thin film limit is featured by surfaces with self-assembled three-dimensional structures having an aspect ratio (height/width) that may increase or decrease with temperature depending on the strength of the step barrier.

Non-human leukocyte antigen antibodies reactive with endothelial cells could be involved in early loss of renal allografts.

Preformed donor-specific human leukocyte antigen (HLA) antibodies have been associated with allograft dysfunction and failure. However, recipients of HLA-identical kidneys can develop acute humoral rejection, implicating putative pathogenic antibodies that are directed against non-HLA antigens. We investigated the presence of endothelial cell-reactive antibodies in 11 patients who experienced early loss of their transplanted kidneys owing to humoral rejection and 1 loss from renal venal thrombosis. We examined the potential efficacy of intravenous immunoglobulin to block the binding of these antibodies, as previously suggested for anti-HLA antibodies.

Liver HLA-G expression is associated with multiple clinical and histopathological forms of chronic hepatitis B virus infection.

As the mechanisms leading to the persistence of hepatitis B virus (HBV) infection are poorly understood and as the histocompatibility leucocyte antigen (HLA)-G is well described as a tolerogenic molecule, we evaluated HLA-G expression in 74 specimens of HBV liver biopsies and in 10 specimens obtained from previously healthy cadaver liver donors. HBV specimens were reviewed and classified by the METAVIR score, and HLA-G expression was assessed by immunohistochemistry. No HLA-G expression was observed in control hepatocytes. In contrast, 57 (77%) of 74 HBV specimens showed soluble and membrane-bound HLA-G expression in hepatocytes, biliary epithelial cells or both. No associations between the intensity of HLA-G expression and patient age or gender, HBeAg status, severity of liver fibrosis, and grade of histological findings were observed. Although significance was not reached (P = 0.180), patients exhibiting HLA-G expression presented a higher median HBV DNA viral load (105 copies/mL) than those who did not express HLA-G (10(3.7) copies/mL). These results indicate that HLA-G is expressed in most cases of chronic HBV infection in all stages and may play a role in the persistency of HBV infection.

Creatine activates airway epithelium in asthma.

Airway epithelium plays important roles in the pathophysiology of asthma. Creatine supplementation (Cr) was shown to increase asthma features in a murine model of allergic asthma; however, the role of the airway epithelium in this inflammatory response is not known. BALB/c mice were divided into control, creatine supplementation, ovalbumin-sensitized (OVA) and OVA plus creatine supplementation groups. OVA sensitization occurred on days 0, 14, 28 and 42, and ovalbumin challenge from days 21-53. Cr was also given on days 21-53. Total and differential cells counts in BALF were evaluated. Quantitative epithelial expression of interleukin (IL)-4, IL-5, IL-13, CCL11, CCL5, CCL2, iNOS, VCAM-1, ICAM-1, NF-κB, VEGF, TGF-ß, IGF-1, EGFR, TIMP-1, TIMP-2, MMP-9, MMP-12 and arginase II were performed. Cr increased the number of total cells and eosinophils in BALF, the epithelial content of goblet cells and the epithelial expression of IL-5, CCL2, iNOS, ICAM-1, NF-κB, TGF-ß, TIMP-1 and MMP-9 when compared to the control group (p<0.05). Creatine supplementation also exacerbated goblet cell proliferation, and IL-5 and iNOS expression by epithelial cells compared to the OVA group (p<0.01). Creatine up-regulates the pro-inflammatory cascade and remodelling process in this asthma model by modulating the expression of inflammatory mediators by epithelial cells.

Effects of the mean free path and relaxation in a model for the aggregation of particles in superfluid media.

In this paper, we study a two-dimensional model for the growth of molecular clusters in superfluid helium at low temperature. In the model, particles of diameter a follow random ballistic moves of length delta = a - 256a. Upon attachment on the cluster surface, particles allow one-step relaxation to the nearest twofold coordinated site. Average coordination numbers of particles show that in the presence of relaxation the screening for incoming particles modifies the microscopic structure of the cluster. These results are in qualitative agreement with experimental aggregation of methane in He droplets, in which large abundance of fully coordinated sites is observed. The average coordination number increases with delta, showing that screening is relevant when relaxation is present. As the cluster size increases, the corresponding structure clusters changes from a compact to a fractal, typical of ballistic and diffusion limited models, respectively. A scaling ansatz describing the crossover between the two regimes is proposed.

Contact process on a Voronoi triangulation.

We study the continuous absorbing-state phase transition in the contact process on the Voronoi-Delaunay lattice. The Voronoi construction is a natural way to introduce quenched coordination disorder in lattice models. We simulate the disordered system using the quasistationary simulation method and determine its critical exponents and moment ratios. Our results suggest that the critical behavior of the disordered system is unchanged with respect to that on a regular lattice, i.e., that of directed percolation.

Aggregation in a mixture of Brownian and ballistic wandering particles.

In this paper, we analyze the scaling properties of a model that has as limiting cases the diffusion-limited aggregation (DLA) and the ballistic aggregation (BA) models. This model allows us to control the radial and angular scaling of the patterns, as well as their gap distributions. The particles added to the cluster can follow either ballistic trajectories, with probability Pba, or random ones, with probability Prw=1-Pba. The patterns were characterized through several quantities, including those related to the radial and angular scaling. The fractal dimension as a function of Pba continuously increases from df approximately 1.72 (DLA dimensionality) for Pba=0 to df approximately 2 (BA dimensionality) for Pba. However, the lacunarity and the active zone width exhibit a distinct behavior: they are convex functions of Pba with a maximum at Pba approximately 1/2. Through the analysis of the angular correlation function, we found that the difference between the radial and angular exponents decreases continuously with increasing Pba and rapidly vanishes for Pba>1/2, in agreement with recent results concerning the asymptotic scaling of DLA clusters.