Detection of 400-year-old Yersinia pestis DNA in human dental pulp: An approach to the diagnosis of ancient septicemia

Ancient septicemic plague epidemics were reported to have killed millions of people for 2 millenniums. However, confident diagnosis of ancient septicemia solely on the basis of historical clinical observations is not possible. The lack of suitable infected material has prevented direct demonstration of ancient septicemia; thus, the history of most infections such as plague remains hypothetical. The durability of dental pulp, together with its natural sterility, makes it a suitable material on which to base such research. We hypothesized that it would be a lasting refuge for Yersinia pestis, the plague agent. DNA extracts were made from the dental pulp of 12 unerupted teeth extracted from skeletons excavated from 16th and 18th century French graves of persons thought to have died of plague (“plague teeth”) and from 7 ancient negative control teeth. PCRs incorporating ancient DNA extracts and primers specific for the human β-globin gene demonstrated the absence of inhibitors in these preparations. The incorporation of primers specific for Y. pestis rpoB (the RNA polymerase β-subunit-encoding gene) and the recognized virulence-associated pla (the plasminogen activator-encoding gene) repeatedly yielded products that had a nucleotide sequence indistinguishable from that of modern day isolates of the bacterium. The specific pla sequence was obtained from 6 of 12 plague skeleton teeth but 0 of 7 negative controls (P < 0.034, Fisher exact test). A nucleic acid-based confirmation of ancient plague was achieved for historically identified victims, and we have confirmed the presence of the disease at the end of 16th century in France. Dental pulp is an attractive target in the quest to determine the etiology of septicemic illnesses detected in ancient corpses. Molecular techniques could be applied to this material to resolve historical outbreaks.

Results of MDR-1 vector modification trial indicate that granulocyte/macrophage colony-forming unit cells do not contribute to posttransplant hematopoietic recovery following intensive systemic therapy

To formally test the hypothesis that the granulocyte/macrophage colony-forming unit (GM-CFU) cells can contribute to early hematopoietic reconstitution immediately after transplant, the frequency of genetically modified GM-CFU after retroviral vector transduction was measured by a quantitative in situ polymerase chain reaction (PCR), which is specific for the multidrug resistance-1 (MDR-1) vector, and by a quantitative GM-CFU methylcellulose plating assay. The results of this analysis showed no difference between the transduction frequency in the products of two different transduction protocols: “suspension transduction” and “stromal growth factor transduction.” However, when an analysis of the frequency of cells positive for the retroviral MDR-1 vector posttransplantation was carried out, 0 of 10 patients transplanted with cells transduced by the suspension method were positive for the vector MDR-1 posttransplant, whereas 5 of 8 patients transplanted with the cells transduced by the stromal growth factor method were positive for the MDR-1 vector transcription unit by in situ or in solution PCR assay (a difference that is significant at the P = 0.0065 level by the Fisher exact test). These data suggest that only very small subsets of the GM-CFU fraction of myeloid cells, if any, contribute to the repopulation of the hematopoietic tissues that occurs following intensive systemic therapy and transplantation of autologous hematopoietic cells.

Screening Subclinical Keratoconus With Placido-Based Corneal Indices

Purpose. To assess in a sample of normal, keratoconic, and keratoconus (KC) suspect eyes the performance of a set of new topographic indices computed directly from the digitized images of the Placido rings. Methods. This comparative study was composed of a total of 124 eyes of 106 patients from the ophthalmic clinics Vissum Alicante and Vissum Almería (Spain) divided into three groups: control group (50 eyes), KC group (50 eyes), and KC suspect group (24 eyes). In all cases, a comprehensive examination was performed, including the corneal topography with a Placidobased CSO topography system. Clinical outcomes were compared among groups, along with the discriminating performance of the proposed irregularity indices. Results. Significant differences at level 0.05 were found on the values of the indices among groups by means of Mann-Whitney-Wilcoxon nonparametric test and Fisher exact test. Additional statistical methods, such as receiver operating characteristic analysis and K-fold cross validation, confirmed the capability of the indices to discriminate between the three groups. Conclusions. Direct analysis of the digitized images of the Placido mires projected on the cornea is a valid and effective tool for detection of corneal irregularities. Although based only on the data from the anterior surface of the cornea, the new indices performed well even when applied to the KC suspect eyes. They have the advantage of simplicity of calculation combined with high sensitivity in corneal irregularity detection and thus can be used as supplementary criteria for diagnosing and grading KC that can be added to the current keratometric classifications.

Impacto da colonização por Pseudomonas aeruginosa na fibrose quística

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Perfil sociodemográfico das pessoas que cometeram suicídio no período de 2007 a 2013 em Arapiraca, Alagoas, e a possível exposição aos agrotóxicos

Trata-se de um estudo descritivo de série histórica, com os dados coletados do Sistema de Informação de Mortalidade, através de relatórios do TABWIN, gerados em Excel, com banco de dados e análise estatística feitas no programa estatístico SPSS. Tem por objetivo determinar a mortalidade por suicídio na população do município de Arapiraca-AL, no período de 2007 a 2013, caracterizar o perfil epidemiológico e verificar a existência da associação entre a exposição a agrotóxicos e o suicídio. Identificamos 76 óbitos por suicidio no periodo, porém 14 óbitos foram eliminados por apresentarem informações ignoradas. Dos 53 óbitos, que apresentou uma média de 7,6 óbitos/ano, 40 foram praticados por homens e 13 por mulheres, a faixa etária inferior a 30 anos teve 45% dos óbitos, concentrados entre 20 a 29 anos, com 32,1%; os solteiros representaram 64,1%; pessoas de cor parda, com 41 mortos, (77,3%); a escolaridade apresentou 50,9% com um a 7 anos de estudos; 73,6% das pessoas residiam na zona urbana; 37,7% eram trabalhadores da agricultura, e o meio mais utilizado foi o enforcamento com 28 dos óbitos, (52,9%), seguido do uso de pesticidas com 16 óbitos, (30,2%). O Teste Exato de Fisher utilizado para avaliar a associação entre os fatores que poderiam influenciar a prática do suicídio, mostrou não existir diferença estatística na prática do suicídio entre os trabalhadores com agrotóxicos (p=0,64), bem como em relação a ocupação (p=0,76). Porém, foram encontradas associações significativas entre o desfecho suicídio e a existência de quadro depressivo (p=0,001) e a utilização de medicamentos (p=0,03). Novos estudos devem ser realizados com o intuíto de melhor explicar a ocorrência de depressão e do suicídio e principalmente determinar a sua relação causal com a exposição aos agrotóxicos. Palavras-chave: Suicídio; Mortalidade; Agrotóxicos.

QT interval prolongation related to psychoactive drug treatment:a comparison of monotherapy versus polytherapy

Background - Several antipsychotic agents are known to prolong the QT interval in a dose dependent manner. Corrected QT interval (QTc) exceeding a threshold value of 450 ms may be associated with an increased risk of life threatening arrhythmias. Antipsychotic agents are often given in combination with other psychotropic drugs, such as antidepressants, that may also contribute to QT prolongation. This observational study compares the effects observed on QT interval between antipsychotic monotherapy and psychoactive polytherapy, which included an additional antidepressant or lithium treatment. Method - We examined two groups of hospitalized women with Schizophrenia, Bipolar Disorder and Schizoaffective Disorder in a naturalistic setting. Group 1 was composed of nineteen hospitalized women treated with antipsychotic monotherapy (either haloperidol, olanzapine, risperidone or clozapine) and Group 2 was composed of nineteen hospitalized women treated with an antipsychotic (either haloperidol, olanzapine, risperidone or quetiapine) with an additional antidepressant (citalopram, escitalopram, sertraline, paroxetine, fluvoxamine, mirtazapine, venlafaxine or clomipramine) or lithium. An Electrocardiogram (ECG) was carried out before the beginning of the treatment for both groups and at a second time after four days of therapy at full dosage, when blood was also drawn for determination of serum levels of the antipsychotic. Statistical analysis included repeated measures ANOVA, Fisher Exact Test and Indipendent T Test. Results - Mean QTc intervals significantly increased in Group 2 (24 ± 21 ms) however this was not the case in Group 1 (-1 ± 30 ms) (Repeated measures ANOVA p < 0,01). Furthermore we found a significant difference in the number of patients who exceeded the threshold of borderline QTc interval value (450 ms) between the two groups, with seven patients in Group 2 (38%) compared to one patient in Group 1 (7%) (Fisher Exact Text, p < 0,05). Conclusions - No significant prolongation of the QT interval was found following monotherapy with an antipsychotic agent, while combination of these drugs with antidepressants caused a significant QT prolongation. Careful monitoring of the QT interval is suggested in patients taking a combined treatment of antipsychotic and antidepressant agents.

Immunohistochemical expression of E-cadherin and beta-catenin in ameloblastomas and tooth germs

OBJECTIVE: The aim was to analyze the expression of E-cadherin and beta-catenin in ameloblastomas and tooth germs to determine their roles in cell differentiation processes and invasiveness compared with odontogenesis. STUDY DESIGN: Twenty-one ameloblastoma cases (16 solid and 5 unicystic tumors) and 5 tooth germs were submitted to the immunohistochemical detection of E-cadherin and beta-catenin. Immunoreactivity was evaluated using descriptive and semiquantitative analysis, investigating the location and intensity of staining. The Fisher exact test was performed, and P values of <.05 were considered to indicate statistical significance. RESULTS: There was no statistically significant difference in the expression of E-cadherin and beta-catenin between solid and unicystic ameloblastomas (P = .59; P = .63; respectively). The same was found when comparing solid and unicystic ameloblastomas with the tooth germs for both E-cadherin (P = .53; P = .44; respectively) and beta-catenin (P = .12; P = .16; respectively). Nuclear staining of beta-catenin was observed in only 4 cases (3 solid and 1 unicystic tumor). CONCLUSION: The results showed no differences in the expression of E-cadherin or beta-catenin between tooth germs and solid and unicystic ameloblastomas. The expression of these molecules seems mainly to be related to the process of cell differentiation.

Diagnóstico de enfermagem risco de quedas em pacientes com angina instável

O risco de quedas pode ser reconhecido como fenômeno ou diagnóstico de enfermagem. Pesquisas relacionam diretamente isquemias miocárdicas, como a angina instável e o risco de cair. Objetivou-se analisar o diagnóstico de enfermagem Risco de quedas na ocorrência de angina instável por um estudo transversal realizado em 57 indivíduos internados em um hospitalescola, mediante exame físico e formulário. Para o tratamento estatístico foram utilizados teste qui-quadrado, teste exato de Fisher, Mann-Whitney, teste-t e Coefi ciente Phi (p<0,05). O Risco de quedas foi o diagnóstico de enfermagem mais prevalente (87,71%), sobretudo em homens, mais velhos, com menos anos de estudo e renda inferior. Presença da angina instável, hipertensão arterial, medicação anti-hipertensiva, doença vascular, difi culdades visuais e insônia apresentaram associação com o diagnóstico de enfermagem Risco de quedas. Conclui-se que é imprescindível o desenvolvimento de parâmetros claros e objetivos à mensuração mais acurada do risco de quedas no âmbito hospitalar

Diagnóstico de enfermagem risco de quedas em pacientes com angina instável

O risco de quedas pode ser reconhecido como fenômeno ou diagnóstico de enfermagem. Pesquisas relacionam diretamente isquemias miocárdicas, como a angina instável e o risco de cair. Objetivou-se analisar o diagnóstico de enfermagem Risco de quedas na ocorrência de angina instável por um estudo transversal realizado em 57 indivíduos internados em um hospitalescola, mediante exame físico e formulário. Para o tratamento estatístico foram utilizados teste qui-quadrado, teste exato de Fisher, Mann-Whitney, teste-t e Coefi ciente Phi (p<0,05). O Risco de quedas foi o diagnóstico de enfermagem mais prevalente (87,71%), sobretudo em homens, mais velhos, com menos anos de estudo e renda inferior. Presença da angina instável, hipertensão arterial, medicação anti-hipertensiva, doença vascular, difi culdades visuais e insônia apresentaram associação com o diagnóstico de enfermagem Risco de quedas. Conclui-se que é imprescindível o desenvolvimento de parâmetros claros e objetivos à mensuração mais acurada do risco de quedas no âmbito hospitalar

Relación entre estrés y desórdenes músculo esqueléticos en trabajadores de una empresa de transporte terrestre de pasajeros, Bogotá, 2015.

Introducción. Los conductores de transporte terrestre de pasajeros están expuestos a factores de riesgo inherentes a su labor, por lo que la intervención sobre estos factores es un aspecto relevante en las empresas de transporte público dado que dicha actividad afecta la calidad de vida de los mismos. Objetivo: Determinar la prevalencia de estrés en el lugar de trabajo y los factores de riesgo biomecánicos asociados en trabajadores de una empresa de transporte terrestre de pasajeros. Materiales y métodos: Estudio de corte transversal con datos secundarios procedentes de una población de 219 empleados, de los cuales 13 eran administrativos y 206 laboraban en la operación de una empresa de transporte terrestre de pasajeros. Las variables incluidas fueron socio demográficas, laborales, variables relacionadas con la medición de estrés y síntomas osteomusculares. El análisis estadístico incluyó medidas de tendencia central y dispersión y para identificar los factores asociados con el estrés se utilizaron pruebas de asociación Chi2 y prueba exacta de Fisher. Resultados: La edad promedio de los participantes fue de 43 años (DS 10 años), siendo en su mayoría trabajadores de sexo masculino (96,3%). Se presentaron síntomas y factores de riesgo biomecánicos en cuello y espalda en un 55.5%. Se encontró asociación significativa entre estrés con los síntomas en pies (p=0,009), con los factores de riesgo biomecánicos, se encontró relación significativa con el tiempo que permanece adoptando las posturas de inclinación hacia delante (p=0,000) y hacia atrás (p=0,001) de espalda/tronco y las posturas en muñecas, (p=0,000), y a la exposición de los conductores a superficies vibrantes (asientos de vehículo) (p=0,021). No se encontró asociación significativa entre estrés y la postura de sedente. Conclusiones: Con este estudio se encontró una prevalencia de estrés de 78% en el lugar de trabajo y de los factores de riesgo biomecánicos asociados a antigüedad, postura y repetitividad de movimientos, con repercusiones en cuello y espalda lumbar, por lo tanto, se requiere de un seguimiento a las condiciones de salud y trabajo para los empleados del sector transporte.

Solastalgia y conductas pro-ambientales en un conflicto socioambiental por la construcción de una hidroeléctrica

Introducción: La construcción de megaproyectos hídricos implica una reconfiguración territorial donde se ven afectadas las fuentes de agua dulce, la biodiversidad terrestre y acuática, y los asentamientos humanos que colindan con dichas construcciones. Objetivo: estimar la asociación entre las conductas proambientales con la solastalgia entre las personas que se encuentran ejerciendo un proceso de resistencia social contra la Central Hidrosogamoso en el departamento de Santander, Colombia. Metodología: se utilizó un diseño de estudio transversal en el que se entrevistaron integrantes y no integrantes de grupos ambientalistas de las zonas de influencia del proyecto. Se realizó un análisis descriptivo de las variables sociodemográficas de los dos grupos de comparación presentando frecuencias absolutas y relativas y diferencias significativas por medio de la prueba ji cuadrado, exacta de Fisher y U de Mann Whitney. Se utilizó un modelo de regresión lineal múltiple en el que la variable dependiente fue el puntaje de solastalgia y las variables independientes fueron las escalas de las conductas proambientales: altruismo, austeridad, equidad, conducta ecológica, deliberación, indignación y aprecio por lo natural, además, se ajustó por algunas variables sociodemográficas de interés. Resultados: los grupos comparados presentaron diferencias importantes en cuanto a la zona de procedencia, condiciones económicas y organización social. El incremento de 5 puntos en la escala del sentimiento de indignación incrementó 0.98 la escala de solastalgia (IC95%: 0.19; 1.78). Las personas sin pareja estable tuvieron 3.02 puntos menos de solastalgia comparadas con personas casadas o en unión libre (IC95%: -4.96; -1.44), mientras que aquellas con alto nivel educativo obtuvieron 2.02 puntos menos que las personas con primaria y bachillerato (IC95%: -3.99; -0.06). Un modelo alterno mostró que no pertenecer a un grupo ambientalista disminuye en 2.29 puntos la solastalgia, comparado con pertenecer a un grupo (IC95%: -4.31; -0.28),. Conclusión: posiblemente las motivaciones por las cuales los actores involucrados se resisten a las transformaciones territoriales ocasionadas por la construcción de las represas son más un reflejo de la condición socioeconómica que de la preocupación de los actores por el daño del medio ambiente y además, esta resistencia es un fenómeno que se limita a aquellos que están afectados directamente en el área de influencia del proyecto

Investigation of an inducible nitric oxide synthase gene (NOS2A) polymorphism in a multiple sclerosis population

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) affecting most commonly the Caucasian population. Nitric oxide (NO) is a biological signaling and effector molecule and is especially important during inflammation. Inducible nitric oxide synthase (iNOS) is one of the three enzymes responsible for generating NO. It has been reported that there is an excessive production of NO in MS concordant with an increased expression of iNOS in MS lesions. This study investigated the role of a bi-allelic tetranucleotide polymorphism located in the promoter region of the human iNOS (NOS2A) gene in MS susceptibility. A group of MS patients (n = 101) were genotyped and compared to an age- and sex-matched group of healthy controls (n = 101). The MS group was subdivided into three subtypes, namely relapsing-remitting MS (RR-MS), secondary-progressive MS (SP-MS) and primary-progressive MS (PP-MS). Results of a chi-squared analysis and a Fisher's exact test revealed that allele and genotype distributions between cases and controls were not significantly different for the total population (chi(2) = 3.4, P(genotype) = 0.15; chi(2) = 3.4, P(allele) = 0.082) and for each subtype of MS (P > 0.05). This suggests that there is no direct association of this iNOS gene variant with MS susceptibility.

Asymptomatic hypoechoic regions on patellar tendon ultrasound : a 4-year clinical and ultrasound followup of 46 tendons

Patellar tendon ultrasound appearance is commonly used in clinical practice to diagnose patellar tendinopathy and guide management. Using a longitudinal study design we examined whether or not the presence of a hypoechoic ultrasonographic lesion in an asymptomatic patellar tendon conferred a risk for developing jumper's knee compared with a tendon that was ultrasonographically normal. Ultrasonographic, symptomatic and anthropometric assessment was completed at baseline and followup. Magnetic resonance imaging was performed on four tendons that resolved ultrasonographically in the study period. Forty-six patellar tendons were followed over 47 ± 11.8 months. Eighteen tendons were hypoechoic at baseline and 28 were ultrasonographically normal. Five tendons resolved ultrasonographically in the study period. Magnetic resonance imaging in four of these tendons was normal. Seven normal patellar tendons at baseline developed a hypoechoic area but only two became symptomatic. Analysis of ultrasonography at baseline and clinical outcome with Fisher's exact test shows there is no association between baseline ultrasound changes and symptoms at followup. In this study there is no statistically significant relationship between ultrasonographic patellar tendon abnormalities and clinical outcome in elite male athletes. Management of jumper's knee should not be solely based on ultrasonographic appearance; clinical assessment remains the cornerstone of appropriate management.

Prognostic value of hTERT mRNA expression in surgical samples of lung cancer patients : the European Early Lung Cancer Project

Lung cancer is the most important cause of cancer-related mortality. Resectability and eligibility for treatment with adjuvant chemotherapy is determined by staging according to the TNM classification. Other determinants of tumour behaviour that predict disease outcome, such as molecular markers, may improve decision-making. Activation of the gene encoding human telomerase reverse transcriptase (hTERT) is implicated in the pathogenesis of lung cancer, and consequently detection of hTERT mRNA might have prognostic value for patients with early stage lung cancer. A cohort of patients who underwent a complete resection for early stage lung cancer was recruited as part of the European Early Lung Cancer (EUELC) project. In 166 patients expression of hTERT mRNA was determined in tumour tissue by quantitative real-time RT-PCR and related to that of a house-keeping gene (PBGD). Of a subgroup of 130 patients tumour-distant normal tissue was additionally available for hTERT mRNA analysis. The correlation between hTERT levels of surgical samples and disease-free survival was determined using a Fine and Gray hazard model. Although hTERT mRNA positivity in tumour tissue was significantly associated with clinical stage (Fisher's exact test p=0.016), neither hTERT mRNA detectability nor hTERT mRNA levels in tumour tissue were associated with clinical outcome. Conversely, hTERT positivity in adjacent normal samples was associated with progressive disease, 28% of patients with progressive disease versus 7.5% of disease-free patients had detectable hTERT mRNA in normal tissue [adjusted HR: 3.60 (1.64-7.94), p=0.0015]. hTERT mRNA level in tumour tissue has no prognostic value for patients with early stage lung cancer. However, detection of hTERT mRNA expression in tumour-distant normal lung tissue may indicate an increased risk of progressive disease.

Differential expression of NADPH-diaphorase between electrophysiologically-defined classes of pyramidal neurons in rat ventral subiculum, in vitro

The subiculum is the major output region of the hippocampal formation. We have studied pyramidal neurons in slices of rat ventral subiculum to determine if there is a correlation between nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) activity and electrophysiological phenotype. The majority of NADPH-d-positive pyramidal neurons were found in the superficial cell layer (i.e. nearest to the hippocampal fissure) of the subiculum and appreciable NADPH-d activity was absent from pyramidal neurons in area CA1. This distribution of NADPH-d activity was mimicked by that of immunoreactivity for the neuronal isoform of nitric oxide synthase. Subicular pyramidal neurons were classified, electrophysiologically, as intrinsically burst-firing or regular spiking. After electrophysiological characterization, neurons were filled with Neurobiotin and revealed using fluorescence immunocytochemistry. The slices containing these neurons were also processed for NADPH-d. NADPH-d activity was found in six out of eight regular spiking neurons but was not found in any of 13 intrinsically burst-firing neurons (P=0.0008, Fisher's Exact Test). We conclude that in rat ventral subiculum, NADPH-d activity is present in a proportion of pyramidal neurons and indicates the presence of the neuronal isoform of nitric oxide synthase. Furthermore, amongst pyramidal neurons, NADPH-d activity is distributed preferentially to those with the regular spiking phenotype. The distribution of regular spiking neurons suggests that they may not be present to the same extent in all subicular output pathways. Thus, the actions of nitric oxide may be relatively specific to particular hippocampal connections.