ABSTRACT
BACKGROUND: There is substantial evidence supporting that remote interventions are useful to change dietary habits. However, the effect of a remote intervention based on Mediterranean diet (MD) in depressive patients has been less explored. OBJECTIVE: This study aims to assess the effectiveness of a remotely provided Mediterranean diet-based nutritional intervention in the context of a secondary prevention trial of depression. METHODS: The PREDIDEP study was a 2-year multicenter, randomized, single-blinded trial designed to assess the effect of the MD enriched with extra virgin olive oil (EVOO) on the prevention of depression recurrence. The intervention group received usual care for depressed patients and remote nutritional intervention every three months which included phone contacts and web-based interventions; and the control group, usual care. At baseline and at 1-year and 2-year follow-up, the 14-item MD Adherence Screener (MEDAS) questionnaire and a semiquantitative food frequency questionnaire (FFQ) were collected by a dietitian. Mixed effects linear models were used to assess changes in nutritional variables according to the group of intervention. The trial was registered at ClinicalTrials.gov NCT03081065. RESULTS: Compared with control group, the MD intervention group showed more adherence to MD (between-group difference: 2.76; 95% CI 2.13-3.39; p < 0.001); and a healthier diet pattern with a significant increase in the consumption of olive oil (p < 0.001), and a significant reduction in refined cereals (p = 0.031) after 2 years of intervention. CONCLUSIONS: The remote nutritional intervention increases adherence to the MD among recovered depression patients.Trial registration: ClinicalTrials.gov identifier: NCT03081065.
Subject(s)
Depression , Diet, Mediterranean , Humans , Depression/prevention & control , Olive Oil , Feeding BehaviorABSTRACT
The preparation of several new truncated analogues of the natural dihydropyrone pironetin is described. They differ from the natural product mainly in the suppression of some of the alkyl pendants in either the side chain or the dihydropyrone ring. Their cytotoxic activity and their interactions with tubulin have been investigated. It has been found that all analogues are cytotoxic towards two either sensitive or resistant tumoral cell lines with similar IC50 values in each case, thus strongly suggesting that, like natural pironetin, they also display a covalent mechanism of action. Their cytotoxicity is, however, lower than that of the parent compound. This indicates that all alkyl pendants are necessary for the full biological activity, with the ethyl group at C-4 seemingly being particularly relevant. Most likely, the alkyl groups cause a restriction in the conformational mobility of the molecule and reduce the number of available conformations. This makes it more probable that the molecule preferentially adopts a shape which fits better into the binding point in α-tubulin.
Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Pyrones/chemistry , Pyrones/pharmacology , Tubulin Modulators/chemistry , Tubulin Modulators/pharmacology , Tubulin/metabolism , Antineoplastic Agents/chemical synthesis , Cell Cycle/drug effects , Cell Line, Tumor , Humans , Neoplasms/drug therapy , Pyrones/chemical synthesis , Tubulin Modulators/chemical synthesisABSTRACT
The preparation of a series of pironetin analogues with simplified structure is described. Their cytotoxic activity and their interactions with tubulin have been investigated. It has been found that, while less active than the parent molecule, the pironetin analogues still share the mechanism of action of the latter and compete for the same binding site to α-tubulin. Variations in the configurations of their stereocenters do not translate into relevant differences between biological activities.
Subject(s)
Antineoplastic Agents/pharmacology , Drug Design , Microtubules/drug effects , Pyrones/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Microtubules/chemistry , Molecular Structure , Pyrones/chemical synthesis , Pyrones/chemistry , Stereoisomerism , Structure-Activity Relationship , Tubulin/chemistry , Tubulin/metabolism , Tumor Cells, CulturedABSTRACT
With the double objective of searching for a physiological brain circuit concerned with time estimation and establishing whether this circuit is dysfunctional in schizophrenia patients, we carried out an activation likelihood estimate (ALE) meta-analysis of published functional neuroimaging studies. Our results reproduce the previous finding of a neurophysiological cortico-cerebellar-thalamic circuit related with time estimation in healthy individuals. In schizophrenia patients, the analysis indicates significantly lower activation of most right hemisphere regions of the circuit, suggesting that it may be subject to a pattern of disconnectivity. The ALE-meta-analysis approach is useful and further studies could elucidate how the timing circuit is connected with other cognitive tasks.
Subject(s)
Brain/physiopathology , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Nerve Net/physiopathology , Positron-Emission Tomography , Schizophrenia/physiopathology , Schizophrenic Psychology , Time Perception/physiology , Attention/physiology , Brain Mapping , Cognition/physiology , Dominance, Cerebral/physiology , Electroencephalography , Humans , Magnetoencephalography , Memory, Short-Term/physiology , Schizophrenia/diagnosis , Signal Processing, Computer-AssistedABSTRACT
BACKGROUND: Depression assessment in population studies is usually based on depressive symptoms scales. However, the use of scales could lead to the choice of an arbitrary cut-off point depending on the sample characteristics and on the patient diagnosis. Thus, the use of a medical diagnosis of depression could be a more appropriate approach. OBJECTIVE: To validate a self-reported physician diagnosis of depression using the Structured Clinical Interview for DSM-IV (SCID-I) as Gold Standard and to assess the factors associated to a valid self-reported diagnosis. METHODS: The SUN Project is a cohort study based on university graduates followed-up through postal questionnaires. The response to the question included in the questionnaire: Have you ever been diagnosed of depression by a physician? was compared to that obtained through the SCID-I applied by a psychiatrist or a clinical psychologist. The percentages of confirmed depression and non-depression were assessed for the overall sample and according to several characteristics. Logistic regression models were fitted to ascertain the association between different factors and a correct classification regarding depression status. RESULTS: The percentage of confirmed depression was 74.2%; 95% confidence interval (95% CI) = 63.3-85.1. Out of 42 participants who did not report a depression diagnosis in the questionnaire, 34 were free of the disease (%confirmed non-depression = 81.1%; 95% CI = 69.1-92.9). The probability of being a true positive was higher among ex-smokers and non-smokers and among those overweight or obese but the differences were not statistically significant. CONCLUSION: The validity of a self-reported diagnosis of depression in the SUN cohort is adequate. Thus, this question about depression diagnosis could be used in further investigations regarding this disease in this graduate cohort study.
Subject(s)
Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/epidemiology , Interview, Psychological , Mass Screening/methods , Surveys and Questionnaires , Adult , Body Mass Index , Cohort Studies , Diagnostic and Statistical Manual of Mental Disorders , Female , Humans , Male , Reproducibility of Results , Severity of Illness IndexABSTRACT
IntroducciÓn: Durante la depresión se producen cambios en la respuesta inmunitaria natural. Conocer mejor estas alteraciones en el laboratorio podría ayudarnos como complemento en el diagnóstico clínico de la depresión. El objetivo fue seleccionar qué parámetros inmunitarios pueden ser más útiles como marcadores biológicos de la depresión. Sujetos y método: Hemos estudiado distintos parámetros inmunitarios de 42 pacientes deprimidos durante la fase aguda y después de la respuesta al tratamiento, y los comparamos con un grupo de 20 controles sanos. Los parámetros estudiados fueron: recuento de monocitos y de células natural killer (NK), expresión de moléculas de superficie monocitaria HLA-II, CD14, y CD16, producción de citocinas monocitarias (IL-1ß, IL-6, y TNF-alfa), actividad oxidativa e índice de fagocitosis monocitarios, y actividad citotóxica de células NK. Resultados: En los pacientes deprimidos se produjo un aumento de monocitos CD16+, células NK, capacidad oxidativa monocitaria y producción de las citocinas estudiadas (IL-1ß, IL-6 y TNF-alfa), y un descenso de la expresión de HLA-II y del índice de fagocitosis monocitario. De estos parámetros, el índice de fagocitosis (especificidad del 90%; valor predictivo negativo del 99%) y, en menor medida, la producción de TNF-alfa (especificidad del 85%; valor predictivo negativo del 98,9%) fueron los que más podrían ayudar en el diagnóstico clínico de la depresión. Conclusiones: Los resultados indican que el índice de fagocitosis y la producción de TNF-alfa podrían ser marcadores biológicos útiles en la depresión, tanto para el diagnóstico como para el seguimiento evolutivo
Introduction: Immune function is altered in adult patients with depression. Laboratory assessment of these alterations could aid clinical diagnosis of depression. Objectives: To assess which immune parameters are the most reliable biological markers of depression. Subjects and method: We studied immune function in 42 depressed patients during the acute depressive phase and after treatment response, and compared it to that of 20 healthy controls. The following immune parameters were evaluated: monocyte and natural killer (NK) cell count; monocyte surface molecule expression (HLA-II, CD14, and CD16); monocyte cytokine proinflammatory production (interleukin [IL]-1ß, IL-6, and tumor necrosis factor [TNF]-alpha); respiratory burst capacity and monocyte phagocytic index; and NK cytotoxic activity. Results: Depressed patients showed an increase of CD16+ monocytes, NK cell count, respiratory burst activity, and monocyte cytokine production (IL-1ß, IL-6, and TNF-alpha). Depressed patients also showed a decrease in HLA-II molecule expression and phagocytic index. The monocyte phagocytic index (specificity = 90%, and negative predictive value = 99%), and to a lesser extent, TNF-alpha production (specificity = 90%, and negative predictive value = 99%) could be the most reliable immune parameters in the clinical diagnosis of depression. Conclusions: Our results suggest that the monocyte phagocytic index and TNF-alpha production are reliable biological markers of depression
Subject(s)
Male , Female , Adult , Middle Aged , Humans , Depressive Disorder/diagnosis , Immunity, Innate/physiology , Psychoneuroimmunology , Biomarkers/analysis , Cytokines/analysis , Monocytes , Killer Cells, NaturalABSTRACT
Después de comentar las diversas opiniones sobre la mayor o menor frecuencia de las tumoraciones malignas en la lepra, se expone la experiencia personal sobre esta observación patológica en Fontilles desde 1945 con un total de 83 casos de cáncer. Se exponen las localizaciones más frecuentes y se observa el aumento en los últimos años de la mortalidad por cáncer en los enfermos de lepra.
Subject(s)
Leprosy , NeoplasmsABSTRACT
Se analisa la toxicidad y los efectos de la rifampicina en el tratamiento de la lepra. En una experiencia terapéutica sobre 131 enfermos se ha observado una buena tolerancia general citándose algunas alteraciones gastro-intestinales y únicamente cuando se empleó como monoterapia la aparición de reacción lepromatosa en un 60%. Cuando se utilizó asociada a la clofazimina fueron escasos los episódios reaccionales. La tolerancia fue buena incluso asociada al isoprodian. En administración intermitente, mensual o semanal, hubo aparición del "Flu síndrome" en un 25% y 2 casos graves de insuficiencias renales agudas y una hepatitis tóxica.