Preferential expression of a HPV genotype in invasive cervical carcinomas infected by multiple genotypes.

Multiple infections by HPV genotypes are frequently detected in HPV+ cervical lesions but the interaction between each viral genotype during carcinogenesis is poorly understood. Here we carried out a comprehensive study to characterize the multiple HPV expression and integration by RNA-seq analyses of 19 invasive cervical carcinomas coinfected by several HPV genotypes. Analysis of tumor DNA by a hybridization assay indicated multiple infections ranging from 2 to 6 different HPV genotypes. RNA-seq analysis showed that a single HPV genotype was preferentially expressed. Finally, the search for HPV/human chimeric transcripts indicated integration from preferentially expressed genotypes. In conclusion, the present study indicated that, in invasive cervical carcinomas infected by multiple HPV genotypes, one HPV was preferentially expressed, supporting the hypothesis that a single HPV genotype was associated with cancer development.

Recommendations for rosacea diagnosis, classification and management: update from the global ROSacea COnsensus 2019 panel.

BACKGROUND: A transition from a subtyping to a phenotyping approach in rosacea is underway, allowing individual patient management according to presenting features instead of categorization by predefined subtypes. The ROSacea COnsensus (ROSCO) 2017 recommendations further support this transition and align with guidance from other working groups. OBJECTIVES: To update and extend previous global ROSCO recommendations in line with the latest research and continue supporting uptake of the phenotype approach in rosacea through clinical tool development. METHODS: Nineteen dermatologists and two ophthalmologists used a modified Delphi approach to reach consensus on statements pertaining to critical aspects of rosacea diagnosis, classification and management. Voting was electronic and blinded. RESULTS: Delphi statements on which the panel achieved consensus of ≥ 75% voting 'Agree' or 'Strongly agree' are presented. The panel recommends discussing disease burden with patients during consultations, using four questions to assist conversations. The primary treatment objective should be achievement of complete clearance, owing to previously established clinical benefits for patients. Cutaneous and ocular features are defined. Treatments have been reassessed in line with recent evidence and the prior treatment algorithm updated. Combination therapy is recommended to benefit patients with multiple features. Ongoing monitoring and dialogue should take place between physician and patients, covering defined factors to maximize outcomes. A prototype clinical tool (Rosacea Tracker) and patient case studies have been developed from consensus statements. CONCLUSIONS: The current survey updates previous recommendations as a basis for local guideline development and provides clinical tools to facilitate a phenotype approach in practice and improve rosacea patient management. What's already known about this topic? A transition to a phenotype approach in rosacea is underway and is being recommended by multiple working groups. New research has become available since the previous ROSCO consensus, necessitating an update and extension of recommendations. What does this study add? We offer updated global recommendations for clinical practice that account for recent research, to continue supporting the transition to a phenotype approach in rosacea. We present prototype clinical tools to facilitate use of the phenotype approach in practice and improve management of patients with rosacea.

Updating the diagnosis, classification and assessment of rosacea: recommendations from the global ROSacea COnsensus (ROSCO) panel.

BACKGROUND: Rosacea is currently diagnosed by consensus-defined primary and secondary features and managed by subtype. However, individual features (phenotypes) can span multiple subtypes, which has implications for clinical practice and research. Adopting a phenotype-led approach may facilitate patient-centred management. OBJECTIVES: To advance clinical practice by obtaining international consensus to establish a phenotype-led rosacea diagnosis and classification scheme with global representation. METHODS: Seventeen dermatologists and three ophthalmologists used a modified Delphi approach to reach consensus on statements pertaining to critical aspects of rosacea diagnosis, classification and severity evaluation. All voting was electronic and blinded. RESULTS: Consensus was achieved for transitioning to a phenotype-based approach to rosacea diagnosis and classification. The following two features were independently considered diagnostic for rosacea: (i) persistent, centrofacial erythema associated with periodic intensification; and (ii) phymatous changes. Flushing, telangiectasia, inflammatory lesions and ocular manifestations were not considered to be individually diagnostic. The panel reached agreement on dimensions for phenotype severity measures and established the importance of assessing the patient burden of rosacea. CONCLUSIONS: The panel recommended an approach for diagnosis and classification of rosacea based on disease phenotype.

Rosacea treatment update: recommendations from the global ROSacea COnsensus (ROSCO) panel.

BACKGROUND: Rosacea is currently treated according to subtypes. As this does not adequately address the spectrum of clinical presentation (phenotypes), it has implications for patient management. The ROSacea COnsensus panel was established to address this issue. OBJECTIVES: To incorporate current best treatment evidence with clinical experience from an international expert panel and establish consensus to improve outcomes for patients with rosacea. METHODS: Seventeen dermatologists and three ophthalmologists reached consensus on critical aspects of rosacea treatment and management using a modified Delphi approach. The panel voted on statements using the responses 'strongly disagree', 'disagree', 'agree' or 'strongly agree'. Consensus was defined as ≥ 75% 'agree' or 'strongly agree'. All voting was electronic and blinded. RESULTS: The panel agreed on phenotype-based treatments for signs and symptoms presenting in individuals with rosacea. First-line treatments were identified for individual major features of transient and persistent erythema, inflammatory papules/pustules, telangiectasia and phyma, underpinned by general skincare measures. Multiple features in an individual patient can be simultaneously treated with multiple agents. If treatment is inadequate given appropriate duration, another first-line option or the addition of another first-line agent should be considered. Maintenance treatment depends on treatment modality and patient preferences. Ophthalmological referral for all but the mildest ocular features should be considered. Lid hygiene and artificial tears in addition to medications are used to treat ocular rosacea. CONCLUSIONS: Rosacea diagnosis and treatment should be based on clinical presentation. Consensus was achieved to support this approach for rosacea treatment strategies.

Intraspecific differentiation of Hancornia speciosa revealed by simple sequence repeat and random amplified polymorphic DNA markers.

Hancornia speciosa, popularly known as mangabeira, is a fruit tree native to the Brazilian Cerrado that shows great economic potential, due to its multiple uses. Intraspecific classification of this species is difficult because it shows high morphological diversity. An early study of the species reported that there are six botanic varieties that differ morphologically mainly in the shapes of their leaves and flowers. Except to note the wide morphological variation and economic potential of this species, few studies have been published about the genetic diversity of mangabeira. Knowledge of the genetic variability of this species among populations would be useful for genetic conservation and breeding programs. Therefore, we tested the transferability of 12 simple sequence repeats from expressed sequence tags (EST-SSRs) from Catharanthus roseus to H. speciosa and used 10 random amplified polymorphic DNA markers to evaluate the genetic variability among botanical varieties of H. speciosa. We obtained a high transferability frequency of EST-SSR markers from C. roseus to H. speciosa (75%). However, EST-SSR markers showed low heterozygosity and locus variability (two or three alleles by locus), which suggest low genetic diversity in the mangabeira samples. The Jaccard dissimilarity index and an examination of geographic distances indicated a non-spatial structuring of the genetic variability. Our markers were unable to distinguish H. speciosa botanical varieties.

Selection of sugar cane full-sib families using mixed models and ISSR markers.

In 2006, an experiment examining families belonging to the first selection stage of the Sugar Cane Breeding Program of Universidade Federal Rural do Rio de Janeiro/Rede Interuniversitária para o Desenvolvimento do Setor Sucroalcooleiro was conducted. Families and plants within families were evaluated to select superior plants for subsequent stages of the breeding program. The experiment was arranged in a randomized block design, in which progenies were grouped into 4 sets, each with 4 replicates and 100 seedlings per plot. The following traits were evaluated: average stem diameter, total plot weight, number of stems, Brix of the lower stem, and Brix of the upper stem. The study of families used the restricted maximum likelihood/best linear unbiased procedure mixed models. After selection, families were genotyped via inter-simple sequence repeat to assess the genetic distance of genotypes. This approach was found to be efficient for selecting new genotypes.

Thielaviopsis paradoxa and cultivable mycobiota associated with carapace of Rhynchophorus palmarum L. (Coleoptera: Curculionidae) in the state of Alagoas, Brazil.

Rhynchophorus palmarum (Coleoptera: Curculionidae) is a significant agricultural pest in palm plantations across tropical America, playing a critical role as a vector of the fungus Thielaviopsis paradoxa, which is the causative agent of stem bleeding disease in coconut palms. This disease has raised concerns due to its rapid spread and subsequent reduction in coconut production in northeastern Brazil. Additionally, this insect can establish mutualistic interactions with various fungi, including saprophytic, phytopathogenic, and entomopathogenic fungi, underscoring the importance of identifying its external mycobiota. The aim of this study was to assess the presence of T. paradoxa in the digestive tract and identify the cultivable mycobiota associated with the carapace of R. palmarum. To achieve this, a mycological study was conducted by culturing the external surface and digestive tract of field-caught adult insects (10 males and 10 females) on potato dextrose agar (PDA) in Maceió, Alagoas, Brazil. Fungal identification was performed by correlating microscopic features with the macroscopic characteristics of the obtained colonies. The results showed that T. paradoxa was detected in 15.0% of carapace isolates but was not found in the insects' intestinal tract. Additionally, nine fungal genera frequently associated with saprophytic or phytopathogenic behaviors were identified on the carapace. Eight of these genera belong to the Ascomycota phylum, while one is classified in the Basidiomycota phylum. The ubiquitous presence of Paecilomyces spp. and the occurrence of Trichosporon spp. in 95% of the assessed insects stand out. Furthermore, other potentially phytopathogenic fungi such as Penicillium spp., Fusarium spp., and Aspergillus spp., as well as fungi with entomopathogenic potential like Paecilomyces spp., Trichoderma spp., Metarhizium spp., and Beauveria bassiana, were detected. These findings enhance the understanding of the complex interactions between R. palmarum and its fungal hosts, providing insights for integrated pest management strategies.

Delay from fracture to hospital admission: a new risk factor for hip fracture mortality?

UNLABELLED: The relationship between surgical timing and hip fracture mortality is unknown in the context of developing countries where large delays to surgery are common. We observed that delay from fracture to hospital admission is associated with decreased survival after a hip fracture. INTRODUCTION: To examine the relationship between the time interval from fracture to surgery as well as its subcomponents (time from fracture to hospital admission and time from admission to surgery) and hip fracture survival. METHODS: The medical records of all patients aged 60 years and older admitted to a public university hospital in the city of Rio de Janeiro with a primary diagnosis of hip fracture between 1995 and 2000 were reviewed. Survival to hospital discharge and at 1 year were examined. RESULTS: Among 343 patients included in the study, there were 18 (5.3%) in-hospital deaths, and 297 (86.6%) patients remained alive 1 year after surgery. Very long delays from the time of fracture to hospital admission (mean 3 days) and from hospital admission to surgery (mean 13 days) were identified. Increased time from fracture to hospital admission was associated with reduced survival to hospital discharge (hazard ratio [HR] 1.09, 95% CI 1.03-1.15, p = 0.005) and reduced survival at 1 year after surgery (HR 1.07, 95% CI 1.03-1.10, p < 0.001). The interval of time from hospital admission to surgery was not associated with reduced survival to hospital discharge (HR 1.03, 95% CI 0.96-1.10, p = 0.379) or at 1 year after surgery (HR 1.03, 95% CI 0.99-1.07, p= 0.185). CONCLUSIONS: If the association estimated in our study is causal, our results provide evidence that some hip fracture-related deaths could be prevented by improved patient access to appropriate and timely hospital care in the context of a developing country.

A snapshot of the striking decrease in cigarette smoking prevalence in Brazil between 1989 and 2008.

OBJECTIVE: To evaluate the differences in cigarette smoking prevalence rates in Brazil between 1989 and 2008. METHODOLOGY: We calculated absolute and relative differences in smoking prevalences, overall and stratified by gender, age, place of residence, educational level and birth cohort. Data were obtained from random samples from two National Household Surveys (1989,n=39,969; 2008,n=38,461). GLM models were specified to obtain estimates and assess whether differences in proportions of smokers differed by categories of the stratification variables. RESULTS: Adjusted absolute and relative differences in smoking prevalence rates between 1989 and 2008 were, respectively, -12.4% and -41.0%. Individuals aged 15-34 years and those with 9 or more years of education presented larger relative declines than their counterparts (p(s)≤0.001). After stratification by birth cohort, men presented larger reductions than women, only in the absolute scale (p(s)≤0.001), with the exception of the youngest birth cohort (i.e.,1965-1974). CONCLUSIONS: In Brazil, several tobacco control measures have been adopted since 1986, in particular increasing taxation of tobacco products and strong health warnings, which may have contributed to the marked decline in smoking prevalence. It is important to understand the evolution of the tobacco epidemic to propose new actions to prevent initiation and encourage cessation among those who started/continued smoking.

Microarray analysis in caudal medulla of cattle orally challenged with bovine spongiform encephalopathy.

Bovine spongiform encephalopathy (BSE) is a fatal disorder in cattle characterized by progressive neurodegeneration of the central nervous system. We investigated the molecular mechanisms involved in neurodegeneration during prion infection through the identification of genes that are differentially expressed (DE) between experimentally infected and non-challenged cattle. Gene expression of caudal medulla from control and orally infected animals was compared by microarray analysis using 24,000 bovine oligonucleotides representing 16,846 different genes to identify DE genes associated with BSE disease. In total, 182 DE genes were identified between normal and BSE-infected tissues (>2.0-fold change, P < 0.01); 81 DE genes had gene ontology functions, which included synapse function, calcium ion regulation, immune and inflammatory response, apoptosis, and cytoskeleton organization; 13 of these genes were found to be involved in 26 different Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The expression of five DE genes associated with synapse function (tachykinin, synuclein, neuropeptide Y, cocaine, amphetamine-responsive transcript, and synaptosomal-associated protein 25 kDa) and three DE genes associated with calcium ion regulation (parvalbumin, visinin-like, and cadherin) was further validated in the medulla tissue of cattle at different infection times (6, 12, 42, and 45 months post-infection) by qRT-PCR. These data will contribute to a better understanding of the molecular mechanisms of neuropathology in bovine species.

Hybrid Training Method for MLP: Optimization of Architecture and Training.

The performance of an artificial neural network (ANN) depends upon the selection of proper connection weights, network architecture, and cost function during network training. This paper presents a hybrid approach (GaTSa) to optimize the performance of the ANN in terms of architecture and weights. GaTSa is an extension of a previous method (TSa) proposed by the authors. GaTSa is based on the integration of the heuristic simulated annealing (SA), tabu search (TS), genetic algorithms (GA), and backpropagation, whereas TSa does not use GA. The main advantages of GaTSa are the following: a constructive process to add new nodes in the architecture based on GA, the ability to escape from local minima with uphill moves (SA feature), and faster convergence by the evaluation of a set of solutions (TS feature). The performance of GaTSa is investigated through an empirical evaluation of 11 public-domain data sets using different cost functions in the simultaneous optimization of the multilayer perceptron ANN architecture and weights. Experiments demonstrated that GaTSa can also be used for relevant feature selection. GaTSa presented statistically relevant results in comparison with other global and local optimization techniques.

Hancornia speciosa serum latex fraction: a non-allergenic biomaterial.

Plant-derived products can assist in the healing process of dermal wounds. It has been demonstrated that Hancornia speciosa latex present angiogenic, osteogenic, anti-inflammatory, and antioxidant activities. Then, it could contribute to the wound healing process. However, natural products in contact with skin may cause dermatitis. The objective of this work was to evaluate the allergic and irritant potential of H. speciosa serum fraction latex using in vitro assays. The obtained results showed that the H. speciosa serum fraction latex has a slightly irritant potential and is not cytotoxic neither allergenic for human cells. Moreover, we identified a remarkable low amount of proteins in this material in comparison to Hevea brasiliensis latex. This result could explain the non-allergenic potential of H. speciosa serum fraction latex because proteins present in latex are the main responsible for allergy. This biomaterial could be used as a non-allergenic source for development of new medicines.

Cytotoxic effect of Vernonanthura polyanthes leaves aqueous extracts.

Vernonanthura polyanthes, popularly known as assa-peixe, is a medicinal plant that has been widely used by Brazilian Cerrado population for treatment of diseases without a detailed evaluation of their effectiveness, toxicity, and proper dosage. Thus, more studies investigating the safety of V. polyanthes aqueous extract before the use are needed. The purpose of this study was to evaluate the toxicity, cytotoxicity and genotoxicity of V. polyanthes leaves aqueous extract using the Artemia salina and Allium cepa assays. For the A. salina assay, three groups of 10 larvae were exposed to V. polyanthes leaves aqueous extract at the concentrations of 5, 10, 20, 40, and 80 mg/ml. For the A. cepa assay, 5 onion bulbs were exposed to V. polyanthes leaves aqueous extract at 10, 20, and 40 mg/ml, and then submitted to macroscopic and microscopic analysis. As result it was identified a toxicity and cytotoxicity of V. polyanthes dependent on the extract concentration. The A. salina assay suggests that the concentration of 24 mg/ml of the V. polyanthes extract is able to kill 50% of naupllis; while the A. cepa assay suggests that V. polyanthes leaves aqueous extract is toxic at concentrations higher than 20 mg/ml; however the cytotoxic effect in A. cepa root cells was observed at 40 mg/ml of the extract. It is important to say that the V. polyanthes leaves aqueous extract concentration commonly used in popular medicine is 20 mg/ml. Thus, the popular concentration used is very close to toxicity limit in A. salina model (24 mg/ml) and is the concentration which showed toxic effect in A. cepa root cells (20 mg/ml). No genotoxic activity of V. polyantes leaves aqueous extract was observed in the conditions used in this study. Because of the antiproliferative action and no genotoxic activity, V. polyanthes leaves aqueous extract may present compounds with potential use for human medicine. However more detailed studies need to be performed to confirm this potential.

Generalized skin drug eruption to natalizumab in a patient with multiple sclerosis.

We report a generalized skin eruption in a young man being treated with natalizumab, a new drug used in patients with multiple sclerosis.

Report of a chimeric origin of transposable elements in a bovine-coding gene.

Despite the wide distribution of transposable elements (TEs) in mammalian genomes, part of their evolutionary significance remains to be discovered. Today there is a substantial amount of evidence showing that TEs are involved in the generation of new exons in different species. In the present study, we searched 22,805 genes and reported the occurrence of TE-cassettes in coding sequences of 542 cow genes using the RepeatMasker program. Despite the significant number (542) of genes with TE insertions in exons only 14 (2.6%) of them were translated into protein, which we characterized as chimeric genes. From these chimeric genes, only the FAST kinase domains 3 (FASTKD3) gene, present on chromosome BTA 20, is a functional gene and showed evidence of the exaptation event. The genome sequence analysis showed that the last exon coding sequence of bovine FASTKD3 is approximately 85% similar to the ART2A retrotransposon sequence. In addition, comparison among FASTKD3 proteins shows that the last exon is very divergent from those of Homo sapiens, Pan troglodytes and Canis familiares. We suggest that the gene structure of bovine FASTKD3 gene could have originated by several ectopic recombinations between TE copies. Additionally, the absence of TE sequences in all other species analyzed suggests that the TE insertion is clade-specific, mainly in the ruminant lineage.

Populational fluctuation and spatial distribution of Alphitobius diaperinus (Panzer) (Coleoptera; Tenebrionidae) in a poultry house, Cascavel, Parana state, Brazil.

Knowledge of the population fluctuation and spatial distribution of pests is fundamental for establishing an appropriate control method. The population fluctuation and spatial distribution of the Alphitobius diaperinus in a poultry house in Cascavel, in the state of Parana, Brazil, was studied between October, 2001 and October 2002. Larvae and adults of the lesser mealworm were sampled weekly using Arends tube traps (n = 22) for six consecutive flock grow-outs. The temperature of the litter and of the poultry house was measured at the same locations of the tube traps. Beetle numbers increased continuously throughout all the sampling dates (average 5,137 in the first week and 18,494 insects on the sixth week). Significantly greater numbers of larvae were collected than adults (1 to 20 times in 95% of the sampling points). There was no correlation between temperature and the number of larvae and adults collected, therefore no fluctuation was observed during the sampling period. The population growth was correlated to litter re-use. The highest temperatures were observed in deep litter. The spatial distribution of larvae and adults in the poultry house was heterogeneous during the whole period of evaluation. Results suggest that monitoring in poultry houses is necessary prior to adopting and evaluating control measures due to the great variability of the insect distribution in the poultry house.

New Species of Tenuisvalvae (Duverger) (Coleoptera: Coccinellidae) Feeding on Parthenolecanium perlatum (Cockerell) (Hemiptera: Coccidae) in Citrus Crop.

A new species of Hyperaspidini, Tenuisvalvae quadripunctata sp. nov. is described and illustrated. The genus is now represented by 11 species, all native of South America, and the new taxon is integrated into the existing key to species of the genus. Ecological data for T. quadripunctata sp. nov. and a list with prey and host plants to the species of the genus Tenuisvalvae are provided.

Learning curve for transbronchial lung cryobiopsy in diffuse lung disease.

INTRODUCTION: Transbronchial lung cryobiopsy (TBLC) is increasingly used in the diagnosis of diffuse lung disease (DLD), but no data have yet been published on the learning curve associated with this technique. AIM: To evaluate diagnostic yield, lung tissue sample length and area, and procedure-related complications in a cohort of TBLC procedures to define the learning curve and threshold for proficiency. METHODS: Retrospective analysis of the first 100 TBLCs performed in different segments of the same lobe in patients with suspected DLD. We compared diagnostic yield, sample length and area, and complications between consecutive groups of patients. RESULTS: The overall diagnostic yield for TBLC was 82%. Median sample length was 5.4mm (IQR, 5-6) and median area was 19.5mm2 (IQR, 13.3-25). Pneumothorax was the most common complication (18%). On comparing the two groups of 50 consecutive patients, a significant difference was found for diagnostic yield (74% vs 90%; p=0.04), sample length (5.0mm [2.5-16] vs 6.0mm [4-12;] p<0.01) and area (17.5mm2 [6-42] vs 21.5mm2 [10-49]; p<0.01). Logarithm regression was applied to median diagnostic yield and sample length and area for groups of 10 consecutive patients to define the learning curve, which plateaued after approximately 70 procedures. CONCLUSIONS: Our findings suggest that proficiency in TBLC is achieved at approximately the 70th procedure; however they need to be validated in more series and cohorts.

GLUT1, MCT1/4 and CD147 overexpression supports the metabolic reprogramming in papillary renal cell carcinoma.

Papillary Renal Cell carcinoma (pRCC) is the second most common type of RCC, accounting for about 15% of all RCCs. Surgical excision is the main treatment option. Still, 10 - 15 % of clinically localized tumours will recur and/or develop metastasis early after surgery, and no reliable prognostic biomarkers are available to identify them. It is known that pRCC cells rely on high rates of aerobic glycolysis, characterized by the up-regulation of many proteins and enzymes related with the glycolytic pathway. However, a metabolic signature enabling the identification of advanced pRCC tumours remains to be discovered. The aim of this study was to characterize the metabolic phenotype of pRCCs (subtypes 1-pRCC1 and 2-pRCC2) by evaluating the expression pattern of the glucose transporters (GLUTs) 1 and 4 and the monocarboxylate transporters (MCTs) 1 and 4, as well as their chaperon CD147. We analysed the clinico-pathological data and the protein and mRNA expression of GLUT1, GLUT4 and MCT1, MCT4 and CD147 in tumours from Porto and TCGA series (http://cancergenome.nih.gov/), respectively. With the exception of GLUT4, plasma membrane expression of all proteins was frequently observed in pRCCs. GLUT1 and MCT1 membrane overexpression was significantly higher in pRCC2 and significantly associated with higher pN-stage and higher Fuhrman grade. Overexpression of GLUT1, MCT1/4 and CD147, supports the metabolic reprograming in pRCCs. MCT1 expression was associated with pRCC aggressiveness, regardless of the tumour histotype.