Synthesis and structural studies on (E)-3-(2,6-difluorophenyl)-1-(4-fluorophenyl)prop-2-en-1-one: a promising nonlinear optical material.

A new fluorinated chalcone (E)-3-(2,6-difluorophenyl)-1-(4-fluorophenyl)prop-2-en-1-one was synthesized in 90% yield and crystallized by a slow evaporation technique. Its full structural characterization and purity were determined by scanning electron microscopy, infrared spectroscopy, gas chromatography-mass spectrometry, 1H, 13C and 19F nuclear magnetic resonance, thermal gravimetric analysis (TGA), differential scanning calorimetry (DSC), Raman microspectroscopy, UV-Vis absorption spectroscopy, single crystal X-ray diffraction (XRD) and Hirshfeld surface (HS) analysis. The fluorinated chalcone crystallized in centrosymmetric space group P21/c stabilized by the C-H⋯O and C-H⋯F interactions and the π⋯π contact. The crystalline environment was simulated through the supermolecule approach where a bulk with 378 000 atoms was built. The electric parameters were calculated at the DFT/CAM-B3LYP/6-311++G(d,p) level as function of the electric field frequency. The macroscopic parameters such as linear refractive index and third-order nonlinear susceptibility (χ (3)) were calculated, and the results were compared with experimental data obtained from the literature. The χ (3)-value for the chalcone crystal is 369.294 × 10-22 m2 V-2, higher than those obtained from a few similar types of molecule, showing that the chalcone crystal can be considered as a nonlinear optical material. Also, molecular theoretical calculations such as infrared spectrum assignments, frontier molecular orbital analysis and MEP were implemented, revealing that the most positive region is around the hydrogen atoms of the aromatic rings, and electrophilic attack occurs on the carbonyl group.

Desfecho perinatal no crescimento intrauterino restrito seletivo em gestações gemelares monocoriônicas acompanhadas de forma expectante / Perinatal outcome in selective intrauterine growth restriction in monochorionic twin pregnancies followed expectantly

Objetivo: Avaliar a morbimortalidade perinatal de gestações gemelares monocoriônicas afetadas por Crescimento Intrauterino Restrito Seletivo (CIUR-s), de acordo com o padrão de fluxo ao Doppler na artéria umbilical do gêmeo menor. Métodos: Esse estudo de coorte retrospectiva tem como objetivo avaliar o desfecho perinatal de gestações gemelares monocoriônicas afetadas por CIUR-s e conduzidas de forma expectante, analisando os resultados de acordo com o padrão Doppler da artéria umbilical do gêmeo menor (Tipo I: persistentemente positivo / Tipo II: persistentemente ausente ou reverso / Tipo III: intermitentemente ausente ou reverso), desde o período pré-natal até a alta hospitalar. Setenta e cinco gestações gemelares monocoriônicas diamnióticas com CIUR-s foram incluídas nesse estudo, no qual definimos restrição seletiva de crescimento como peso fetal estimado (PFE) abaixo do terceiro percentil para a idade gestacional ou ou pela presença de pelo menos dois dos quatro parâmetros contributivos: PFE abaixo do décimo percentil, circunferência abdominal abaixo do percentil 10, índice de pulsatilidade da artéria umbilical do gêmeo menor acima do percentil 95 ou discordância entre os pesos fetais estimados de 25% ou mais. Os desfechos perinatais incluíram morte perinatal, lesão neurológica, retinopatia da prematuridade (ROP), displasia broncopulmonar (DBP), enterocolite necrosante (ECN) e sepse. Resultados: A taxa de mortalidade foi de 1,33% nessa coorte. A taxa de morbidade geral foi de 28,66%, com menor incidência em gestações gemelares do Tipo I. Conclusão: Esse estudo mostra que o CIUR-s Tipo I apresenta menor morbidade do que os Tipos II e III em conduta expectante.

Objective: To evaluate perinatal morbidity and mortality of monochorionic twin pregnancies affected by Selective Intrauterine Growth Restriction (sIUGR), according to the Doppler flow pattern in the umbilical artery of the smaller twin. Methods: This retrospective cohort study aims to assess the perinatal outcome of monochorionic twin pregnancies affected by this disorder and conducted expectantly, analyzing the results according to the umbilical artery Doppler pattern of the smaller twin (Type I: persistently forward / Type II: persistently absent or reversed / Type III: intermittently absent or reversed, from prenatal period to hospital discharge. Seventy five monochorionic diamniotic twin pregnancies with sIUGR were included in this study, in which we defined selective growth restriction as estimated fetal weight (EFW) of one twin less than the third centile or in the presence of at least two out of four contributory parameters: EFW less than the 10th percentile when associated with AC of one twin less than the 10th centile, EFW discordance of 25% or more, and umbilical artery (UA) pulsatility index (PI) of the smaller twin above the 95th centile. Perinatal outcomes included perinatal death, neurological injury, retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC) and sepsis. Results: The mortality rate was 1.33% in this cohort. Overall morbidity rate was 28.66%, with lower incidence in Type I twin pregnancies. Conclusion: This study shows that sIUGR Type I has lower morbidity than Types II and III in expectant management.

Encuesta de Percepción en Capacidad Instalada para la Formación de Médicos Residentes en Ortopedia (Traumatología) y Necesidades de la Atención en Patología Musculoesquelética Aguda y Crónica en México. Primera Parte / Installed Capacity Perception Survey for the Training of Resident's Program in Orthopedics and Care Needs in Acute and Chronic Musculoskeletal Pathology in Mexico

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Abstract: Introduction: It is essential that orthopaedic resident physicians be highly proficient in all aspects, considering the balance between supply, demand, need and context. Fundamental to identify the capacity and quality installed for their training in Mexico. Material and methods: Observational Study, transverse, non-probabilistic sampling-conglomerates, in two phases. The instrument has 8 domains, 57 variables and 4,867 items. 60 graduate professors of 20 states, 50 hospital sites, 22 university programs. Results: 1,038 years of experience (collective intelligence), 17 years of experience/teacher (01 to 50 years). Identified: acute pathology 30 (2 to 90%), chronic pathology 30 (5 to 96%), patients ˂ 15 years, 10 (3 to 30%), patients between 15 and 65 years, 47 (2 to 78%), patients ˃ 65 years, 20 (2 to 60%), number of beds/seat 20 (2 to 510), number of clinics 3 (1 to 48), number of surgical procedures/headquarters per year at the national level, was 960 (50 to 24,650). The national average per resident doctor is 362 surgeries/year with 1,450 surgical times/year. Conclusions: The needs and resources for the training of physicians specializing in orthopedics/traumatology are highly heterogeneous, so it should be adapted to the epidemiological needs of the region of influence, in an area of epidemiological transition. 62.2% expressed not having or have bad academic and scientific infrastructure at its headquarters, more than 50% without rotation overseas and ˃ 90% without regular scientific production.

[Installed Capacity Perception Survey for the Training of Residents Program in Orthopedics and Care Needs in Acute and Chronic Musculoskeletal Pathology in Mexico]. / Encuesta de Percepción en Capacidad Instalada para la Formación de Médicos Residentes en Ortopedia (Traumatología) y Necesidades de la Atención en Patología Musculoesquelética Aguda y Crónica en México. Primera Parte.

INTRODUCTION: It is essential that orthopaedic resident physicians be highly proficient in all aspects, considering the balance between supply, demand, need and context. Fundamental to identify the capacity and quality installed for their training in Mexico. MATERIAL AND METHODS: Observational Study, transverse, non-probabilistic sampling-conglomerates, in two phases. The instrument has 8 domains, 57 variables and 4,867 items. 60 graduate professors of 20 states, 50 hospital sites, 22 university programs. RESULTS: 1,038 years of experience (collective intelligence), 17 years of experience/teacher (01 to 50 years). Identified: acute pathology 30 (2 to 90%), chronic pathology 30 (5 to 96%), patients 15 years, 10 (3 to 30%), patients between 15 and 65 years, 47 (2 to 78%), patients 65 years, 20 (2 to 60%), number of beds/seat 20 (2 to 510), number of clinics 3 (1 to 48), number of surgical procedures/headquarters per year at the national level, was 960 (50 to 24,650). The national average per resident doctor is 362 surgeries/year with 1,450 surgical times/year. CONCLUSIONS: The needs and resources for the training of physicians specializing in orthopedics/traumatology are highly heterogeneous, so it should be adapted to the epidemiological needs of the region of influence, in an area of epidemiological transition. 62.2% expressed not having or have bad academic and scientific infrastructure at its headquarters, more than 50% without rotation overseas and 90% without regular scientific production.

INTRODUCCIÓN: Es fundamental que los médicos residentes de ortopedia (traumatología) sean altamente competentes en todos los aspectos, considerando el equilibrio entre la oferta, demanda, necesidad y contexto. Es primordial identificar la capacidad y calidad instalada para su formación en México. MATERIAL Y MÉTODOS: Estudio observacional, transversal, muestreo no probabilístico-conglomerados, en dos fases. El instrumento tiene ocho dominios, 57 variables y 4,867 ítems. Sesenta profesores de postgrado de 20 estados, 50 sedes hospitalarias, 22 programas universitarios. RESULTADOS: 1,038 años de experiencia (inteligencia colectiva), 17 años de experiencia/profesor (01 a 50 años). Se identificó: patología aguda 30 (2 a 90%), patología crónica 30 (5 a 96%), pacientes 15 años, 10 (3 a 30%), pacientes entre 15 y 65 años, 47 (2 a 78%), pacientes 65 años, 20 (2 a 60%), número de camas/sede 20 (2 a 510), número de consultorios 3 (1 a 48), el número de procedimientos quirúrgicos/sede al año a nivel nacional fue de 960 (50 a 24,650). La media nacional por médico residente es de 362 cirugías/año con 1,450 momentos quirúrgicos/año. CONCLUSIONES: Las necesidades y recursos para la formación de médicos especialistas en ortopedia/traumatología son en alto grado heterogéneos, por lo cual se debería adaptar a las necesidades epidemiológicas de la región de influencia, en un ámbito de transición epidemiológica. Sesenta y dos punto dos por ciento expresó no tener o tener deficiente infraestructura académica y científica en su sede, más de 50% sin rotación al extranjero y 90% sin producción científica regular.

Prevalence and identification of Salmonella spp. in water buffaloes from São Paulo State, Brazil / Prevalência e identificação de Salmonella spp. em búfalos do Estado de São Paulo, Brasil

O objetivo do estudo foi investigar a prevalência de Salmonella spp. em amostras de fezes de búfalos do estado de São Paulo, Brasil, e identificar os sorotipos isolados. Foram examinadas 116 amostras de suabes retais de búfalos das raças Jafarabadi e Murrah, coletadas em triplicata, em seis propriedades rurais localizadas nas regiões Central, Centro-Oeste e Nordeste do estado de São Paulo, Brasil. Para avaliar a presença de Salmonella spp., foram utilizados três diferentes caldos de enriquecimento (caldo selenito cistina, caldo tetrationado Muller-Kauffmann e caldo Rappaport-Vassiliadis) e dois diferentes meios de cultura (ágar verde brilhante modificado e ágar XLT4). Das 116 amostras de suabes retais examinadas, oito amostras (6,90%; 8/116) foram positivas para Salmonella spp., incluindo quatro sorotipos: S. Panama (50%; 4/8), S. Agona (25%; 2/8) , S. Newport (12,5%; 1/8) e S. Saintpaul (12,5%; 1/8), todos isolados de búfalos sem sinais clínicos de salmonelose, indicando a importância dos animais assintomáticos como fonte de infecção para outros animais e seres humanos. Das seis propriedades rurais avaliadas, apenas em duas fazendas (33,3%; 2/6) não foi detectada Salmonella spp. O uso de mais de um caldo de enriquecimento seletivo e de mais de um meio de cultura é indicado para o isolamento de Salmonella.(AU)

A novel dihydrocoumarin under experimental and theoretical characterization.

Coumarins are natural and synthetic active ingredients widely applied in diverse types of medicinal treatments, such as cancer, inflammation, infection, and enzyme inhibition (monoamine oxidase B). Dihydrocoumarin compounds are of great interest in organic chemistry due to their structural versatilities and, as part of our investigations concerning the structural characterization of small molecules, this work focuses on crystal structure and spectroscopic characterization of the synthesized and crystallized compound 4-(4-methoxyphenyl)-3,4-dihydro-chromen-2-one (C16H14O3). Additionally, a theoretical calculation was performed using density functional theory to analyze the sites where nucleophilic or electrophilic attack took place and to examine the molecular electrostatic potential surface. Throughout all of these calculations, both density functional theory and Car-Parrinello molecular dynamics were performed by fully optimized geometry. The spectroscopic analysis indicated the presence of aromatic carbons and hydrogen atoms, and also the carbonyl and methoxy groups that were confirmed by the crystallographic structure. The C16H14O3 compound has a non-classical intermolecular interaction of type C-H⋅⋅⋅O that drives the molecular arrangement and the crystal packing. Moreover, the main absorbent groups were characterized throughout calculated harmonic vibrational frequencies. Also, natural bond orbital analysis successfully locates the molecular orbital with π-bonding symmetry and the molecular orbital with π* antibonding symmetry. Finally, the gap between highest occupied and lowest unoccupied molecular orbitals implies in a high kinetic stability and low chemical reactivity of title molecule.

Autophagy analysis in oral carcinogenesis.

OBJECTIVE: The aim of this study was to evaluate the levels of autophagy in oral leukoplakia and squamous cell carcinoma and to correlate with clinical pathological features, as well as, the evolution of these lesions. METHODOLOGY: 7 Normal oral mucosa, 51 oral leukoplakias, and 120 oral squamous cell carcinomas (OSCC) were included in the study. Histological sections of the mucosa and leukoplakias were evaluated throughout their length, while the carcinomas were evaluated using Tissue Microarray. After the immunohistochemical technique, LC3-II positive cells were quantified in the different epithelial layers of the mucosa and leukoplakias and in the microarrays of the squamous cell carcinomas. The correlation between positive cells with the different clinical-pathological variables and with the evolution of the lesions was tested using the t test, ANOVA, and Kaplan-Meier survival analysis. RESULTS: We observed increased levels of autophagy in the oral squamous cell carcinomas (p<0.001) in relation to the other groups, but without any association with poorer evolution or survival of these patients. Among the leukoplakias, we observed a higher percentage of positive cells in the intermediate layer of the dysplastic leukoplakias (p=0.0319) and in the basal layer of lesions with poorer evolution (p=0.0133). CONCLUSION: The levels of autophagy increased during the process of oral carcinogenesis and are correlated with poorer behavior of the leukoplakias.

Synthesis, characterization, and computational study of the supramolecular arrangement of a novel cinnamic acid derivative.

In this work, we present the synthesis, characterization, and computational study of the supramolecular arrangement of a new cinnamic acid derivative: ethyl-(2E)-3-(4-hydroxy-3,5-dimethoxyphenyl)-prop-2-enoate (EHD). Single crystals of EHD were obtained using ethyl ether as solvent and a slow evaporation technique. Its crystallographic structure, derived from X-ray diffraction experiments, includes a disordered water molecule on the EHD supramolecular structure. This water molecule participates in four O-H···O hydrogen bonds, which are arranged as a centrosymmetric H-bond array with the water at the center. Electronic and structural properties of the isolated EHD molecule and of the EHD molecule in the presence of one water molecule were calculated at the B3LYP/6-311++G(2d,2p) level of theory. These calculations show that the HOMO-LUMO energy gap of EHD decreases upon the introduction of the water molecule, suggesting that EHD becomes a stronger electron acceptor. These results indicate that the water molecule helps to stabilize the crystal structure in this system containing unequal numbers of acceptor and donor atoms. The supramolecular synthon involving the disordered water molecule and the supramolecular features presented here provide new possibilities in the design of functional materials and should also help us to gain a deeper understanding of the processes by which molecules recognize biological targets.

Improving neuromuscular performance in young basketball players: plyometric vs. technique training.

AIM: The aim of this study was to compare the effects of plyometric training versus basketball technique training on improving neuro-muscular performance. METHODS: Thirty-six (age 14.9±0.9 years, body height 164.0±7.6 cm, body weight 54.0±8.7 kg, BMI 20.1±2.4 kg·m-2) basketball players girls were randomly allocated to 2 groups: Basketball Plyometric Training (BPT, N.=18) and Basketball Technique Training (BTT, N.=18). The players were tested by two specific tests: counter movement jump (CMJ) and squat jump (SJ) before and after 6 training weeks. RESULTS: The jump height, as dependent variable, showed a different trend as an effect of the different training protocols, in contrast with the current knowledge. Manova did not show significant interactions between the two groups for the height of jumps, while significant differences were found for interaction time × training (P<0.05) and for main effect × time (P<0.001). After training, the BPT group increased significantly CMJ performance by 11.3% (P<0.05), whereas the BTT group increased by 4.6%. Likewise, the BPT group demonstrated a significant greater improvement of jump height than BTT group (an increase of 15.4% vs. 7.5%, P<0.01; respectively). CONCLUSION: These results suggest that both training protocols proposed in this study improved vertical jump performance. However, a combination of the two protocols, plyometric training and sport-specific-exercises, could be useful to optimize performance by an easy transition from controlled a-specific to sport-specific performance requirements. In conclusion, BPT is a safe and effective method of achieving a favourable neuro-muscular performance than BTT in female basketball players.

IS2-mediated overexpression of kfoC in E. coli K4 increases chondroitin-like capsular polysaccharide production.

Transposons are developing molecular tools commonly used for several applications: one of these is the delivery of genes into microorganisms. These mobile genetic elements are characterised by two repeated insertion sequences that flank a sequence encoding one or more orfs for a specific transposase that moves these sequences to other DNA sites. In the present paper, the IS2 transposon of Escherichia coli K4 was modified in vitro by replacing the sequence coding for the transposase with that of the kfoC gene that codes for chondroitin polymerase. KfoC is responsible for the polymerisation of the bacterial capsular polysaccharide whose structure is analogous to that of chondroitin sulphate, a glycosaminoglycan with established and emerging biomedical applications. The recombinant construct was stably integrated into the genome of E. coli K4 by exploiting the transposase from endogenous copies of IS2 in the E. coli chromosome. A significant improvement of the polysaccharide production was observed, resulting in 80 % higher titres in 2.5-L fed-batch cultivations and up to 3.5 g/L in 22-L fed-batch cultures.

The role of E-cadherin down-regulation in oral cancer: CDH1 gene expression and epigenetic blockage.

BACKGROUND: The prognosis of the oral squamous cell carcinoma (OSCC) patients remains very poor, mainly due to their high propensity to invade and metastasize. E-cadherin reduced expression occurs in the primary step of oral tumour progression and gene methylation is a mode by which the expression of this protein is regulated in cancers. In this perspective, we investigated E-cadherin gene (CDH1) promoter methylation status in OSCC and its correlation with Ecadherin protein expression, clinicopathological characteristics and patient outcome. METHODS: Histologically proven OSCC and paired normal mucosa were analyzed for CDH1 promoter methylation status and E-cadherin protein expression by methylation-specific polymerase chain reaction and immunohistochemistry. Colocalization of E-cadherin with epidermal growth factor (EGF) receptor (EGFR) was evidenced by confocal microscopy and by immunoprecipitation analyses. RESULTS: This study indicated E-cadherin protein down-regulation in OSCC associated with protein delocalization from membrane to cytoplasm. Low E-cadherin expression correlated to aggressive, poorly differentiated, high grade carcinomas and low patient survival. Moreover, protein down-regulation appeared to be due to E-cadherin mRNA downregulation and CDH1 promoter hypermethylation. In an in vitro model of OSCC the treatment with EGF caused internalization and co-localization of E-cadherin with EGFR and the addition of demethylating agents increased E-cadherin expression. CONCLUSION: Low E-Cadherin expression is a negative prognostic factor of OSCC and is likely due to the hypermethylation of CDH1 promoter. The delocalization of E-cadherin from membrane to cytoplasm could be also due to the increased expression of EGFR in OSCC and the consequent increase of E-cadherin co-internalization with EGFR.

Psychological well-being and social participation assessment in visually impaired subjects playing Torball: a controlled study.

The aim of this study was to evaluate the differences in psychological well-being, symptomatic psychological disorders and social participation, between blind Torball players and non-players. Thirty blind male participants were recruited, 17 Torball players (aged 36.27±3.46) and 13 non-players (aged 34.80±2.53), and evaluated for social participation level, psychological well-being and symptomatic psychological disorders, using three validated self-report questionnaires: Participation Scale (PS), Psychological Well-Being Scale (PWBS) and Symptom Checklist 90 R (SCL-90-R) respectively. ANOVA showed significant overall differences between the two groups. The social restriction score in the non-player group was significantly higher (p<0.01) than the player group. The Torball player group showed significant better scores than non-player group in 5 of the 6 dimensions of the PWB Scale (p<0.01) and in 8 of the 10 dimensions of the SCL-90-R (7 dimensions p<0.01; 1 dimension p<0.05) and in the three global scores of the SCL-90-R (p<0.01). The results of this study showed a relationship between psychological well-being and social skills of visually impaired people and their Torball practice.

Prevalence of methicillin-resistant Staphylococci on a farm: staff can harbour MRS when animals do not.

The aim of this work was to establish the prevalence of methicillin-resistant Staphylococci (MRS) in the animals and staff of a teaching and research farm. Samples of dairy cattle (36), beef cattle (26), sheep (19), horses (21), pigs (23), goats (23) and humans (13) were collected and screened for the presence of MRS. The detection of mecA gene was performed by PCR to determine the resistance of the samples to methicillin. Antimicrobial-resistance testing to penicillin, meropenem, ceftriaxone, cephalothin, oxacillin, levofloxacin, enrofloxacin, chloramphenicol, ciprofloxacin, gentamicin, clindamycin, erytromycin, linezolid, sulfamethoxazole/trimethoprim, tetracycline, doxycycline and vancomycin was performed on the mecA+ isolates. From the 161 samples, four methicillin-resistant coagulase-negative Staphylococci (MRCoNS) were isolated from human beings (31%), whereas none was isolated from animals (0%). No methicillin-resistant Staphylococcus aureus (MRSA) were isolated. All of the MRCoNS isolates from this work presented different antimicrobial resistance patterns. MRCoNS may be present in humans associated with animals while not present in the animals. Selective pressure outside of the farm and a lack of MRCoNS transmission between humans and animals may be responsible for this lack of correlation.

(E)-1-(4-Meth-oxy-phen-yl)-3-(3,4,5-trimeth-oxy-phen-yl)prop-2-en-1-one.

The title compound, C(19)H(20)O(5), was synthesized by reaction of 4-meth-oxy-acetophenone and 3,4,5-trimeth-oxy-benzaldehyde. The aromatic rings form a dihedral angle of 36.39 (7)°. Two intramolecular C-H⋯O hydrogen bonds occur. The crystal packing features weak C-H⋯O inter-actions.

Validation of quantitative analysis method for triamcinolone in ternary complexes by UV-Vis spectrophotometry / Validação de método de análise quantitativa para a triancinolona a partir de complexo ternário por espectrofotometria de UV-Vis

Triamcinolone (TRI), a drug widely used in the treatment of ocular inflammatory diseases, is practically insoluble in water, which limits its use in eye drops. Cyclodextrins (CDs) have been used to increase the solubility or dissolution rate of drugs. The purpose of the present study was to validate a UV-Vis spectrophotometric method for quantitative analysis of TRI in inclusion complexes with beta-cyclodextrin (B-CD) associated with triethanolamine (TEA) (ternary complex). The proposed analytical method was validated with respect to the parameters established by the Brazilian regulatory National Agency of Sanitary Monitoring ANVISA). The analytical measurements of absorbance were made at 242nm, at room temperature, in a 1-cm path-length cuvette. The precision and accuracy studies were performed at five concentration levels (4, 8, 12, 18 and 20µg.mL-1. The B-CD associated with TEA did not provoke any alteration in the photochemical behavior of TRI. The results for the measured analytical parameters showed the success of the method. The standard curve was linear (r2 > 0.999) in the concentration range from 2 to 24 µg.mL-1. The method achieved good precision levels in the inter-day (relative standard deviation-RSD <3.4%) and reproducibility (RSD <3.8%) tests. The accuracy was about 80% and the pH changes introduced in the robustness study did not reveal any relevant interference at any of the studied concentrations. The experimental results demonstrate a simple, rapid and affordable UV-Vis spectrophotometric method that could be applied to the quantitation of TRI in this ternary complex.

A triancinolona (TRI) é um fármaco amplamente utilizado no tratamento de doenças inflamatórias do globo ocular e é praticamente insolúvel em água, o que limita sua utilização na forma de colírio. As ciclodextrinas (CDs) têm sido utilizadas com sucesso para aumentar a solubilidade ou velocidade de dissolução de fármacos. O presente estudo teve como objetivo a validação de uma metodologia analítica para a TRI a partir de complexos de inclusão com beta-ciclodextrina (B-CD) associada com a trietanolamina (TEA) (complexo ternário) por espectrofotometria de UV-Vis. A validação do método proposto foi realizada de acordo com os parâmetros analíticos estabelecidos pela Agência Nacional de Vigilância Sanitária (ANVISA). As análises quantitativas foram realizadas a 242nm a temperatura ambiente, utilizando cubeta de quartzo de 1cm. Os estudos de precisão e exatidão foram realizados para cinco níveis de concentração (4, 8, 12, 18 e 20µg.mL-1). A B-CD associada a TEA não alterou o comportamento fotoquímico da TRI. Os resultados da avaliação dos parâmetros analíticos demonstraram o sucesso da metodologia. A curva padrão apresentou linearidade (r2 > 0.999) na faixa de concentração de 2 a 24µg.mL-1. A metodologia apresentou bons níveis de precisão para o estudo inter dia (desvio padrão relativo-DPR <3.4%) e reprodutibilidade (DPR<3.8%). A exatidão ficou em torno de 80% e a variação de pH inserida no estudo de robustez não revelou uma interferência significativa em todas as concentrações estudadas. Os resultados experimentais demonstraram um simples, rápido e viável método de espectrofotometria de UV-Vis com aplicabilidade para a análise quantitativa da TRI a partir do complexo ternário.

WNT pathway in oral cancer: epigenetic inactivation of WNT-inhibitors.

Epigenetic DNA methylations plays an important role in oral carcinogenesis. The soluble frizzled receptor protein (SFRP) family together with WIF-1 and DKK-3 encodes antagonists of the WNT pathway. Silencing of these genes leads to constitutive WNT signalling. Because aberrant expression of beta-catenin might be associated with the epigenetic inactivation of WNT inhibitors, we analyzed, in a collection of primary OSCC with matched normal oral mucosa, the methylation status of a complete panel of genes, SFRP-1, SFRP-2, SFRP-4, SFRP-5, WIF-1, DKK-3, that are involved directly and indirectly in WNT pathway, in order to demonstrate WNT-pathway activation in the absence of beta-catenin and/or APC/Axin mutations during oral carcinogenesis. Methylation-specific PCR (MSP) was performed to study inactivation of SFRP-1, SFRP-2, SFRP-4, SFRP-5, WIF-1, DKK-3 genes in 37 cases of paraffin embedded oral cancer. This study showed that the methylation is an important epigenetic alteration in oral cancer. In particular, SFRP-2, SFRP-4, SFRP-5, WIF-1, DKK-3 revealed methylation status of their promoter in OSCC, whereas SFRP-1 showed demethylation in cancer. Fisher's exact test revealed statistically significant results (p<0.05) for all genes. The Wald test confirmed the statistically significant association between SFRP2-4-5 gene methylation and OSCC (p<0.05). SFRP-1 was also characterized by a different statistically significant epigenetic behaviour, because of it was demethylated in cancer (p<0.05). Statistical regression test showed high levels of sensitivity, specificity and accuracy for SFRP genes, while WIF-1 and DKK-3 have reportedly high specificity, moderate accuracy but low sensitivity. This study suggests that a cause of catenin delocalization in oral cancer could be due to WNT pathway activation, by epigenetic alterations of SFRP, WIF-1 and DKK-3 genes.

Capacity building for international tuberculosis control through operations research training.

SETTING: In resource-poor countries, few tuberculosis (TB) program staff at the national, provincial, and even district levels have the basic analytical and epidemiological skills necessary for collecting and analyzing quality data pertaining to national TB control program (NTP) improvements. This includes setting program priorities, operations planning, and implementing and evaluating program activities. OBJECTIVES: To present a model course for building capacity in basic epidemiology and operations research (OR). DESIGN: A combination of didactic lectures and applied field exercises were used to achieve the main objectives of the 6-day OR course. These were to increase the understanding of quantitative and qualitative research concepts, study design, and analytic methods, and to increase awareness of how these methods apply to the epidemiology and control of TB; and to demonstrate the potential uses of OR in answering practical questions on NTP effectiveness. As a final outcome, course participants develop OR proposals that are funded and later implemented. RESULTS: Since 1997, this OR course has been conducted nine times in five countries; 149 key NTP and laboratory staff have been trained in OR methods, and 44 OR protocols have been completed or are underway. CONCLUSION: This low-cost model course can be adapted to a wide range of public health issues.

Encouraging outcomes in the first year of a TB control demonstration program: Orel Oblast, Russia.

SETTING: Orel, Russia. OBJECTIVE: To evaluate outcomes of tuberculosis (TB) patients treated in the first year of a TB control demonstration project using a revised strategy of directly observed treatment, short-course (DOTS). Standard methods recommended by World Health Organization (WHO) were adapted to include mycobacterial cultures. DESIGN: Retrospective cohort analysis of TB patients diagnosed between October 1999 and September 2000. RESULTS: Among 749 TB patients, 65% had bacteriologic confirmation of pulmonary TB, 31% were diagnosed clinically, and 4% had extra-pulmonary TB. Most (92%) had no previous TB treatment, but 8% were identified as retreatment cases. Of all patients, 41% had new sputum smear-positive TB. No patients were HIV-infected. Multidrug-resistant (MDR) TB levels were 3% among new and 17% among retreatment patients. Among new smear-positive patients, treatment success was 79% (72% cure, 7% completion); remaining outcomes were 8% failure, 3% default, 8% death, and 1% transfer. Success rates for new culture-positive and clinically diagnosed patients were 81% and 91%, respectively. CONCLUSION: Despite historical differences, successful implementation of the revised TB strategy in Russia is possible. Treatment success rates were high, suggesting WHO targets of 85% cure for smear-positive patients is attainable. Obstacles include drug resistance and elevated death rates among smear-positive patients.

Teaching technology with technology: computer assisted lessons in the medical school the first Italian experience in nephrology and dialysis.

BACKGROUND: Dialysis is often neglected in academic teaching. At the University of Torino, Italy, teaching Nephrology (4th year of Medical School) consists of 21 hours of formal lessons, 10 hours/student of interactive lessons (4/10 dedicated to dialysis) and 10 optional lessons (3 regarding dialysis). Interactive and optional lessons widely employ computer assisted teaching. Aim of the study was to evaluate student satisfaction on this approach. METHODS: Student satisfaction was assessed on 4 sample lessons (166 students), by two short dedicated questionnaires (0-10 scale, open questions). RESULTS: High scores were given to the dialysis lessons (median 8/10). Computer assisted interface (median 8/10, range 6-10) was of help in check of knowledge in real time (86%), enhancing participation (61%); 62% suggest extending this experience to selected courses, 38% to all. CONCLUSIONS: Medical students consider dialysis an important part of the academic teaching of Nephrology; new interfaces may help to enhance student satisfaction.