Rationale, design and methodology of TESEO study: a registry of thrombosis and neoplasia of SEOM (Spanish Society of Medical Oncology).

BACKGROUND AND RATIONALE: Thromboembolic complications are a serious, preventable and common event in cancer patients that contributes to increasing morbidity and mortality. Despite increasing knowledge on cancer-associated thrombosis (CAT), there are still several aspects of diagnosis, clinical management, treatment and prognosis with uncertainties that are under-represented in randomized clinical trials. For this reason, the Spanish Society of Medical Oncology (SEOM) launched in June 2018 a registry of CAT. METHODS/DESIGN: TESEO is an ongoing prospective, non-interventional, multicentric study in consecutive cancer patients with newly diagnosed of thromboembolic event (TEE). Eligibility criteria include being > 18 years with a histologically confirmed diagnosis of cancer and a symptomatic or incidental TEE confirmed with an imaging technique in the previous month or any time after the cancer diagnosis and signing of informed consent. The study consists of two types of integrated but independent prospective registries. Regular CAT sub-registry includes information on patient's cancer´s characteristics, anticoagulant treatment provided and outcome data. Special CAT sub-registry includes variables related to special situations of CAT that comprise patients with severe kidney failure, thrombocytopenia, high risk of bleeding related to the cancer or with coexistence of bleeding and patients who receive new treatments such a targeted therapy, antiangiogenics agents and immunotherapy. The registry considers the status of the cancer and the time to assess how the prognosis is changed based on when the thrombus occurs. Some outcomes such as rethrombosis, major bleeding, tumor progression and survival will be valued in various time intervals including 1, 3, 6 and 12 months after the even in the first year; and then every 6 months until the patient's death. RESULTS: After 18 months and with 35 centers and researchers, the registry has 1128 patients. CONCLUSION: TESEO registry will provide clinical real-world evidence for prevention, treatment and complications of CAT in different scenarios that are under-represented in randomized clinical trials.

Dissociation of the effects of ethanol on memory, anxiety, and motor behavior in mice tested in the plus-maze discriminative avoidance task.

RATIONALE: Several studies have shown the amnestic effects of ethanol (ETOH). However, while memory tasks in rodents can be markedly influenced by anxiety-like behavior and motor function, ETOH induces anxiolysis and different effects on locomotion, depending on the dose. OBJECTIVE: Verify the effects of ETOH in mice tested in the plus-maze discriminative avoidance task (PMDAT) concomitantly evaluating memory, anxiety-like behavior, and motor behavior. METHODS: ETOH acutely or repeatedly treated mice were submitted to the training session in a modified elevated plus-maze with two open and two enclosed arms, aversive stimuli in one of the enclosed arms, and tested 24 h later without aversive stimuli. Learning/memory, locomotion, and anxiety-related behavior were evaluated by aversive arm exploration, number of entries in all the arms and open arms exploration, respectively. RESULTS: Acute ETOH: (1) either increased (1.2-1.8 g/kg) or decreased (3.0 g/kg) locomotion; (2) decreased anxiety levels (1.2-3.0 g/kg); and (3) induced learning deficits (1.2-3.0 g/kg) and memory deficits (0.3-3.0 g/kg). After repeated treatment, sensitization and tolerance to hyperlocomotion and anxiolysis induced by 1.8 g/kg ETOH were observed, respectively, and tolerance to the amnestic effect of 0.6 (but not 1.8) g/kg ETOH occurred. CONCLUSION: Neither the anxiolytic nor the locomotor effects of ETOH seem to be related to its amnestic effect in the PMDAT. Additionally, data give support to the effectiveness of the PMDAT in simultaneously evaluating learning, memory, anxiety-like behavior, and motor activity by different parameters. Possible relationships between the behavioral alterations found are discussed.

Effects of morphine on the plus-maze discriminative avoidance task: role of state-dependent learning.

RATIONALE: The amnesic effects of morphine may be related to its action on nociception, anxiety, or locomotion. This effect is also suggested to be related to state dependency. OBJECTIVES: The aims of this study were to verify the effects of morphine on mice tested in the plus-maze discriminative avoidance task (DAT) that uses light and noise as aversive stimuli and allows the concomitant evaluation of learning, memory, anxiety, and locomotion and also to verify the possible role of state-dependent learning in the effects of morphine. METHODS AND RESULTS: The DAT was conducted in a modified elevated plus-maze. In the training, the aversive stimuli were applied when mice entered in one of the enclosed arms, whereas in the test, no stimuli were applied. The main results showed that (1) pretraining morphine (5-20 mg/kg i.p.) induced retrieval deficits (evaluated by the time spent in the aversive arm in the test) but not acquisition deficits (evaluated by the decrease in aversive arm exploration along the training); (2) pretest morphine (5-10 but not 20 mg/kg) counteracted this deficit; (3) morphine induced hypolocomotion (decreased number of entries in the arms), irrespective of memory alterations; and (4) morphine did not alter anxiety-like behavior (evaluated by the time spent in the open arms) during the training. CONCLUSIONS: Morphine given before training induces retrieval deficits in mice tested in the DAT, and these deficits could be related to morphine-induced state-dependent learning. Neither the memory deficit induced by pretraining morphine nor the reversal of this deficit by pretest morphine seems to be related to anxiety levels or locomotor alterations.

Role of learning of open arm avoidance in the phenomenon of one-trial tolerance to the anxiolytic effect of chlordiazepoxide in mice.

A single exposure to the elevated plus-maze (EPM) test of anxiety reduces or abolishes the anxiolytic efficacy of benzodiazepines on a second trial. Some possible explanations to the occurrence of this phenomenon (one-trial tolerance-OTT) involve behavioral modifications thought to be consequence of some kind of learning in the first trial. In the present study, the influence of learning-impairing situations on the effects of the benzodiazepine chlordiazepoxide on mice re-tested in the EPM is investigated. The results showed that: (1) as expected, the administration of chlordiazepoxide to mice re-tested in the EPM- under the same conditions of the first trial- failed to induce anxiolysis; (2) a decreased percent time in the open arms was observed on the second trial of mice exposed to both trials under the same experimental conditions; (3) neither the increase in open arm avoidance by mice re-exposed to the EPM nor the OTT to chlordiazepoxide effect were modified by administration of the amnestic agent scopolamine; (4) the decrement of the duration of the first trial to 1 min or the change in light and noise conditions in both trials counteracted the increase in open arm avoidance on trial 2; (5) none of the later procedures modified the phenomenon of OTT. Although not discarding the modulation exerted by other memory processes in the OTT phenomenon, the results indicate that situations that impair the learned avoidance response to the open arms in the EPM do not modify the phenomenon of OTT.

Effects of social isolation on aging-induced orofacial movements in rats.

World population is becoming older, and aging is a common risk factor for a number of pathologies. In this respect, it is important to study possible factors that could modify alterations implicated in the process of aging. The aim of the present study is to verify the effects of social isolation on the expression of orofacial movements in adult and old rats. Adult and old rats were housed isolated for 5 days or kept in their home cages in groups of six. Before and after this period, orofacial movements and open-field general activity were evaluated. Aging-induced orofacial movements were abolished by isolation. On the other hand, isolated adult rats presented an increase in orofacial movements. General activity was decreased by aging but was not modified by isolation. Our results indicate that social isolation produces different effects in adult and old rats, and these effects are specific for orofacial movements and not related to a decrease in general motor activity.

Alcohol drinking patterns and differences in alcohol-related harm: a population-based study of the United States.

Alcohol use and associated alcohol-related harm (ARH) are a prevalent and important public health problem, with alcohol representing about 4% of the global burden of disease. A discussion of ARH secondary to alcohol consumption necessitates a consideration of the amount of alcohol consumed and the drinking pattern. This study examined the association between alcohol drinking patterns and self-reported ARH. Pearson chi-square test (χ (2)) and logistic regression analyses were used on data from the National Comorbidity Survey Replication (NCS-R). The NCS-R is a cross-sectional nationally representative sample. Data was obtained by face-to-face interviews from 9282 adults aged ≥ 18 years in the full sample, and 5,692 respondents in a subsample of the full sample. Results presented as odds ratio (OR) and 95% confidence intervals (95% CI). Alcohol drinking patterns (frequency of drinking, and drinks per occasion) were associated with increased risks of self-reported ARH; binge or "risky" drinking was strongly predictive of ARH than other categories of drinks per occasion or frequency of drinking; and men had significantly higher likelihood of ARH in relation to frequency of drinking and drinks per occasion. Findings provide evidence for public health practitioners to target alcohol prevention strategies at the entire population of drinkers.

Role of anxiety levels in memory performance of spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHR) show behavioural differences when compared to their strain-matched controls. These differences include decreased anxiety-like behaviour in SHR, while both improved performance and behavioural deficits have been reported in learning/memory studies. Considering that alterations in anxiety levels during the training session can modify retention performance in animal models of memory, the aim of the present study was to investigate the role of anxiety levels in the performance of SHR rats in the plus-maze discriminative avoidance task (PM-DAT), in which memory and anxiety are evaluated simultaneously. Adult (5-month-old) and young (45-day-old) SHR and normotensive Wistar rats (NWR) were treated with chlordiazepoxide (CDZ) or saline. Thirty minutes later, rats were submitted to the PM-DAT training session. After 24 h, the test session was performed. The results showed that: (1) adult SHR showed lower anxiety levels compared to adult NWR; (2) adult SHR and NWR, as well as young NWR, showed significant retention of the task, while young SHR showed impaired performance; (3) 5.0 mg/kg CDZ decreased anxiety levels in adult NWR and young and adult SHR; (4) 5.0 mg/kg CDZ impaired retention in adult SHR and NWR and increased retention in young SHR. Our data suggest an important role of anxiety levels in the performance of SHR in a plus-maze discriminative avoidance task.