A conceptual framework to safeguard the neuroright to personal autonomy

In this article, we propose a philosophical exploration on the main problems involved in two neurorights that concern autonomous action, namely free will and cognitive liberty, and sketch a possible solution to these problems by resourcing to a holistic interpretation of human actions. First, we expose the main conceptual and practical issues arising from the neuroright to free will, which are far from minor: the term itself is denied by some trends participating in the neurorights debate, the related concept of ultimate control is also disputed, the understanding of free will depends on cultural context, and the exercise of being free to act in several domains may be covered by other regulations. Second, we analyze the historical origin of cognitive liberty, its current status, and its relation with free will. Third, we criticize the concept of decision in mainstream action theory and propose to conceive action as a unified process constituted by three explanatory, non-sequential dimensions: intention, decision, and action realization. Fourth, we discuss two possible cases involving neurotechnologies and suggest ways to interpret them according to a unified framework in which free will and cognitive liberty fall under a single neuroright to personal autonomy. Finally, we outline a recommendation to introduce freedom of thought and personal autonomy as complementary neurorights to protect both the internal and external dimensions of thought and action

Dietary Iron, Anemia Markers, Cognition, and Quality of Life in Older Community-Dwelling Subjects at High Cardiovascular Risk

Anemia causes hypo-oxygenation in the brain, which could lead to cognitive disorders. We examined dietary iron intake as well as anemia markers (i.e., hemoglobin, hematocrit, mean corpuscular volume) and diabetes coexistence in relation to neuropsychological function and quality of life. In this study, 6117 community-dwelling adults aged 55-75 years (men) and 60-75 years (women) with overweight/obesity and metabolic syndrome were involved. We performed the Mini-Mental State Examination (MMSE), the Trail Making Test parts A and B (TMT-A/B), Semantic Verbal Fluency of animals (VFT-a), Phonological Verbal Fluency of letter P (VFT-p), Digit Span Test (DST), the Clock Drawing Test (CDT), and the Short Form-36 Health Survey (SF36-HRQL test). Dietary iron intake did not influence neuropsychological function or quality of life. However, anemia and lower levels of anemia markers were associated with worse scores in all neurophysiological and SF36-HRQL tests overall, but were especially clear in the MMSE, TMT-B (cognitive flexibility), and the physical component of the SF36-HRQL test. The relationships between anemia and diminished performance in the TMT-A/B and VFT tasks were notably pronounced and statistically significant solely among participants with diabetes. In brief, anemia and reduced levels of anemia markers were linked to inferior cognitive function, worse scores in different domains of executive function, as well as a poorer physical, but not mental, component of quality of life. It was also suggested that the coexistence of diabetes in anemic patients may exacerbate this negative impact on cognition. Nevertheless, dietary iron intake showed no correlation with any of the outcomes. To make conclusive recommendations for clinical practice, our findings need to be thoroughly tested through methodologically rigorous studies that minimize the risk of reverse causality

RICORS2040 : The need for collaborative research in chronic kidney disease

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Causalidad mental y neurociencia: el modelo de la poda semántica

En este artículo proponemos un modelo hipotético de causalidad mental que denominamos poda semántica y que podría definirse como la influencia causal de los contenidos y significados sobre la configuración espacial de la red de sinapsis de un individuo. Nos guiaremos por dos principios centrales: 1) la influencia causal de lo mental se produce en virtud de constricciones semánticas externas y consiste en la activación selectiva de ciertos poderes físicos, 2) cuando la activación selectiva es continuada, desencadena un proceso de poda sináptica en la red neural y neuromuscular.In this paper I propose a hypothetical model of mental causation that I call semantic pruning and which could be defined as the causal influence of contents and meanings on the spatial configuration of the network of synapses of an individual. I will be guided by two central principles: 1) the causal influence of the mental occurs by virtue of external semantic constraints and consists in the selective activation of certain physical powers, 2) when the selective activation is continual, it triggers a process of synaptic pruning in the neural and neuromuscular network

A conceptual framework to safeguard the neuroright to personal autonomy

In this article, we propose a philosophical exploration on the main problems involved in two neurorights that concern autonomous action, namely free will and cognitive liberty, and sketch a possible solution to these problems by resourcing to a holistic interpretation of human actions. First, we expose the main conceptual and practical issues arising from the neuroright to free will, which are far from minor: the term itself is denied by some trends participating in the neurorights debate, the related concept of ultimate control is also disputed, the understanding of free will depends on cultural context, and the exercise of being free to act in several domains may be covered by other regulations. Second, we analyze the historical origin of cognitive liberty, its current status, and its relation with free will. Third, we criticize the concept of decision in mainstream action theory and propose to conceive action as a unified process constituted by three explanatory, non-sequential dimensions: intention, decision, and action realization. Fourth, we discuss two possible cases involving neurotechnologies and suggest ways to interpret them according to a unified framework in which free will and cognitive liberty fall under a single neuroright to personal autonomy. Finally, we outline a recommendation to introduce freedom of thought and personal autonomy as complementary neurorights to protect both the internal and external dimensions of thought and action

Billary obstruction.Review of our experience(11 cases)

Se presenta un estudio retrospectivo de 11 casos de íleo biliar diagnosticados y tratados en el Servicio de Urgencias de Cirugía General del Hospital Universitario Virgen Macarena de Sevilla en el período comprendido entre enero de 1987 y diciembre de 1992. Se han valorado los antecedentes personales, el tiempo transcurrido desde el inicio de los síntomas, el cuadro clínico, los resultados analíticos y de radiología, el tiempo transcurrido hasta la intervención, los hallazgos operatorios y la técnica quirúrgica, la evolución postoperatoria y las complicaciones. Se destacan la importancia de la aerobilia en el diagnóstico radiológico del proceso, así como los datos ecográficos característicos. Se hace hincapié en el tratamiento precoz de la oclusión y secundariamente de la fistula biliodigestiva, discutiendo en último lugar las complicaciones de la enfermedad.A retrospective study is presented Of ll cases Of biliary Obstruction diagnosed and treated in the General Surgery Emergency Room Of Hospital Universitario Virgen Macarena in Sevilla hetween January 1987 and December 1992. The aspects assessed included personal history, time elapsed since onset Of symptoms, clinical pictnre, analytical and radiologicsl results, time elapsed until surgery, intraoperative findings, surgical technique, postoperative course and complications. The importance Of aerobilia in the radiological diagnosis Of the process is pointed out, as is the characteristic ultrnsonographic data. Emphasis is placed on the benefits of early treatment Of the occlusion and, secondly, on the bilioenteric anastomosis. Finally, the complications of the disease are discussed

Rapid decrease in titer and breadth of neutralizing anti-HCV antibodies in HIV/HCV-coinfected patients who achieved SVR

The main targets for neutralizing anti-hepatitis C virus (HCV) antibodies (HCV-nAbs) are the E1 and E2 envelope glycoproteins. We have studied the characteristics of HCV-nAbs through a retrospective study involving 29 HIV/HCV-coinfected patients who achieved sustained virological response (SVR) with peg-IFNα + ribavirin anti-HCV therapy. Plasma samples at baseline and week 24 after SVR were used to perform neutralization assays against five JFH1-based HCV recombinant viruses coding for E1 and E2 from genotypes 1a (H77), 1b (J4), 2a (JFH1), 3a (S52) and 4a (ED43). At baseline, the majority of plasma samples neutralized 1a, 1b, 2a, and 4a, but not 3a, genotypes. Twenty-four weeks following SVR, most neutralizing titers declined substantially. Furthermore, titers against 3a and 2a were not detected in many patients. Plasma samples with high HCV-nAb titers neutralized all genotypes, and the highest titers at the starting point correlated with the highest titers at week 24 after SVR. In conclusion, high titers of broad-spectrum HCV-nAbs were detected in HIV/HCV-coinfected individuals, however, those titers declined soon after SVR

Comprehensive analysis and insights gained from long-term experience of the Spanish DILI Registry

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER); Agencia Española del Medicamento; Consejería de Salud de Andalucía.Background & Aims: Prospective drug-induced liver injury (DILI) registries are important sources of information on idiosyncratic DILI. We aimed to present a comprehensive analysis of 843 patients with DILI enrolled into the Spanish DILI Registry over a 20-year time period. Methods: Cases were identified, diagnosed and followed prospectively. Clinical features, drug information and outcome data were collected. Results: A total of 843 patients, with a mean age of 54 years (48% females), were enrolled up to 2018. Hepatocellular injury was associated with younger age (adjusted odds ratio [aOR] per year 0.983; 95% CI 0.974-0.991) and lower platelet count (aOR per unit 0.996; 95% CI 0.994-0.998). Anti-infectives were the most common causative drug class (40%). Liver-related mortality was more frequent in patients with hepatocellular damage aged ≥65 years (p = 0.0083) and in patients with underlying liver disease (p = 0.0221). Independent predictors of liver-related death/transplantation included nR-based hepatocellular injury, female sex, higher onset aspartate aminotransferase (AST) and bilirubin values. nR-based hepatocellular injury was not associated with 6-month overall mortality, for which comorbidity burden played a more important role. The prognostic capacity of Hy's law varied between causative agents. Empirical therapy (corticosteroids, ursodeoxycholic acid and MARS) was prescribed to 20% of patients. Drug-induced autoimmune hepatitis patients (26 cases) were mainly females (62%) with hepatocellular damage (92%), who more frequently received immunosuppressive therapy (58%). Conclusions: AST elevation at onset is a strong predictor of poor outcome and should be routinely assessed in DILI evaluation. Mortality is higher in older patients with hepatocellular damage and patients with underlying hepatic conditions. The Spanish DILI Registry is a valuable tool in the identification of causative drugs, clinical signatures and prognostic risk factors in DILI and can aid physicians in DILI characterisation and management. Lay summary: Clinical information on drug-induced liver injury (DILI) collected from enrolled patients in the Spanish DILI Registry can guide physicians in the decision-making process. We have found that older patients with hepatocellular type liver injury and patients with additional liver conditions are at a higher risk of mortality. The type of liver injury, patient sex and analytical values of aspartate aminotransferase and total bilirubin can also help predict clinical outcomes