Inteligencia Artificial en Medicina y Salud: revisión y clasificación de las aplicaciones actuales y del futuro cercano y su impacto ético y social

This paper provides an overview of the current and near-future applications of Artificial Intelligence (AI) in Medicine and Health Care and presents a classification according to their ethical and societal aspects, potential benefits and pitfalls, and issues that can be considered controversial and are not deeply discussed in the literature. This work is based on an analysis of the state of the art of research and technology, including existing software, personal monitoring devices, genetic tests and editing tools, personalized digital models, online platforms, augmented reality devices, and surgical and companion robotics. Motivated by our review, we present and describe the notion of “extended personalized medicine”, we then review existing applications of AI in medicine and healthcare and explore the public perception of medical AI systems, and how they show, simultaneously, extraordinary opportunities and drawbacks that even question fundamental medical concepts. Many of these topics coincide with urgent priorities recently defined by the World Health Organization for the coming decade. In addition, we study the transformations of the roles of doctors and patients in an age of ubiquitous information, identify the risk of a division of Medicine into “fake-based”, “patient-generated”, and “scientifically tailored”, and draw the attention of some aspects that need further thorough analysis and public debate

Association between diet-quality scores, adiposity, total cholesterol and markers of nutritional status in European adults: findings from the Food4Me study

Diet-quality scores (DQS), which are developed across the globe, are used to define adherence to specific eating patterns and have been associated with risk of coronary heart disease and type-II diabetes. We explored the association between five diet-quality scores (Healthy Eating Index, HEI; Alternate Healthy Eating Index, AHEI; MedDietScore, MDS; PREDIMED Mediterranean Diet Score, P-MDS; Dutch Healthy Diet-Index, DHDI) and markers of metabolic health (anthropometry, objective physical activity levels (PAL), and dried blood spot total cholesterol (TC), total carotenoids, and omega-3 index) in the Food4Me cohort, using regression analysis. Dietary intake was assessed using a validated Food Frequency Questionnaire. Participants (n = 1480) were adults recruited from seven European Union (EU) countries. Overall, women had higher HEI and AHEI than men (p < 0.05), and scores varied significantly between countries. For all DQS, higher scores were associated with lower body mass index, lower waist-to-height ratio and waist circumference, and higher total carotenoids and omega-3-index (p trends < 0.05). Higher HEI, AHEI, DHDI, and P-MDS scores were associated with increased daily PAL, moderate and vigorous activity, and reduced sedentary behaviour (p trend < 0.05). We observed no association between DQS and TC. To conclude, higher DQS, which reflect better dietary patterns, were associated with markers of better nutritional status and metabolic health

Distortion in a 7xxx aluminum alloy during liquid phase sintering

The distortion in a sintered 7xxx aluminum alloy, Al-7Zn-2.5Mg-1Cu (wt. pct), has been investigated by sintering three rectangular bars in each batch at 893 K (620 °C) for 0 to 40 minutes in nitrogen, followed by air or furnace cooling. They were placed parallel to each other, equally spaced apart at 2 mm, with their long axes being perpendicular to the incoming nitrogen flow. Pore evolution in each sample during isothermal sintering was examined metallographically. The compositional changes across sample mid-cross section and surface layers were analyzed using energy dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy depth profiling, respectively. The two outer samples bent toward the middle one, while the middle sample was essentially distortion free after sintering. The distortion in the outer samples was a result of differential shrinkage between their outer and inner surfaces during isothermal sintering. The porous outer surface showed an enrichment of oxygen around the large pores as well as lower magnesium and zinc contents than the interior and inner surface of the same sample, while the inner surface was distinguished by the presence of AlN. The differential shrinkage was caused by different oxygen contents in local sintering atmosphere and unbalanced loss of magnesium and zinc between the outer and inner surfaces

Analysis of dietary pattern impact on weight status for personalised nutrition through on-line advice: The food4Me Spanish cohort

Obesity prevalence is increasing. The management of this condition requires a detailed analysis of the global risk factors in order to develop personalised advice. This study is aimed to identify current dietary patterns and habits in Spanish population interested in personalised nutrition and investigate associations with weight status. Self-reported dietary and anthropometrical data from the Spanish participants in the Food4Me study, were used in a multidimensional exploratory analysis to define specific dietary profiles. Two opposing factors were obtained according to food groups’ intake: Factor 1 characterised by a more frequent consumption of traditionally considered unhealthy foods; and Factor 2, where the consumption of “Mediterranean diet” foods was prevalent. Factor 1 showed a direct relationship with BMI (β = 0.226; r2 = 0.259; p < 0.001), while the association with Factor 2 was inverse (β = −0.037; r2 = 0.230; p = 0.348). A total of four categories were defined (Prudent, Healthy, Western, and Compensatory) through classification of the sample in higher or lower adherence to each factor and combining the possibilities. Western and Compensatory dietary patterns, which were characterized by high-density foods consumption, showed positive associations with overweight prevalence. Further analysis showed that prevention of overweight must focus on limiting the intake of known deleterious foods rather than exclusively enhance healthy products

Mediterranean Diet Adherence and Genetic Background Roles within a Web-Based Nutritional Intervention: The Food4Me Study

Mediterranean Diet (MedDiet) adherence has been proven to produce numerous health benefits. In addition, nutrigenetic studies have explained some individual variations in the response to specific dietary patterns. The present research aimed to explore associations and potential interactions between MedDiet adherence and genetic background throughout the Food4Me web-based nutritional intervention. Dietary, anthropometrical and biochemical data from volunteers of the Food4Me study were collected at baseline and after 6 months. Several genetic variants related to metabolic risk features were also analysed. A Genetic Risk Score (GRS) was derived from risk alleles and a Mediterranean Diet Score (MDS), based on validated food intake data, was estimated. At baseline, there were no interactions between GRS and MDS categories for metabolic traits. Linear mixed model repeated measures analyses showed a significantly greater decrease in total cholesterol in participants with a low GRS after a 6-month period, compared to those with a high GRS. Meanwhile, a high baseline MDS was associated with greater decreases in Body Mass Index (BMI), waist circumference and glucose. There also was a significant interaction between GRS and the MedDiet after the follow-up period. Among subjects with a high GRS, those with a high MDS evidenced a highly significant reduction in total carotenoids, while among those with a low GRS, there was no difference associated with MDS levels. These results suggest that a higher MedDiet adherence induces beneficial effects on metabolic outcomes, which can be affected by the genetic background in some specific markers

Photodynamic fungicidal efficacy of hypericin and dimethyl methylene blue against azole-resistant Candida albicans strains.

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Relationship between degree of cellular differentiation in colorectal cancer and topographical distribution.

Objetivos: intentar establecer la relación existente entre el grado diferenciación celular del cáncer colon y su distribución topográfica: en 215 pacientes diagnosticados de cáncer colorrectal entre los años 1997 y 2000. Material y métodos: se estudiaron de forma prospectiva 215 pacientes (129 hombres y 86 mujeres) de edades comprendidas entre 23 y 84 años, con edad media de 64 años. En todos se realizó colonoscopia completa con varias tomas de biopsia. En los casos de estenosis tumoral con imposibilidad para sobrepasar la lesión se realizó enema opaco. Los estudios de extensión incluyeron TAC y ecografía abdominal, hemograma, perfil bioquímico completo y marcadores tumorales Ca 19-9 y alfafetoproteina). La distribución topográfica de los cánceres colorrectales fue la siguiente: recto 78 (35%), sigrna 66 (31%), descendente 21 (10%), transverso 12 (6%), ascendente 19 (9%), ciego 11 (5%), y anorrectal 8 (4%). Resultados: siendo el objetivo de nuestro estudio el establecer la relación entre el asentamiento tumoral en el colon y su grado de diferenciación celular encontramos: a) bien diferenciados 101/215 (47%); b) moderadamente diferenciados 98/215 y c) pobremente diferenciados 16/215 (7 El cáncer bien diferenciado lo encontramos en 49% de los hombres y en el 43% de las mujeres, el moderadamente diferenciado fue del 43% entre los hombres y del 49% entre las mujeres, el pobremente diferenciado fue del 7,5% entre los hombres y de 7,2% entre las mujeres. Según su distribución: en el colon izquierdo,80 adenocarcinomas eran bien diferenciados, 77 moderadamente diferenciados y 8 pobremente diferenciados; en el colon transverso; 7 adenocarcinomas eran bien diferenciados 3 moderadamente diferenciados y 2 pobremente diferenciados, en el colon derecho 11 adenocarcinomas eran bien diferenciados, 15 moderadamente diferenciados y 4 pobremente diferenciados. De los 8 cánceres recto-anales, 3 eran bien diferenciados, 3 moderadamente diferenciados y 2 pobremente diferenciados, habiendo observado que dicho grado de diferenciación no tiene un significado estadístico de relación con la distribución topográfica del tumor. Según la clasificación fueron más frecuentes en los estadios, los bien diferenciados (101/215) fueron más frecuentes en los estadios BI (32,6%) y C2 (20, los moderadamente diferenciados (98/215) lo fueron en los estadios Bi y C2 el de los estadios C2 fueron tumores pobremente diferenciados. No apreciamos diferencias estadísticamente significativas en la distribución de los grados de diferenciación estadios (p—ns). Conclusiones: nuestros resultados, no hemos observado que el grado de diferenciación celular del cáncer colorrectal se relacione con su localización inicial en el colon y es, independiente del sexo y de la edad. En cuanto a su posible relación con la estadios de Dukes y Astler-Coller tampoco hemos demostrarla.To demonstrate the relationship between degree of cellular differentiation in colorectal cancer and topographical distribution in 215 patients diagnosed with colorectal cancer from 1997 to 2000. MATERIAL AND METHODS: 215 patients (129 men and 86 women) were studied prospectively with a mean age of 64 years (range: 23-84 years). In all patients we performed a full colonoscopy with several biopsies (in patients with colon stenosis we used barium enema), radiographic studies (CT, abdominal ultrasounds), and laboratory tests for serum tumour markers (CEA, Ca 19-9, alpha-fetoprotein). The topographic location of colorectal cancer was: rectum 35%, sigmoid colon 31%, descending colon 10%, transverse colon 6%, ascending colon 9%, caecum 5%, and we included anorectal cancer 4%. RESULTS: According to histological differentiation we found: A) well-differentiated tumours 101/215 (47%); B) moderately-differentiated tumours 98/215 (45.5%), and C) poorly-differentiated tumours 16/215 (7.5%). We found no significant association among histological differentiation, topographic location, stage according to the Astler-Coller classification, sex or age (p = ns). The prevalence of well-differentiated tumours in men was 49% and 43% in women; of moderately-differentiated cancers in men was 43%, and 49% in women; for poorly-differentiated tumours in men was 7.5%, and 7.2% in women. Regarding tumour location, 165 cancers were found in the left colon: 80 were well differentiated, 77 moderately differentiated and 8 poorly differentiated. In the transverse colon we found 12 tumours: 7 well differentiated, 3 moderately differentiated and 2 poorly differentiated. 30 cancers were localized in the right colon: 11 well differentiated, 15 moderately differentiated and 4 poorly differentiated. In the anorectum 8 tumours were found: 3 well differentiated, 3 moderately differentiated and 2 poorly differentiated. According to staging classification, well differentiated tumours (101/215) were more common in Dukes' C2 (20.7%) and B1 (32.6%), moderately differentiated cancers (98/215) were in B1 (28.5%) and C2 (20.4%), and poorly differentiated tumours (16) were more common in Dukes' C2 (25%), without differences among other stages (p = ns). CONCLUSIONS: According to our results we have found that histological differentiation of colorectal cancer has no association with topographic location, and it is independent of sex or age. We have not found any relationship either between histological differentiation and stage in the Astler-Coller classification, but well differentiated cancers were more common at any location, age or sex

Overexpression of SET is a recurrent event associated with poor outcome and contributes to protein phosphatase 2A inhibition in acute myeloid leukemia

BACKGROUND: Protein phosphatase 2A is a novel potential therapeutic target in several types of chronic and acute leukemia, and its inhibition is a common event in acute myeloid leukemia. Upregulation of SET is essential to inhibit protein phosphatase 2A in chronic myeloid leukemia, but its importance in acute myeloid leukemia has not yet been explored. DESIGN AND METHODS: We quantified SET expression by real time reverse transcriptase polymerase chain reaction in 214 acute myeloid leukemia patients at diagnosis. Western blot was performed in acute myeloid leukemia cell lines and in 16 patients' samples. We studied the effect of SET using cell viability assays. Bioinformatics analysis of the SET promoter, chromatin immunoprecipitation, and luciferase assays were performed to evaluate the transcriptional regulation of SET. RESULTS: SET overexpression was found in 60/214 patients, for a prevalence of 28%. Patients with SET overexpression had worse overall survival (P<0.01) and event-free survival (P<0.01). Deregulation of SET was confirmed by western blot in both cell lines and patients' samples. Functional analysis showed that SET promotes proliferation, and restores cell viability after protein phosphatase 2A overexpression. We identified EVI1 overexpression as a mechanism involved in SET deregulation in acute myeloid leukemia cells. CONCLUSIONS: These findings suggest that SET overexpression is a key mechanism in the inhibition of PP2A in acute myeloid leukemia, and that EVI1 overexpression contributes to the deregulation of SET. Furthermore, SET overexpression is associated with a poor outcome in acute myeloid leukemia, and it can be used to identify a subgroup of patients who could benefit from future treatments based on PP2A activators

Integration of SNP and mRNA arrays with microRNA profiling reveals that MiR-370 is upregulated and targets NF1 in acute myeloid leukemia

Abstract Background: Deregulated miRNA expression plays a crucial role in carcinogenesis. Recent studies show different mechanisms leading to miRNA deregulation in cancer; however, alterations affecting miRNAs by DNA copy number variations (CNV) remain poorly studied. Results: Our integrative analysis including data from high resolution SNPs arrays, mRNA expression arrays, and miRNAs expression profiles in 16 myeloid cell lines highlights that CNV are alternative mechanisms to deregulate the expression of miRNAs in acute myeloid leukemia (AML), and represent a novel approach to identify novel candidate genes involved in AML. We found association between the expression levels of 19 miRNAs and CNVs affecting their loci. Functional analysis showed that NF1 is a direct target of miR-370, and that overexpression of miR-370 has similar effects that NF1 inactivation, increasing proliferation and colony formation in AML cells. Moreover, real time RT-PCR showed that NF1 downregulation is a recurrent event in AML (30.8%), and western blot analysis confirmed this result. MiR-370 overexpression and deletions affecting the NF1 locus were identified as alternative mechanisms to downregulate NF1. Conclusions: NF1 downregulation is a common event in AML, and both deletions in the NF1 locus and overexpression of miR-370 are alternative mechanisms to downregulate NF1 in this disease. Our results suggest a leukemogenic role of miR- 370 through NF1 downregulation in AML cells. Since NF1 deficiency leads to RAS activation, patients with AML and overexpression of miR-370 may potentially benefit from additional treatment with either RAS or mTOR inhibitors