Trastuzumab deruxtecan versus treatment of physician's choice in previously treated Asian patients with HER2-low unresectable/metastatic breast cancer: subgroup analysis of the DESTINY-Breast04 study.

BACKGROUND: In the global phase 3 DESTINY-Breast04 study (NCT03734029), the anti-human epidermal growth factor 2 (HER2) antibody-drug conjugate trastuzumab deruxtecan (T-DXd) demonstrated a statistically significant improvement in progression-free survival (PFS) and overall survival (OS), with manageable safety compared with treatment of physician's choice (TPC) in patients with HER2-low metastatic breast cancer (mBC) who had received 1-2 prior lines of chemotherapy. METHODS: This subgroup analysis examined the efficacy and safety of T-DXd versus TPC in 213 patients from Asian countries and regions who were enrolled in the DESTINY-Breast04 trial and randomized to T-DXd (n = 147) or TPC (n = 66). RESULTS: Median PFS with T-DXd and TPC was 10.9 and 5.3 months, respectively, in Asian patients with hormone receptor-positive mBC, and 10.9 and 4.6 months, respectively, in the overall Asian population. In both populations, median OS was not reached with T-DXd and was 19.9 months with TPC. The objective response rate was higher with T-DXd versus TPC in all Asian patients. Median treatment duration was 8.4 months with T-DXd and 3.5 months with TPC. The most common grade ≥ 3 drug-related treatment-emergent adverse events in Asian patients treated with T-DXd were neutropenia (16.3%), anemia (12.9%), and leukopenia (11.6%); the incidences of neutropenia and leukopenia were higher with TPC versus T-DXd. Adjudicated drug-related interstitial lung disease or pneumonitis with T-DXd was 14.3%; the majority of events were grade 1-2. CONCLUSIONS: T-DXd demonstrated clinically meaningful survival benefits versus TPC in Asian HER2-low mBC patients, regardless of hormone receptor status, with no new safety signals. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT03734029.

Altered Vaginal Microbiota Composition Correlates With Human Papillomavirus and Mucosal Immune Responses in Women With Symptomatic Cervical Ectopy.

Cervical ectopy is a benign condition of the lower genital tract that is frequently detected in women of reproductive age. Although cervical ectopy is regarded as a physiological condition, some women experience symptoms such as leucorrhoea, persistent bleeding and recurrent vaginal infections that require medical intervention. Cervical ectopy has not been linked to cervical cancer, but it is thought to facilitate the acquisition of sexually transmitted diseases (STDs), like Human Papillomavirus (HPV) infection, as it provides a favorable microenvironment for virus infection and dissemination. We and others have described the presence of oncogenic HPV types in women with symptomatic cervical ectopy. The relevance of this finding and the impact of symptomatic cervical ectopy on the cervicovaginal microenvironment (vaginal microbiota, immune and inflammatory responses) are currently unknown. To shed some light into the interplay between HPV, the vaginal microbiota and mucosal immune and inflammatory responses in the context of this condition, we enrolled 156 women with symptomatic cervical ectopy and determined the presence of HPV using a type-specific multiplex genotyping assay. Overall, HPV was detected in 54.48% women, oncogenic HPV types were found in more than 90% of HPV-positive cases. The most prevalent HPV types were HPV16 (29.4%), HPV31 (21.17%) and HPV18 (15.29%). Next, we evaluated the vaginal microbial composition and diversity by 16S rDNA sequencing, and quantified levels of cytokines and chemokines by flow cytometry using bead-based multiplex assays in a sub-cohort of 63 women. IL-21 and CXCL9 were significantly upregulated in HPV-positive women (p=0.0002 and p=0.013, respectively). Women with symptomatic cervical ectopy and HPV infection had increased diversity (p<0.001), and their vaginal microbiota was enriched in bacterial vaginosis-associated anaerobes (Sneathia, Shuttleworthia, Prevotella, and Atopobium) and depleted in Lactobacillus spp. Furthermore, the vaginal microbiota of women with symptomatic cervical ectopy and HPV infection correlated with vaginal inflammation (IL-1ß, rho=0.56, p=0.0004) and increased mucosal homeostatic response (IL-22, rho=0.60, p=0.0001). Taken together, our results suggest that HPV infection and dysbiotic vaginal communities could favor a vaginal microenvironment that might delay the recovery of the cervical epithelium in women with symptomatic cervical ectopy and favor STDs acquisition.

[Neurology and COVID-19: Case Series of Neurological Complications in 96 patients Admitted at a University Hospital]. / Neurología hospitalaria y COVID-19: serie de 96 pacientes evaluados en un hospital universitario.

BACKGROUND: There are multisystemic consequences secondary to SARS- CoV-2 infection. AIM: To characterize neurological complications in patients admitted due to SARS-CoV-2 infection. METHODS: Review of medical records of patients aged over 15 years with COVID-19 evaluated by the neurology team between April and August 2020 at a university hospital. Severity of the infection, referral reasons, neurological diagnoses and laboratory results were registered. The diagnoses were defined by consensus among the members of the hospital neurology group. Cerebrovascular and inflammatory diseases of the central and peripheral nervous system were defined as "probably associated" or "possibly associated" to COVID-19. RESULTS: Ninety-six patients had at least 1 new neu- rological complication. 74% were admitted due to pneumonia and 20% due to a neurological disease. The most common reasons for neurological referral were impaired consciousness (39%), focal neurological deficit (24%), headache (9%) and seizures (5%). The most relevant neurological diagnoses were delirium in 48 patients, stroke in 24, critical illness polyneuropathy and myopathy in 17, seizures in 14, brachial plexopathy in 3, compressive neuropathies in 5, encephalitis in 1, possible vasculitis in 1 and Guillain-Barré syndrome in 1. Stroke and epilepsy were associated with increased length of hospital stay, but without differences in mortality. CONCLUSIONS: The spectrum of neurological complications of COVID-19 is wide. There are clinical entities typical of critically ill patients and also diseases associated directly and indirectly with the SARS-CoV2 infection.

Neurología hospitalaria y COVID-19: serie de 96 pacientes evaluados en un hospital universitario / Neurology and COVID-19: Case Series of Neurological Complications in 96 patients Admitted at a University Hospital

Background: There are multisystemic consequences secondary to SARS- CoV-2 infection. Aim: To characterize neurological complications in patients admitted due to SARS-CoV-2 infection. Methods: Review of medical records of patients aged over 15 years with COVID-19 evaluated by the neurology team between April and August 2020 at a university hospital. Severity of the infection, referral reasons, neurological diagnoses and laboratory results were registered. The diagnoses were defined by consensus among the members of the hospital neurology group. Cerebrovascular and inflammatory diseases of the central and peripheral nervous system were defined as "probably associated" or "possibly associated" to COVID-19. Results: Ninety-six patients had at least 1 new neu- rological complication. 74% were admitted due to pneumonia and 20% due to a neurological disease. The most common reasons for neurological referral were impaired consciousness (39%), focal neurological deficit (24%), headache (9%) and seizures (5%). The most relevant neurological diagnoses were delirium in 48 patients, stroke in 24, critical illness polyneuropathy and myopathy in 17, seizures in 14, brachial plexopathy in 3, compressive neuropathies in 5, encephalitis in 1, possible vasculitis in 1 and Guillain-Barré syndrome in 1. Stroke and epilepsy were associated with increased length of hospital stay, but without differences in mortality. Conclusions: The spectrum of neurological complications of COVID-19 is wide. There are clinical entities typical of critically ill patients and also diseases associated directly and indirectly with the SARS-CoV2 infection.

Erythropoietin promotes expression of survivin via STAT3 activation and reduces sensitivity to cisplatin in cervical cancer cells.

Erythropoietin (Epo) is used for the treatment of cancer­associated anaemia. However, certain studies have identified that the administration of Epo mediates the acquisition of resistance to cisplatin, which is widely used to treat cervical cancer. Our group previously reported that cervical cancer cells express Epo receptor and that exogenous Epo induces cell proliferation and migration. However, the effect of Epo on cervical cancer cell death mediated by chemotherapeutic agents has not yet been evaluated. Thus, the aim of the present study was to assess the potential effect of Epo on the cytotoxic activity of cisplatin in cervical cancer cells. The effect of Epo was assessed in 3 cervical cancer­derived cell lines. It was observed that pre­incubation with Epo induced a significant reduction of cisplatin­induced apoptosis in vitro and in vivo. Incubation with Epo induced the expression and activation of the transcriptional factor signal transducer and activator of transcription 3 (STAT3), which in turn stimulated the expression and activation of the anti­apoptotic protein survivin. The cytotoxicity of cisplatin was partially restored by treating the cells with MY155, an inhibitor of survivin. Conversely, inhibition of STAT3 activation using sub­lethal doses of WP1066, completely abolished the cytoprotective effect of Epo. These observations indicated that Epo was able to hinder the cytotoxic effect of cisplatin in cervical cancer cells by activating anti­apoptotic responses regulated by STAT3.

Assessment of depression, anxiety, hopelessness and suicidal risk in HIV+ inpatients / Evaluación de depresión, ansiedad, desesperanza y riesgo suicida en pacientes con VIH hospitalizados

Abstract Introduction. People living with HIV frequently experience anxiety, depression, hopelessness and suicide risk, particularly if they are hospitalized due to HIV complications. Objective. The aim of this study was to evaluate the presence of anxiety, depression, hopelessness and suicide risk in HIV+ inpatients at admission and discharge. Method. A comparative study was conducted with the HIV+ inpatient population of the National Institute for Respiratory Diseases in Mexico City, from February to November 2013. The Hospital Anxiety and Depression Scale, the Beck Hopelessness Scale and the Plutchik Suicide Risk Scale were applied at hospital admission and discharge. Results. One hundred and fifteen patients completed all three assessments. Upon admission, 10.4% of the patients scored above the cut-off point for suicide risk; 1.7% presented high levels of hopelessness; 5.2% had clinical depression, and 7% had clinical anxiety. The comparison of scores at admission and discharge showed significant decreases in all symptom levels. Discussion and conclusion. Most of the patients presented low levels of all symptoms assessed at admission and these decreased at discharge. Further research is necessary with the hospitalized HIV population.

Resumen Introducción. Las personas que viven con VIH experimentan con frecuencia ansiedad, depresión, desesperanza y riesgo suicida, particularmente si son hospitalizadas debido a complicaciones por el VIH. Objetivo. El propósito del presente estudio fue evaluar y comparar la presencia de ansiedad, depresión, desesperanza y riesgo suicida en pacientes hospitalizados con VIH, a su ingreso y su egreso. Método. Se llevó a cabo un estudio comparativo con pacientes de VIH+ hospitalizados en el Instituto Nacional de Enfermedades Respiratorias en la Ciudad de México de febrero a noviembre de 2013. Se aplicaron la Escala de Ansiedad y Depresión Hospitalaria, la Escala de Desesperanza de Beck y la Escala de Riesgo Suicida de Plutchik. Resultados. Ciento quince pacientes completaron las tres escalas. A su ingreso, 10.4% de los pacientes obtuvieron puntajes por encima del punto de corte en la Escala de Riesgo Suicida; 1.7% presentaron niveles altos de desesperanza; 5.2% puntuaron con depresión clínica; y 7% puntuaron para ansiedad clínica. La comparación entre los resultados obtenidos al ingreso y el egreso hospitalario mostró una disminución significativa en todos los síntomas al egreso. Discusión y conclusión. La mayoría de los pacientes presentaron niveles bajos de los síntomas evaluados y éstos disminuyeron al egreso. Son necesarias investigaciones adicionales de salud mental en población hospitalizada con VIH.

Erythropoietin protects neuroblastoma cells against etoposide and vincristine by activating ERK and AKT pathways but has no effect in kidney cells.

AIMS: Chemotherapy induces anaemia in neuroblastoma patients. Cancer-associated anaemia may be treated with recombinant erythropoietin. However, the potential effects of erythropoietin on neuroblastoma and kidney cells have not been extensively evaluated. The present study was designed to investigate the effect of erythropoietin on the proliferation, and protection against vincristine- and etoposide-induced cell death in neuroblastoma (MSN), and embryonic kidney (HEK 293) cells. MAIN METHODS: The expression of erythropoietin and its receptor in MSN and HEK 293 was analysed by RT-PCR, immunocytochemistry, and Western blotting. The effect of erythropoietin on cell viability and proliferation was evaluated by the MTT assay, and by the Click-iT EdU Alexa Fluor 647 kit, respectively. For the cyto-protective assays, cells were incubated with erythropoietin before etoposide and vincristine treatment. Activation of signalling pathways was studied by Western blotting. KEY FINDINGS: MSN and HEK 293 cells expressed the erythropoietin receptor, but not erythropoietin. Erythropoietin induced proliferation and protection against vincristine and etoposide in MSN cells. HEK 293 cells were not affected by erythropoietin. Erythropoietin showed an anti-apoptotic effect which was dependent on the activation of ERK1/2 and AKT. HEK 293 cells presented constitutively phosphorylated AKT, and showed no activation of ERK1/2 upon erythropoietin stimulation. SIGNIFICANCE: These results indicate that erythropoietin induces proliferation of MSN cells, and that it can ameliorate vincristine- and etoposide-induced apoptosis of these cells. Erythropoietin-mediated neuroprotection was regulated by the combined effect of the ERK1/2 and AKT signalling pathways. Our findings provide further insights into the potential effect of erythropoietin on neuroblastoma cells.

Social Media, Higher Education, and Community Colleges: A Research Synthesis and Implications for the Study of Two-Year Institutions.

The boundaries between on-line and "real-world" communities are rapidly deteriorating, particularly for the generation of young people whose lives are pervaded by social media. For this generation, social media exchanges are a primary means of communication, social engagement, information seeking, and possibly, a central component of their identity and community-building. Given these realities, postsecondary educators should begin to seriously explore the potential to intentionally and strategically harness the power of these revolutionary transformations in technology use to better serve the needs of students to enhance their success. Therefore, this review of books, academic journals, higher education news, research reports, individual blogs and other online media on the use of social media technology (SMT) in higher education provides a baseline sense of current uses nationally, providing a descriptive overview of the social media phenomenon. Additionally, the review clarifies how colleges and college students use SMT and also challenges assumptions in two areas: how institutions can best exploit social media's features and its impact on student outcomes. The review further provides a foundation to develop conceptual frameworks that would better capture the role and impact of SMT among colleges and college students, and community colleges in particular.

Co-stimulation with stem cell factor and erythropoietin enhances migration of c-Kit expressing cervical cancer cells through the sustained activation of ERK1/2.

The cytokines erythropoietin (Epo) and stem cell factor (SCF), coupled with the cooperation between their receptors (EpoR and c-Kit), are essential components of normal physiological erythropoiesis. In earlier studies, we demonstrated the expression of c-Kit and EpoR in cervical cancer cells. It was identified that SCF is a survival factor, whereas Epo promotes cell proliferation. Cooperation between EpoR and SCF in cervical cancer has rarely been studied, despite the fact that cell migration and anchorage independent growth are considered initial steps in metastasis. Thus, the aim of this study was to analyse the effect of SCF and Epo alone, or in combination, on the migration and anchorage independent growth of two cervical cancer-derived cell lines. First, we demonstrated the expression of EpoR and c-Kit in the cell lines. Next, we evaluated anchorage independent growth, and identified that Epo and SCF produced a modest number of colonies, whereas the combination Epo/SCF induced a significantly higher number of colonies. Migration was then evaluated in Boyden chambers. Co-stimulation with Epo/SCF induced a significantly higher number of migrating cells than either cytokine alone. SCF-, Epo- and Epo/SCF-induced migration was inhibited by blocking phosphorylation of Janus kinase 2 (JAK2). Accordingly, western blot analysis demonstrated that the JAK2/signal transducer and activator of transcription-5 (STAT5) axis was activated in all cases. By contrast, inhibition of extracellular signal-related kinase (ERK) 1/2 abrogated migration induced by SCF and Epo/SCF only. Concurrently, Epo induced a modest, transient activation of ERK1/2, whereas SCF and Epo/SCF prompted a strong, sustained phosphorylation of ERK1/2. The results from this study have revealed that co-stimulation with Epo/SCF promotes migration and anchorage independent cell growth, and that co-signalling from EpoR and c-Kit converge on JAK2/STAT5 activation. Furthermore, SCF- and Epo/SCF-induced migration depends on the sustained activation of ERK1/2. These results indicate that co-signalling from different cytokine receptors induces migration, and this suggests that migratory behaviour may be regulated by the cooperative activity of Epo and SCF in cells expressing their cognate receptors.

Pre-conditioning with CDP-choline attenuates oxidative stress-induced cardiac myocyte death in a hypoxia/reperfusion model.

BACKGROUND: CDP-choline is a key intermediate in the biosynthesis of phosphatidylcholine, which is an essential component of cellular membranes, and a cell signalling mediator. CDP-choline has been used for the treatment of cerebral ischaemia, showing beneficial effects. However, its potential benefit for the treatment of myocardial ischaemia has not been explored yet. AIM: In the present work, we aimed to evaluate the potential use of CDP-choline as a cardioprotector in an in vitro model of ischaemia/reperfusion injury. METHODS: Neonatal rat cardiac myocytes were isolated and subjected to hypoxia/reperfusion using the coverslip hypoxia model. To evaluate the effect of CDP-choline on oxidative stress-induced reperfusion injury, the cells were incubated with H2O2 during reperfusion. The effect of CDP-choline pre- and postconditioning was evaluated using the cell viability MTT assay, and the proportion of apoptotic and necrotic cells was analyzed using the Annexin V determination by flow cytometry. RESULTS: Pre- and postconditioning with 50 mg/mL of CDP-choline induced a significant reduction of cells undergoing apoptosis after hypoxia/reperfusion. Preconditioning with CDP-choline attenuated postreperfusion cell death induced by oxidative stress. CONCLUSION: CDP-choline administration reduces cell apoptosis induced by oxidative stress after hypoxia/reperfusion of cardiac myocytes. Thus, it has a potential as cardioprotector in ischaemia/reperfusion-injured cardiomyocytes.

Bioconversion of Agave tequilana fructans by exo-inulinases from indigenous Aspergillus niger CH-A-2010 enhances ethanol production from raw Agave tequilana juice.

Agave tequilana fructans are the source of fermentable sugars for the production of tequila. Fructans are processed by acid hydrolysis or by cooking in ovens at high temperature. Enzymatic hydrolysis is considered an alternative for the bioconversion of fructans. We previously described the isolation of Aspergillus niger CH-A-2010, an indigenous strain that produces extracellular inulinases. Here we evaluated the potential application of A. niger CH-A-2010 inulinases for the bioconversion of A. tequilana fructans, and its impact on the production of ethanol. Inulinases were analyzed by Western blotting and thin layer chromatography. Optimal pH and temperature conditions for inulinase activity were determined. The efficiency of A. niger CH-A-2010 inulinases was compared with commercial enzymes and with acid hydrolysis. The hydrolysates obtained were subsequently fermented by Saccharomyces cerevisiae to determine the efficiency of ethanol production. Results indicate that A. niger CH-A-2010 predominantly produces an exo-inulinase activity. Optimal inulinase activity occurred at pH 5.0 and 50 °C. Hydrolysis of raw agave juice by CH-A-2010 inulinases yielded 33.5 g/l reducing sugars, compared with 27.3 g/l by Fructozyme(®) (Novozymes Corp, Bagsværd, Denmark) and 29.4 g/l by acid hydrolysis. After fermentation of hydrolysates, we observed that the conversion efficiency of sugars into ethanol was 97.5 % of the theoretical ethanol yield for enzymatically degraded agave juice, compared to 83.8 % for acid-hydrolyzed juice. These observations indicate that fructans from raw Agave tequilana juice can be efficiently hydrolyzed by using A. niger CH-A-2010 inulinases, and that this procedure impacts positively on the production of ethanol.

Autocrine/paracrine erythropoietin signalling promotes JAK/STAT-dependent proliferation of human cervical cancer cells.

Erythropoietin (Epo) regulates erythropoiesis by binding to its receptor (EpoR) and promoting cell proliferation, differentiation and inhibition of apoptosis. Epo is widely used to treat cervical cancer-related anaemia. However, there are data suggesting that administration of Epo is associated with an increment in recurrence rate, and decreased disease-free and overall survival. In the present study, we investigated the expression of Epo and EpoR on cervical cancer cell lines. We observed that both EpoR and extracellular Epo are constitutively expressed in cervical cancer cells. Inhibition of either Epo or EpoR expression with siRNA attenuated cell proliferation, whereas addition of exogenous Epo led to a significant increase in cell growth, both in vitro and in vivo. Epo-induced proliferation was associated with the activation of JAK2, JAK3, STAT3 and STAT5 but not JAK1 and STAT1. Our results are consistent with the existence of a functional, endogenous Epo/EpoR system in cervical cancer with the capacity to activate the transduction of signals resulting in an increased proliferation potential.

Cambios en la función vascular de hombres saludables, después de ejercicio físico prolongado y vigoroso: (función vascular y ejercicio vigoroso) / Changes in vascular function in healthy men after prolonged strenuous exercise: (vascular function and strenuous exercise)

Se investigó el efecto del ejercicio prolongado y vigoroso sobre la función endotelial en nueve corredores no-élite, determinando la función dependiente del endotelio de la arteria femoral (FDE-AF). Se observó que el ejercicio prolongado y vigoroso se asocia con menor FDE-AF, con tendencia no significativa a la recuperación a partir de las 24 horas hasta siete días después de la carrera. Se requieren estudios que involucren más participantes para determinar el impacto del ejercicio prolongado y vigoroso sobre la función endotelial.

The effect of prolonged and strenuous exercise on endothelial function in 9 non-elite runners was researched determining the endothelium-dependent function of the femoral artery (EDF-FA). We realized that prolonged and vigorous exercise is associated with lower EDF-FA, with non significant trend toward recovery from 24 hours to 7 days after the race. Studies with more participants are required to determine the impact of prolonged and vigorous exercise on endothelial function.

Effect of prolonged strenuous exercise on endothelial function in non-elite runners / Efeito de exercício extenuante e prolongado sobre a função endotelial em corredores não elite

Background: Prolonged exercise has been shown to result in an acute depression in endothelial function. However, little is known about the effect of this type of exercise in non-ekite runners. Objective: To determine the impact of prolonged strenuous exercise on endothelial function in non-elite runners. Methods: Nine males participating as recreatuional runners (age: 49,5 + ou -5.1y) at the Santiago of Cali Half-marathon (21.097m) were studied. Endothelium dependent femoral artery flow-mediated dilatation (FA-FMD) was evaluated one day before the race and at 1h, 24h, 48h, and 6 days after finishing the half-marathon. Results: A decrease on FA-FMD was observed at 1h after Half-marathon, followed by a non-significant recovery trend starting at 24h up to 6 days after the race. Increase in the posthyperemic diameter of the femoral artery was observed at 1h after race ending, with a trend to baseline values in subsequent measures. Conclusion: Femoral artery diameter increased after prolonged running could explain the reduction of FAFMD. More studies with larger sample size are needed to determine the effects of prolonged running on femoral artery endothelial function.

Fundamentos: O exercício prolongado tem se mostrado resultar em uma depressão aguda da função endotelial. No entanto, pouco se sabe sobre o efeito desse tipo de exercício em corredores não elite. Objetivos: Determinar o impacto do exercício prolongado e extenuante sobre a função endotelial em corredores não elite. Métodos: Foram estudados nove homens participando como corredores de lazer (idade: 49,5±5,1 anos) na Meia-Maratona de Santiago de Cali (21,097m). A dilatação fluxomediada endotélio-dependente da artéria femoral (DFMAF) foi avaliada um dia antes da corrida e em 1h, 24h, 48he em 6 dias depois de completar a Meia-Maratona. Resultados: Um decréscimo foi observado na DFM-AF 1h depois da Meia-Maratona, seguido por uma tendência à recuperação não significativa, começando em 24h e em6 dias depois da corrida. Um aumento no diâmetro póshiperêmico da artéria femoral foi observado 1h depois do final da corrida, com uma tendência a atingir valores de base nas medidas subsequentes. Conclusão: O diâmetro da artéria femoral aumentado depois de uma corrida prolongada poderia explicar a redução no DFM-AF. Estudos adicionais com amostras maiores são necessários para determinar os efeitos de corridas prolongadas sobre a função endotelial da artéria femoral.

Prevalence of human papillomavirus genotypes, and mucosal IgA anti-viral responses in women with cervical ectopy.

BACKGROUND: Data on the prevalence of different human papillomavirus (HPV) genotypes and the associated mucosal immune response in women with cervical ectopy are scarce. OBJECTIVE: To assess the prevalence of different HPV genotypes and the mucosal anti-viral immune response in cervical ectopy. STUDY DESIGN: Detection and typing of HPV DNA was determined in 141 women with cervical ectopy, 272 cytologically normal controls and 98 low-grade squamous intraepithelial lesions (LSIL) by PCR and direct sequencing. Mucosal IgA antibodies to HPV16 and HPV18 were evaluated in cervical mucus by ELISA. RESULTS: The prevalence of HPV in cervical ectopy was higher (73.7%) than that observed in control samples (30.5% in endocervix, and 1.8% in exocervix), but similar to the prevalence in LSIL (62.2%). Typing showed that the overall distribution frequency concerned 14 different genotypes, with HPV18 being the most prevalent in cervical ectopy (53.9%), whereas HPV16 predominated in LSIL (38.7%). High-risk HPV genotypes were 2.2 times more frequent in cervical ectopy than in the normal endocervix (p<0.0001). HPV infection in cervical ectopy patients was accompanied by a mucosal IgA-antibody response. Antibody reactivity to HPV18 was significantly higher than the response to HPV16. CONCLUSION: Cervical ectopy is a risk factor for infection with high-risk HPV genotypes, in particular HPV18. Our results emphasize the need of further studies to clarify the oncogenic potential of this virus in cervical ectopy.

Chromosome mapping of 5S rRNA genes differentiates Brazilian populations of Leporellus vittatus (Anostomidae, Characiformes)

Among the anostomid fishes, the genus Leporellus is represented by only three species: L. nattereri, endemic of the Amazon River, L. retropinnis, endemic of the Piracicaba River, and L. vittatus, widely distributed in rivers from Peru, Colombia, Guianas, and different major hydrographic basins of Brazil. A cytogenetic study carried out on specimens of Leporellus vittatus from three major Brazilian hydrographic basins evidenced a karyotype of 54 metacentric and submetacentric chromosomes. C-banding analysis revealed the presence of large pericentromeric heterochromatic segments in all chromosomes and a telomeric block coincident with the NOR sites. Ag, CMA3 or MM staining, and FISH with ribosomal probes located the 45S ribosomal genes on the terminal region of the long arm of the 12th chromosome pair of all populations. Nevertheless, in the specimens from the Paraná and São Francisco Basins the 5S rDNA clusters were interstitially located by FISH on the long arm of the 2nd chromosome pair, while in the specimens from the Tocantins-Araguaia Basin these sites were observed on the long arm of the 9th chromosome pair and on the short arm of the 17th chromosome pair. These data suggest that the species currently named Leporellus vittatus may comprise a complex of cryptic species.

Assessing genetic diversity of Brazilian reef fishes by chromosomal and DNA markers.

Little is known on genetics of Brazilian coral reef fish and most of this information is limited to chromosome characterization of major representative species. The diploid chromosome number in marine fish varies from 2n= 22-26 to 2n = 240-260. Despite of this apparent diversity, most studied marine species have a diploid complement with 48 acrocentric chromosomes. This latter trend is mostly observed among Perciformes, an important major taxon of coral reef fishes. Studies in the families Pomacentridae, Pomacanthidae and Chaetodontidae, for example, have shown a common karyotype pattern entirely formed by 48 uniarmed chromosomes. However, rare numerical and structural chromosome polymorphisms and cryptic chromosome rearrangements involving heterochromatin segments and/or nucleolar organizing sites have been reported among such fishes. Although new chromosome forms can contribute to the establishment of genetically isolated populations, their role in reef fish speciation at marine realm still is an open question. More recently, genomic DNA analyses using RAPD and microsatellites, and sequencing and RFLP of mitochondrial DNA have increasingly been used in Atlantic reef fish species. Genetic homogeneity over wide geographical ranges has been reported for different fish groups, in contrast to several cases of population substructuring related to environmental constraints or evolutionary history. Amazonas outflow and upwelling on the Southeastern coast of Brazil are believed to be strong barriers to dispersal of some reef species. Moreover, it is suggested that the pattern of speciation and population structure at South Atlantic is quite distinctive from Pacific Ocean, even when comparing closely related taxa. Further genetic studies are strongly encouraged in Brazilian reef fishes in order to provide a reliable scenario of the genetic structure in this important and diverse fish group.

[Congenital bronchobiliary fistula detected by cholescintigraphy]. / Fistula broncobiliar congénita detectada por colescintigrafía.

A case of a six-year-old female patient diagnosed with congenital bronchobiliary fistula is presented. Only 20 cases have been reported in the literature of this disease in this institution. The patient showed signs and symptoms of a respiratory illness from birth that complicated progressively. She was submitted to multiple imaging studies like chest X rays, CT, ultrasound and Tc-99m HIDA cholescintigraphy. This procedure confirmed the presence of a bronchobiliary fistula that was corrected by surgery, with subsequent improvement of clinical symptoms.