La funzione cognitiva nell'anziano nel periodo perioperatorio

Nel paziente anziano possiamo identificare due forme di alterazione delle funzioni cognitive nel postoperatorio: la Disfunzione Cognitiva (POCD) ed il Delirium (POD). La POCD \ue8 un\u2019alterazione dello stato cognitivo che pu\uf2 persistere anche dopo settimane dall\u2019intervento che pu\uf2 essere dimostrata solo con test neuropsicologici. Il POD, invece, insorge a breve distanza di tempo dall\u2019intervento chirurgico, \ue8 acuto, fluttuante e transitorio. Il paziente presenta un disturbo dell\u2019attenzione (ridotta capacit\ue0 di dirigere, focalizzare e sostenere l\u2019attenzione) e consapevolezza (ridotto orientamento di s\ue9 nell\u2019ambiente). Per il POD esistono fattori predisponenti e fattori precipitanti, la cui conoscenza permette di prevenire o ridurne la comparsa. Per il POCD, invece, \ue8 dimostrato che l'intervento chirurgico e l'ospedalizzazione precipitano una condizione (deficit cognitivi) preesistente e che tale peggioramento \ue8 transitorio (in genere inferiore a 6-12 mesi)

Informed consent in elderly people: assessing the patient’s decision-making capacity = Consenso informato al trattamento medico: valutazione della capacità decisionale del paziente anziano

La capacit\ue0 di un paziente anziano di prendere delle decisioni mediche deve essere considerata sempre valida, indipendentemente dall\u2019et\ue0. Quando il paziente, per\uf2, non \ue8 in grado di accettare o rifiutare un trattamento, non pu\uf2 comprendere e ricordare le informazioni ricevute e/o non pu\uf2 utilizzare tali informazioni quando deve esprimere la propria decisione, \ue8 necessario valutare la sua capacit\ue0 decisionale mediante strumenti clinici obiettivi, poich\ue9 il consenso ottenuto da un paziente privo di capacit\ue0 decisionale non \ue8 legalmente valido. Lo strumento per la valutazione della capacit\ue0 decisionale dovrebbe essere semplice e di facile uso, obiettivo e replicabile; dovrebbe poter essere somministrato in breve tempo e, possibilmente, non richiedere alcun addestramento formale. MATERIALI E METODI Nel presente lavoro sono stati presi in considerazione i metodi di screening pi\uf9 frequentemente utilizzati per valutare la capacit\ue0 decisionale del paziente: il MacArthur Competence Assessment Tool for Treatment (MacCAT-T), l\u2019Aid to Capacity Evaluation (ACE) e il Mini Mental State Examination (MMSE). RISULTATI Il MMSE \ue8 uno strumento clinico di semplice utilizzo, non richiede una formazione specifica, pu\uf2 essere somministrato in meno di 10 minuti, \ue8 un test obiettivo e, anche se non \ue8 stato creato specificamente per valutare l\u2019incapacit\ue0, utilizza punteggi facilmente fruibili dal medico. Il punteggio va da 0 a 30: un punteggio MMSE da 0 a 17 si associa a elevata probabilit\ue0 di incapacit\ue0 decisionale; un punteggio da 18 a 23 indica un lieve deficit cognitivo, mentre il punteggio da 24 a 30 riduce significativamente la probabilit\ue0 di perdita dell\u2019autonomia decisionale. CONCLUSIONI Il Mini Mental State Examination pu\uf2 essere considerato lo strumento clinico pi\uf9 adatto per il medico nella pratica quotidiana. Nei pazienti con un basso punteggio MMSE, che suggerisce la probabilit\ue0 di mancanza di capacit\ue0 decisionale, sar\ue0 necessario che il consenso alle procedure mediche sia concesso da un tutore legale o dall\u2019amministratore di sostegno, secondo le leggi e la giurisdizione del paese coinvolto.OBJECTIVE Elderly patients are legally assumed to be competent to give consent to medical treatment. When patients are unable to make a decision on assenting or refusing treatment; if they cannot understand and remember the information provided, andor cannot use that information when considering their decision, the decision-making capacity of the patient should be evaluated with specific clinical tools, since consent obtained from an incompetent patient is invalid. The clinical tool should be simple and easy to use, be replicable, and should require a short administration time and, possibly, no formal training. MATERIALS AND METHODS We have considered frequently used clinical screening methods for cognitive impairment, such as the MacArthur Competence Assessment Tool for Treatment (Mac-CAT-T), the Aid to Capacity Evaluation (ACE) and the Mini Mental State Examination (MMSE), to evaluate the decision-making capacity of the patient. RESULTS The MMSE is a very simple bedside clinical tool, does not require specific training, takes less than 10 minutes to complete, is objective and uses scores indicating decreasing cognitive function. The scores range from 0 to 30: a MMSE score of 0 to 17 increases the likelihood of lack of capacity, a score of 18 to 23 indicates mild cognitive impairment, while a score of 24 to 30 significantly reduces the likelihood of incapacity. CONCLUSIONS The Mini Mental State Examination can be considered the clinical tool more suitable for the physician in the daily practice. In patients with a low MMSE score, suggesting likelihood of lack of capacity, it will be necessary that the consent to medical procedures be granted by a surrogate decision maker, according to the laws and jurisdiction of the country involved

Epstein-Barr virus nuclear antigen 3A protein regulates CDKN2B transcription via interaction with MIZ-1

The Epstein-Barr virus (EBV) nuclear antigen 3 family of protein is critical for the EBV-induced primary B-cell growth transformation process. Using a yeast two-hybrid screen we identified 22 novel cellular partners of the EBNA3s. Most importantly, among the newly identified partners, five are known to play direct and important roles in transcriptional regulation. Of these, the Myc-interacting zinc finger protein-1 (MIZ-1) is a transcription factor initially characterized as a binding partner of MYC. MIZ-1 activates the transcription of a number of target genes including the cell cycle inhibitor CDKN2B. Focusing on the EBNA3A/MIZ-1 interaction we demonstrate that binding occurs in EBV-infected cells expressing both proteins at endogenous physiological levels and that in the presence of EBNA3A, a significant fraction of MIZ-1 translocates from the cytoplasm to the nucleus. Moreover, we show that a trimeric complex composed of a MIZ-1 recognition DNA element, MIZ-1 and EBNA3A can be formed, and that interaction of MIZ-1 with nucleophosmin (NPM), one of its coactivator, is prevented by EBNA3A. Finally, we show that, in the presence of EBNA3A, expression of the MIZ-1 target gene, CDKN2B, is downregulated and repressive H3K27 marks are established on its promoter region suggesting that EBNA3A directly counteracts the growth inhibitory action of MIZ-1

Local cerebral blood flow with fentanyl-induced seizures.

Local cerebral blood flow (LCBF) was evaluated with the [ 14 C]iodoantipyrine quantitative autoradiographic technique in 29 brain structures in conscious control rats and during fentanyl-induced electroencephalographic (EEG) spike and/or seizure activity and in the postseizure EEG suppression phase. During spike activity, LCBF increased in all structures; the increase reached statistical significance (p<0.05) in the superior colliculus, sensorimotor cortex, and pineal body (+130%, +187%, and +185% from control, respectively). With progressive development of seizure activity, LCBF significantly increased in 24 brain structures (range, +58% to +231% from control). During the postseizure EEG suppression phase, LCBF remained elevated in all structures (+80% to +390% from control). The local cerebrovascular resistance (LCVR) significantly decreased in 10 of 29 structures with the onset of spike activity (range, -24% to -64%), and remained decreased in all brain structures during seizure activity (range, -34% to -67%) and during the EEG suppression phase (range, -24% to 74%). This reduction of LCVR represents a near maximal state of cerebrovasodilation during fentanyl-induced EEG seizure or postseizure suppression activity. The global nature of the LCBF elevation indicates that factors other than local metabolic control are responsible for CBF regulation during local seizure activit

Morphological evaluation of buffelgrass cultivar “Lucero INTA-PEMAN” in drought conditions

In searching for new cultivars that are better adapted to edapho-climatic constraints existing in northwestern Argentina, mainly drought and salinity stress, a hybrid of buffelgrass (Cenchrus ciliaris L.) named Lucero INTA PEMAN was obtained by controlled crosses at the Instituto de Fitopatología y Fisiología Vegetal, INTA. The objective was to morphologically evaluate and compare Cenchrus ciliaris cv Lucero with Texas-4464, Biloela and Molopo cultivars in Dean Funes (North of the Province of Córdoba, Argentina) under drought field conditions using a randomized complete block design with three replications in two crop cycles (2006/2007 and 2007/2008) considering one-year plant and re-growth as ontogenic stages of the plant, respectively. Thirteen morphological characters were analyzed by ANOVA and DGC testing (p <0.05). Although most of the thirteen morphological characters evaluated showed decreased re-growth over one-year plants, Lucero was least affected by low water availability, showed highest values for seed production components in both ontogenic stages and was superior to Texas-4464 in biomass production characters and to Biloela and Molopo cultivars in most of them. Lucero showed a promising and considerable forage value for drought-affected regions, such as northwestern Argentina

Passive SOBP generation from a static proton pencil beam using 3D-printed range modulators for FLASH experiments

The University Proton Therapy facility in Dresden (UPTD), Germany, is equipped with an experimental room with a beamline providing a static pencil beam. High proton beam currents can be achieved at this beamline which makes it suitable for FLASH experiments. However, the established experimental setup uses only the entrance channel of the proton Bragg curve. In this work, a set of 3D-printed range modulators designed to generate spread out Bragg peaks (SOBPs) for radiobiological experiments at ultra-high dose rate at this beamline is described. A new method to optimize range modulators specifically for the case of a static pencil beam based on the central depth dose profile is introduced. Modulators for two different irradiation setups were produced and characterized experimentally by measurements of lateral and depth dose distributions using different detectors. In addition, Monte Carlo simulations were performed to assess profiles of the dose averaged linear energy transfer (LETD) in water. These newly produced range modulators will allow future proton FLASH experiments in the SOBP at UPTD with two different experimental setups

Mmf1p, a novel yeast mitochondrial protein conserved throughout evolution and involved in maintenance of the mitochondrial genome

A novel protein family (p14.5, or YERO57c/YJGFc) highly conserved throughout evolution has recently been identified. The biological role of these proteins is not yet well characterized. Two members of the p14.5 family are present in the yeast Saccharomyces cerevisiae. In this study, we have characterized some of the biological functions of the two yeast proteins. Mmf1p is a mitochondrial matrix factor, and homologous Mmf1p factor (Hmf1p) copurifies with the soluble cytoplasmic fraction. Δmmf1 cells lose mitochondrial DNA (mtDNA) and have a decreased growth rate, while Δhmf1 cells do not display any visible phenotype. Furthermore, we demonstrate by genetic analysis that Mmf1p does not play a direct role in replication and segregation of the mtDNA. rho(+) Δmmf1 haploid cells can be obtained when tetrads are directly dissected on medium containing a nonfermentable carbon source. Our data also indicate that Mmf1p and Hmf1p have similar biological functions in different subcellular compartments. Hmf1p, when fused with the Mmf1p leader peptide, is transported into mitochondria and is able to functionally replace Mmf1p. Moreover, we show that homologous mammalian proteins are functionally related to Mmf1p. Human p14.5 localizes in yeast mitochondria and rescues the Δmmf1-associated phenotypes. In addition, fractionation of rat liver mitochondria showed that rat p14.5, like Mmf1p, is a soluble protein of the matrix. Our study identifies a biological function for Mmf1p and furthermore indicates that this function is conserved between members of the p14.5 family