Cetuximab chemotherapy resistance: Insight into the homeostatic evolution of head and neck cancer (Review).

The complex evolution of genetic alterations in cancer that occurs in vivo is a selective process involving numerous factors and mechanisms. Chemotherapeutic agents that prevent the growth and spread of cancer cells induce selective pressure, leading to rapid artificial selection of resistant subclones. This rapid evolution is possible because antineoplastic drugs promote alterations in tumor­cell metabolism, thus creating a bottleneck event. The few resistant cells that survive in this new environment obtain differential reproductive success that enables them to pass down the newly selected resistant gene pool. The present review aims to summarize key findings of tumor evolution, epithelial­mesenchymal transition and resistance to cetuximab therapy in head and neck squamous cell carcinoma.

Probiogenomics of Leuconostoc Mesenteroides Strains F-21 and F-22 Isolated from Human Breast Milk Reveal Beneficial Properties.

Bacteria of the Leuconostoc genus are Gram-positive bacteria that are commonly found in raw milk and persist in fermented dairy products and plant food. Studies have already explored the probiotic potential of L. mesenteroides, but not from a probiogenomic perspective, which aims to explore the molecular features responsible for their phenotypes. In the present work, probiogenomic approaches were applied in strains F-21 and F-22 of L. mesenteroides isolated from human milk to assess their biosafety at the molecular level and to correlate molecular features with their potential probiotic characteristics. The complete genome of strain F-22 is 1.99 Mb and presents one plasmid, while the draft genome of strain F-21 is 1.89 Mb and presents four plasmids. A high percentage of average nucleotide identity among other genomes of L. mesenteroides (≥ 96%) corroborated the previous taxonomic classification of these isolates. Genomic regions that influence the probiotic properties were identified and annotated. Both strains exhibited wide genome plasticity, cell adhesion ability, proteolytic activity, proinflammatory and immunomodulation capacity through interaction with TLR-NF-κB and TLR-MAPK pathway components, and no antimicrobial resistance, denoting their potential to be candidate probiotics. Further, the strains showed bacteriocin production potential and the presence of acid, thermal, osmotic, and bile salt resistance genes, indicating their ability to survive under gastrointestinal stress. Taken together, our results suggest that L. mesenteroides F-21 and F-22 are promising candidates for probiotics in the food and pharmaceutical industries.

Type I multivariate zero-inflated COM-Poisson regression model.

In this paper, we present the Type I multivariate zero-inflated Conway-Maxwell-Poisson distribution, whose development is based on the extension of the Type I multivariate zero-inflated Poisson distribution. We developed important properties of the distribution and present a regression model. The AIC and BIC criteria are used to select the best fitted model. Two real data sets have been used to illustrate the proposed model. Moreover, we conclude by stating that the Type I multivariate zero-inflated Conway-Maxwell-Poisson distribution produces a better fitted model for multivariate count data with excess of zeros.

Correlated geometric models of order k and its application to intensive care unit and leprosy data.

Geometric models are used to analyse the discrete time until the occurrence of an event of interest (success or consecutive successes). In two real data sets, named leprosy and intensive care unit (ICU), the events correspond, respectively, to abandoning the clinical treatment of leprosy, where abandonment corresponds to four consecutive patient absences from treatment, and the patient's discharge from the ICU. The distribution proposed in this article, called the correlated geometric distribution of order k (or correlated k-order geometric distribution), k≥1 , consists of including a correlation parameter in the geometric distribution of order k, thus considering the dependence between patient responses until the occurrence of the event. This model proves to be a better option for real data analysis where the effect of individual correlation is considered. The model is applied to real leprosy data to estimate the treatment abandonment probability. Bayesian methods are used to determine the parameter estimators of the models and to evaluate regression models. The covariates are related to the probability of the event by an appropriate link function chosen by Bayesian selection criteria. A diagnostic analysis evaluates the models fit by posterior randomized quantile residuals and influential observations by ψ -divergence measures. This methodology is illustrated by simulation studies and real ICU admission data analysis. Studies show a good fit of the proposed model. Real data analyses also find that the probabilities of the event of interest can be overestimated or underestimated when modeled without considering the effect of dependency on the model.

Production and performance of sugarcane seeds (caryopses) from different hybridizations involving RB92579.

A major challenge in sugarcane breeding program is the obtaining of enough number of seeds (caryopses) for the development of new improved cultivars. Genotypes differ in their function as pollen recipient and pollen donor, which also affect the seed performance. Thus, the aim of this study was to verify the production and performance of sugarcane seeds from different hybridizations involving RB92579 as pollen recipient and pollen donor. Twelve bi-parental crossings were carried out involving RB92579 and other different genotypes randomly chosen. Seed production potential was evaluated by percentage of fertile spikelets and caryopsis fresh weight. The seed physiological potential was determined by evaluating germination and vigor (index of germination rate, number of normal seedlings per gram of fuzz, and seedling dry weight). The results showed better performance for RB92579 as pollen donor for all characteristics studied. Therefore, RB92579 sugarcane cultivar should be used as pollen donor during hybridizations, condition that permits a greater production and physiological performance of seeds for the sugarcane breeding programs.

Quadruplex PCR assay for identification of Corynebacterium pseudotuberculosis differentiating biovar Ovis and Equi.

BACKGROUND: Corynebacterium pseudotuberculosis is classified into two biovars, nitrate-negative biovar Ovis which is the etiologic agent of caseous lymphadenitis in small ruminants and nitrate-positive biovar Equi, which causes abscesses and ulcerative lymphangitis in equines. The aim of this study was to develop a quadruplex PCR assay that would allow simultaneous detection and biovar-typing of C. pseudotuberculosis. METHODS: In the present study, genomes of C. pseudotuberculosis strains were used to identify the genes involved in the nitrate reduction pathway to improve a species identification three-primer multiplex PCR assay. The nitrate reductase gene (narG) was included in the PCR assay along with the 16S, rpoB and pld genes to enhance the diagnosis of the multiplex PCR at biovar level. RESULTS: A novel quadruplex PCR assay for C. pseudotuberculosis species and biovar identification was developed. The results of the quadruplex PCR of 348 strains, 346 previously well-characterized clinical isolates of C. pseudotuberculosis from different hosts (goats, sheep, horse, cattle, buffalo, llamas and humans), the vaccine strain 1002 and the type strain ATCC 19410T, were compared to the results of nitrate reductase identification by biochemical test. The McNemar's Chi-squared test used to compare the two methods used for C. pseudotuberculosis biovar identification showed no significant difference (P = 0.75) [95% CI for odds ratio (0.16-6.14)] between the quadruplex PCR and the nitrate biochemical test. Concordant results were observed for 97.13% (338 / 348) of the tested strains and the kappa value was 0.94 [95% CI (0.90-0.98)]. CONCLUSIONS: The ability of the quadruplex assay to discriminate between C. pseudotuberculosis biovar Ovis and Equi strains enhances its usefulness in the clinical microbiology laboratory.

Exploration of Nitrate Reductase Metabolic Pathway in Corynebacterium pseudotuberculosis.

Based on the ability of nitrate reductase synthesis, Corynebacterium pseudotuberculosis is classified into two biovars: Ovis and Equi. Due to the presence of nitrate reductase, the Equi biovar can survive in absence of oxygen. On the other hand, Ovis biovar that does not have nitrate reductase is able to adapt to various ecological niches and can grow on certain carbon sources. Apart from these two biovars, some other strains are also able to carry out the reduction of nitrate. The enzymes that are involved in electron transport chain are also identified by in silico methods. Findings about pathogen metabolism can contribute to the identification of relationship between nitrate reductase and the C. pseudotuberculosis pathogenicity, virulence factors, and discovery of drug targets.

Genome Sequence of Lactococcus lactis subsp. lactis NCDO 2118, a GABA-Producing Strain.

Lactococcus lactis subsp. lactis NCDO 2118 is a nondairy lactic acid bacterium, a xylose fermenter, and a gamma-aminobutyric acid (GABA) producer isolated from frozen peas. Here, we report the complete genome sequence of L. lactis NCDO 2118, a strain with probiotic potential activity.

A generalized approach to the modeling of the species-area relationship.

This paper proposes a statistical generalized species-area model (GSAM) to represent various patterns of species-area relationship (SAR), which is one of the fundamental patterns in ecology. The approach enables the generalization of many preliminary models, as power-curve model, which is commonly used to mathematically describe the SAR. The GSAM is applied to simulated data set of species diversity in areas of different sizes and a real-world data of insects of Hymenoptera order has been modeled. We show that the GSAM enables the identification of the best statistical model and estimates the number of species according to the area.

Complete genome sequence of Streptococcus agalactiae strain SA20-06, a fish pathogen associated to meningoencephalitis outbreaks.

Streptococcus agalactiae (Lancefield group B; GBS) is the causative agent of meningoencephalitis in fish, mastitis in cows, and neonatal sepsis in humans. Meningoencephalitis is a major health problem for tilapia farming and is responsible for high economic losses worldwide. Despite its importance, the genomic characteristics and the main molecular mechanisms involved in virulence of S. agalactiae isolated from fish are still poorly understood. Here, we present the genomic features of the 1,820,886 bp long complete genome sequence of S. agalactiae SA20-06 isolated from a meningoencephalitis outbreak in Nile tilapia (Oreochromis niloticus) from Brazil, and its annotation, consisting of 1,710 protein-coding genes (excluding pseudogenes), 7 rRNA operons, 79 tRNA genes and 62 pseudogenes.

The pan-genome of the animal pathogen Corynebacterium pseudotuberculosis reveals differences in genome plasticity between the biovar ovis and equi strains.

Corynebacterium pseudotuberculosis is a facultative intracellular pathogen and the causative agent of several infectious and contagious chronic diseases, including caseous lymphadenitis, ulcerative lymphangitis, mastitis, and edematous skin disease, in a broad spectrum of hosts. In addition, Corynebacterium pseudotuberculosis infections pose a rising worldwide economic problem in ruminants. The complete genome sequences of 15 C. pseudotuberculosis strains isolated from different hosts and countries were comparatively analyzed using a pan-genomic strategy. Phylogenomic, pan-genomic, core genomic, and singleton analyses revealed close relationships among pathogenic corynebacteria, the clonal-like behavior of C. pseudotuberculosis and slow increases in the sizes of pan-genomes. According to extrapolations based on the pan-genomes, core genomes and singletons, the C. pseudotuberculosis biovar ovis shows a more clonal-like behavior than the C. pseudotuberculosis biovar equi. Most of the variable genes of the biovar ovis strains were acquired in a block through horizontal gene transfer and are highly conserved, whereas the biovar equi strains contain great variability, both intra- and inter-biovar, in the 16 detected pathogenicity islands (PAIs). With respect to the gene content of the PAIs, the most interesting finding is the high similarity of the pilus genes in the biovar ovis strains compared with the great variability of these genes in the biovar equi strains. Concluding, the polymerization of complete pilus structures in biovar ovis could be responsible for a remarkable ability of these strains to spread throughout host tissues and penetrate cells to live intracellularly, in contrast with the biovar equi, which rarely attacks visceral organs. Intracellularly, the biovar ovis strains are expected to have less contact with other organisms than the biovar equi strains, thereby explaining the significant clonal-like behavior of the biovar ovis strains.

Whole-genome sequence of Corynebacterium pseudotuberculosis strain Cp162, isolated from camel.

Corynebacterium pseudotuberculosis is a pathogen of great veterinary and economic importance, since it affects livestock, mainly sheep and goats, worldwide, together with reports of its presence in camels in several Arabic, Asiatic, and East and West African countries, as well as Australia. In this article, we report the genome sequence of Corynebacterium pseudotuberculosis strain Cp162, collected from the external neck abscess of a camel in the United Kingdom.

Complete genome sequence of Corynebacterium pseudotuberculosis strain Cp267, isolated from a llama.

In this work we report the genome of Corynebacterium pseudotuberculosis strain 267, isolated from a llama. This pathogen is of great veterinary and economic importance, as it is the cause of caseous lymphadenitis in several livestock species around the world and causes significant losses due to the high cost of treatment.

Complete genome sequence of Corynebacterium pseudotuberculosis biovar ovis strain P54B96 isolated from antelope in South Africa obtained by rapid next generation sequencing technology.

The Actinobacteria, Corynebacterium pseudotuberculosis strain P54B96, a nonmotile, non-sporulating and a mesophile bacterium, was isolated from liver, lung and mediastinal lymph node lesions in an antelope from South Africa. This strain is interesting in the sense that it has been found together with non-tuberculous mycobacteria (NTMs) which could nevertheless play a role in the lesion formation. In this work, we describe a set of features of C. pseudotuberculosis P54B96, together with the details of the complete genome sequence and annotation. The genome comprises of 2.34 Mbp long, single circular genome with 2,084 protein-coding genes, 12 rRNA, 49 tRNA and 62 pseudogenes and a G+C content of 52.19%. The analysis of the genome sequence provides means to better understanding the molecular and genetic basis of virulence of this bacterium, enabling a detailed investigation of its pathogenesis.

Estudo epidemiológico do setor madeireiro atendido em uma unidade técnica de reabilitação profissional / Epidemiological study of the timber sector seen in a unit technical vocational rehabilitation

Analisar a ocorrência, as características e as perdas funcionais decorrentes dos acidentes e doenças relacionados ao trabalho em indivíduos do setor madeireiro encaminhados à reabilitação profissional. Método: realizou-se um estudo seccional, a partir de dados secundários, coletados na Unidade Técnica de Reabilitação Profissional (UTRP) do INSS em Belém - Pará, com 53 trabalhadores. Resultados: o perfil sócio-demográfico dos beneficiários foi constituído predominantemente por: homens (98,1%); adulto-jovens em idade produtiva entre 20 a 49 anos (96,2%); casados (64,2%); de 1 a 3 filhos (69,8%); com até o ensino fundamental (81,2%) e com renda familiar entre 230 a 485 reais. Os agravos que mais geraram benefício e posterior indicação para a reabilitação profissional são os acidentes envolvendo o punho e mão, as doenças do sistema nervoso e as doenças do sistema osteomuscular. Considerações finais: confirmou-se que o setor madeireiro é uma atividade de condições, que ocasiona doenças e acidentes graves, muitas das vezes, incapacitando os trabalhadores para a atividade produtiva; situação agravada, pelo fato da maioria ter baixo nível de escolaridade e baixa remuneração.

To analyze the occurrence, characteristics and the functional losses resulting from accidents and work-related diseases in individuals of the logging industry referred to vocational rehabilitation. Method: it was a cross-sectional study from secondary data, collected at the Technical Unit of Vocational Rehabilitation (UTRP)/INSS in Belém - Pará, with 53 employees. Results: the socio-demographic profile of beneficiaries was composed mainly of: men (98.1%), adult-productive young people aged 20 to 49 years (96.2%), married (64.2%) with one or three children (69.8%), with some schooling (81.2%) and family income between 230 to 485 reais. The grievances that led to more effective and further indication for the vocational rehabilitation are accidents involving the wrist and hand, diseases of the nervous system and diseases of the musculoskeletal system. Conclusion: it was confirmed that the timber industry is an activity conditions, which causes serious illness and accidents, many times, incapacitating workers into productive activity, a situation aggravated by the fact that most have low education and low pay.

Aneurisma de veia poplítea: relato de caso e revisão de literatura / Popliteal vein aneurysm: case report and review of the literature

Os aneurismas venosos são entidades raras, porém com potencialidade de causar complicações tromboembólicas. Na maioria das vezes, são encontrados incidentalmente, como achados de exame físico ou de imagem. Os aneurismas sintomáticos de veia poplítea são obrigatoriamente tratados por reparo cirúrgico, devido ao alto risco de recorrência de embolia pulmonar. A técnica mais utilizada é a aneurismectomia tangencial com venorrafia lateral. Na impossibilidade de se empregar essa técnica, faz-se a ressecção com reconstrução venosa. Os autores relatam o caso de uma paciente com aneurisma de veia poplítea, cujo diâmetro era de 47 mm, submetido a aneurismectomia tangencial e venorrafia lateral, com sucesso.

Venous aneurysms are considered to be a rare disease; however they can be a potential cause for the development of thromboembolism. They are mostly detected by physical examination or imaging exams. Symptomatic aneurysms of the popliteal vein must be surgically treated, due to high risk of recurrent pulmonary embolism. The most widely used procedure is tangential aneurysmectomy and lateral venorrhaphy. If not possible, the aneurysm should be removed and a venous reconstruction should be performed. The authors report a case of a patient with a popliteal vein aneurysm measuring 47 mm in diameter. Tangential aneurysmectomy and lateral venorrhaphy were successfully used for treatment.

Avaliação ergonômica de movelarias e ocorrências de queixas osteoarticulares entre os moveleiros, em Tomé-Açu (PA) / Ergonomic evaluation of movelarias and occurrences of complaints osteoarthropatys between the moveleiros, in Tomé-Açu (Pará)

Objetivo: avaliar ergonomicamente os ambientes em fábricas de móveis no município de Tomé-açu (PA), verificando a ocorrência de queixas osteoarticulares relacionadas à atividade laboral entre os trabalhadores moveleiros. Método: estudo epidemiológico transversal onde foram selecionados 40 trabalhadores de 13 movelarias, os quais foram submetidos a um questionário com itens referentes ao perfil sócio-demográfico, à percepção do trabalhador sobre seu ambiente de trabalho e a presença de queixas osteo-articulares. Resultados: a maior porcentagem dos entrevistados são adultos jovens, com baixo nível de escolaridade, casados, acima do peso ideal e apontaram o acabamento do móvel como atividade mais cansativa e a poeira como fator ambiental que mais incomoda. Os trabalhadores não utilizavam Equipamento de Proteção Individual (EPIs), citaram a concentração e atenção como essenciais para realizarem suas atividades e ficavam a maior parte do tempo em pé com semi-flexão do tronco. A principal queixa dos trabalhadores foi a dor, principalmente em região lombar e 25% já faltaram ao trabalho por causa da mesma. Conclusão: o trabalho nas movelarias do município de Tomé-açu é realizado em condições inadequadas de segurança, oferecendo riscos à saúde dos trabalhadores.

Objective: ergonomicaly ta evaluate environments in plants af furniture in the city of Tomé-açu (Pará, verifying the occurrence of related complaints osteo-to articulate to the labor activity between the moveleiro workers. Method: study transversal epidemiologist where 40 workers of 13 referring movelarias had bee selected which they had been submitted to a questionnaire with itens to the partner-demographic profile, the perception of the worker on its environment of work and the presence of complaints osteo-to articulate. Results: the biggest percentage of the interviewed ones is adult young, with low level of escolaridade, married, above of ideal weight e, had pointed the finishing of the furniture as more tiring activity and the dust as ambient factor that more bothers. The workers did not use Equipment of Individual Protection (EPIs), had cited the concentration and attention as essential to carry through its activities and, they were most of the time in foot with half-flexão of the trunk. The main complaint of the workers was pain, mainly in lumbar region, and 25%already had lacked to the work because of the same one. Conclusion: the work in the movelarias oft he city of Tomé-açu is carried through in inadequate conditions of security, having offered risks to the health of the workers.

Evaluation of neurodevelopmental effects on rats exposed prenatally to sulfentrazone.

Although some studies have pointed to embryo/fetal toxicity at treatment levels that were not maternally toxic, knowledge about the potential toxic effects of the herbicide sulfentrazone is still limited. Since the results of these studies have raised some concern, the present work studied the effects of sulfentrazone maternal exposure on the physical and neurobehavioral endpoints in the development of rat pups. To accomplish that, the effects of the herbicide sulfentrazone (25 and 50mg/kg) were examined at two different developmental stages in rats: during the first 6 days of gestation, or in the organogenesis period (6-15 days). After parturition, pups were tested in a developmental test battery including measures of growth, maturational milestones, and neurobehavioral development. Maternal exposure to the herbicide resulted in significant alterations of the postnatal age at which the developmental milestones of ear and eye opening and testes descent were observed. There was a reduced weight gain rate in pups and their mothers when treated during the gestational period at the highest dose tested. Also, the functional state of the rat pup nervous system at different stages of postnatal development showed some neurodevelopmental delays in righting reflex, negative geotaxis, grip response, and motor coordination-locomotion and rearing (21-90 days of life) in the treated groups. Herbicide genotoxicity was investigated in fresh leukocytes both in mothers and pups using the comet assay: the data did not show any significant genotoxic effect induced by the herbicide. The findings of this study emphasize that sulfentrazone maternal exposure may lead to some neuromuscular and behavioral deficits in nursing pups.

Pseudo-aneurisma de artéria tibial posterior pós-tratamento de fratura de perna com fixador externo: relato de caso e revisão da literatura / Pseudoaneurysm of the posterior tibial artery after external fixation for leg fracture: case report and review of the literature

Este trabalho descreve um caso de pseudo-aneurisma da artéria tibial posterior devido ao uso de fixador externo para tratamento de fratura dos ossos da perna (técnica de Ilizarov), bem como as técnicas utilizadas para seu tratamento. A compressão guiada por ultra-som e a injeção de trombina guiada por ultra-som foram realizadas, sem sucesso. O tratamento definitivo do pseudo-aneurisma e reconstrução arterial foi conseguido através do tratamento cirúrgico clássico, usando enxerto interposto de veia safena magna homóloga invertida. As indicações, vantagens e desvantagens das técnicas de tratamento não invasivo (compressão guiada por ultra-som e injeção de trombina guiada por ultra-som) e as possíveis causas de sua incapacidade na obliteração do pseudo-aneurisma são discutidas. Também foi realizada a revisão de casos de pseudo-aneurisma da artéria tibial posterior na literatura médica, encontrando-se apenas um caso semelhante, entre 24 publicados.

We describe a case of pseudoaneurysm in the posterior tibial artery following treatment for tibial and fibula fractures using external fixation (Ilizarov technique), as well as the techniques used for its treatment. Ultrasound-guided compression and ultrasound-guided thrombin injection were unsuccessfully performed. Definite treatment of pseudoaneurysm and arterial reconstruction was achieved through the traditional surgical treatment, using interposed graft of inverted homologous great saphenous vein. Indications, advantages and disadvantages of noninvasive treatment techniques (ultrasound-guided compression and ultrasound-guided thrombin injection) and the possible causes of their inability in obliterating the pseudoaneurysm are discussed. A literature review of pseudoaneurysms of the posterior tibial artery was also carried out, resulting in only one similar case out of 24 published cases.

Neurodevelopmental effects of perinatal fenarimol exposure on rats.

Knowledge about the potential toxic effects of fenarimol, a widely used fungicide, is still limited. Fenarimol is an aromatase inhibitor and therefore can affect estrogen/androgen levels in vivo in rodents. In view of these facts, the aim of the present work was to study the effects of fenarimol maternal exposure during different critical phases in the development of central nervous system in rat pups, on early physical and neurobehavioral endpoints essential to their development. For that, the effects of the fungicide fenarimol (150 and 300 mg/kg) were examined at three different developmental stages in the rat: during the first 6 days of gestation, prenatal (15-21 days), or first 6 days of lactation. Three categories of the impact of fenarimol on neonatal growth and neurobehavioral development of offspring were assessed: (1) physical, (2) reflex and strength, and (3) motor coordination. Findings on the pups' physical development did not indicate any significant alterations of the postnatal age at which specific developmental milestones were observed (pinna detachment, development of the fur, eruption of the incisor teeth, opening of the ears and eyes and testes descent). However, there was a reduced rate of weight gain in pups of mothers treated during lactation related to the earlier testing time periods (1-23 days of life). The study of the functional state of the rat pup nervous systems at different stages of postnatal development revealed some neurodevelopmental delays in righting reflex, climbing and grip response and locomotion (20-90 days of life) in the treated groups. Taken together, findings of this study emphasize that, as a result of fenarimol maternal exposure, some neuromuscular and behavioral deficits in nursing pups may occur principally during the last gestational period and lactation. These results could be the basis for further studies on molecular actions of fenarimol in order to predict better the biological consequences of this fungicide.