Structure-activity relationships reveal a 2-furoyloxychalcone as a potent cytotoxic and apoptosis inducer for human U-937 and HL-60 leukaemia cells.

Synthetic flavonoids with new substitution patterns have attracted attention as potential anticancer drugs. Here, twelve chalcones were synthesized and their antiproliferative activities against five human tumour cells were evaluated. This series of chalcone derivatives was characterized by the presence of an additional aromatic or heterocyclic ring linked by an ether, in the case of a benzyl radical, or an ester or amide functional group in the case of a furoyl radical. In addition, the influence on cytotoxicity by the presence of one or three methoxy groups or a 2,4-dimethoxy-3-methyl system on the B ring of the chalcone scaffold was also explored. The results revealed that the most cytotoxic chalcones contain a furoyl substituent linked by an ester or an amide through the 2'-hydroxy or the 2'-amino group of the A ring of the chalcone skeleton, with IC50 values between 0.2 ±â€¯0.1 µM and 1.3 ±â€¯0.1 µM against human leukaemia cells. The synthetic chalcone 2'-furoyloxy-4-methoxychalcone (FMC) was, at least, ten-fold more potent than the antineoplastic agent etoposide against U-937 cells and displayed less cytotoxicity against human peripheral blood mononuclear cells. Treatment of U-937 and HL-60 cells with FMC induced cell cycle arrest at the G2-M phase, an increase in the percentage of sub-G1 and annexin-V positive cells, the release of mitochondrial cytochrome c, activation of caspase and poly(ADP-ribose) polymerase cleavage. In addition, it inhibited tubulin polymerization in vitro in a concentration dependent manner. Cell death triggered by this chalcone was decreased by the pan-caspase inhibitor z-VAD-fmk and was dependent of the generation of reactive oxygen species. We conclude that this furoyloxychalcone may be useful in the development of a potential anti-leukaemia strategy.

Factores limitantes del rendimiento académico en residentes de la especialidad de Estomatología General Integral

RESUMEN Fundamento Los resultados académicos tienen gran relevancia en la etapa de postgrado del profesional de la salud, al ser determinantes en su ubicación laboral y excelencia en el desempeño profesional. Por ello, resulta provechoso el estudio de los factores que pudieran limitar el rendimiento académico en dicho contexto. Objetivo caracterizar los factores limitantes del desempeño académico de los residentes de Estomatología General Integral durante los exámenes de promoción. Métodos se realizó un estudio descriptivo transversal, con la participación de residentes (n=29) de la especialidad de Estomatología General Integral, en el periodo de examen de promoción en los meses de junio (para segundo año) y julio (para primer año) de 2020, en el municipio de Campechuela, provincia de Granma. Se aplicaron cuestionario y entrevista a residentes y profesores del tribunal examinador, respectivamente. Se incluyeron como variables del estudio elementos intrísecos y extrínsecos, la situación socio-éconómica y las manifestaciones de estrés. Resultados el 82,76 % identificó a la falta de sistematicidad en el estudio como elemento responsable de los resultados negativos; y el 100 % refirió haber sentido ansiedad, cansancio o agotamiento; en este aspecto, el tribunal constató ansiedad en el 100 % de los residentes, y cansancio o agotamiento en el 79,31 %. Conclusión cuestiones como el nivel económico bajo, y la convivencia con personas enfermas resultaron de las más frecuentes entre las percibidas como factores limitantes del rendimiento académico; sin embargo, otros elementos de carácter subjetivo y mejorables a través del esfuerzo individual, se mostraron en mayor medida aún.

ABSTRACT Background The academic results have great relevance in the postgraduate stage of the health professional, as they are determinant in their work location and excellence in professional performance. Therefore, it is useful to study the factors that could limit academic performance in this context. Objective to characterize the limiting factors of the Comprehensive General Stomatology residents academic performance during the promotion test. Methods a cross-sectional descriptive study was carried out, with the participation of residents (n=29) of the Comprehensive General Stomatology specialty, during the promotion examination in June (for the second year) and July (for the first year) of 2020, in the Campechuela municipality, Granma province. Questionnaire and interview were applied to residents and professors of the examining board, respectively. Intrinsic and extrinsic elements, socioeconomic status, and stress manifestations were included as study variables. Results 82.76% identified the lack of systematicity in the study as the element responsible for the negative results; and 100 % reported having felt anxiety, tiredness or exhaustion; in this regard, the court found anxiety in 100 % of the residents, and tiredness or exhaustion in 79.31 %. Conclusion issues such as low economic level, and living with sick people were the most frequent among those perceived as limiting factors of academic performance; however, other subjective elements that could be improved through individual effort were shown to an even greater extent.

Wilson disease: revision of diagnostic criteria in a clinical series with great genetic homogeneity.

BACKGROUND: Wilson disease is an autosomal recessive disorder of copper metabolism caused by mutations in the ATP7B gene. An early diagnosis is crucial to prevent evolution of the disease, as implantation of early therapeutic measures fully prevents its symptoms. As population genetics data predict a higher than initially expected prevalence, it was important to define the basic diagnostic tools to approach population screening. METHODS: A highly genetically homogeneous cohort of 70 patients, belonging to 50 unrelated families, has been selected as a framework to analyze all their clinical, biochemical and genetic characteristics, to define the disease in our population, with an estimated prevalence of 1 in 12,369, and determine the most useful features that reach diagnostic value. RESULTS: Serum ceruloplasmin below 11.5 mg/dL and cupremia below 60 µg/mL, were the best analytical predictors of the disease in asymptomatic individuals, while cupruria or hepatic copper determination were less powerful. Genetic analysis reached a conclusive diagnosis in all 65 patients available for complete testing. Of them, 48 were carriers of at least one p.Leu708Pro mutant allele, with 24 homozygotes. Nine patients carried a promoter deletion mutation, revealing that extended sequencing beyond the ATP7B gene-coding region is essential. All mutations caused hepatic damage since early ages, increasing its severity as diagnosis was delayed, and neurological symptoms appear. CONCLUSION: Serum ceruloplasmin determination followed by genetic screening would reduce costs and favor the prioritization of non-invasive procedures to reach a definitive diagnosis, even for asymptomatic cases.

Predictors of Response to Exclusive Enteral Nutrition in Newly Diagnosed Crohn´s Disease in Children: PRESENCE Study from SEGHNP.

Exclusive enteral nutrition (EEN) has been shown to be more effective than corticosteroids in achieving mucosal healing in children with Crohn´s disease (CD) without the adverse effects of these drugs. The aims of this study were to determine the efficacy of EEN in terms of inducing clinical remission in children newly diagnosed with CD, to describe the predictive factors of response to EEN and the need for treatment with biological agents during the first 12 months of the disease. We conducted an observational retrospective multicentre study that included paediatric patients newly diagnosed with CD between 2014-2016 who underwent EEN. Two hundred and twenty-two patients (140 males) from 35 paediatric centres were included, with a mean age at diagnosis of 11.6 ± 2.5 years. The median EEN duration was 8 weeks (IQR 6.6-8.5), and 184 of the patients (83%) achieved clinical remission (weighted paediatric Crohn's Disease activity index [wPCDAI] < 12.5). Faecal calprotectin (FC) levels (µg/g) decreased significantly after EEN (830 [IQR 500-1800] to 256 [IQR 120-585] p < 0.0001). Patients with wPCDAI ≤ 57.5, FC < 500 µg/g, CRP >15 mg/L and ileal involvement tended to respond better to EEN. EEN administered for 6-8 weeks is effective for inducing clinical remission. Due to the high response rate in our series, EEN should be used as the first-line therapy in luminal paediatric Crohn's disease regardless of the location of disease and disease activity.

Manifestations and evolution of Wilson disease in pediatric patients carrying ATP7B mutation L708P.

OBJECTIVES: The aim of the study was to characterize a group of 11 pediatric patients, ages 3 to 13 years, affected by Wilson disease (WD) in the island of Gran Canaria, Spain. PATIENTS AND METHODS: Genetic, biochemical, and pathological features, together with their response to treatment and clinical evolution, have been analyzed for this group of patients. RESULTS: Genetically, the group was rather homogeneous, with an extremely high prevalence of the L708P mutation (4 homozygotes and 5 heterozygotes). Despite being initially screened because of asymptomatic hypertransaminemia, all of the patients presented with some degree of liver damage that was never accompanied by any neurological manifestation. Hepatic damage was most severe in a compound heterozygote with a novel mutation, G1266W, affecting a motif in the ATP7B polypeptide that is greatly conserved in similar proteins among metazoans. Ceruloplasmin and copper serum levels, together with the determination of hepatic copper content, were found to be of great diagnostic value, whereas urine copper measurements were found to be much less conclusive. All of the patients responded well to treatment with D-penicillamine with no documented adverse reactions. CONCLUSIONS: The patients in Gran Canaria constitute, overall, one of the largest groups of patients with WD with a high incidence of a single mutation, allowing us to define the early clinical symptoms and the evolution of the disease in patients carrying the ATP7B L708P mutant allele, and the study of WD in a genetically homogeneous background.

Atención integral a un grupo de adolescentes de la ESBU Pedro RiveroPeña en el período de enero-junio/2001 / Integral assistance for a group of teenagers from Pedro Rivera Peña School. January June 2001

¿Será posible crear un espacio informal donde las manifestaciones artísticas y técnicas afectivo - participativas sean capaces de elevar el nivel de educación para la salud fomentar cambios de conductas en los adolescentes?. Se realizó un estudio de intervención comunitaria con un grupo de 18 alumnos perteneciente a la ESBU Pedro Rivera Peña de Campechuela, Granma, en el período enero a junio del 2001 para comprobar los efectos de la aplicación de técnicas afectivo participativas y actividades culturales con vistas a influir en la psiquis del adolescentes en aras de elevar sus conocimientos de educación para la salud. Los resultados fueron evaluados antes y después de las diferentes técnicas. Al finalizar la investigación se logró una real identificación de los adolescentes con los temas referidos a la higiene y mantenimiento de la salud bucal, observándose cambios de conductas y actitudes positivas en el 90 por ciento de los casos(AU)

Will it be possible to create a space where technical and artistic affective- participative manifestations would increase the level of health education and would also encourage the behavior changes in the adolescents? It was performed a community intervention study with a group of 18 students from Pedro Rivera Peña school in Campechuela, Granma, during the period of January to June, 2001 in order to verify the effects of the application of the affective participative techniques and cultural activities, with the purpose to influence in the adolescent psyche, increasing their knowledge about health education. The results were evaluated before and after the application of the techniques. At the end of the research it was obtained a real identification of adolescents with the topics of the hygene and maintenance of buccal health, demonstrating the changes in behaviour and positive actitudes in 90 percent of the cases(EU)