A co-designed curriculum for cultural safety training of Colombian health professionals: sequential-consensual qualitative study.

Background: Although traditional and cultural health practices are widely used in Colombia, physicians are not trained to address intercultural tensions that arise in clinical practice. Cultural safety encourages practitioners to examine how their own culture shapes their clinical practice and to respect their patients' culture. It requires inviting patients of non-dominant cultures to co-design culturally safe health care. We co-designed a curriculum for cultural safety training of Colombian health professionals. Methods: A sequential-consensual qualitative study defined the learning objectives of the curriculum. Semi-structured questionnaires and focus groups explored the opinions of traditional medicine users, medical students, and intercultural health experts to inform the content of the curriculum. Deliberative dialogue between key intercultural health experts settled the academic content of the curriculum. A member-checking strategy modified and approved the final version. Results: Seven traditional medicine users, six medical students, and four intercultural health experts participated in the study. The stakeholders defined five learning objectives: (a) culturally unsafe practices: acknowledge the intercultural tensions and its consequences; (b) cultural awareness: examine their attitudes, beliefs, and values, and how they shape their professional practice; (c) cultural humility: listen and learn from the patients' traditional practices; (d) cultural competence: describe current pedagogical approaches to address intercultural tensions; and (e) cultural safety: discuss with patients to reach an agreement on their treatment. Conclusion: This study integrated the perspectives of different stakeholders and proposed new applications of cultural safety that are relevant to other countries. Researchers and educators can use these results to inform future cultural safety initiatives.

Contexte: Bien que les pratiques traditionnelles et culturelles en matière de santé soient largement utilisées en Colombie, les médecins ne sont pas formés pour faire face aux tensions interculturelles qui peuvent surgir dans le contexte clinique. La sécurité culturelle encourage les praticiens à s'interroger sur les façons dont leur propre culture influence leur pratique clinique et à respecter la culture de leurs patients. Elle exige qu'ils invitent leurs patients de cultures non dominantes à co-concevoir des soins de santé culturellement sûrs. Nous avons co-conçu un programme de formation en sécurité culturelle pour les professionnels de santé colombiens. Méthodes: Les objectifs d'apprentissage du programme ont été définis sur la base d'une étude qualitative séquentielle-consensuelle. Par le biais de questionnaires semi-structurés et de groupes de discussion, nous avons exploré les opinions d'utilisateurs de la médecine traditionnelle, d'étudiants en médecine et d'experts en santé interculturelle dans le but de définir le contenu du cursus de façon éclairée. Son contenu académique a été finalisé à la suite d'un dialogue délibératif entre les principaux experts en santé interculturelle. Une vérification par les membres a permis de modifier et d'approuver la version finale. Résultats: Sept utilisateurs de la médecine traditionnelle, six étudiants en médecine et quatre experts en santé interculturelle ont participé à l'étude. Les parties prenantes ont défini cinq objectifs d'apprentissage : (a) pratiques culturellement non sécuritaires : reconnaître les tensions interculturelles et leurs conséquences; (b) prise de conscience culturelle : examiner leurs attitudes, croyances et valeurs, et la manière dont elles façonnent s pratiques professionnelles; (c) humilité culturelle : écouter et apprendre des pratiques traditionnelles des patients; (d) compétence culturelle : décrire les approches pédagogiques actuelles sur la question des tensions interculturelles; et (e) sécurité culturelle : discuter avec les patients pour parvenir à un terrain d'entente sur leur traitement. Conclusion: Cette étude intègre les perspectives de différentes parties prenantes et propose de nouvelles applications de la sécurité culturelle qui seraient également pertinentes dans d'autres pays. Les chercheurs et les enseignants peuvent utiliser ces résultats pour alimenter des initiatives futures en matière de sécurité culturelle.

Regulation of p14ARF expression by HPV-18 E6 variants.

A common causative agent for uterine cervical cancer is the human papillomavirus type 18 (HPV-18) which has three phylogenic variants: Asian-Amerindian, European, and African. Each variant shows significant molecular differences in the E6 gene. E6 oncoprotein is a negative regulator of tumor suppressor protein p53, hence, this oncoprotein indirectly regulates the expression of tumor-suppressor p14(ARF) . p14(ARF) and p16(INK4A) genes are overexpressed in--and have been proposed as markers for--HPV-related cervical cancer. In order to dissect the role of E6 on the regulation of p14(ARF) expression, separating it from that of other intervening factors, transfection of E6 variants to MCF-7 cells was performed, assessing cDNA transcript levels by RT-PCR, whereas p14(ARF) and p53 expression were evaluated by immunocytochemistry and Western blot. E6 transfected cells differentially expressed transcripts of two molecular forms: E6 and E6*. The ratio of these two forms varied with the transfected E6 variant. With the Asian-Amerindian variant, the ratio was E6 > E6*, whereas with the European and the African the ratio was E6* > E6. As expected with the E6* construct, E6* transcripts were solely observed. In addition, when E6 > E6* and p53 expression was low, p14(ARF) was high and when E6* > E6 and p53 expression was high, p14(ARF) was low. In conclusion, each E6 variant distinctively affects p53 levels and consequently p14(ARF) expression, finding that could be related with the differences in oncogenic effect of infection with the diverse high-risk HPV variants.

[RNA interference (RNAi) and its therapeutic potential in cancer]. / RNA de interferencia y su potencial terapéutico en cáncer.

Small RNAs belong to a newly discovered strain of molecules. These molecules are composed of double strand RNA comprised by just about 19-31 nucleotides. They have two main characteristics that make them unique. Firstly, they are noncoding for proteins and second they interfere post-transcriptional with mRNA. This interfering action is the distinguishing hallmark, therefore known as interfering RNA or RNAi. There are three main subclasses of which micro-RNA and siRNA are the most widely studied. Interference RNAs participate in a myriad of cellular functions mainly through modulation of genetic expression. Due to these capabilities it has been used as therapeutic weapon in a number of diseases including cancer. It is known that both miRNA and siRNA participate in carcinogenesis, either inhibiting suppressor genes, or stimulating oncogenes. It has been demonstrated that manipulating small interfering RNAs in cell lines and animal models, the malignant and metastatic phenotype can be reversed. Up to now a few clinical trials using RNAi as a therapeutic agent have demonstrated some success and feasibility. It is forseeable that in the near future cancer treatment with small RNAs will be widely applicable, once the many constrains for its systemic application are surpassed.

Nuclear co-expression of p14ARF and p16INK4A in uterine cervical cancer-derived cell lines containing HPV.

The Papanicolaou test (Pap) has been responsible for a significant reduction of cervical cancer-related morbimortality. In order to increase its sensitivity and specificity new markers have been studied and incorporated to cytological and histological methods for diagnosis for cervical cancer, such as p16INK4A that has been considered the immunocytochemical marker of choice for detection of HPV related cancers. We considered that p14ARF could be a complementary marker in order to improve the accuracy of cytological diagnosis because its genetic proximity to p16INK4A. We performed a systematic analysis of several putative cervical cancer markers in order to evaluate their performance in the detection of malignancy, in comparison with p16INK4A and p14ARF, using immunocytochemistry (ICC), immunofluorescence (IF) and Western blot analyses. Most markers were non-specific and could not discriminate HPV infected cancer cell lines from other non HPV malignant. In contrast, nuclear co-expression of p16INK4A and p14ARF was observed only in HPV-transformed cancer cell lines. Notably, in C-33A cervical cancer cells (HPV negative), p14ARF was present in the nucleoli, but p16INK4A was conspicuously absent from the nuclei of these cells. We conclude that both markers; p16INK4A and p14ARF are complementary and should be evaluated jointly in order to improve the accuracy of cytological diagnosis of cervical cancer.

Prolonged idiotypic vaccination against follicular lymphoma.

During the last 2 decades, idiotypic vaccination has provided proof of principle of biological efficacy, clinical efficacy and clinical benefit in small follicular lymphoma trials. However, with the exception of anecdotal reports, most patients have received no more than 10 doses of their customised idiotype (Id) vaccine. Therefore, it is not known whether prolonged usage of idiotypic vaccination is safe. Since 2002, 18 previously treated patients with follicular lymphoma have received extended idiotypic vaccination at our institution outside clinical trials. Vaccination was provided as a compassionate alternative to no further treatment, and was meant to be stopped only upon complete consumption of the available patient- and tumor-specific vaccine [Id-keyhole limpet hemocyanin + granulocyte-macrophage colony-stimulating factor (Id-KLH + GM-CSF)], or in case of disease relapse or any serious non-local toxicity. So far, 18 patients have received an average of 18 doses of Id vaccine (median: 17; mean: 18; range: 10-31). Eleven patients are still actively receiving idiotypic vaccination: some of them are now over more than 6 years. Toxicity has been systematically negligible and mostly local. No patient has abandoned the vaccination program because of toxicity. Prolonged idiotypic vaccination with the soluble protein Id-KLH + GM-CSF formulation is safe and well tolerated.

Clinical benefit associated with idiotypic vaccination in patients with follicular lymphoma.

BACKGROUND: Follicular lymphoma is considered incurable, although cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy can induce sequential remissions. A patient's second complete response is typically shorter than that patient's first complete response. Idiotype vaccines can elicit specific immune responses and molecular remissions in patients with follicular lymphoma. However, a clinical benefit has never been formally proven. METHODS: Thirty-three consecutive follicular lymphoma patients in first relapse received six monthly cycles of CHOP-like chemotherapy. Patients who achieved a second complete response were vaccinated periodically for more than 2 years with autologous lymphoma-derived idiotype protein vaccine. Specific humoral and cellular responses were assessed, and patients were followed for disease recurrence. Statistical tests were two-sided. RESULTS: Idiotype vaccine could be produced for 25 patients who had a second complete response. In 20 patients (80%), a humoral (13/20) and/or a cellular (18/20) idiotype-specific response was detected. The median duration of the second complete response has not been reached, but it exceeds 33 months (range = 20+ to 51+ months). None of the 20 responders relapsed while undergoing active vaccination. All responders with enough follow-up for the comparison to be made experienced a second complete response that was statistically significantly (P<.0001) longer than both their first complete response (18 of 18 patients) and than the median duration of a CHOP-induced second complete response, i.e., 13 months (20 of 20 patients). The five nonresponders all had a second complete response that was shorter (median = 10 months; range = 8-13 months) than their first complete response (median = 17 months; range = 10-39 months). CONCLUSIONS: Idiotypic vaccination induced a specific immune response in the majority of patients with follicular lymphoma. Specific immune response was associated with a dramatic and highly statistically significant increase in disease-free survival. This is the first formal demonstration of clinical benefit associated with the use of a human cancer vaccine.

Differences in anti-apoptotic and multidrug resistance phenotypes in elderly and young acute myeloid leukemia patients are related to the maturation of blast cells.

BACKGROUND AND OBJECTIVES: Elderly patients with acute myeloid leukemia (AML) have a less favorable outcome, which has been related, among other factors, to multidrug resistance (MDR) phenotypes. DESIGN AND METHODS: Freshly obtained erythrocyte-lysed bone marrow samples from 150 elderly patients (> 65 years) with de novo AML and 30 younger AML patients were analyzed using a 4-color immunofluorescence technique for quantitative expression of proteins associated with apoptosis (bcl-2, bax, APO2.7) and MDR (P-gp, MRP, LRP) in 3 blast cell subpopulations, defined according to their maturation stage. RESULTS: Although a homogeneous CD34+ blast cell population was more frequent in the elderly patients, (25% vs 7%, p=0.02), no statistically significant differences were detected between the two age groups in the expression of either apoptosis- or MDR-associated proteins, except for slightly higher quantities of LRP protein in the more immature CD34+ blast cell subset in the elderly AML cases (p=0.04). Interestingly, when different blast cell populations were compared, immature (CD34+) blast cells were characterized by higher levels of bcl-2 in both age groups and lower levels of APO2.7 in the elderly group. In addition, higher P-gp levels were found in CD34+ blast cells than in CD34-- ones in elderly AML patients. Reactivity for LRP was low in both elderly and younger patients. INTERPRETATION AND CONCLUSIONS: In summary, our results suggest that the higher resistance to chemotherapy observed in elderly AML patients could be related to a higher incidence of cases with a CD34+ homogeneous blast cell population, since these blast cells frequently display a more pronounced anti-apoptotic and MDR1 phenotype.

CD34+ cells from acute myeloid leukemia, myelodysplastic syndromes, and normal bone marrow display different apoptosis and drug resistance-associated phenotypes.

Myelodysplastic syndromes and acute myeloid leukemia (AML) are heterogeneous disorders in which conflicting results in apoptosis and multidrug resistance (MDR) have been reported. We have evaluated by multiparameter flow cytometry the expression of apoptosis- (APO2.7, bcl-2, and bax) and MDR-related proteins [P-glycoprotein (P-gp), multidrug resistance protein (MRP), and lung resistance protein (LRP)] specifically on bone marrow (BM) CD34+ cells, and their major CD32-/dim and CD32+ subsets, in de novo AML (n=90), high-risk myelodysplastic syndrome (n=9), and low-risk myelodysplastic syndrome (n=21) patients at diagnosis, and compared with normal BM CD34+ cells (n=6). CD34+ myeloid cells from AML and high-risk myelodysplastic syndrome patients displayed higher expression of bcl-2 (P <0.0001) and lower reactivity for APO2.7 (P=0.002) compared with low-risk myelodysplastic syndrome and normal controls. Similar results applied to the two predefined CD34+ myeloid cell subsets. No significant differences were found in the expression of P-gp, MRP, and LRP between low-risk myelodysplastic syndrome patients and normal BM, but decreased expression of MRP (P <0.03) in AML and high-risk myelodysplastic syndromes and P-gp (P=0.008) in high-risk myelodysplastic syndromes were detected. Hierarchical clustering analysis showed that low-risk myelodysplastic syndrome patients were clustered next to normal BM samples, whereas high-risk myelodysplastic syndromes were clustered together and mixed with the de novo AML patients. In summary, increased resistance to chemotherapy of CD34+ cells from both AML and high-risk myelodysplastic syndromes would be explained more appropriately in terms of an increased antiapoptotic phenotype rather than a MDR phenotype. In low-risk myelodysplastic syndromes abnormally high apoptotic rates would be restricted to the CD34- cell compartments.

Evaluación de los reactivos hemoclasificadores monoclonales cubanos HEMO CIM ANTI-A y HEMO CIM ANTI-B en pacientes VIH/SIDA / Evaluation of the reagents hemoclasificadores Cuban monoclonales HEMO CIM ANTI-TO and HEMO CIM ANTI-B in patient VIH/SIDA

Se describe un estudio realizado con los hemoclasificadores monoclonales cubanos Hemo CIM anti-A y anti-B producidos por el Centro de Inmunología Molecular (CIM) y comercializados por CIMAB S.A, para ser evaluados en pacientes VIH/SIDA. Se analizaron un total de 130 pacientes en el Servicio de Transfusiones del Instituto Pedro Kourí. Se utilizaron en paralelo los antisueros policlonales de producción nacional (Laboratorios Betera) y los reactivos monoclonales comerciales producidos y donados por International Blood Group Reference Laboratory; Bristol, UK. Se demostró que los reactivos Hemo CIM anti-A y Hemo CIM anti-B se comportaron de forma similar a sus homólogos comerciales y policlonales. Al comparar la efectividad de la aglutinación para los 3 reactivos pudimos comprobar que con el reactivo monoclonal, Hemo CIM anti-A y anti-B se obtuvieron los mejores resultados expresados en cruces(AU)

Evaluación de los reactivos hemoclasificadores monoclonales cubanos HEMO CIM ANTI-A y HEMO CIM ANTI-B en pacientes VIH/SIDA / Evaluation of the Cuban anti-A Hemo CIM and anti-B Hemo CIM monoclonal hemoclassifiers in HIV/AIDS patients

Se describe un estudio realizado con los hemoclasificadores monoclonales cubanos Hemo CIM anti-A y anti-B producidos por el Centro de Inmunología Molecular (CIM) y comercializados por CIMAB S.A, para ser evaluados en pacientes VIH/SIDA. Se analizaron un total de 130 pacientes en el Servicio de Transfusiones del Instituto "Pedro Kourí". Se utilizaron en paralelo los antisueros policlonales de producción nacional (Laboratorios Betera) y los reactivos monoclonales comerciales producidos y donados por International Blood Group Reference Laboratory; Bristol, UK. Se demostró que los reactivos Hemo CIM anti-A y Hemo CIM anti-B se comportaron de forma similar a sus homólogos comerciales y policlonales. Al comparar la efectividad de la aglutinación para los 3 reactivos pudimos comprobar que con el reactivo monoclonal, Hemo CIM anti-A y anti-B se obtuvieron los mejores resultados expresados en cruces.

A study conducted with the Cuban anti-A and anti-B Hemo CIM monoclonal hemoclassifiers produced by the Center of Molecular Immunology (CMI) and commercialized by CIMAB S.A. to be evaluated in HIV/AIDS patients is described. 130 patients were analyzed at the Service of Transfusions of "Pedro Kouri" Institute. The polyclonal antisera of national production (Betera Laboratories) and the commercial monoclonal reagents produced and donated by the International Blood Group Reference Laboratory; Bristol, UK, were used at the same time. It was proved that the anti-A Hemo CIM and anti-B Hemo CIM reagents behaved similarly to their commercial and polyclonal homologues. On comparing the effectiveness of the agglutination for the 3 reagents, we were able to verify that the best results expressed in crosses were obtained with the anti-A and anti-B Hemo CIM monoclonal reagents.