Effectiveness and safety of botulinum toxin in comparison with surgery for drooling in paediatric patients with neurological disorders: a systematic review.

Different therapeutic methods for chronic drooling in paediatric patients with neurological problems have been described in the scientific literature. However, there is no consensus on the ideal strategy of treatment. The aim of this study was to compare botulinum toxin injection therapy and surgical modalities to control drooling in paediatric patients with neurological disorders. A systematic literature search was conducted on nine electronic databases for publications until April 2020. Six articles were included with a total sample of 209 patients, 67.4% (n = 141) of whom had cerebral palsy. All studies used injections of botulinum toxin type A with application to the submandibular and/or parotid salivary glands. The surgical treatments were duct ligation in the parotid and/or submandibular salivary glands, duct relocation in the submandibular salivary glands, and glandular excision of the submandibular and sublingual salivary glands. There were complications in only 16.1% (n = 27) of the sample (11 cases due to botulinum toxin application and 16 due to surgery). Drooling control was assessed by objective and subjective measures. Although surgical procedures presented a higher risk of adverse effects than botulinum toxin type A in all the studies and measurements performed, they presented larger and longer-lasting positive effects on drooling. We suggest bilateral submandibular duct relocation with bilateral sublingual gland excision or isolated bilateral submandibular duct ligation, which were the surgical techniques with the largest samples in this review. Nevertheless, further studies are necessary to compare samples with botulinum toxin type A and surgical treatment.

ANP32A represses Wnt signaling across tissues thereby protecting against osteoarthritis and heart disease.

OBJECTIVES: To investigate how ANP32A, previously linked to the antioxidant response, regulates Wnt signaling as unraveled by transcriptome analysis of Anp32a-deficient mouse articular cartilage, and its implications for osteoarthritis (OA) and diseases beyond the joint. METHODS: Anp32a knockdown chondrogenic ATDC5 cells were cultured in micromasses. Wnt target genes, differentiation markers and matrix deposition were quantified. Wnt target genes were determined in articular cartilage from Anp32a-deficient mice and primary human articular chondrocytes upon ANP32A silencing, using qPCR, luciferase assays and immunohistochemistry. Co-immunoprecipitation, immunofluorescence and chromatin-immunoprecipitation quantitative PCR probed the molecular mechanism via which ANP32A regulates Wnt signaling. Anp32a-deficient mice were subjected to the destabilization of the medial meniscus (DMM) OA model and treated with a Wnt inhibitor and an antioxidant. Severity of OA was assessed by cartilage damage and osteophyte formation. Human Protein Atlas data analysis identified additional organs where ANP32A may regulate Wnt signaling. Wnt target genes were determined in heart and hippocampus from Anp32a-deficient mice, and cardiac hypertrophy and fibrosis quantified. RESULTS: Anp32a loss triggered Wnt signaling hyper-activation in articular cartilage. Mechanistically, ANP32A inhibited target gene expression via histone acetylation masking. Wnt antagonist treatment reduced OA severity in Anp32a-deficient mice by preventing osteophyte formation but not cartilage degradation, contrasting with antioxidant treatment. Dual therapy ameliorated more OA features than individual treatments. Anp32a-deficient mice also showed Wnt hyper-activation in the heart, potentially explaining the cardiac hypertrophy phenotype found. CONCLUSIONS: ANP32A is a novel translationally relevant repressor of Wnt signaling impacting osteoarthritis and cardiac disease.

Long noncoding RNA polymorphisms influence susceptibility to endemic pemphigus foliaceus.

BACKGROUND: Pemphigus foliaceus (PF) is an epidermal autoimmune disease, characterized by the presence of autoantibodies against the desmosomal protein desmoglein 1. Genetic and environmental factors contribute to PF, a complex disease that is endemic in Brazil and Colombia and neighbouring countries, and in Tunisia. Long noncoding RNAs (lncRNAs) may participate in gene regulation by interacting with DNA, proteins and other RNAs. Dysregulation of lncRNAs has recently been recognized as an important coplayer in the onset or progression of complex diseases. In addition, single-nucleotide polymorphisms (SNPs) located in lncRNA genes have been associated with differential risk to cancer, autoimmunity and infection. OBJECTIVES: Here, we aimed to investigate whether SNPs in lncRNA genes are associated with differential susceptibility to endemic PF. MATERIALS AND METHODS: We integrated data from the lncRNA SNP database with genome-wide genotype data obtained for 229 patients and 6681 controls. We tested the association between endemic PF and 2080 SNPs located in lncRNAs applying logistic regression. RESULTS: The most significantly associated SNP was rs7144332 (OR = 1·63, P = 2·8 × 10-6 ), located in the lncRNA gene AL110292·1. Results for five other SNPs were suggestive of association (P < 0·001). In silico analysis indicated that five of the six SNPs impact transcription, three may influence lncRNA's secondary structure, and three may alter microRNA-lncRNA interactions. CONCLUSIONS: We showed, for the first time, that variation in lncRNA genes may influence pemphigus pathogenesis. Our findings highlight the importance of lncRNA variation in autoimmune and possibly other complex diseases and suggest polymorphisms for functional validation.

Three-dimensional surface models of the facial soft tissues acquired with a low-cost scanner.

Although there has been an increase in three-dimensional (3D) scanning methods available on the market, they are generally expensive. The DI3D system is considered a good scanner for the acquisition of soft tissue surface images. The Microsoft Kinect scanner is a much more affordable alternative for acquiring 3D models. The aim of this study was to determine whether the precision and accuracy of Kinect are similar to those of DI3D. To verify the accuracy, 10 patients were scanned with both methods The models of each patient acquired from the two scanners were superimposed using a surface-to-surface registration technique, and the distances between the models were recorded for 10 different anatomical regions of interest. For the evaluation of precision, one patient was scanned 11 different times with the Kinect scanner, and these models were compared using the same superimposition method. It was found that the average difference between the two methods was 0.3±2.03mm. The assessment of reproducibility showed an average difference between the images taken with Kinect of 0.1±0.6mm (P<0.05, one-sample t-test). Thus, Kinect showed good precision and reasonable accuracy, and appears to be an interesting and promising resource for facial analysis.

A HYBRID THREE-SCALE MODEL OF TUMOR GROWTH.

Cancer results from a complex interplay of different biological, chemical, and physical phenomena that span a wide range of time and length scales. Computational modeling may help to unfold the role of multiple evolving factors that exist and interact in the tumor microenvironment. Understanding these complex multiscale interactions is a crucial step towards predicting cancer growth and in developing effective therapies. We integrate different modeling approaches in a multiscale, avascular, hybrid tumor growth model encompassing tissue, cell, and sub-cell scales. At the tissue level, we consider the dispersion of nutrients and growth factors in the tumor microenvironment, which are modeled through reaction-diffusion equations. At the cell level, we use an agent based model (ABM) to describe normal and tumor cell dynamics, with normal cells kept in homeostasis and cancer cells differentiated apoptotic, hypoxic, and necrotic states. Cell movement is driven by the balance of a variety of forces according to Newton's second law, including those related to growth-induced stresses. Phenotypic transitions are defined by specific rule of behaviors that depend on microenvironment stimuli. We integrate in each cell/agent a branch of the epidermal growth factor receptor (EGFR) pathway. This pathway is modeled by a system of coupled nonlinear differential equations involving the mass laws of 20 molecules. The rates of change in the concentration of some key molecules trigger proliferation or migration advantage response. The bridge between cell and tissue scales is built through the reaction and source terms of the partial differential equations. Our hybrid model is built in a modular way, enabling the investigation of the role of different mechanisms at multiple scales on tumor progression. This strategy allows representating both the collective behavior due to cell assembly as well as microscopic intracellular phenomena described by signal transduction pathways. Here, we investigate the impact of some mechanisms associated with sustained proliferation on cancer progression. Specifically, we focus on the intracellular proliferation/migration-advantage-response driven by the EGFR pathway and on proliferation inhibition due to accumulation of growth-induced stresses. Simulations demonstrate that the model can adequately describe some complex mechanisms of tumor dynamics, including growth arrest in avascular tumors. Both the sub-cell model and growth-induced stresses give rise to heterogeneity in the tumor expansion and a rich variety of tumor behaviors.

Selection, calibration, and validation of models of tumor growth.

This paper presents general approaches for addressing some of the most important issues in predictive computational oncology concerned with developing classes of predictive models of tumor growth. First, the process of developing mathematical models of vascular tumors evolving in the complex, heterogeneous, macroenvironment of living tissue; second, the selection of the most plausible models among these classes, given relevant observational data; third, the statistical calibration and validation of models in these classes, and finally, the prediction of key Quantities of Interest (QOIs) relevant to patient survival and the effect of various therapies. The most challenging aspects of this endeavor is that all of these issues often involve confounding uncertainties: in observational data, in model parameters, in model selection, and in the features targeted in the prediction. Our approach can be referred to as "model agnostic" in that no single model is advocated; rather, a general approach that explores powerful mixture-theory representations of tissue behavior while accounting for a range of relevant biological factors is presented, which leads to many potentially predictive models. Then representative classes are identified which provide a starting point for the implementation of OPAL, the Occam Plausibility Algorithm (OPAL) which enables the modeler to select the most plausible models (for given data) and to determine if the model is a valid tool for predicting tumor growth and morphology (in vivo). All of these approaches account for uncertainties in the model, the observational data, the model parameters, and the target QOI. We demonstrate these processes by comparing a list of models for tumor growth, including reaction-diffusion models, phase-fields models, and models with and without mechanical deformation effects, for glioma growth measured in murine experiments. Examples are provided that exhibit quite acceptable predictions of tumor growth in laboratory animals while demonstrating successful implementations of OPAL.

Influence of anxiety on temporomandibular disorders--an epidemiological survey with elders and adults in Southern Brazil.

The socio-economic and psychological factors and the use of and need for dental prostheses have been associated with prevalence and severity of temporomandibular disorders (TMD). The aim of this study was to evaluate the association of socio-economic and psychological factors, use of and need for dental prostheses with the prevalence and severity of signs and symptoms of temporomandibular disorders (TMD). A cross-sectional study was conducted in Luzerna/Brazil. All individuals aged 35-44 (adults) and 65-74 (elders) were invited to participate in this study. The measuring instrument included a questionnaire application and the clinical evaluation regarding signs and symptoms of TMD. Descriptive analyses, chi-squared test, unadjusted and adjusted Poisson regression were used for the statistic analysis. The level of statistical significance was given when P ≤ 0·05. In total, 568 individuals (338 adults and 230 elders) were included; among them, 43·5% had absent, 42·6% mild, 11·3% moderate and 2·6% severe TMD. The presence of higher TMD rates was found in females (P = 0·001), and the TMD occurrence increased with anxiety level (P = 0·001). Other socio-economic factors, such as colour (P = 0·115), family structure (P = 0·478), age (P = 0·143), social class (P = 0·935) and education (P = 0·678) showed no influence. In conclusion, the female gender and individuals with higher levels of anxiety had increased prevalence of signs and symptoms of TMD. Additionally, was not founded association between TMD and use of and need for dental prostheses.

Bacteriophage amplification assay for detection of Listeria spp. using virucidal laser treatment

A protocol for the bacteriophage amplification technique was developed for quantitative detection of viable Listeria monocytogenes cells using the A511 listeriophage with plaque formation as the end-point assay. Laser and toluidine blue O (TBO) were employed as selective virucidal treatment for destruction of exogenous bacteriophage. Laser and TBO can bring a total reduction in titer phage (ca. 10(8) pfu/mL) without affecting the viability of L. monocytogenes cells. Artificially inoculated skimmed milk revealed mean populations of the bacteria as low as between 13 cfu/mL (1.11 log cfu/mL), after a 10-h assay duration. Virucidal laser treatment demonstrated better protection of Listeria cells than the other agents previously tested. The protocol was faster and easier to perform than standard procedures. This protocol constitutes an alternative for rapid, sensitive and quantitative detection of L. monocytogenes.

Bacteriophage amplification assay for detection of Listeria spp. using virucidal laser treatment.

A protocol for the bacteriophage amplification technique was developed for quantitative detection of viable Listeria monocytogenes cells using the A511 listeriophage with plaque formation as the end-point assay. Laser and toluidine blue O (TBO) were employed as selective virucidal treatment for destruction of exogenous bacteriophage. Laser and TBO can bring a total reduction in titer phage (ca. 10(8) pfu/mL) without affecting the viability of L. monocytogenes cells. Artificially inoculated skimmed milk revealed mean populations of the bacteria as low as between 13 cfu/mL (1.11 log cfu/mL), after a 10-h assay duration. Virucidal laser treatment demonstrated better protection of Listeria cells than the other agents previously tested. The protocol was faster and easier to perform than standard procedures. This protocol constitutes an alternative for rapid, sensitive and quantitative detection of L. monocytogenes.

Soft tissue response to mandibular advancement using 3D CBCT scanning.

This prospective longitudinal study assessed the 3D soft tissue changes following mandibular advancement surgery. Cranial base registration was performed for superimposition of virtual models built from cone beam computed tomography (CBCT) volumes. Displacements at the soft and hard tissue chin (n = 20), lower incisors and lower lip (n = 21) were computed for presurgery to splint removal (4-6-week surgical outcome), presurgery to 1 year postsurgery (1-year surgical outcome), and splint removal to 1 year postsurgery (postsurgical adaptation). Qualitative evaluations of color maps illustrated the surgical changes and postsurgical adaptations, but only the lower lip showed statistically significant postsurgical adaptations. Soft and hard tissue chin changes were significantly correlated for each of the intervals evaluated: presurgery to splint removal (r = 0.92), presurgery to 1 year postsurgery (r = 0.86), and splint removal to 1 year postsurgery (r = 0.77). A statistically significant correlation between lower incisor and lower lip was found only between presurgery and 1 year postsurgery (r = 0.55). At 1 year after surgery, 31% of the lower lip changes were explained by changes in the lower incisor position while 73% of the soft tissue chin changes were explained by the hard chin. This study suggests that 3D soft tissue response to mandibular advancement surgery is markedly variable.

Prevalência e fatores de risco para a leptospirose em bovinos de Mato Grosso do Sul / Prevalence and risk factors for bovine leptospirosis in Mato Grosso do Sul, Brazil

Foi investigada a prevalência de anticorpos antileptospira em fêmeas bovinas com idade igual ou superior a 24 meses, provenientes de 178 rebanhos de 22 municípios do estado de Mato Grosso do Sul, bem como identificados fatores de risco associados à infecção. Foram analisadas 2.573 amostras de soro sangüíneo por meio do teste de soroaglutinação microscópica perante 10 sorovares de leptospira. Títulos iguais ou superiores a 100 para um ou mais sorovares foram detectados em 1.801 fêmeas (98,8 por cento) de 161 (96,5 por cento) rebanhos. O sorovar Hardjo (65,6 por cento) foi apontado como o mais provável, seguido do sorovar Wolffi (12,3 por cento). Os resultados demonstram que a leptospirose bovina se encontra presente em todos os municípios estudados, com alta prevalência, tanto em animais como em rebanhos. Os fatores de risco identificados neste estudo e associados à infecção por bactérias do gênero lepstopira foram o tipo de exploração pecuária de corte e a raça Zebu.

The prevalence of anti-Leptospira spp. antibodies was estimated for female cattle aged 24 months or older. The sample comprised 178 herds from 22 counties in the state of Mato Grosso do Sul, Brazil. The risk factors associated with the presence of infeccion were investigated. A total of 2,573 blood serum samples were tested against 10 leptospira serovars using the microagglutination test (MAT). Titers of 100 or higher for one or more serovars were detected in 1,801 females (98.8 percent) from 161 herds (96.5 percent). Serovar Hardjo (65.6 percent) was the most frequent, followed by serovar Wolffi (12.3 percent). These results suggest that bovine leptospirosis is widespread in all the counties under study, with a high prevalence both at the animal and the herd level. Beef farms and the Zebu breed were associated to the higher risk of herd infection by leptospiras.

Perception of oral maxillofacial surgery by health-care professionals.

Oral and Maxillofacial Surgery (OMFS), a dentistry specialty recognized by the Federal Dentistry Board in the mid-1960s, is responsible for the diagnosis, and clinical and surgical treatment of traumatic, congenital, developmental and iatrogenic lesions in the maxillofacial complex. Even today, difficulties are experienced owing to the lack of knowledge of the general public and health professionals concerning the scope of OMFS. To investigate recognition of the scope of OMFS, 400 questionnaires were sent to dentistry students, medical students, dentists and doctors, in 4 equal groups. The questionnaire covered 26 clinical situations in four different specialties (OMFS, Plastic Surgery, Ear Nose and Throat Surgery, Head and Neck Surgery) and an option with no specialty specified. Each interviewee had to correlate the clinical situation with the respective specialist. For facial trauma, dento-facial deformities, mandibular reconstruction and temporomandibular joint surgery, most respondents would consult the OMF surgeon for treatment (mean, 90%). In cases of oral biopsy and treatment of benign mandibular tumours the mean referral rate to OMFS was low (48%). On the basis of the questionnaire responses, a good level of knowledge of the scope of OMFS was found. In order to ensure the correct referral of all patients, the specialty needs to broaden its horizons.

Investigação epidemiológica da brucelose bovina em um estrato do Estado de Mato Grosso do Sul / Epidemiological investigation of bovine brucellosis in an extract of Mato Grosso do Sul, Brazil

O objetivo deste estudo foi estimar a prevalência da brucelose bovina nos 22 municípios que compõem a região denominada Estrato 1 do Estado de Mato Grosso do Sul, e identificar os fatores de risco associados à infecção. A região amostrada constitui uma área de 70.214,1 km2, que representa 19,7% do Estado. O rebanho de região estudada é de, aproximadamente, 5,7 milhões de cabeças, correspondente a 23% do efetivo de 24,9 milhões de bovinos de Mato Grosso do Sul. Nas 210 propriedades amostradas, no período de dezembro de 2003 a março de 2004, foram colhidas 2.376 amostras de sangue de fêmeas com idade igual ou superior a 24 meses, submetidas a testes diagnósticos em série. A triagem, realizada por meio do teste do antígeno acidificado tamponado, foi seguida pelo teste confirmatório 2-mercaptoetanol. Na mesma ocasião da colheita das amostras, foi preenchido um questionário com informações de identificação, tipo de criação e práticas de manejo. Em animais, a prevalência real foi estimada em 5,6%, e em rebanhos, 37,3%. As variáveis que apresentaram associação, por meio da análise univariada odds ratio (OR) e intervalo de confiança (IC) de 95%, com a soropositividade à brucelose foram: o tipo de exploração corte (OR = 2,82, IC 95% = 1,49-5,34), a raça Zebu (OR = 2,62, IC 95% = 1,40-4,88) e o aborto (OR= 1,83, IC 95% = 1,01-3,33). Os resultados demonstram que, além da brucelose ser prevalente no estrato estudado em Mato Grosso do Sul, o controle da doença pode consistir na adoção de programa com especial atenção à exploração do tipo corte, à raça Zebu e à presença do aborto.

The study aimed to estimate the prevalence of bovine brucellosis in 22 counties which make up the region Extract 1 of the State of Mato Grosso do Sul, Brazil, in order to identify risk factors associated with the infection. The sample region encompasses an area of 70,214.1 km2 and represents 19.7% of the State. The region studied has about 5.7 million head of cattle, corresponding to 23% of the total of 24.9 million cattle in the State of Mato Grosso do Sul. On 210 farms, between December 2003 and March 2004, 2,376 blood samples were collected from cows, aged 24 months or older, for serial diagnostic tests. Screening through the buffered acidified antigen test was confirmed by the 2-mercaptoetanol test. On the occasion of sample collection a questionnaire with information related to identification, kind of cattle and management practices was filled out. In individual animals the real prevalence was estimated at 5.6%, and in the cattle herds at 37.3%. The variables, which presented association through odds ratio (OR), univariate analysis and 95% confidence interval (CI) with serum positivity for brucellosis, were: the exploration of beef cattle (OR = 2.82, 95% CI = 1.49-5.34), Zebu breed (OR = 2.62, 95% CI = 1.40-4.88) and abortion (OR = 1.83, 95% CI = 1.01-3.33). The results shown here demonstrate, despite the prevalence of brucellosis in the extract of Mato Grosso do Sul studied, that the control of the disease may depend on adoption of a program focusing upon the exploration of beef cattle, the Zebu breed and the occurrence of abortion.

Occurrence of Listeria spp. in critical control points and the environment of Minas Frescal cheese processing.

Critical control points (CCPs) associated with Minas Frescal cheese (a Brazilian soft white cheese, eaten fresh) processing in two dairy factories were determined using flow diagrams and microbiological tests for detection of Listeria monocytogenes and other species of Listeria. A total of 218 samples were collected along the production line and environment. The CCPs identified were reception of raw milk, pasteurization, coagulation and storage. Thirteen samples were positive for Listeria; 9 samples were Listeria innocua, 2 were Listeria grayi and 2 were L. monocytogenes. In factory A, Listeria was found in 50% of raw milk samples, 33.3% of curd samples, 16.7% of pasteurized milk samples, 16.7% of cheese samples and 25% of rubber pipes used to transport the whey. The microorganism was not obtained from environmental samples in this plant. In factory B, Listeria was found in one sample of raw milk (16.7%) and in three samples of environment (17.6%) and L. monocytogenes was obtained from raw milk (16.7%) and the floor of the cheese refrigeration room (14.3%). Two serotypes, 4b and 1/2a, were observed among the strains of L. monocytogenes isolated, both which are frequently involved in outbreaks of food-borne listeriosis and sporadic cases of the disease all over the world.

Nosocomial infection in long-term care facilities. A survey in a Brazilian psychiatric hospital.

Nosocomial infection among male patients in a public psychiatric hospital was studied and the definitions for use in long-term care facilities were employed for diagnosis. The overall nosocomial infection rate was 6.7 per 1,000 day inpatients; 55.6% of these infections were identified in the respiratory tract, 50% of them being respiratory viral diseases; 38.9% of the nosocomial infections involved the eyes, ears, nose, throat and mouth, and 5.6% involved the skin and soft tissues. The epidemiological characteristics and the main clinical alterations of these inpatients were also identified.

[Evaluation and control of the microbiological quality of hands in foodhandlers]. / Avaliacao e controle da qualidade microbiologica de maos de manipuladores de alimentos.

Microbiological analyses of workers' hands were made for the common indicators, including aerobic mesophilic plate counts (APC), as well as the common food pathogens. Opportunities were observed for cross-contamination of roast beef by workers' hands during slicing operations. Workers' hands showed APC counts of up to 10(7) CFU/hand and the presence of S. aureus and C. perfringens. Salmonella spp were not isolated from hands. These results show that handling of these foods by such workers would be a risk in transmitting pathogenic microorganisms to the foods and is apparent that it is necessary for these workers to take care of personal hygiene. Decimal reductions obtained in the microbiological counts after washing and antisepsis of workers' hands were at 2,6 logs cycles and still demonstrated the importance of this practice in food services by the fact that pathogens such as S. aureus and C. perfringens were inhibited or killed.