Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 52
Filtrar
1.
Environ Pollut ; 348: 123765, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38503351

RESUMO

Indoor air quality (IAQ) is critical to the health and wellbeing of people. As the majority of people spend greater amounts of time indoors, either in office spaces or households, the level of air pollutants in such environments is critical. Building materials and furniture are known sources of air pollutants such as Volatile Organic Compounds (VOCs) and may be associated with discomfort, detrimental health of the occupants, etc. In this study, the VOCs found in a brand new office complex were monitored over a period of 6 months, with an emphasis on monitoring and quantifying harmful VOCs and identifying their emission source. Air samples were taken from a closed, unoccupied office space on a weekly basis and analysed using Thermal Desorption-Gas Chromatography-Mass Spectrometry (TD-GC-MS), while continuous monitoring of the air quality was performed using two commercially available IAQ sensors. To identify the source of the emitted VOCs, pieces of all construction material that were used in the office, including flooring, finished wall material, and adhesive glues, were removed, and placed in air-tight glass containers prior to analysis confirming that the source of VOCs is indeed the flooring. Identified compounds included mainly material origin VOCs such as BTEX (benzene, toluene, ethylbenzene, xylene) and styrene, but also common VOCs such as acetone and propan-2-ol. Of significant importance was the concentration of toluene that was found to be the most abundant VOC in both the flooring material and the indoor air.


Assuntos
Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Compostos Orgânicos Voláteis , Humanos , Compostos Orgânicos Voláteis/análise , Monitoramento Ambiental/métodos , Cromatografia Gasosa-Espectrometria de Massas , Poluentes Atmosféricos/análise , Materiais de Construção , Poluição do Ar em Ambientes Fechados/análise , Tolueno/análise
2.
iScience ; 26(12): 108527, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38162029

RESUMO

Ketamine is a treatment for both refractory depression and chronic pain syndromes. In order to explore ketamine's potential mechanism of action and whether ketamine or its metabolites cross the blood brain barrier, we examined the pharmacokinetics of ketamine and its metabolites-norketamine (NK), dehydronorketamine (DHNK), and hydroxynorketamines (HNKs)-in cerebrospinal fluid (CSF) and plasma, as well as in an exploratory proteomic analysis in the CSF of nine healthy volunteers who received ketamine intravenously (0.5 mg/kg IV). We found that ketamine, NK, and (2R,6R;2S,6S)-HNK readily crossed the blood brain barrier. Additionally, 354 proteins were altered in the CSF in at least two consecutive timepoints (p < 0.01). Proteins in the classes of tyrosine kinases, cellular adhesion molecules, and growth factors, including insulin, were most affected, suggesting an interplay of altered neurotransmission, neuroplasticity, neurogenesis, synaptogenesis, and neural network functions following ketamine administration.

3.
Front Vet Sci ; 9: 863910, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36051539

RESUMO

In this study, the effects of orange essential oil (OEO) on the rumen fermentation, nutrient utilization, and methane (CH4) emissions of beef heifers fed a diet of bermudagrass (Cynodon dactylon) were examined. In addition, in vitro and in situ experiments were conducted. The in vitro experiment consisted of three treatments: control (CTL, no OEO), OEO1 (0.25% OEO), and OEO2 (0.5% OEO). The forage to concentrate ratio was 70:30 (dry matter [DM] basis) in all treatments. No changes in pH, proportions of volatile fatty acids, and the acetate:propionate ratio were observed (P > 0.05). The addition of 0.25% OEO resulted in a reduction in CH4 production (mL/g) relative to the control (P < 0.05). In the in situ experiment, 5 g of total mixed ration (CTL, OEO1, and OEO2) were incubated for 6, 12, 24, 48, and 72 h. Potential and effective degradability were not affected by OEO supplementation (P > 0.05). In the in vivo study, six crossbred beef heifers (Bos indicus × Bos taurus), fitted with rumen cannulas, were assigned to three different treatments: no additive (CTL), 0.25% OEO (OEO1), and 0.5% OEO (OEO2) in a replicated 3 × 3 Latin square (21-day periods). Heifers were fed at 2.8% body weight. In vivo CH4 production was measured in open-circuit respiration chambers. Reductions in gross energy consumption, apparent total tract digestibility, and rumen valerate concentration were observed for OEO2 compared to the control (P < 0.05). Additionally, decreases in CH4 emissions (g/day; P < 0.05) and CH4 (MJ gross energy intake/day; P < 0.05) were observed in response to supplementation of 0.5% OEO as compared to the CTL treatment. Thus, supplementation of 0.5% OEO reduced CH4 emissions (g/day) by 12% without impacting the DM intake of heifers fed bermudagrass hay as a basal ration.

4.
Eur Heart J Suppl ; 24(Suppl E): E4-E11, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35991621

RESUMO

Sympathetic activation has been long appreciated exclusively as a fundamental compensatory mechanism of the failing heart and, thus, welcome and to be supported. In the initial clinical phases of heart failure (HF), the sympathetic nervous system overdrive plays a compensatory function aimed at maintaining an adequate cardiac output despite the inotropic dysfunction affecting the myocardium. However, when the sympathetic reflex response is exaggerated it triggers a sequence of unfavourable remodelling processes causing a further contractile deterioration that unleashes major adverse cardiovascular consequences, favouring the HF progression and the occurrence of fatal events. Eventually, the sympathetic nervous system in HF was demonstrated to be a 'lethality factor' and thus became a prominent therapeutic target. The existence of an effective highly specialized intracardiac neuronal network immediately rules out the old concept that sympathetic activation in HF is merely the consequence of a drop in cardiac output. When a cardiac damage occurs, such as myocardial ischaemia or a primary myocardial disorder, the adaptive capability of the system may be overcame, leading to excessive sympatho-excitation coupled with attenuation till to abolishment of central parasympathetic drive. Myocardial infarction causes, within a very short time, both a functional and anatomical remodelling with a diffuse up-regulation of nerve growth factor (NGF). The subsequent nerve sprouting signal, facilitated by a rise in the levels of NGF in the left stellate ganglion and in the serum, triggers an increase in cardiac nerve density in both peri-infarct and non-infarcted areas. Finally, NFG production decreases over time, supposedly as an adaptative response to the prolonged exposure to sympathetic overactivity, leading in the end to a reduction in sympathetic nerve density. Accordingly, NGF levels were markedly reduced in patients with severe congestive heart failure. The kidney is the other key player of the sympathetic response to HF as it indeed reacts to under-perfusion and to loop diuretics to preserve filtration at the cost of many pathological consequences on its physiology. This vicious loop ultimately participates to the chronic and disruptive sympathetic overdrive. In conclusion, sympathetic activation is the natural physiological consequence to life stressors but also to any condition that may harm our body. It is the first system of reaction to any potential life-threatening event. However, in any aspect of life over reaction is never effective but, in many instances, is, actually, life threatening. One for all is the case of ischaemia-related ventricular fibrillation which is, strongly facilitated by sympathetic hyperactivity. The take home message? When, in a condition of harm, everybody is yelling failure is just around the corner.

5.
Rev. esp. cardiol. (Ed. impr.) ; 75(6): 506-514, Jun. 2022. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-205108

RESUMO

Introducción y objetivos: La puntuación de calcio arterial coronario (CAC) mejora la precisión de la estratificación del riesgo de enfermedad cardiovascular ateroesclerótica (ECVA) en comparación con los factores de riesgo cardiovascular tradicionales. Se evaluó la interacción de la carga ateroesclerótica coronaria determinada por la puntuación de CAC con el beneficio pronóstico de los tratamientos hipolipemiantes en el contexto de la prevención primaria. Métodos: Se revisaron las bases de datos MEDLINE, EMBASE y Cochrane en busca de estudios que incluyeran a individuos sin ECVA previa y con datos sobre la puntuación de CAC y el tratamiento hipolipemiante según los valores de CAC. El objetivo primario fue la aparición de ECVA. Se evaluó el efecto del tratamiento hipolipemiante agrupado y estratificado por grupos de CAC (0, 1-100 y> 100) mediante un modelo de efectos aleatorios. Resultados: Se incluyeron 5 estudios (1 aleatorizado, 2 de cohortes prospectivas y 2 retrospectivas) que incluyeron a 35.640 individuos (el 38,1% mujeres) con medias de edad de 62,2 (rango, 49,6-68,9) años, colesterol unido a lipoproteínas de baja densidad de 128 (114-146) mg/dl y seguimiento de 4,3 (2,3-11,1) años. La aparición de la ECVA aumentó de manera constante en los estratos crecientes de CAC tanto en los pacientes con como en aquellos sin tratamiento hipolipemiante. Al comparar a los pacientes con (34,9%) y sin (65,1%) exposición al tratamiento hipolipemiante, este se asoció con menos aparición de ECVA en los pacientes con CAC> 100 (OR=0,70; IC95%, 0,53-0,92), pero no en aquellos con CAC de 1-100 o 0. Los resultados concordaron al agrupar los datos ajustados. Conclusiones: Entre los individuos sin ECVA previa, una puntuación de CAC> 100 identifica a los sujetos con mayor probabilidad de beneficiarse del tratamiento hipolipemiante, mientras que un CAC indetectable indica ausencia de beneficio (AU)


Introduction and objectives: Coronary artery calcium (CAC) score improves the accuracy of risk stratification for atherosclerotic cardiovascular disease (ASCVD) events compared with traditional cardiovascular risk factors. We evaluated the interaction of coronary atherosclerotic burden as determined by the CAC score with the prognostic benefit of lipid-lowering therapies in the primary prevention setting. Methods: We reviewed the MEDLINE, EMBASE, and Cochrane databases for studies including individuals without a previous ASCVD event who underwent CAC score assessment and for whom lipid-lowering therapy status stratified by CAC values was available. The primary outcome was ASCVD. The pooled effect of lipid-lowering therapy on outcomes stratified by CAC groups (0, 1-100,> 100) was evaluated using a random effects model. Results: Five studies (1 randomized, 2 prospective cohort, 2 retrospective) were included encompassing 35 640 individuals (female 38.1%) with a median age of 62.2 [range, 49.6-68.9] years, low-density lipoprotein cholesterol level of 128 (114-146) mg/dL, and follow-up of 4.3 (2.3-11.1) years. ASCVD occurrence increased steadily across growing CAC strata, both in patients with and without lipid-lowering therapy. Comparing patients with (34.9%) and without (65.1%) treatment exposure, lipid-lowering therapy was associated with reduced occurrence of ASCVD in patients with CAC> 100 (OR, 0.70; 95%CI, 0.53-0.92), but not in patients with CAC 1-100 or CAC 0. Results were consistent when only adjusted data were pooled. Conclusions: Among individuals without a previous ASCVD, a CAC score> 100 identifies individuals most likely to benefit from lipid-lowering therapy, while undetectable CAC suggests no treatment benefit (AU)


Assuntos
Humanos , Calcificação Vascular/tratamento farmacológico , Lipídeos/sangue , Doença da Artéria Coronariana/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Fatores de Risco
6.
Transl Psychiatry ; 12(1): 179, 2022 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-35501309

RESUMO

Subanesthetic-dose racemic (R,S)-ketamine (ketamine) produces rapid, robust, and sustained antidepressant effects in major depressive disorder (MDD) and bipolar disorder (BD) and has also been shown to effectively treat neuropathic pain, complex regional pain syndrome, and post-traumatic stress disorder (PTSD). However, to date, its mechanism of action remains unclear. Preclinical studies found that (2 R,6 R;2 S,6 S)-hydroxynorketamine (HNK), a major circulating metabolite of ketamine, elicits antidepressant effects similar to those of ketamine. To help determine how (2 R,6 R)-HNK contributes to ketamine's mechanism of action, an exploratory, targeted, metabolomic analysis was carried out on plasma and CSF of nine healthy volunteers receiving a 40-minute ketamine infusion (0.5 mg/kg). A parallel targeted metabolomic analysis in plasma, hippocampus, and hypothalamus was carried out in mice receiving either 10 mg/kg of ketamine, 10 mg/kg of (2 R,6 R)-HNK, or saline. Ketamine and (2 R,6 R)-HNK both affected multiple pathways associated with inflammatory conditions. In addition, several changes were unique to either the healthy human volunteers and/or the mouse arm of the study, indicating that different pathways may be differentially involved in ketamine's effects in mice and humans. Mechanisms of action found to consistently underlie the effects of ketamine and/or (2 R,6 R)-HNK across both the human metabolome in plasma and CSF and the mouse arm of the study included LAT1, IDO1, NAD+, the nitric oxide (NO) signaling pathway, and sphingolipid rheostat.


Assuntos
Transtorno Depressivo Maior , Ketamina , Animais , Antidepressivos/uso terapêutico , Encéfalo/metabolismo , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/metabolismo , Humanos , Ketamina/uso terapêutico , Metabolômica , Camundongos
7.
Body Image ; 41: 32-45, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35228102

RESUMO

Most body image studies assess only linear relations between predictors and outcome variables, relying on techniques such as multiple Linear Regression. These predictor variables are often validated multi-item measures that aggregate individual items into a single scale. The advent of machine learning has made it possible to apply Nonlinear Regression algorithms-such as Random Forest and Deep Neural Networks-to identify potentially complex linear and nonlinear connections between a multitude of predictors (e.g., all individual items from a scale) and outcome (output) variables. Using a national dataset, we tested the extent to which these techniques allowed us to explain a greater share of the variance in body-image outcomes (adjusted R2) than possible with Linear Regression. We examined how well the connections between body dissatisfaction and dieting behavior could be predicted from demographic factors and measures derived from objectification theory and the tripartite-influence model. In this particular case, although Random Forest analyses sometimes provided greater predictive power than Linear Regression models, the advantages were small. More generally, however, this paper demonstrates how body image researchers might harness the power of machine learning techniques to identify previously undiscovered relations among body image variables.


Assuntos
Imagem Corporal , Aprendizado de Máquina , Imagem Corporal/psicologia , Humanos , Modelos Lineares
8.
Innov Clin Neurosci ; 18(1-3): 35-38, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34150362

RESUMO

Objective: The goal was to review the impact of the COVID-19 pandemic on psychiatric drug development and clinical trials. Main Points of Discussion: Disruption of pharmaceutical industry- sponsored clinical trials for psychiatric disorders by the COVID-19 pandemic, prompted by concerns regarding the safety of trial participants and the feasibility of trial conduct, has adversely impacted psychiatric drug development. In response, psychiatry trial sites have modified clinical trials and adapted trial conduct, through the use of social distancing, personal protective equipment, laboratory testing, and remote assessments, to reduce the risks of COVID-19. We review the implications of these modifications for participant safety, safe trial conduct, and data integrity. Conclusion: Given these implications, ongoing communication and consultation are needed between trials sites, sponsors, and all other stakeholders to ensure continued progress in psychiatric drug development during the pandemic.

9.
Analyst ; 146(12): 4010-4021, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34019607

RESUMO

Here we show a new and significant application area for mass spectrometry imaging. The potential for fingerprints to reveal drug use has been widely reported, with potential applications in forensics and workplace drug testing. However, one unsolved issue is the inability to distinguish between drug administration and contamination by contact. Previous work using bulk mass spectrometry analysis has shown that this distinction can only be definitively made if the hands are washed prior to sample collection. Here, we illustrate how three mass spectrometry imaging approaches, desorption electrospray ionisation (DESI), matrix assisted laser desorption ionisation (MALDI) and time of flight secondary ion mass spectrometry (ToF-SIMS) can be used to visualise fingerprints at different pixel sizes, ranging from the whole fingerprint down to the pore structure. We show how each of these magnification scales can be used to distinguish between cocaine use and contact. We also demonstrate the first application of water cluster SIMS to a fingerprint sample, which was the sole method tested here that was capable of detecting excreted drug metabolites in fingerprints, while providing spatial resolution sufficient to resolve individual pore structure. We show that after administration of cocaine, lipids and salts in the fingerprint ridges spatially correlate with the cocaine metabolite, benzoylecgonine. In contrast after contact, we have observed that cocaine and its metabolite show a poor spatial correlation with the flow of the ridges.


Assuntos
Cocaína , Lipídeos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectrometria de Massa de Íon Secundário , Detecção do Abuso de Substâncias
11.
J Intern Med ; 289(2): 179-192, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32686253

RESUMO

BACKGROUND: Pro-protein convertase subtilisin/kexin 9 (PCSK9) is a proenzyme primarily known to regulate low-density lipoprotein receptor re-uptake on hepatocytes. Whether PCSK9 can concurrently trigger inflammation or not remains unclear. Here, we investigated the potential association between circulating levels of PCSK9 and mortality in patients with severe sepsis or septic shock. METHODS: Plasma PCSK9 levels at days 1, 2 and 7 were measured in 958 patients with severe sepsis or septic shock previously enrolled in the Albumin Italian Outcome Sepsis (ALBIOS) trial. Correlations between levels of PCSK9 and pentraxin 3 (PTX3), a biomarker of disease severity, were evaluated with ranked Spearman's coefficients. Cox proportional hazards models were used to assess the association of PCSK9 levels at day 1 with 28- and 90-day mortality. RESULTS: Median plasma PCSK9 levels were 278 [182-452] ng mL-1 on day 1. PCSK9 correlated positively with PTX3 at the three time-points, and patients with septic shock within the first quartile of PCSK9 showed higher levels of PTX3. Similar mortality rates were observed in patients with severe sepsis across PCSK9 quartiles. Patients with septic shock with lower PCSK9 levels on day 1 (within the first quartile) showed the highest 28- and 90-day mortality rate as compared to other quartiles. CONCLUSION: In our sub-analysis of the ALBIOS trial, we found that patients with septic shock presenting with lower plasma PCSK9 levels experienced higher mortality rate. Further studies are warranted to better evaluate the pathophysiological role of PCSK9 in sepsis.


Assuntos
Pró-Proteína Convertase 9/sangue , Choque Séptico/mortalidade , Idoso , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Sepse/mortalidade , Sepse/terapia , Componente Amiloide P Sérico/metabolismo , Choque Séptico/terapia
12.
J Psychiatr Res ; 130: 280-285, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32861983

RESUMO

Ketamine has rapid-acting antidepressant properties but also potentially concerning transient dissociative side effects (SEs). Recent studies noted a positive correlation between treatment response to ketamine and general dissociative SEs, as well as "floating", a depersonalization SE (a subtype of the dissociative SEs). This analysis sought to determine whether floating mediates treatment response to ketamine. Data were pooled from three double-blind, crossover, placebo-controlled ketamine clinical trials across which 82 participants with treatment-resistant depression (TRD) (44 with bipolar depression and 38 with major depressive disorder) received placebo and ketamine (0.5 mg/kg) infusions. SEs were actively solicited in a standardized fashion before and after ketamine infusion. The hypothesis that a post-infusion experience of floating would mediate antidepressant response to ketamine was assessed at 230 min post-infusion and at Day 1. Montgomery-Asberg Depression Rating Scale (MADRS) total score was the dependent variable in a linear mixed effects model. Ketamine significantly decreased MADRS scores (p < 0.0001), but no relationship was detected between floating and MADRS score at either 230 min or Day 1 post-infusion. The hypothesized mediation effect of floating was also not detected at either 230 min or Day 1 post-infusion. Taken together, the findings do not support the hypothesis that ketamine's antidepressant effects are mediated by the dissociative depersonalization subtype SE of floating.


Assuntos
Transtorno Depressivo Maior , Transtorno Depressivo Resistente a Tratamento , Ketamina , Depressão , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Método Duplo-Cego , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
13.
Clin Transl Oncol ; 22(9): 1603-1610, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32048158

RESUMO

PURPOSE: Since the role of resistin was evaluated only in patients with non-small cell lung cancer (NSCLC) not treated with immunotherapy, we aimed to evaluate levels of resistin during immunotherapy (nivolumab) and its prognostic role with regard to OS. METHODS/PATIENTS: From a cohort of 78 patients with advanced NSCLC enrolled in a prospective study at Ospedale Policlinico San Martino in Genoa (Italy), 43 patients have been considered for this sub-analysis because of the availability of samples. Before and during nivolumab administration, clinical information and blood samples were collected and resistin, matrix metalloproteinase (MMP)-8, MMP-9, and myeloperoxidase were evaluated by enzyme-linked immunosorbent assay (ELISA). RESULTS: Median age was 71 with a prevalence of males and former smokers. Median resistin levels presented a peak at cycle 2 and then dropped down until the last cycle. Resistin correlated with all neutrophil degranulation products at cycle 1 (except for MMP-9) and at cycle 2 as well as with white blood cells and neutrophils. By a ROC curve analysis, a resistin value at cycle 2 of 19 ng/mL was tested as the best cut-off point for OS. Kaplan-Meier analysis demonstrated that patients above the resistin cut-off experienced a reduced OS (median OS 242.5 vs. 470 days, p = 0.0073), as confirmed by Cox proportional hazards regression analysis. CONCLUSIONS: Resistin levels > 19 ng/mL at the time of the second cycle of nivolumab treatment independently predict a reduced OS in patients with advanced NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/sangue , Neoplasias Pulmonares/sangue , Nivolumabe/uso terapêutico , Resistina/sangue , Idoso , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Neutrófilos/citologia , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Resultado do Tratamento
14.
Cancer Epidemiol ; 64: 101665, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31911395

RESUMO

BACKGROUND: Progression free survival (PFS) and tumour response (TR) have been investigated as surrogate endpoints for overall survival (OS) in advanced colorectal cancer (aCRC), however their validity has been shown to be suboptimal. In recent years, meta-analytic methods allowing for use of multiple surrogate endpoints jointly have been proposed. Our aim was to assess if PFS and TR used jointly as surrogate endpoints to OS improve their predictive value. METHODS: Data were obtained from a systematic review of randomised controlled trials investigating effectiveness of pharmacological therapies in aCRC, including systemic chemotherapies, anti-epidermal growth factor receptor therapies and anti-angiogenic agents. Multivariate meta-analysis was used to model the association patterns between treatment effects on the surrogate endpoints (TR, PFS) and the final outcome (OS). RESULTS: Analysis of 33 trials reporting treatment effects on all three outcomes showed reasonably strong association between treatment effects on PFS and OS, however the association parameters were obtained with a large uncertainty. A weak surrogate relationship was noted between the treatment effects on TR and OS. Modelling the two surrogate endpoints, TR and PFS, jointly as predictors of treatment effect on OS gave no marked improvement to surrogate association patterns. Modest improvement in the precision of the predicted treatment effects on the final outcome was noted in studies investigating anti-angiogenic therapy, however it was likely due to chance. CONCLUSION: The joint use of two surrogate endpoints did not lead to marked improvement in the association between treatment effects on surrogate and final endpoints in advanced colorectal cancer.


Assuntos
Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/terapia , Biomarcadores , Humanos , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de Sobrevida , Revisões Sistemáticas como Assunto , Resultado do Tratamento
15.
J Affect Disord ; 263: 568-575, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31791675

RESUMO

BACKGROUND: Concerns about ketamine for treating depression include abuse potential and the occurrence of psychotomimetic effects. This study sought to comprehensively assess side effects (SEs) associated with a single subanesthetic-dose intravenous ketamine infusion. A secondary aim was to examine the relationship between Clinician-Administered Dissociative States Scale (CADSS) scores and dissociative symptoms reported on a comprehensive, clinician-administered SE questionnaire. METHODS: Data from 188 participants were pooled from four placebo-controlled, crossover ketamine trials and one open-label study (n = 163 with either treatment-resistant major depressive disorder or bipolar disorder and 25 healthy controls). SEs were actively solicited in a standardized fashion and monitored over the time-course of each study. Statistical analyses assessed the effect of drug (ketamine, placebo) on SEs and measured the relationship between CADSS total score and SEs contemporaneously endorsed during structured interviews. RESULTS: Forty-four of 120 SEs occurred in at least 5% of participants over all trials. Thirty-three of these 44 SEs were significantly associated with active drug administration (versus placebo). The most common SE was feeling strange/weird/loopy. Most SEs peaked within an hour of ketamine administration and resolved completely by two hours post-infusion. No serious drug-related adverse events or increased ketamine craving/abuse post-administration were observed. A positive correlation was found between dissociative SEs and total CADSS score. LIMITATIONS: The post-hoc nature of the analysis; the limited generalizability of a single subanesthetic-dose ketamine infusion; and the lack of formal measures to assess ketamine's cognitive, urological, or addictive potential. CONCLUSIONS: No long-lasting significant SEs occurred over the approximately three-month follow-up period.


Assuntos
Transtorno Depressivo Maior , Transtorno Depressivo Resistente a Tratamento , Ketamina , Antidepressivos/efeitos adversos , Depressão , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Humanos , Ketamina/efeitos adversos
17.
Sleep Breath ; 23(1): 287-291, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29948858

RESUMO

PURPOSE: Adaptive servo-ventilation (ASV) is a ventilator algorithm able to correct breathing through anticyclic support of breathing in patients with central sleep apnea (CSA). So far, very few data exist regarding the role of ASV on acute heart failure with preserved ejection fraction (HFpEF). METHODS: We performed a single-center prospective, randomized, case-control study in consecutive acute HFpEF (left ventricle ejection fraction, LVEF ≥ 45%) patients with sleep-disordered breathing (SDB, apnea-hypopnea index, AHI > 15/h) and prevalence of CSA. RESULTS: We included ten consecutive patients randomized for ASV on top of standard therapy for acute heart failure (group 1) versus standard care alone (group 2). ASV therapy significantly reduced AHI and CSA. An improvement in cardiac diastolic function was seen in group 1 compared to group 2 (E/E' 17.5 to 9.6, p < 0.02 vs 18.5 to 14.5, p = 0.4). Brain natriuretic peptide (BNP) markedly decreased in cases, but not in controls (298 to 84 pg/ml, p < 0.02 vs 280 to 120 pg/ml, p = 0.06). Right ventricle (RV) function significantly improved in group 1, differently from group 2. CONCLUSIONS: An acute use of ASV seems effective in reducing BNP and improving diastolic and RV function in acute HFpEF patients with SDB and CSA, compared to standard treatment.


Assuntos
Pressão Positiva Contínua nas Vias Aéreas/métodos , Diástole/fisiologia , Insuficiência Cardíaca/terapia , Peptídeo Natriurético Encefálico/sangue , Síndromes da Apneia do Sono/terapia , Apneia do Sono Tipo Central/terapia , Volume Sistólico/fisiologia , Doença Aguda , Idoso , Estudos de Casos e Controles , Comorbidade , Ecocardiografia , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Síndromes da Apneia do Sono/fisiopatologia , Apneia do Sono Tipo Central/fisiopatologia , Função Ventricular Direita/fisiologia
18.
Chemosphere ; 210: 52-56, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29986223

RESUMO

Unlike the well-known simplified molecular input-line entry system (SMILES), the so-called quasi-SMILES contains information related to physicochemical and biochemical conditions by a special additional symbols (codes), each standing for different conditions (time exposure, concentration, type of cell, etc.). Thus, quasi-SMILES can be used to build up models for cytotoxicity of functionalized nanozeolites using a mathematical function of eclectic information. These calculations were done with the Monte Carlo CORAL software. The statistical quality of models based on quasi-SMILES was usually considerably better than the statistical quality of models based on traditional SMILES.


Assuntos
Citotoxinas/química , Relação Quantitativa Estrutura-Atividade , Zeolitas/química , Modelos Moleculares , Método de Monte Carlo , Nanopartículas/química , Software
19.
Schizophr Res ; 197: 557-561, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29510926

RESUMO

BACKGROUND: Untangling catatonia and delirium can be challenging. Furthermore, treatment of one syndrome can potentially worsen another. CASE PRESENTATION: We present the case of a 71-year-old patient with a history of schizoaffective disorder, bipolar subtype, who developed catatonia and delirium with prominent psychotic symptoms, during a single hospitalization. Treatment of this patient's catatonia with benzodiazepines exacerbated delirium, while treatment of psychotic symptoms precipitated by delirium with antipsychotics led to catatonia. Catatonia and psychotic symptoms were eventually successfully managed with electroconvulsive therapy (ECT). DISCUSSION: This case report highlights some of the treatment challenges faced when delirium and catatonia overlap in a medically ill patient. The use of benzodiazepines, valproic acid, antipsychotics, ECT and alternate medications to treat catatonia are also discussed.


Assuntos
Catatonia/terapia , Delírio/terapia , Transtornos Psicóticos/terapia , Idoso , Antipsicóticos/efeitos adversos , Benzodiazepinas/efeitos adversos , Catatonia/tratamento farmacológico , Delírio/tratamento farmacológico , Eletroconvulsoterapia , Humanos , Masculino , Transtornos Psicóticos/tratamento farmacológico
20.
Scand J Med Sci Sports ; 27(11): 1411-1416, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27747933

RESUMO

Athletes may have electrocardiogram (ECG) repolarization abnormalities during stress test suggestive for ischemia in the absence of ischemic coronary artery disease, often in a setting of myocardial septum hypertrophy. Global longitudinal strain (GLS) might be altered in these athletes compared to hypertensive patients with the same degree of septal thickness. About 735 consecutive athletes were screened for mandatory assessment of fitness to participate in competitive sports. At the stress test, 23 (19 M, 4 F) were found to have ECG repolarization abnormalities suggestive for ischemia in the presence of normal coronary vessels. They were matched to a control group of 23 hypertensive patients with no ECG abnormalities during stress test and the same degree of septal thickness. A transthoracic echocardiography for evaluation of global longitudinal strain (GLS) was performed. Interventricular septum thickness (IST) and relative wall thickness (RWT) were also calculated. A preserved ventricular function was seen in both groups (64 ± 8% in cases vs 60 ± 6% in controls, P = 0.42). IST and RWT were not significantly different. GLS was significantly lower in athletes vs hypertensive patients (-18.7 ± 2.5 vs -21.67 ± 0.27, P = 0.001). In athletes with septal hypertrophy and a positive stress test not associated to coronary disease, GLS is lower with respect to a population of hypertensive patient with the same degree of septal hypertrophy. Further investigations in a larger population are required to better define the potentiality of GLS in differentiating pathological vs physiological septum hypertrophy.


Assuntos
Septos Cardíacos/patologia , Hipertensão/fisiopatologia , Miocárdio/patologia , Aptidão Física , Adulto , Atletas , Ecocardiografia , Teste de Esforço , Feminino , Coração/diagnóstico por imagem , Septos Cardíacos/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...