Longitudinal change of inhibitory control functional connectivity associated with the development of heavy alcohol drinking.

Introduction: Heavy drinking (HD) prevalent pattern of alcohol consumption among adolescents, particularly concerning because of their critical vulnerability to the neurotoxic effects of ethanol. Adolescent neurodevelopment is characterized by critical neurobiological changes of the prefrontal, temporal and parietal regions, important for the development of executive control processes, such as inhibitory control (IC). In the present Magnetoencephalography (MEG) study, we aimed to describe the relationship between electrophysiological Functional Connectivity (FC) during an IC task and HD development, as well as its impact on functional neuromaturation. Methods: We performed a two-year longitudinal protocol with two stages. In the first stage, before the onset of HD, we recorded brain electrophysiological activity from a sample of 67 adolescents (mean age = 14.6 ± 0.7) during an IC task. Alcohol consumption was measured using the AUDIT test and a semi-structured interview. Two years later, in the second stage, 32 of the 67 participants (mean age 16.7 ± 0.7) completed a similar protocol. As for the analysis in the first stage, the source-space FC matrix was calculated, and then, using a cluster-based permutation test (CBPT) based on Spearman's correlation, we calculated the correlation between the FC of each cortical source and the number of standard alcohol units consumed two years later. For the analysis of longitudinal change, we followed a similar approach. We calculated the symmetrized percentage change (SPC) between FC at both stages and performed a CBPT analysis, analyzing the correlation between FC change and the level of alcohol consumed in a regular session. Results: The results revealed an association between higher beta-band FC in the prefrontal and temporal regions and higher consumption years later. Longitudinal results showed that greater future alcohol consumption was associated with an exacerbated reduction in the FC of the same areas. Discussion: These results underline the existence of several brain functional differences prior to alcohol misuse and their impact on functional neuromaturation.

Mediation role of cardiorespiratory fitness on the association between fatness and cardiometabolic risk in European adolescents: The HELENA study.

PURPOSE: This study was aimed to analyze the mediation role of cardiorespiratory fitness (CRF) on the association between fatness and cardiometabolic risk scores (CMRs) in European adolescents. METHODS: A cross-sectional study was conducted in adolescents (n = 525; 46% boys; 14.1 ± 1.1 years old, mean ± SD) from 10 European cities involved in the Healthy Lifestyle in Europe by Nutrition in Adolescence study. CRF was measured by means of the shuttle run test, while fatness measures included body mass index (BMI), waist to height ratio, and fat mass index estimated from skinfold thicknesses. A clustered CMRs was computed by summing the standardized values of homeostasis model assessment, systolic blood pressure, triglycerides, total cholesterol/high-density lipoprotein cholesterol ratio, and leptin. RESULTS: Linear regression models indicated that CRF acted as an important and partial mediator in the association between fatness and CMRs in 12-17-year-old adolescents (for BMI: coefficients of the indirect role ß = 0.058 (95% confidence interval (95%CI): 0.023-0.101), Sobel test z = 3.11 (10.0% mediation); for waist to height ratio: ß = 4.279 (95%CI: 2.242-7.059), z =3.86 (11.5% mediation); and for fat mass index: ß = 0.060 (95%CI: 0.020-0.106), z = 2.85 (9.4% mediation); all p < 0.01). CONCLUSION: In adolescents, the association between fatness and CMRs could be partially decreased with improvements to fitness levels; therefore, CRF contribution both in the clinical field and public health could be important to consider and promote in adolescents independently of their fatness levels.

Abnormal organization of inhibitory control functional networks in future binge drinkers.

BACKGROUND AND AIMS: Adolescent Binge drinking has become an increasing health and social concern, which cause several detrimental consequences for brain integrity. However, research on neurophysiological traits of vulnerability for binge drinking predisposition is limited at this time. In this work, we conducted a two-year longitudinal study with magnetoencephalography (MEG) over a cohort of initially alcohol-naive adolescents with the purpose of characterize inhibitory cortical networks' anomalies prior to alcohol consumption onset in those youths who will transit into binge drinkers years later. METHODS: Sixty-seven participant's inhibitory functional networks, and dysexecutive/impulsivity traits were measured by means of inhibitory task (go/no-go) and questionnaires battery. After a follow-up period of two years, we evaluated their alcohol consumption habits, sub-dividing them in two groups according to their alcohol intake patterns: future binge drinkers (fBD): n = 22; future Light/non-drinkers (fLD): n = 17. We evaluated whole-brain and seed-based functional connectivity profiles, as well as its correlation with impulsive and dysexecutive behaviours, searching for early abnormalities before consumption onset. RESULTS: For the first time, abnormalities in MEG functional networks and higher dysexecutive and impulsivity profiles were detected in alcohol-naïve adolescents who two years later became binge drinkers. Concretely, fBD exhibit a distinctive pattern of beta band hyperconnectivity among crucial regions of inhibitory control networks, positively correlated with behavioral traits and future alcohol intake rate. CONCLUSIONS: These findings strongly support the idea of early neurobiological vulnerabilities for substances consumption initiation, with inhibitory functional networks' abnormalities as a relevant neurophysiological marker of subjects at risk- we hypothesize this profile is due to neurodevelopmental and neurobiological differences involving cognitive control networks and neurotransmission pathways.

Alcohol Binge Drinking and Executive Functioning during Adolescent Brain Development.

Alcohol consumption in adolescents causes negative effects on familiar, social, academic life, as well as neurocognitive alterations. The binge drinking (BD) pattern of alcohol is characterized by the alternation of episodes of heavy drinking in a short interval of time, and periods of abstinence, a practice that can result in important brain alterations; even more than regular alcohol consumption. The prefrontal cortex, which acts as neural support for the executive processes, is particularly affected by alcohol; however, not all studies are in agreement about how BD alcohol consumption affects executive functioning. Some research has found that alcohol consumption in adolescence does not significantly affect executive functioning while others found it does. It is possible that these discrepancies could be due to the history of alcohol consumption, that is, at what age the subjects started drinking. The aim of our study is to assess the performance on executive functioning tasks of 13-19-year-old adolescents according to their pattern of alcohol consumption. We hypothesize that BD adolescents will perform worse than non-BD subjects in tasks that evaluate executive functions, and these differences will increase depending on how long they have been consuming alcohol. Three hundred and twenty-two students (48.14% females; age range 13-22 years; mean aged 16.7 ± 2.59) participated in the study; all of them had begun drinking at the age of 13 years. Participant were divided into three groups, according to their age range (13-15, 16-18, and 19-22 years) and divided according to their pattern of alcohol consumption (BD and control groups). Then, the subjects were evaluated with neuropsychological tasks that assess executive functions like working memory, inhibition, cognitive flexibility, or self-control among others. The entire sample showed a normal improvement in their executive performance, but this improvement was more stable and robust in the control group. Regarding the executive performance among age groups, control subjects only obtained better results than BDs in the 19-22-year-old range, whereas the performance was quite similar at younger ages. Considering that all the BD subjects started drinking at the same age (13 years old), it is possible that a kind of compensation mechanism exists in the adolescent brain which allows them to reach a normal performance in executive tasks. This theoretical mechanism would depend upon neuronal labor, which could lose efficacy over time with further alcohol ingestion. This process would account for the differences in neuropsychological performance, which were only observed in older students with a longer history of alcohol consumption.

Early alcohol use and psychopathological symptoms in university students.

BACKGROUND: Adolescent brain may be particularly vulnerable to alcohol.  Plus, psychopathological disorders tend to emerge in this period. Consequently, early alcohol use may increase the risk of psychopathological disorders, with time and sex-dependent effects. However, few studies have analyzed the relationship between alcohol consumption and adolescent psychopathology in the general population. The objective was to determine the association between age of onset of alcohol use and psychopathological symptoms in university students, separately for both sexes. METHOD: A cross-sectional study involving first-year university students (n = 3,696) was conducted. Symptoms were measured by the Symptom Checklist-R (SCL-90-R). The independent variable was age of first alcohol use. Dependent variables were the SCL-90-R dimensions, dichotomized. Alcohol consumption was considered a mediator variable. Data were analyzed separately for males and females. RESULTS: The findings showed that a younger age of onset is a risk factor for the following global indexes: Global Severity Index, Positive Symptom Total for females, and Positive Symptom Distress Index, for males. Alcohol consumption showed a higher mediator effect for females than for males. CONCLUSION: Early age of alcohol use is associated with increased psychopathological symptomatology in both sexes during the college freshman year. The pattern of symptomatology is different in each sex.

Executive performance and dysexecutive symptoms in binge drinking adolescents.

Alcohol is probably the most common legal drug of abuse in Western countries. The prevalence of binge drinking (BD) pattern of alcohol consumption among adolescents is a worrisome phenomenon. Adolescents and university students who practice a BD pattern have difficulty performing tasks involving prefrontal cortex functions, such as working memory, planning, attention, and decision making. The aim of the present study was to investigate the association between BD and executive functioning in adolescents. Two hundred twenty-three high-school students between 12 and 18 years old (15.19 ± 2.13) participated in our study. They were assigned to one of three groups according to their pattern of alcohol consumption: BD (subjects who consumed alcohol intensively, n = 48), MAC (subjects who consumed alcohol moderately, n = 53), and CTR (non-drinking subjects, n = 122). The students were evaluated with two groups of testing tools: a set of performance neuropsychological tests and two questionnaires of executive functioning. The results showed that the students who drank alcohol exhibited a more pronounced dysexecutive symptomatology (disinhibition, executive dysfunction, intentionality, executive memory), but they obtained better results than controls on some of the neuropsychological tests such as Spatial Location, Five Digit Tests, or Stroop Test. According to the results, we can deduce that heavy alcohol drinking in adolescents brings a certain dysfunction of prefrontal circuits. This prefrontal dysfunction is not so clearly demonstrated in the neuropsychological tests used, but it was observed in the performance of daily activities. In the Discussion section we raise issues about sociodemographic features of the sample and ecological validity of the traditional neuropsychological tests. The neurotoxic effects of BD on prefrontal cortex can be less evident throughout adolescence, but if alcohol consumption persists, the executive dysfunction would be exacerbated.

Acute and chronic ethanol intake: effects on spatial and non-spatial memory in rats.

Abusive alcohol consumption produces neuronal damage and biochemical alterations in the mammal brain followed by cognitive disturbances. In this work rats receiving chronic and acute alcohol intake were evaluated in a spontaneous delayed non-matching to sample/position test. Chronic alcohol-treated rats had free access to an aqueous ethanol solution as the only available liquid source from the postnatal day 21 to the end of experiment (postnatal day 90). Acute alcoholic animals received an injection of 2 g/kg ethanol solution once per week. Subjects were evaluated in two tests (object recognition and spatial recognition) based on the spontaneous delayed non-matching to sample or to position paradigm using delays of 1 min, 15 min and 60 min. Results showed that chronic and acute alcohol intake impairs the rats' performance in both tests. Moreover, chronic alcohol-treated rats were more altered than acute treated animals in both tasks. Our results support the idea that chronic and acute alcohol administration during postnatal development caused widespread brain damage resulting in behavioral disturbances and learning disabilities.

Post-burn hypertrophic scars are characterized by high levels of IL-1ß mRNA and protein and TNF-α type I receptors.

Post-burn hypertrophic scars are characterized by increased collagen synthesis and hyperplasia, and may be associated with erythema, pain, dysesthesia, pruritus, and skin border elevation. Although the etiopathogenesis of hypertrophic scarring remains unclear, proinflammatory and profibrogenic cytokines are known to play an important role in general skin dysfunction. This study assessed mRNA expression, proteins, and type I receptors of tumor necrosis factor-alpha (TNF-α) and interleukin 1-beta (IL-1ß) in normal skin, normotrophic and post-burn hypertrophic scars. Skin biopsies were obtained from 10 hypertrophic and 9 normotrophic scars, and 4 normal skin sites. Only post-burn scars covering more than 10% of the body were included. Ex vivo histopathological analysis evaluated scar maturity, in situ hybridization assessed mRNA expression, and cytokine protein and cytokine/cell colocalization were performed using single- and double-label immunohistochemistry, respectively. IL-1ß is overexpressed in hypertrophic scars at the post-transcriptional level, associated primarily with keratinocytes and CD1a(+) cells. Type I receptors for TNF-α are overexpressed in blood vessels of hypertrophic scars. The coordinated overexpression of IL-1ß and TNF-α type I receptor may maintain the fibrogenic phenotypes of hypertrophic scars, even those in "remission".

Weekend alcoholism in youth and neurocognitive aging.

Numerous studies have shown that alcohol intake causes neuropsychological disorders that affect various brain structures. The «premature ageing¼ hypothesis proposes that the brain areas of alcoholics undergo deterioration similar to that observed in old age. We investigated whether alcohol abuse by young people (binge drinking) causes alterations comparable to some found in elderly people. Ninety-one people were divided into four groups: a) young people who abused alcohol; b) young people who drank alcohol in moderation; c) young people who did not drink alcohol; and d) elderly adults without any significant cognitive deterioration. All of them were assessed with a neuropsychological battery. We observed some similarities in the results obtained by young drinkers and the elderly participants, which would provide some support for the hypothesis of premature aging. The tasks that young drinkers performed worse were those related to executive functions, in which the prefrontal cortex plays an essential role. We also found differences between the two groups of young drinkers (moderate and high consumption), which leads us to believe that the amount of alcohol consumed and the pattern of consumption are factors to consider in relation to cognitive impairment.

Erroneous diagnoses in children referred with acute rheumatic fever.

We reviewed 53 patients referred to a pediatric rheumatology clinic in Asuncion, Paraguay. In 6 patients, a diagnosis of rheumatic fever was confirmed and in 47 patients other clinically significant diagnoses were made. Eighteen children had nonspecific findings and did not develop a rheumatologic condition on follow-up. Overdiagnosis of rheumatic fever can falsely inflate incidence and prevalence statistics and clinically significant diagnoses may be overlooked.

Alcohol tolerance in rats submitted to different periods of chronic and acute ethanol intake / Tolerancia al alcohol en ratas sometidas a diferentes períodos de consumo agudo y crónico de etanol

The development of tolerance to the effects of ethanol is not uniform and may vary according to the actual and previous pattern of consumption. In this experiment we assessed body temperature and the recovery of two reflexes after a high dose of ethanol in rats submitted to chronic and acute ethanol consumption. Animals were previously submitted to chronic or acute alcohol consumption from postnatal day 21 until postnatal days 56 and 84. On the testing days, the animals received a single dose of 25% ethanol (5 g/kg, i.p.) or the same amount of saline solution. The results showed that animals were affected in the day 56 to a greater extent than in the day 84 by chronic heavy consumption of ethanol solution. With moderate and acute ethanol consumption, the 56-day-old animals developed greater tolerance. However, tolerance was not developed for the motor-impairing effects, since all groups required a long time to recover reflexes (AU)

El desarrollo de tolerancia a los efectos del alcohol no es uniforme, y suele variar según el patrón de consumo previo y actual. En este trabajo se evaluó la temperatura corporal y el tiempo de recuperación de dos reflejos tras el consumo crónico y agudo de elevadas dosis de etanol. Previamente, los animales bebieron alcohol de forma crónica o aguda desde los 21 hasta los 56 y 84 días de edad. Durante los días de evaluación, los animales recibieron una única dosis de etanol al 25% (5 g/kg, i.p.), o la misma cantidad de solución salina. Los resultados mostraron una mayor afectación a los 56 días de consumo crónico elevado de etanol respecto a los 84 días. Con un consumo moderado o agudo de etanol, los animales de 56 días desarrollaron una mayor tolerancia. Sin embargo, esta tolerancia no se observó en cuanto a los déficits motores, dado que todos los grupos necesitaron un largo período de tiempo para recuperar los reflejos (AU)

Chronic ethanol intake and object recognition in young and adult rats.

Alcoholism is one of the most important problems today. Chronic alcohol intake produces many cognitive deficits in humans, especially in memory. To evaluate the memory deficits in alcoholism it is very common to use animal models. In the present work, rats receiving chronic alcohol intake and not submitted to withdrawal were evaluated in a spontaneous delayed nonmatching-to-sample test (EDNMS). Ninety-six male Wistar rats, 90 and 180 days old, were used in the experiment. Alcohol-treated rats (ALCY and ALCA) had free access to an aqueous ethanol solution as the only available liquid source from 21 days of age to the end of experiment for both groups (90 and 180 days). Animals were then evaluated in a nonspatial memory test based on the paradigm EDNMS using delays of 1, 15, and 60 min. The results show that chronic alcohol intake impairs the rats' performance, both at 90 and 180 days old, in this test of object recognition when the delay interval is of 1 h. Chronic alcohol intake with no withdrawal periods produces memory deficits and these effects of alcohol begin in the early period of intake. Moreover, we may state that the paradigm of EDNMS with a delay interval of 60 min is useful to evaluate several cognitive deficits such as hippocampal-derived memory impairment.

Brain Ag-NOR activity in cholestatic rats with hepatic encephalopathy.

The serious repercussions of cholestasis in the liver and other organic systems have led to the creation of many experimental models in efforts to understand better its pathogenesis, prophylaxis and treatment. The extrahepatic cholestasis produces an encephalopathy by the deposition of neurotoxins in the brain similar to alcoholic and other hepatic encephalopathies. This work was designed to assess the effects of cholestasis and hepatic encephalopathy on argyrophilic nucleolar organiser region (Ag-NOR) activity in the hippocampus and inferotemporal cortex (INF). Twenty-eight male Wistar rats were used and the parameters evaluated were the area of nucleus, the area of Ag-NORs, the number of Ag-NORs per cell and the ratio of the area of Ag-NORs to that of the nucleus. The results show that cholestasis decreased neuronal synthetic activity significantly and affected the nuclear cytoarchitecture in the hippocampus and the INF.