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Asymptotic giant branch stars are responsible for the production of most of the heavy isotopes beyond Sr observed in the solar system. Among them, isotopes shielded from the r-process contribution by their stable isobars are defined as s-only nuclei. For a long time the abundance of ^{204}Pb, the heaviest s-only isotope, has been a topic of debate because state-of-the-art stellar models appeared to systematically underestimate its solar abundance. Besides the impact of uncertainties from stellar models and galactic chemical evolution simulations, this discrepancy was further obscured by rather divergent theoretical estimates for the neutron capture cross section of its radioactive precursor in the neutron-capture flow, ^{204}Tl (t_{1/2}=3.78 yr), and by the lack of experimental data on this reaction. We present the first ever neutron capture measurement on ^{204}Tl, conducted at the CERN neutron time-of-flight facility n_TOF, employing a sample of only 9 mg of ^{204}Tl produced at the Institute Laue Langevin high flux reactor. By complementing our new results with semiempirical calculations we obtained, at the s-process temperatures of kT≈8 keV and kT≈30 keV, Maxwellian-averaged cross sections (MACS) of 580(168) mb and 260(90) mb, respectively. These figures are about 3% lower and 20% higher than the corresponding values widely used in astrophysical calculations, which were based only on theoretical calculations. By using the new ^{204}Tl MACS, the uncertainty arising from the ^{204}Tl(n,γ) cross section on the s-process abundance of ^{204}Pb has been reduced from â¼30% down to +8%/-6%, and the s-process calculations are in agreement with the latest solar system abundance of ^{204}Pb reported by K. Lodders in 2021.
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^{140}Ce(n,γ) is a key reaction for slow neutron-capture (s-process) nucleosynthesis due to being a bottleneck in the reaction flow. For this reason, it was measured with high accuracy (uncertainty ≈5%) at the n_TOF facility, with an unprecedented combination of a high purity sample and low neutron-sensitivity detectors. The measured Maxwellian averaged cross section is up to 40% higher than previously accepted values. Stellar model calculations indicate a reduction around 20% of the s-process contribution to the Galactic cerium abundance and smaller sizeable differences for most of the heavier elements. No variations are found in the nucleosynthesis from massive stars.
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The ß-delayed one- and two-neutron emission probabilities (P_{1n} and P_{2n}) of 20 neutron-rich nuclei with N≥82 have been measured at the RIBF facility of the RIKEN Nishina Center. P_{1n} of ^{130,131}Ag, ^{133,134}Cd, ^{135,136}In, and ^{138,139}Sn were determined for the first time, and stringent upper limits were placed on P_{2n} for nearly all cases. ß-delayed two-neutron emission (ß2n) was unambiguously identified in ^{133}Cd and ^{135,136}In, and their P_{2n} were measured. Weak ß2n was also detected from ^{137,138}Sn. Our results highlight the effect of the N=82 and Z=50 shell closures on ß-delayed neutron emission probability and provide stringent benchmarks for newly developed macroscopic-microscopic and self-consistent global models with the inclusion of a statistical treatment of neutron and γ emission. The impact of our measurements on r-process nucleosynthesis was studied in a neutron star merger scenario. Our P_{1n} and P_{2n} have a direct impact on the odd-even staggering of the final abundance, improving the agreement between calculated and observed Solar System abundances. The odd isotope fraction of Ba in r-process-enhanced (r-II) stars is also better reproduced using our new data.
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The reduced transition probabilities for the 4_{1}^{+}â2_{1}^{+} and 2_{1}^{+}â0_{1}^{+} transitions in ^{92}Mo and ^{94}Ru and for the 4_{1}^{+}â2_{1}^{+} and 6_{1}^{+}â4_{1}^{+} transitions in ^{90}Zr have been determined in this experiment making use of a multinucleon transfer reaction. These results have been interpreted on the basis of realistic shell-model calculations in the f_{5/2}, p_{3/2}, p_{1/2}, and g_{9/2} proton valence space. Only the combination of extensive lifetime information and large scale shell-model calculations allowed the extent of the seniority conservation in the N=50 g_{9/2} orbital to be understood. The conclusion is that seniority is largely conserved in the first πg_{9/2} orbital.
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B-cell acute lymphoblastic leukemia (B-ALL) is a hematologic disorder characterized by the abnormal proliferation and accumulation of immature B-lymphoblasts arrested at various stages of differentiation. Despite advances in treatment, a significant percentage of pediatric patients with precursor B-ALL still relapse. Therefore, alternative therapies are needed to improve the cure rates for pediatric patients. TPEN (N, N, N', N'-tetrakis(2-pyridylmethyl)-ethylenediamine) is a pro-oxidant agent capable of selectively inducing apoptosis in leukemia cell lines. Consequently, it has been suggested that TPEN could be a potential agent for oxidative therapy. However, it is not yet known whether TPEN can selectively destroy leukemia cells in a more disease-like model, for example, the bloodstream and bone marrow (BM), ex vivo. This investigation is an extension of a previous study that dealt with the effect of TPEN on ex vivo isolated/purified refractory B-ALL cells. Here, we evaluated the effect of TPEN on whole BM from nonleukemic patients (control) or pediatric patients diagnosed with de novo B-ALL or refractory B-ALL cells by analyzing the hematopoietic cell lineage marker CD34/CD19. Although TPEN was innocuous to nonleukemic BM (n = 3), we found that TPEN significantly induced apoptosis in de novo (n = 5) and refractory B-ALL (n = 6) leukemic cell populations. Moreover, TPEN significantly increased the counts of cells positive for the oxidation of the stress sensor protein DJ-1, a sign of the formation of H2O2, and significantly increased the counts of cells positive for the pro-apoptotic proteins TP53, PUMA, and CASPASE-3 (CASP-3), indicative of apoptosis, in B-ALL cells. We demonstrate that TPEN selectively eliminates B-ALL cells (CD34 + /CD19 +) but no other cell populations in BM (CD34 + /CD19-; CD34-/CD19 + ; CD34-/CD19-) independent of age, diagnosis status (de novo or refractory), sex, karyotype, or immunophenotype. Understanding TPEN-induced cell death in leukemia cells provides insight into more effective therapeutic oxidation-inducing anticancer agents.
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Médula Ósea , Leucemia-Linfoma Linfoblástico de Células Precursoras , Antígenos CD19/metabolismo , Médula Ósea/metabolismo , Niño , Etilenodiaminas , Humanos , Peróxido de Hidrógeno/metabolismo , Inmunofenotipificación , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológicoRESUMEN
Neutron capture reaction cross sections on 74 Ge are of importance to determine 74 Ge production during the astrophysical slow neutron capture process. We present new resonance data on 74 Ge( n , γ ) reactions below 70 keV neutron energy. We calculate Maxwellian averaged cross sections, combining our data below 70 keV with evaluated cross sections at higher neutron energies. Our stellar cross sections are in agreement with a previous activation measurement performed at Forschungszentrum Karlsruhe by Marganiec et al., once their data has been re-normalised to account for an update in the reference cross section used in that experiment.
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The neutron capture cross sections of several unstable nuclides acting as branching points in the s process are crucial for stellar nucleosynthesis studies. The unstable ^{171}Tm (t_{1/2}=1.92 yr) is part of the branching around mass Aâ¼170 but its neutron capture cross section as a function of the neutron energy is not known to date. In this work, following the production for the first time of more than 5 mg of ^{171}Tm at the high-flux reactor Institut Laue-Langevin in France, a sample was produced at the Paul Scherrer Institute in Switzerland. Two complementary experiments were carried out at the neutron time-of-flight facility (n_TOF) at CERN in Switzerland and at the SARAF liquid lithium target facility at Soreq Nuclear Research Center in Israel by time of flight and activation, respectively. The result of the time-of-flight experiment consists of the first ever set of resonance parameters and the corresponding average resonance parameters, allowing us to make an estimation of the Maxwellian-averaged cross sections (MACS) by extrapolation. The activation measurement provides a direct and more precise measurement of the MACS at 30 keV: 384(40) mb, with which the estimation from the n_TOF data agree at the limit of 1 standard deviation. This value is 2.6 times lower than the JEFF-3.3 and ENDF/B-VIII evaluations, 25% lower than that of the Bao et al. compilation, and 1.6 times larger than the value recommended in the KADoNiS (v1) database, based on the only previous experiment. Our result affects the nucleosynthesis at the Aâ¼170 branching, namely, the ^{171}Yb abundance increases in the material lost by asymptotic giant branch stars, providing a better match to the available pre-solar SiC grain measurements compared to the calculations based on the current JEFF-3.3 model-based evaluation.
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The low-lying energy spectrum of the extremely neutron-deficient self-conjugate (N=Z) nuclide _{44}^{88}Ru_{44} has been measured using the combination of the Advanced Gamma Tracking Array (AGATA) spectrometer, the NEDA and Neutron Wall neutron detector arrays, and the DIAMANT charged particle detector array. Excited states in ^{88}Ru were populated via the ^{54}Fe(^{36}Ar,2nγ)^{88}Ru^{*} fusion-evaporation reaction at the Grand Accélérateur National d'Ions Lourds (GANIL) accelerator complex. The observed γ-ray cascade is assigned to ^{88}Ru using clean prompt γ-γ-2-neutron coincidences in anticoincidence with the detection of charged particles, confirming and extending the previously assigned sequence of low-lying excited states. It is consistent with a moderately deformed rotating system exhibiting a band crossing at a rotational frequency that is significantly higher than standard theoretical predictions with isovector pairing, as well as observations in neighboring N>Z nuclides. The direct observation of such a "delayed" rotational alignment in a deformed N=Z nucleus is in agreement with theoretical predictions related to the presence of strong isoscalar neutron-proton pair correlations.
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Parkinson disease (PD) is characterized by the loss of dopaminergic (DAergic) neurons linked to environmental toxicants that cause oxidative stress (OS). The aim of this investigation was to establish the molecular response of human mesenchymal stroma cells (MSCs) depleted of glutathione (GSH) by the specific inhibitor L-buthionine-sulfoximine (BSO) to 6-hydroxydopamine (6-OHDA) and/or N-acetylcysteine (NAC) co-treatment. We found that treatment with BSO (10 mM) plus 6-OHDA (200 µM) induced apoptosis in MSCs through an oxidative stress (OS) mechanism involving H2O2, reflected by the detection of dichlorofluorescein-positive (DCF+) cells and oxidation of DJ-1 Cys106-SH into DJ-1 Cys106-SO3; an almost complete reduction in glutathione peroxidase 1 (GPX1) expression; activation of the transcription factor c-JUN, the pro-apoptotic protein BAX and BH-3-only protein PUMA; loss of mitochondrial membrane potential (∆Ψm); activation of the protease caspase-3 (CASP3) and apoptosis-inducing factor (AIF); chromatin condensation; and DNA fragmentation. Strikingly, co-treatment of MSCs with NAC (5 mM) and BSO + 6-OHDA significantly reduced the expression of OS and cell death markers but were unable to restore the expression of GPX1 compared to the expression in untreated or treated cells with NAC only. These findings highlighted the importance of the maintenance of the GSH-dependent (e.g., GPX1, GSH synthesis) and -independent (e.g., ROS scavenger molecules and thiol reducing activity) antioxidant systems (e.g., NAC) in the protection of MSCs from detrimental stress stimuli, thereby increasing the survival of stromal cells.
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Acetilcisteína/farmacología , Apoptosis/efectos de los fármacos , Células Madre Mesenquimatosas/efectos de los fármacos , Antioxidantes/metabolismo , Butionina Sulfoximina/metabolismo , Muerte Celular/efectos de los fármacos , Glutatión/metabolismo , Glutatión Peroxidasa , Humanos , Peróxido de Hidrógeno/farmacología , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Oxidación-Reducción , Estrés Oxidativo/efectos de los fármacos , Oxidopamina/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Glutatión Peroxidasa GPX1RESUMEN
BACKGROUND AIMS: Stem cell transplantation is an excellent option for regenerative or replacement therapy. However, deleterious microenvironmental and endogenous factors (e.g., oxidative stress) compromise ongoing graft survival and longevity. Therefore, (transient or stable) genetically modified cells may be reasonably thought to resist oxidative stress-induced damage. Genetic engineering of mesenchymal stromal cells (MSCs) obtained from Wharton's jelly tissue may offer some therapeutic potential. PARKIN is a multifunctional ubiquitin ligase able to protect dopaminergic cells against stress-related signaling. We, therefore, evaluated the effect of the neurotoxicant 6-hydroxydopamine (6-OHDA) on regulated cell death signaling in MSCs and investigated whether overexpression of PARKIN in MSCs was capable of modulating the effect of 6-OHDA. METHODS: We transiently transfected Wharton's jelly-derived MSCs with an mCherry-PARKIN vector using the Lipofectamine LTX method. Naïve MSCs and MSCs overexpressing PARKIN were exposed to increasing concentrations of 6-OHDA. We used light and fluorescence microscopy, flow cytometry, immunocytochemistry staining, in-cell Western and Western blot analysis. RESULTS: After 12-24 h of 6-OHDA exposure, we detected dichlorofluorescein (DCF)-positive cells (80%) indicative of reactive oxygen species (H2O2) production, reduced cell viability (40-50%), decreased mitochondrial membrane potential (ΔΨm, ~35-45%), DNA fragmentation (18-30%), and G1-arrested cell cycle in the MSCs. 6-OHDA exposure increased the expression of the transcription factor c-JUN, increased the expression of the mitochondria maintenance Phosphatase and tensin homologue-induced putative kinase 1 (PINK1) protein and increased the expression of pro-apoptotic PUMA, caspase-3 and apoptosis-inducing factor (AIF). 6-OHDA exposure also significantly augmented the oxidation of the oxidative stress sensor, DJ-1. Overexpression of PARKIN in MSCs not only significantly reduced the expression of cell death and oxidative stress markers but also significantly reduced DCF-positive cells (~50% reduction). DISCUSSION: 6-OHDA induced apoptosis in MSCs via generation of H2O2, activation of c-JUN and PUMA, mitochondrial depolarization and nuclei fragmentation. Our findings suggest that PARKIN protects MSCs against 6-OHDA toxicity by partly interacting with H2O2, reducing the expression of c-JUN, PUMA, AIF and caspase-3, and maintaining the mitochondrial ΔΨm.
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Apoptosis , Células Madre Mesenquimatosas/metabolismo , Enfermedad de Parkinson/patología , Enfermedad de Parkinson/terapia , Ubiquitina-Proteína Ligasas/metabolismo , Gelatina de Wharton/citología , Apoptosis/efectos de los fármacos , Caspasa 3 , Supervivencia Celular , Humanos , Peróxido de Hidrógeno/farmacología , Potencial de la Membrana Mitocondrial , Trasplante de Células Madre Mesenquimatosas , Mitocondrias/metabolismo , Estrés Oxidativo , Oxidopamina , Fenotipo , Especies Reactivas de Oxígeno/metabolismo , Transducción de SeñalRESUMEN
The shell structure of atomic nuclei is associated with 'magic numbers' and originates in the nearly independent motion of neutrons and protons in a mean potential generated by all nucleons. During ß(+)-decay, a proton transforms into a neutron in a previously not fully occupied orbital, emitting a positron-neutrino pair with either parallel or antiparallel spins, in a Gamow-Teller or Fermi transition, respectively. The transition probability, or strength, of a Gamow-Teller transition depends sensitively on the underlying shell structure and is usually distributed among many states in the neighbouring nucleus. Here we report measurements of the half-life and decay energy for the decay of (100)Sn, the heaviest doubly magic nucleus with equal numbers of protons and neutrons. In the ß-decay of (100)Sn, a large fraction of the strength is observable because of the large decay energy. We determine the largest Gamow-Teller strength so far measured in allowed nuclear ß-decay, establishing the 'superallowed' nature of this Gamow-Teller transition. The large strength and the low-energy states in the daughter nucleus, (100)In, are well reproduced by modern, large-scale shell model calculations.
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Prompt γ-ray spectroscopy of the neutron-rich ^{96}Kr, produced in transfer- and fusion-induced fission reactions, has been performed using the combination of the Advanced Gamma Tracking Array and the VAMOS++ spectrometer. A second excited state, assigned to J^{π}=4^{+}, is observed for the first time, and a previously reported level energy of the first 2^{+} excited state is confirmed. The measured energy ratio R_{4/2}=E(4^{+})/E(2^{+})=2.12(1) indicates that this nucleus does not show a well-developed collectivity contrary to that seen in heavier N=60 isotones. This new measurement highlights an abrupt transition of the degree of collectivity as a function of the proton number at Z=36, of similar amplitude to that observed at N=60 at higher Z values. A possible reason for this abrupt transition could be related to the insufficient proton excitations in the g_{9/2}, d_{5/2}, and s_{1/2} orbitals to generate strong quadrupole correlations or to the coexistence of competing different shapes. An unexpected continuous decrease of R_{4/2} as a function of the neutron number up to N=60 is also evidenced. This measurement establishes the Kr isotopic chain as the low-Z boundary of the island of deformation for N=60 isotones. A comparison with available theoretical predictions using different beyond mean-field approaches shows that these models fail to reproduce the abrupt transitions at N=60 and Z=36.
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INTRODUCTION AND OBJECTIVES: The Relevant Outcome Scale for Alzheimer's Disease (ROSA) is a useful tool for evaluating and monitoring dementia patients. This study aims to evaluate the validity and reliability of the Spanish version of ROSA. PATIENTS AND METHODS: Spanish multicentre study involving 39 researchers and including 237 patients with Alzheimer disease (78 mild, 79 moderate, and 80 severe). The patients were tested with the following: Mini-Mental State Examination (MMSE), Fototest, Neuropsychiatric Inventory (NPI), Blessed dementia scale, and a Spanish-language version of ROSA. A subsample of 40 subjects was retested in the 14 days following the initial evaluation. The construct validity was evaluated with the Spearman correlation coefficient (r), internal consistency with Cronbach's alpha (alpha), and test-retest reliability with the intraclass correlation coefficient (ICC). RESULTS: ROSA requires 13.8±7.4minutes to administer and its results show a significant association with the clinical stage of AD (mild, 116.7±23.1; moderate, 92.9±19.8; and severe, 64.3±22.6), and with results on the MMSE (r=0.68), Fototest (r=0.63), NPI (r=0.53), and Blessed dementia scale (r=-0.80). ROSA shows high internal consistency (alpha=0.90) and excellent test-retest reliability (ICC0.97). CONCLUSION: The Spanish version of ROSA is a brief, valid, and reliable tool permitting overall evaluation of patients with dementia.
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Enfermedad de Alzheimer/diagnóstico , Escalas de Valoración Psiquiátrica , Traducción , Anciano , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , EspañaRESUMEN
The energy-dependent cross section of the ^{7}Be(n,α)^{4}He reaction, of interest for the so-called cosmological lithium problem in big bang nucleosynthesis, has been measured for the first time from 10 meV to 10 keV neutron energy. The challenges posed by the short half-life of ^{7}Be and by the low reaction cross section have been overcome at n_TOF thanks to an unprecedented combination of the extremely high luminosity and good resolution of the neutron beam in the new experimental area (EAR2) of the n_TOF facility at CERN, the availability of a sufficient amount of chemically pure ^{7}Be, and a specifically designed experimental setup. Coincidences between the two alpha particles have been recorded in two Si-^{7}Be-Si arrays placed directly in the neutron beam. The present results are consistent, at thermal neutron energy, with the only previous measurement performed in the 1960s at a nuclear reactor. The energy dependence reported here clearly indicates the inadequacy of the cross section estimates currently used in BBN calculations. Although new measurements at higher neutron energy may still be needed, the n_TOF results hint at a minor role of this reaction in BBN, leaving the long-standing cosmological lithium problem unsolved.
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The ß-delayed neutron emission probabilities of neutron rich Hg and Tl nuclei have been measured together with ß-decay half-lives for 20 isotopes of Au, Hg, Tl, Pb, and Bi in the mass region Nâ³126. These are the heaviest species where neutron emission has been observed so far. These measurements provide key information to evaluate the performance of nuclear microscopic and phenomenological models in reproducing the high-energy part of the ß-decay strength distribution. This provides important constraints on global theoretical models currently used in r-process nucleosynthesis.
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Plasmid-mediated quinolone resistance mechanisms have become increasingly prevalent among Enterobacteriaceae strains since the 1990s. Among these mechanisms, AAC(6')-Ib-cr is the most difficult to detect. Different detection methods have been developed, but they require expensive procedures such as Sanger sequencing, pyrosequencing, polymerase chain reaction (PCR) restriction, or the time-consuming phenotypic method of Wachino. In this study, we describe a simple matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) method which can be easily implemented in clinical laboratories that use the MALDI-TOF technique for bacterial identification. We tested 113 strains of Enterobacteriaceae, of which 64 harbored the aac(6')-Ib-cr gene. We compared two MALDI-TOF strategies, which differed by their norfloxacin concentration (0.03 vs. 0.5 g/L), and the method of Wachino with the PCR and sequencing strategy used as the reference. The MALDI-TOF strategy, performed with 0.03 g/L norfloxacin, and the method of Wachino yielded the same high performances (Se = 98 %, Sp = 100 %), but the turnaround time of the MALDI-TOF strategy was faster (<5 h), simpler, and inexpensive (<1 Euro). Our study shows that the MALDI-TOF strategy has the potential to become a major method for the detection of many different enzymatic resistance mechanisms.
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Antibacterianos/metabolismo , Técnicas Bacteriológicas/métodos , Biotransformación , Farmacorresistencia Bacteriana , Enterobacteriaceae/efectos de los fármacos , Norfloxacino/metabolismo , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Antibacterianos/farmacología , Enterobacteriaceae/metabolismo , Norfloxacino/farmacología , Sensibilidad y Especificidad , Factores de TiempoRESUMEN
INTRODUCTION: Very few studies describe the demographic and social profile of epilepsy in vulnerable low-income populations. METHODS: Observational, descriptive, cross-sectional study prospectively recording data from all patients diagnosed with epilepsy who attended a specialist neurology consultation between January and March 2014. Data were analysed using descriptive epidemiology tools. RESULTS: A total of 107 patients were evaluated, of whom 24.2% were illiterate and only 10.2% had completed a higher education programme. Most of the patients (86.8%) had a low socioeconomic status; 73.8% were single and 76.7% were unemployed. The main risk factors for epilepsy in this population were recorded as follows: delayed psychomotor development (n=24, 22.4%), head trauma (n=16, 14.9%), and central nervous system infection (n=13, 12.1%). Most patients (70.1%) responded to antiepileptic drugs (controlled cases) and 15.4% (n=15) had drug-resistant epilepsy (refractory cases). CONCLUSION: The demographic and clinical profiles of the patients included in this study resemble those published for high-income populations; differences are mostly limited to aetiological classification and risk factors. The social profile of the patients evaluated in this study shows high rates of unemployment, illiteracy, and single marital status. These findings seem to be more frequent and prevalent in this group than in high income populations.
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Epilepsia/epidemiología , Pobreza/estadística & datos numéricos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Colombia/epidemiología , Estudios Transversales , Escolaridad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Medición de Riesgo , Clase Social , Factores Socioeconómicos , Adulto JovenRESUMEN
INTRODUCTION: Brief cognitive tests (BCT) may help detect cognitive impairment (CI) in the clinical setting. Several BCT have been developed and/or validated in our country, but we lack specific recommendations for use. DEVELOPMENT: Review of studies on the diagnostic accuracy of BCT for CI, using studies conducted in Spain with BCT which take less than 20 min. We provide recommendations of use based on expert consensus and established on the basis of BCT characteristics and study results. CONCLUSION: The Fototest, the Memory Impairment Screen (MIS) and the Mini-Mental State Examination (MMSE) are the preferred options in primary care; other BCT (Clock Drawing Test [CDT], test of verbal fluency [TVF]) may also be administered in cases of negative results with persistent suspected CI or concern (stepwise approach). In the specialised care setting, a systematic assessment of the different cognitive domains should be conducted using the Montreal Cognitive Assessment, the MMSE, the Rowland Universal Dementia Assessment, the Addenbrooke's Cognitive Examination, or by means of a stepwise or combined approach involving more simple tests (CDT, TVF, Fototest, MIS, Memory Alteration Test, Eurotest). Associating an informant questionnaire (IQ) with the BCT is superior to the BCT alone for the detection of CI. The choice of instruments will depend on the patient's characteristics, the clinician's experience, and available time. The BCT and IQ must reinforce - but never substitute - clinical judgment, patient-doctor communication, and inter-professional dialogue.
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Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/psicología , Cognición , Pruebas Neuropsicológicas , Anciano , Anciano de 80 o más Años , Demencia/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los ResultadosRESUMEN
PURPOSE: To evaluate the impact of a history of harmful use of alcohol (HUA) on sedoanalgesia practices and outcomes in patients on mechanical ventilation (MV). METHODS: A prospective, observational multicentre study was made of all adults consecutively admitted during 30 days to 8 Spanish ICUs. Patients on MV >24h were followed-up on until discharge from the ICU or death. Data on HUA, smoking, the use of illegal (IP) and medically prescribed psychotropics (MPP), sedoanalgesia practices and their related complications (sedative failure [SF] and sedative withdrawal [SW]), as well as outcome, were prospectively recorded. RESULTS: A total of 23.4% (119/509) of the admitted patients received MV >24h; 68.9% were males; age 57.0 (17.9) years; APACHE II score 18.8 (7.2); with a medical cause of admission in 53.9%. Half of them consumed at least one psychotropic agent (smoking 27.7%, HUA 25.2%; MPP 9.2%; and IP 7.6%). HUA patients more frequently required PS (86.7% vs. 64%; p<0.02) and the use of >2 sedatives (56.7% vs. 28.1%; p<0.02). HUA was associated to an eightfold (p<0.001) and fourfold (p<0.02) increase in SF and SW, respectively. In turn, the duration of MV and the stay in the ICU was increased by 151h (p<0.02) and 4.4 days (p<0.02), respectively, when compared with the non-HUA group. No differences were found in terms of mortality. CONCLUSIONS: HUA may be associated to a higher risk of SF and WS, and can prolong MV and the duration of stay in the ICU in critical patients. Early identification could allow the implementation of specific sedation strategies aimed at preventing these complications.
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Consumo de Bebidas Alcohólicas/efectos adversos , Etanol/efectos adversos , Hipnóticos y Sedantes/farmacocinética , Unidades de Cuidados Intensivos , Respiración Artificial , APACHE , Adulto , Anciano , Consumo de Bebidas Alcohólicas/epidemiología , Interacciones Farmacológicas , Etanol/farmacocinética , Femenino , Humanos , Hipnóticos y Sedantes/administración & dosificación , Hipnóticos y Sedantes/efectos adversos , Drogas Ilícitas/farmacocinética , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Psicotrópicos/efectos adversos , Psicotrópicos/farmacocinética , Psicotrópicos/uso terapéutico , Fumar/epidemiología , España/epidemiología , Síndrome de Abstinencia a Sustancias/etiología , Trastornos Relacionados con Sustancias/epidemiología , Insuficiencia del TratamientoRESUMEN
The widespread and sustainable exploitation of the entomopathogen Bacillus thuringiensis (Bt) in pest control is threatened by the evolution of resistance. Although resistance is often associated with loss of binding of the Bt toxins to the insect midgut cells, other factors have been implicated. Here we used suppressive subtractive hybridization and gene expression suppression to identify additional molecular components involved in Bt-resistance in Plutella xylostella. We isolated transcripts from genes that were differentially expressed in the midgut of larvae from a resistant population, following ingestion of a Bt kurstaki HD1 strain-based commercial formulation (DiPel), and compared with a genetically similar susceptible population. Quantitative real-time polymerase-chain reaction (RT-PCR) analysis confirmed the differential basal expression of a subset of these genes. Gene expression suppression of three of these genes (P. xylostella cyclin-dependent kinase 5 regulatory subunit associated protein 1-like 1, stromal cell-derived factor 2-like 1 and hatching enzyme-like 1) significantly increased the pathogenicity of HD1 to the resistant population. In an attempt to link the multitude of factors reportedly influencing resistance to Bt with the well-characterized loss of toxin binding, we also considered Bt-resistance models in P. xylostella and other insects.