Overcoming Resistance of Caco-2 Cells to 5-Fluorouracil through Diruthenium Complex Encapsulation in PMMA Nanoparticles.

Drug resistance, one of the main drawbacks in cancer chemotherapy, can be tackled by employing a combination of drugs that target different biological processes in the cell, enhancing the therapeutic efficacy. Herein, we report the synthesis and characterization of a new paddlewheel diruthenium complex that includes 5-fluorouracil (5-FU), a commonly used anticancer drug. This drug was functionalized with a carboxylate group to take advantage of the previously demonstrated release capacity of carboxylate ligands from the diruthenium core. The resulting hydrophobic complex, [Ru2Cl(DPhF)3(5-FUA)] (Ru-5-FUA) (DPhF = N,N'-diphenylformamidinate; 5-FUA = 5-fluorouracil-1-acetate) was subsequently entrapped in poly(methyl methacrylate) (PMMA) nanoparticles (PMMA@Ru-5-FUA) via a reprecipitation method to be transported in biological media. The optimized encapsulation procedure yielded particles with an average size of 81.2 nm, a PDI of 0.11, and a zeta potential of 29.2 mV. The cytotoxicity of the particles was tested in vitro using the human colon carcinoma cell line Caco-2. The IC50 (half maximal inhibitory concentration) of PMMA@Ru-5-FUA (6.08 µM) was just slightly lower than that found for the drug 5-FU (7.64 µM). Most importantly, while cells seemed to have developed drug resistance against 5-FU, PMMA@Ru-5-FUA showed an almost complete lethality at ∼30 µM. Conversely, an analogous diruthenium complex devoid of the 5-FU moiety, [Ru2Cl(DPhF)3(O2CCH3)] (PMMA@RuA), displayed a reduced cytotoxicity at equivalent concentrations. These findings highlight the effect of combining the anticancer properties of 5-FU with those of diruthenium species. This suggests that the distinct modes of action of the two chemical species are crucial for overcoming drug resistance.

Mustard seed major allergen Sin a1 activates intestinal epithelial cells and also dendritic cells that drive type 2 immune responses.

Mustard seeds belong to the food category of mandatory labelling due to the severe reactions they can trigger in allergic patients. However, the mechanisms underlying allergic sensitization to mustard seeds are poorly understood. The aim of this work is to study type 2 immune activation induced by the mustard seed major allergen Sin a1 via the intestinal mucosa, employing an in vitro model mimicking allergen exposure via the intestinal epithelial cells (IECs). Sin a1 was isolated from the total protein extract and exposed to IEC, monocyte derived dendritic cells (DCs) or IEC/DC co-cultures. A system of consecutive co-cultures was employed to study the generic capacity of Sin a1 to induce type 2 activation leading to sensitization: IEC/DC, DC/T-cell, T/B-cell and stem cell derived mast cells (MCs) derived from healthy donors. Immune profiles were determined by ELISA and flow cytometry. Sin a1 activated IEC and induced type-2 cytokine secretion in IEC/DC co-culture or DC alone (IL-15, IL-25 and TSLP), and primed DC induced type 2 T-cell skewing. IgG secretion in the T-cell/B-cell phase was enhanced in the presence of Sin a1 in the first stages of the co-culture. Anti-IgE did not induce degranulation but promoted IL-13 and IL-4 release by MC primed with the supernatant from B-cells co-cultured with Sin a1-IEC/DC or -DC primed T-cells. Sin a1 enhanced the release of type-2 inflammatory mediators by epithelial and dendritic cells; the latter instructed generic type-2 responses in T-cells that resulted in B-cell activation, and finally MC activation upon anti-IgE exposure. This indicates that via activation of IEC and/or DC, mustard seed allergen Sin a1 is capable of driving type 2 immunity which may lead to allergic sensitization.

Efficacy of clozapine versus standard treatment in adult individuals with intellectual disability and treatment-resistant psychosis (CLOZAID): study protocol of a multicenter randomized clinical trial.

Background: Intellectual disability (ID) affects approximately 1% of the worldwide population and individuals with ID have a higher comorbidity with mental illness, and specifically psychotic disorders. Unfortunately, among individuals with ID, limited research has been conducted since ID individuals are usually excluded from mental illness epidemiological studies and clinical trials. Here we perform a clinical trial to investigate the effectiveness of clozapine in the treatment of resistant psychosis in individuals with ID. The article highlights the complexity of diagnosing and treating psychopathological alterations associated with ID and advocates for more rigorous research in this field. Methods: A Phase IIB, open-label, randomized, multicenter clinical trial (NCT04529226) is currently ongoing to assess the efficacy of oral clozapine in individuals diagnosed with ID and suffering from treatment-resistant psychosis. We aim to recruit one-hundred and fourteen individuals (N=114) with ID and resistant psychosis, who will be randomized to TAU (treatment as usual) and treatment-with-clozapine conditions. As secondary outcomes, changes in other clinical scales (PANSS and SANS) and the improvement in functionality, assessed through changes in the Euro-QoL-5D-5L were assessed. The main outcome variables will be analyzed using generalized linear mixed models (GLMM), assessing the effects of status variable (TAU vs. Clozapine), time, and the interaction between them. Discussion: The treatment of resistant psychosis among ID individuals must be directed by empirically supported research. CLOZAID clinical trial may provide relevant information about clinical guidelines to optimally treat adults with ID and treatment-resistant psychosis and the benefits and risks of an early use of clozapine in this underrepresented population in clinical trials. Trial registration: Clinicaltrials.gov: NCT04529226. EudraCT: 2020-000091-37.

Identification of New Allergens in Macadamia Nut and Cross-Reactivity with Other Tree Nuts in a Spanish Cohort.

The consumption of macadamia nuts has increased due to their cardioprotective and antioxidant properties. However, this rise is consistent with an increase in the cases of macadamia nut allergy, leading to severe reactions. Although two Macadamia integrifolia allergens (Mac i 1 and Mac i 2) have been identified in Australian and Japanese patients, the allergenic sensitization patterns in Western European populations, particularly in Spain, remain unclear. For this purpose, seven patients with macadamia nut allergy were recruited in Spain. Macadamia nut protein extracts were prepared and, together with hazelnut and walnut extracts, were used in Western blot and inhibition assays. IgE-reactive proteins were identified using MALDI-TOF/TOF mass spectrometry (MS). Immunoblotting assays revealed various IgE-binding proteins in macadamia nut extracts. Mass spectrometry identified three new allergens: an oleosin, a pectin acetylesterase, and an aspartyl protease. Cross-reactivity studies showed that hazelnut extract but not walnut extract inhibited macadamia nut oleosin-specific IgE binding. This suggests that oleosin could be used as marker for macadamia-hazelnut cross-reactivity. The results show an allergenic profile in the Spanish cohort different from that previously detected in Australian and Japanese populations. The distinct sensitization profiles observed highlight the potential influence of dietary habits and environmental factors exposure on allergenicity.

Beyond allergic progression: From molecules to microbes as barrier modulators in the gut-lung axis functionality.

The "epithelial barrier hypothesis" states that a barrier dysfunction can result in allergy development due to tolerance breakdown. This barrier alteration may come from the direct contact of epithelial and immune cells with the allergens, and indirectly, through deleterious effects caused by environmental changes triggered by industrialization, pollution, and changes in the lifestyle. Apart from their protective role, epithelial cells can respond to external factors secreting IL-25 IL-33, and TSLP, provoking the activation of ILC2 cells and a Th2-biased response. Several environmental agents that influence epithelial barrier function, such as allergenic proteases, food additives or certain xenobiotics are reviewed in this paper. In addition, dietary factors that influence the allergenic response in a positive or negative way will be also described here. Finally, we discuss how the gut microbiota, its composition, and microbe-derived metabolites, such as short-chain fatty acids, alter not only the gut but also the integrity of distant epithelial barriers, focusing this review on the gut-lung axis.

First PCR-free electrochemical bioplatform for the detection of mustard Sin a 1 protein as a potential "hidden" food allergen.

A disposable electrochemical PCR-free biosensor for the selective detection of a fragment encoding the protein Sin a 1, a 2S albumin considered a diagnostic marker for sensitization to mustard, is reported. The methodology is based on the formation of DNA/RNA heterohybrids by sandwich hybridization of a specific fragment of the Sin a 1 allergen coding sequence with appropriately designed RNA probes. Labeling with commercial antibodies specific to the heteroduplexes and secondary antibodies conjugated with horseradish peroxidase (HRP) was carried out onto the surface of magnetic beads (MBs). Amperometric transduction was undertaken on screen-printed electrodes using H2O2 as enzyme substrate and hydroquinone (HQ) a redox mediator. The electrochemical biosensor allows the simple and fast detection (75 min) of Sin a 1 reaching a limit of detection of 3 pM. The bioplatform was successfully applied to the analysis of the targeted Sin a 1 gene specific region using just 50 ng of non-fragmented denatured genomic DNA extracted from yellow mustard seeds.

Impact of the implementation of a Sepsis Code Program in medical patient management: a cohort study in an Internal Medicine ward / Impacto de la implementación del Programa Código Sepsis en una planta de hospitalización médica: estudio de una cohorte de pacientes de Medicina Interna

Introduction. Sepsis is the main cause of death in hospitals and the implementation of diagnosis and treatment bundles has shown to improve its evolution. However, there is alack of evidence about patients attended in conventional units.Methods. A 3-year retrospective cohort study was conducted. Patients hospitalized in Internal Medicine units withsepsis were included and assigned to two cohorts according toSepsis Code (SC) activation (group A) or not (B). Baseline andevolution variables were collected.Results. A total of 653 patients were included. In 296 cases SC was activated. Mean age was 81.43 years, median Charlson comorbidity index (CCI) was 2 and 63.25% showed somefunctional disability. More bundles were completed in group A:blood cultures 95.2% vs 72.5% (p < 0.001), extended spectrumantibiotics 59.1% vs 41.4% (p < 0.001), fluid resuscitation96.62% vs 80.95% (p < 0.001). Infection control at 72 hourswas quite higher in group A (81.42% vs 55.18%, odds ratio3.55 [2.48-5.09]). Antibiotic was optimized more frequently ingroup A (60.77% vs 47.03%, p 0.008). Mean in-hospital staywas 10.63 days (11.44 vs 8.53 days, p < 0.001). Complicationsduring hospitalization appeared in 51.76% of patients, especially in group B (45.95% vs 56.58%, odds ratio 1.53 [1.12-2.09]). Hospital readmissions were higher in group A (40% vs24.76%, p < 0.001). 28-day mortality was significantly lower ingroup A (20.95% vs 42.86%, odds ratio 0.33 [0.23-0.47]).Conclusions. Implementation of SC seems to be effectivein improving short-term outcomes in IM patients, althoughtherapy should be tailored in an individual basis (AU)

Introducción. La sepsis es la principal causa de muerte enlos hospitales y la implantación de códigos para su manejo hademostrado mejorar su evolución. Sin embargo, es escasa laevidencia relativa a los pacientes atendidos en unidades médicas convencionales.Métodos. Se realizó un estudio de cohortes retrospectivode 3 años. Se incluyeron pacientes con sepsis hospitalizados enunidades de Medicina Interna y se asignaron a dos cohortessegún la activación del Código Sepsis (CS) (grupo A) o no (B).Se recogieron variables basales y de evolución.Resultados. Se incluyeron 653 pacientes. En 296 casos seactivó el SC. La edad media fue de 81,43 años, la mediana delíndice de comorbilidad de Charlson (ICC) fue de 2 y el 63,25%presentaba alguna limitación funcional. Se realizaron más acciones diagnósticas y terapéuticas en el grupo A: hemocultivos95,2% vs 72,5% (p < 0,001), antibióticos de espectro extendido59,1% vs 41,4% (p < 0,001), reanimación con líquidos 96,62%vs 80,95% (p < 0,001). El control de la infección a las 72 horasfue superior en el grupo A (81,42% vs 55,18%, odds ratio 3,55[2,48-5,09]). La optimización de los antibióticos fue más frecuente en el grupo A (60,77% vs 47,03%, p 0,008). La estanciamedia en el hospital fue de 10,63 días (11,44 vs 8,53 días, p <0,001). Aparecieron complicaciones durante la hospitalizaciónen el 51,76% de los pacientes, especialmente en el grupo B(45,95% vs 56,58%, odds ratio 1,53 [1,12-2,09]). Los pacientesdel grupo A reingresaron más (40% vs 24,76%, p < 0,001). Lamortalidad a los 28 días fue significativamente menor en elgrupo A (20,95% frente a 42,86%, odds ratio 0,33 [0,23-0,47]). (AU)

Gender-Based Differences by Age Range in Patients Hospitalized with COVID-19: A Spanish Observational Cohort Study.

There is some evidence that male gender could have a negative impact on the prognosis and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The aim of the present study was to compare the characteristics of coronavirus disease 2019 (COVID-19) between hospitalized men and women with confirmed SARS-CoV-2 infection. This multicenter, retrospective, observational study is based on the SEMI-COVID-19 Registry. We analyzed the differences between men and women for a wide variety of demographic, clinical, and treatment variables, and the sex distribution of the reported COVID-19 deaths, as well as intensive care unit (ICU) admission by age subgroups. This work analyzed 12,063 patients (56.8% men). The women in our study were older than the men, on average (67.9 vs. 65.7 years; p < 001). Bilateral condensation was more frequent among men than women (31.8% vs. 29.9%; p = 0.007). The men needed non-invasive and invasive mechanical ventilation more frequently (5.6% vs. 3.6%, p < 0.001, and 7.9% vs. 4.8%, p < 0.001, respectively). The most prevalent complication was acute respiratory distress syndrome, with severe cases in 19.9% of men (p < 0.001). In men, intensive care unit admission was more frequent (10% vs. 6.1%; p < 0.001) and the mortality rate was higher (23.1% vs. 18.9%; p < 0.001). Regarding mortality, the differences by gender were statistically significant in the age groups from 55 years to 89 years of age. A multivariate analysis showed that female sex was significantly and independently associated with a lower risk of mortality in our study. Male sex appears to be related to worse progress in COVID-19 patients and is an independent prognostic factor for mortality. In order to fully understand its prognostic impact, other factors associated with sex must be considered.

Headache during SARS-CoV-2 infection as an early symptom associated with a more benign course of disease: a case-control study.

BACKGROUND AND PURPOSE: Headache is an important manifestation during SARS-CoV-2 infection. In this study, the aim was to identify factors associated with headache in COVID-19 and headache characteristics. METHODS: This case-control study includes COVID-19 hospitalized patients with pneumonia during March 2020. Controls comprise COVID-19 patients without headache and the cases are COVID-19 patients with headache. Demographic, clinical and laboratory data were obtained from the medical records. Headache characteristics were evaluated by semi-structured telephonic interview after discharge. RESULTS: Of a total of 379 COVID-19 patients, 48 (13%) developed headache. Amongst these, 30 (62%) were men and the median age was 57.9 (47-73) years. Headache was associated with younger age, fewer comorbidities and reduced mortality, as well as with low levels of C-reactive protein, mild acute respiratory distress syndrome and oropharyngeal symptoms. A logistic multiple regression model revealed that headache was directly associated with D-dimer and creatinine levels, the use of high flow nasal cannula and arthromyalgia, whilst urea levels, beta-lactamic treatment and hypertension were negatively associated with headache. COVID-19-associated headache characteristics were available for 23/48 (48%) patients. Headache was the onset symptom in 8/20 (40%) patients, of mild or moderate intensity in 17/20 (85%) patients, with oppressive characteristics in 17/18 (94%) and of holocranial 8/19 (42%) or temporal 7/19 (37%) localization. CONCLUSIONS: Our results show that headache is associated with a more benign SARS-CoV-2 infection. COVID-19-associated headache appears as an early symptom and as a novel headache with characteristics of headache attributed to systemic viral infection. Further research addressing the underlying mechanisms to confirm these findings is warranted.

Under the face mask: Racial-ethnic minority student-athletes and mental health use.

Objective: To investigate racial-ethnic minority student-athletes' (REMSA) symptoms of distress (mental health need), mental health use (usage rate), and factors that influence mental health usage. Participants: There were 241 varsity athletes (African American = 108, Latinos = 66, Asian American= 67) from the American College Health Association Fall 2015 data set. Results: Seventy-eight percent of REMSA reported some form of mental health need and only 11% of these athletes in need reported using mental health services in the past year. Additionally, a binominal logistic regression was run to identify demographic and mental health predictors of mental health use. Higher stress (ß = 1.58, OR = 3.49, p < .01) and having upperclassman standing (ß = 1.07, OR = 3.91, p < .05) predicted service use for athletes. Conclusions: Mental health professionals should be aware of the high mental health need for REMSA and the low usage rate of mental health services.

A caballo regalao no se le mira el colmillo: Colonial mentality and Puerto Rican depression.

Dignifying the colonizer and depreciating the colonized is a reflection of internalized colonial oppression (i.e., colonial mentality). The current study examined the effect of colonial mentality on depression symptoms in a sample of mainland Puerto Ricans (N = 352). A structural equation model was examined, in which colonial mentality was hypothesized to be directly and positively associated with depression symptoms. The proposed model also tested the indirect effect of colonial mentality on depression symptoms via acculturative stress. Results indicated that a full mediation structural equation model (SEM) had a better fit to the data than our hypothesized partial mediation model. Bias-corrected bootstrapping indicated that the effect of colonial mentality on depressive symptoms was mediated by acculturative stress. That is, colonial mentality increased the risk of experiencing depression symptoms in Puerto Ricans when they felt pressured to maintaining a connection with Puerto Rican culture and society and when they experienced rejection by the society they want to emulate (acculturative stress). The current results underscore the need for researchers and clinicians to consider and assess colonial mentality when conceptualizing depression symptoms among mainland Puerto Ricans. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

On the Development of Virtual Reality Scenarios for Computer-Assisted Biomedical Applications.

The modelling of virtual environments and scenarios is an important area of research for the development of new computer-assisted systems in the areas of engineering and medicine, particularly in the area of biomechanics and biomedical engineering. One of the main issues while designing a virtual environment is the level of realism, which depends on the computing capacity and the level of accuracy and usefulness of the generated data. Thus, the dilemma is between the aesthetic realism and the information utility. This paper proposes a methodology to develop low-cost and high-quality virtual environments and scenarios for computer-aided biomedical applications. The proposed methodology is based on the open-source software Blender and the Visualization Toolkit libraries (VTK). In order to demonstrate the usability of the proposed methodology, the design and development of a computer-assisted biomedical application is presented and analysed.

Epidemiología de los trastornos de personalidad en el anciano: prevalencia asistida, comorbilidad y uso de servicios / No disponible

Este trabajo actualiza la evidencia científica sobre aspectos epidemiológicos y de comorbilidad de los trastornos de personalidad en el anciano. Los diagnósticos de trastorno de personalidad en el anciano deben ser adaptados a la especial configuración de los factores psicológicos que ocurren en edades avanzadas. Los trastornos de personalidad en edades avanzadas continúan siendo un tema inexplorado, existiendo pocos estudios y resultados contradictorios. Decidimos realizar una breve revisión de la literatura y un estudio para determinar la comorbilidad con eje I en pacientes diagnosticados de T. de Personalidad y estudiar las posibles diferencias de comorbilidad entre población joven y anciana con un diagnóstico de eje II. 2.082 pacientes diagnosticados de T. de Personalidad mediante criterios DSM-IV fueron incluidos en este trabajo, de los cuales el 9,55 % eran mayores de 65 años. Estudiamos los grupos de edad por separado; examinamos diferencias por sexo, por clústers de personalidad, por subtipos de personalidad y por la comorbilidad con eje I por edades y clústers; también examinamos funcionalidad y consumo de recursos sanitarios. Hallamos diferencias estadísticamente significativas en los diagnósticos para los grupos de distintas edades, y fueron los trastornos más frecuentes entre los ancianos los del clúster A, mientras que en los jóvenes fueron los Trastornos no especificados; también existieron diferencias en la distribución de sexos. El nivel de funcionalidad era menor entre las personas de mayor edad. Existe gran variedad de resultados en este área, esto es posiblemente debido a problemas para el diagnóstico a estas edades. Es importante en el futuro estudiar la personalidad normal en el anciano para poder generar instrumentos válidos (AU)

No disponible

Epidemiología del deterioro Cognitivo: Estudios sobre su asociación con depresión y con factores genéticos, vasculares y ambientales / No disponible

Esta monografía es un resumen de la tesis doctoral del Dr. Jorge A. Cervilla Ballesteros. La tesis fue codirigida por los Profesores A. Mann y M. Prince del Instituto de Psiquiatría de la Universidad de Londres y por el Prof. A. Bulbena de la Universidad Autónoma de Barcelona. La monografía, que versa sobre la epidemiología del deterioro cognitivo, comienza con una introducción histórica del concepto de deterioro cognitivo e introduce la metodología de los tres estudios en los que se basan los ocho artículos incluidos en la tesis. Dichos estudios son: el subestudio psiquiátrico inserto en el ensayo clínico sobre hipertensión en el anciano del Medical Research Council; el estudio de cohorte sobre morbilidad psiquiátrica en el anciano de Gospel Oak; y, El estudio del registro de casos de demencia de Camberwell. La monografía está estructurada en tres partes: a) Deterioro Cognitivo y Depresión; b) Deterioro Cognitivo y factores genéticos; c) Deterioro Cognitivo y factores vasculares y ambientales. Deterioro Cognitivo y Depresión. La asociación transversal entre depresión y deterioro cognitivo está mediada por factores de limitación funcional tipo discapacidad o minusvalía. No obstante, la naturaleza de dicha asociación es, cuando menos, de tipo dual, sugiriéndose dos vías etiopatogénicas diferentes en la depresión del anciano: la psicosocial (mediada por life-events o déficits de apoyo social) y la orgánica (deterioro cognitivo). La asociación longitudinal entre depresión y posterior deterioro cognitivo sugiere la existencia de un posible factor neurodegenerativo (vascular, endocrino, etc.) común en la etiología de ambos trastornos. La presencia de depresión clínica aumenta el riesgo de deterioro cognitivo a largo plazo, aunque sólo en varones. Deterioro Cognitivo y Factores Genéticos. La variabilidad polimórfica en el locus del CYP2D6 no aumenta el riesgo de enfermedad de Alzheimer (EA) ni modifica el efecto que sobre ésta confieren los alelos e4 de la Apolipoproteina E (APOE). Ello distingue a la EA de la demencia por cuerpos de Lewi y de la Enfermedad de Parkinson a nivel genético, al menos para este locus. La presencia de alelos APOE e4 aumenta el riesgo de deterioro cognitivo y demencia (sobre todo EA) y la de alelos APOE e2 disminuye dicho riesgo. En nuestra muestra de hipertensos el riesgo de los alelos APOE no estaba mediado por su vinculación a factores vasculares. Deterioro Cognitivo y Factores vasculares o ambientales. El nivel intelectual más alto predispone a una menor incidencia de deterioro cognitivo lo cual ratifica la hipótesis de la «reserva cerebral» desde un punto de vista epidemiológico. El tratamiento precoz de la hipertensión, la abstinencia del tabaco y el consumo moderado de alcohol disminuyen el riesgo de deterioro cognitivo y pueden ser medidas profilácticas eficientes para la prevención del deterioro cognitivo (AU)

This monographic volume summarises Dr. J. Cervilla’s doctoral thesis on the epidemiology of cognitive impairment. The thesis was co-directed by Prof. Anthony Mann and Prof. M. Prince from the Institute of Psychiatry, University of London and by Prof. A. Bulbena from the Universitat Autònoma de Barcelona. The volume begins with a historical introduction on the concept of cognitive impairment. A description of the three studies on which all eight papers included in the thesis are based follows, i.e. the Medical Research Council psychiatric substudy on hypertensive volunteers, the one-year longitudinal prospective psychiatric morbidity study of Gospel Oak, and the Camberwell Dementia Case Register study. The volume is structured on three areas, namely: a) Cognitive impairment and depression; b) Cognitive impairment and genetic factors; and, c) Cognitive Impairment and vascular or environmental factors. Cognitive Impairment and Depression. The cross-sectional association between depression and cognitive impairment seems to be confounded by functional limitations, such as impairment or handicap. Nevertheless, we postulate at least two different etiological pathways to elderly depression: one via social distress and another via neurodegeneration clinically manifested as cognitive impairment. The longitudinal association between baseline depression and incident cogntive impairment suggests a potential common factor in the etiology of both disorders. This common factor might be neurodegenerative in nature (vascular, hormonal, etc.). Being depressed at baseline predicts higher risk of cogntive impairment in the long term in men only. Cognitive Impairment and Genetic factors. Polymorphic variability at the CYP2D6 locus is not associated with risk of Alzheimer’s disease (AD) nor does it modify the effect of Apolipoprotein E (APOE) e4 on AD. This suggests that, at this locus, AD is genetically different from Parkinson’s disease and Lewy body dementia. APOE e4 alleles increase, and APOE e2 alleles decrease, the risk for cognitive impairment and dementia (especially of the AD type). In our moderately hypertensive sample these associations are not mediated by dyslipidaemia or vascular disease. Cognitive Impairment and Vascular or Environmental factors. Higher intellectual level predicts lower incidence of cognitive impairment. This supports the so-called «brain reserve» hypothesis from an epidemiological perspective. Early detection and treatment of high blood pressure, abstinence from cigarette smoking and moderate intake of alcohol, decrease the risk of cognitive impairment and may constitute the basis for modest but efficient additive profilactic measures to prevent cognitive impairment (AU)

Causas de muerte y hallazgos necrópsicos en 423 pacientes diabéticos (años 1976-1990) / Causes of death and postmortem findings in 423 diabetic patients (1976-1990)

Se estudiaron los protocolos de necropsia de 423 fallecidos diabéticos, 275 del sexo femenino (61,0 por ciento ) y 166 del masculino (39,0 por ciento ). El grupo más numeroso fue el de 65 años y más con el 67 por ciento . Las causas directas de muertes más frecuentes fueron el infarto agudo del miocardio (14 por ciento ), la cardiopatía arteriosclerótica (10,2 por ciento ), el trombolismo pulmonar (9,4 por ciento ), la glomeruloesclerosis (9,2 por ciento ) y los accidentes vasculoencefálicos (6,6 por ciento ). La mortalidad por cetoacidosis fue de 3,5 por ciento . Se comparó la extensión de la lesión arteriosclerótica en diabéticos y no diabéticos y se observó el predominio de los primeros 15 pacientes (4,0 por ciento ) correspondían a la diabetes tipo 1 o insulinodependiente y 408 a la diabetes tipo 2 o no insulinodependiente (96 por ciento ). La bronconeumonía (20 por ciento ) y la pielonefritis complicada (5,4 por ciento ) fueron las complicaciones infecciosas más frecuentes

Causas de muerte y hallazgos necrópsicos en 423 pacientes diabéticos (años 1976-1990) / Causes of death and postmortem findings in 423 diabetic patients (1976-1990)

Se estudiaron los protocolos de necropsia de 423 fallecidos diabéticos, 275 del sexo femenino (61,0

) y 166 del masculino (39,0

). El grupo más numeroso fue el de 65 años y más con el 67

. Las causas directas de muertes más frecuentes fueron el infarto agudo del miocardio (14

), la cardiopatía arteriosclerótica (10,2

), el trombolismo pulmonar (9,4

), la glomeruloesclerosis (9,2

) y los accidentes vasculoencefálicos (6,6

). La mortalidad por cetoacidosis fue de 3,5

. Se comparó la extensión de la lesión arteriosclerótica en diabéticos y no diabéticos y se observó el predominio de los primeros 15 pacientes (4,0

) correspondían a la diabetes tipo 1 o insulinodependiente y 408 a la diabetes tipo 2 o no insulinodependiente (96

). La bronconeumonía (20

) y la pielonefritis complicada (5,4

) fueron las complicaciones infecciosas más frecuentes (AU)

Carcinoma metaplásico de la mama: presentación de 2 casos / Metaplastic breast carcinoma: report of two cases

Se presentaron 2 casos de carcinoma metaplásico de la mama, uno del Hospital "Enrique Cabrera" y otro del Hospital "Hermanos Ameijeiras". Se describieron sus aspectos clínicos y anatomopatológicos, y se incluyó el estudio ultraestructural de uno de ellos. Se realizaron los diagnósticos diferenciales con el carcinoma, los sarcomas que producen cartílago y hueso, el carcinoma epidermoide de piel que invade secundariamente la mama y con el adenoma pleomórfico o tumor mixto benigno de mama

Carcinoma metaplásico de la mama. presentación de 2 casos / Metaplastic breast carcinoma: report of two cases

Se presentaron 2 casos de carcinoma metaplásico de la mama, uno del Hospital "Enrique Cabrera" y otro del Hospital "Hermanos Ameijeiras". Se describieron sus aspectos clínicos y anatomopatológicos, y se incluyó el estudio ultraestructural de uno de ellos. Se realizaron los diagnósticos diferenciales con el carcinoma, los sarcomas que producen cartílago y hueso, el carcinoma epidermoide de piel que invade secundariamente la mama y con el adenoma pleomórfico o tumor mixto benigno de mama

Cistosarcoma phyllodes limítrofe de la mama / Bounding cystosarcoma phyllodes of the breast

Se presentaron dos casos de cistosarcoma phyllodes limítrofe de la mama, desde el punto de vista anatomopatológico que incluyeron el estudio ultraestructural. Se compararon con dos casos de cistosarcoma phyllodes maligno y 2 de tumor phyllodes benigno, estudiados previamente en el Departamento de Anatomía Patológica. El cistosarcoma phyllodes limítrofe es un tumor poco frecuente, que está entre la variedad benigna y la maligna de phyllodes de la mama, que puede recidivar como benigna, transformarse en maligna o simplemente aparecer de nuevo como limítrofe. El phyllodes limítrofe no es aceptado por todos los autores, pero es aceptado como entidad por los patólogos y oncólogos y en su tratamiento se recomienda al cirujano ser conservador(AU)

Miofibroblastoma de la mama / Myofibroblastoma of the breast

Se presentó un miofibroblastoma de la mama, tumor extremadamente raro de estirpe conjuntiva, de comportamiento benigno, en una paciente de 30 años de edad, no reportado antes en nuestro país. Se comprobó con un fibroadenoma de la mama y con un tumor phyllodes benigno, ambos con predominio del tejido conjuntivo y también benignos. Se estudiaron los tres casos por microscopía óptica y por microscopía electrónica(AU)