Nucleus accumbens D1- and D2-expressing neurons control the balance between feeding and activity-mediated energy expenditure.

Accumulating evidence points to dysregulations of the Nucleus Accumbens (NAc) in eating disorders (ED), however its precise contribution to ED symptomatic dimensions remains unclear. Using chemogenetic manipulations in male mice, we found that activity of dopamine D1 receptor-expressing neurons of the NAc core subregion facilitated effort for a food reward as well as voluntary exercise, but decreased food intake, while D2-expressing neurons have opposite effects. These effects are congruent with D2-neurons being more active than D1-neurons during feeding while it is the opposite during running. Chronic manipulations of each subpopulations had limited effects on energy balance. However, repeated activation of D1-neurons combined with inhibition of D2-neurons biased behavior toward activity-related energy expenditure, whilst the opposite manipulations favored energy intake. Strikingly, concomitant activation of D1-neurons and inhibition of D2-neurons precipitated weight loss in anorexia models. These results suggest that dysregulations of NAc dopaminoceptive neurons might be at the core of EDs.

What causes obesity in children and adolescents?

OBJECTIVE: To present the different aspects that may be involved in the genesis and maintenance of obesity in children and adolescents. DATA SOURCE: Narrative review of articles published in the PubMed, Scielo, Lilacs, Scopus and Google Scholar databases, using the search terms: overweight, obesity, pre-conception, prenatal, infants, schoolchildren, children, and adolescents. The search was conducted in studies written in Portuguese, English and Spanish, including narrative, integrative or systematic reviews, meta-analyses, cross-sectional, case-control and cohort studies, published between 2003 and 2023. DATA SYNTHESIS: A total of 598 studies were initially screened and 60 of them, which showed the main biopsychosocial aspects related to greater risks of excessive adiposity in the pediatric age, were included in the review. The data were presented taking into account the incidence of risk factors and their consequences in six periods: pre-conception, pre-natal, infant, preschool, school age, and adolescence. CONCLUSIONS: The causal factors described in the scientific literature that have been shown to be related to obesity in childhood and adolescence are presented.

Clinical Evolution of Preschool Picky Eater Children Receiving Oral Nutritional Supplementation during Six Months: A Prospective Controlled Clinical Trial.

OBJECTIVE: To determine if oral nutritional supplementation of picky eater children has a beneficial effect in addition to nutritional guidance on anthropometric parameters, nutrient intake, appetite, physical activity, and health complications. METHODS: This is a randomized, single-blind, controlled clinical trial that included Brazilian picky eater children aged 24 to 60 months. The individuals were randomized into a control group (CG) (n = 17) and an intervention group (IG) (n = 18), and were followed up in seven meetings for 180 days (baseline plus one meeting every 30 days). The CG received nutritional guidance for food selectivity, while the IG received the same guidance plus oral nutritional supplementation. Anthropometric and nutrient intake assessments were carried out, and appetite, physical activity and health complications were investigated. RESULTS: In the IG, the z-score of weight and height increased significantly over time (p < 0.05), while the body fat percentage (BFP) and BMI z-score remained unchanged. The percentage of inadequate intake of vitamins D, C and folate reduced in the IG over time compared to the CG (p < 0.05). In the IG, the score assigned by parents to the appetite scale increased over time (p < 0.05). There was no difference between the groups in the scores on the physical activity and global health scales, and in the number of health complications. CONCLUSIONS: Picky eater children that were supplemented increased their weight not by gaining fat, but due to an increase in stature, as shown by BMI z-score and BFP, that remained unchanged. Furthermore, they showed a decrease in inadequate micronutrient intake during the intervention. An improvement in appetite was also observed over time, attesting to the benefit of supplementation.

Anthropometric Indicators of Body Composition Associated With Lipid and Glycemic Profiles in Overweight Brazilian Children and Adolescents From 2008 to 2020.

Background: Anthropometric indicators have been used to predict health problems. The objective was to determine which indicators present better correlation with dyslipidemia, hyperglycemia and peripheral insulin resistance, as well as the cutoff points capable of predicting lipid and glycemic alterations in Brazilian children and adolescents. Methods: A cross-sectional study conducted with 568 overweight individuals, aged between 5 and 18 years, living in Southeast and South Brazilian regions, submitted to anthropometric and body composition evaluation by bioimpedance, in addition to fasting laboratory tests [total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), fasting glycemia, and homeostasis model assessment-insulin resistance (HOMA-IR)]. Pearson's correlation was used to evaluate the association between anthropometric indicators and serum biomarkers. The ROC curve with Youden's J index was used to suggest anthropometric cutoff points with better ability to predict or rule out lipid and glycemic changes. Results: Cutoff points obtained for the z-score of body mass index (BMI), waist circumference (WC), and waist circumference for height (WC/H) showed high specificity (52 to 87%) and low sensitivity (23 to 59%), indicating greater ability to exclude changes in HDL-c, TG, and HOMA-IR levels. Cutoff points suggested for BMI ranged from +1.86 to +2.20 z-score. WC cutoff points ranged from +1.29 to +1.72, and, for the WC/H index, from +1.21 to +1.25. It was suggested the use of the following cutoff points to rule out changes in HDL-c, TG, and HOMA-IR values in clinical practice: BMI < z-score +2 and WC/H < z-score +1.29. In body fat percentage (BFP) analyses, the cutoff point < of 34% may be able to rule out changes in HDL-c (specificity of 70%), while the cutoff point > 36.6% may be able to predict changes in the HOMA-IR index (sensitivity of 76%). Conclusion: It is not yet possible to state which anthropometric parameter has the best correlation with lipid and glycemic alterations in overweight children and adolescents. We suggest considering BMI, WC, and WC/H cutoff points together to rule out changes in HDL-c, TG, and HOMA-IR, and use the BFP cutoff point to predict changes in HOMA-IR.

COVID-19 Vaccination in Cancer Patients Older Than 70 Years Undergoing Active Treatment. Seroconversion Rate and Safety.

Patients with cancer have a high risk of intubation, intensive care unit admission, or death from the coronavirus disease (COVID-19); age and comorbidities are additional risk factors. Vaccination is effective against COVID-19; however, patients with cancer have been excluded from pivotal clinical trials for COVID-19 vaccines. Data on COVID-19 vaccination in cancer patients who are older are lacking. This observational study was conducted to evaluate the seropositivity rate and safety of a two-dose regimen of the BNT162b2 or mRNA1273 vaccine in older patients (age ≥ 70 years) with solid tumors or with hematological malignances who are undergoing active anticancer treatment or whose treatment has been terminated within 6 months of vaccination. The control group was composed of healthy volunteers that were age-matched with the patient group. The primary endpoint was the seropositivity rate, and the secondary endpoints were safety, the factors influencing seroconversion, the IgG titers of patients versus healthy volunteers, and post-vaccine COVID-19 infection between 20 March 2021 and 14 July 2021. At our Institution (Oncology and Hematology Department, Hospital of Piacenza, North Italy), 443 patients with cancer underwent a program for COVID-19 vaccination; 115 (25.95%) were older than 70 (range 71-86 years) and form the basis of this study. All 115 patients accepted the vaccination. There were 64 female patients (55.65%), 94 patients (81.74%) with solid tumors, and 21 patients (18.26%) with hematological malignances. The primary endpoint of seropositivity was observed in 75 patients (65.22%)-70.21% in patients with solid tumors and 42.86% in patients with hematological malignances-versus in 100% of patients in the control group. Of the secondary endpoints, no grade 3-4 side effects and no COVID-19 infections were reported. The factor influencing seroconversion was the type of cancer. The patients' median IgG titers were significantly lower than in the control groups. The COVID-19 vaccines BNT162b2 and mRNA1273 were effective and safe among older patients with cancer when administered in real-world conditions.

Pediatric multisystem inflammatory syndrome associated with COVID-19: urgent attention required.

OBJECTIVE: To identify epidemiological and clinical characteristics of multisystemic inflammatory syndrome associated with coronavirus infection as one of the severe forms of COVID-19 involvement in children and adolescents. METHODS: review was based on articles published in 2020 in the PubMed, Medline, Scopus, SciELO and Cochrane databases. SUMMARY: Multisystemic inflammatory syndrome is a serious clinical disorder that affects children and adolescents and is associated with the detection of previous exposure to SARS-CoV-2. It is characterized by the installation of a shock picture, with a significant increase in inflammatory markers such as presentations of Kawasaki Disease or shock syndrome related to Kawasaki Disease, or even toxic shock syndrome, with the clinical picture being characterized by fever of difficult control, rash, conjunctivitis, peripheral edema, generalized pain in the extremities and gastrointestinal symptoms. CONCLUSIONS: Although the vast majority of children with COVID-19 have mild symptoms, it is necessary to consider that some have a hyperinflammatory response. It is essential that health professionals receive information that can assist in the recognition of this clinical condition, differentiating it from other diagnoses, so that early and appropriate treatment is instituted.

Prevalence of childhood anaemia in Brazil: still a serious health problem: a systematic review and meta-analysis.

OBJECTIVE: To estimate the prevalence of anaemia in Brazilian children up to 83·9 months old. DESIGN: Systematic review and meta-analysis, using databases PubMed, Scopus, SciELO, Lilacs, Google Scholar, Periódicos Capes, Arca, Biblioteca Virtual em Saúde, Microsoft Academic Search and Cochrane Library using search terms: anaemia, prevalence, child and Brazil. PROSPERO Registration number: CRD42020208818. SETTING: Cross-sectional, cohort, case-control and intervention studies published between 2007 and 2020 were searched, excluding those who assessed children with an illness or chronic condition. The main outcome was anaemia prevalence. Random effects models based on the inverse variance method were used to estimate pooled prevalence measures. Sensitivity analyses removed studies with high contribution to overall heterogeneity. PARTICIPANTS: From 6790 first screened, 134 eligible studies were included, totalling 46 978 children aged zero to 83·9 months analysed, with adequate regions representativeness. RESULTS: Pooled prevalence of anaemia was 33 % (95 % CI 30, 35). Sensitivity analyses showed that withdrawal of studies that contributed to high heterogeneity did not influence national average prevalence. CONCLUSIONS: Childhood anaemia is still a serious public health problem in Brazil, exposing 33 % of Brazilian children to the anaemia repercussions. The main limitation of the study is the estimation of national prevalence based on local surveys, but a large number of studies were included, with representation in all regions of the country, giving strength to the results. In Brazil, more public policies are needed to promote supplementation, fortification and access to healthy eating to reduce the high level of anaemia among children.

Pediatric multisystem inflammatory syndrome associated with COVID-19: urgent attention required

SUMMARY OBJECTIVE: To identify epidemiological and clinical characteristics of multisystemic inflammatory syndrome associated with coronavirus infection as one of the severe forms of COVID-19 involvement in children and adolescents. METHODS: review was based on articles published in 2020 in the PubMed, Medline, Scopus, SciELO and Cochrane databases. SUMMARY: Multisystemic inflammatory syndrome is a serious clinical disorder that affects children and adolescents and is associated with the detection of previous exposure to SARS-CoV-2. It is characterized by the installation of a shock picture, with a significant increase in inflammatory markers such as presentations of Kawasaki Disease or shock syndrome related to Kawasaki Disease, or even toxic shock syndrome, with the clinical picture being characterized by fever of difficult control, rash, conjunctivitis, peripheral edema, generalized pain in the extremities and gastrointestinal symptoms. CONCLUSIONS: Although the vast majority of children with COVID-19 have mild symptoms, it is necessary to consider that some have a hyperinflammatory response. It is essential that health professionals receive information that can assist in the recognition of this clinical condition, differentiating it from other diagnoses, so that early and appropriate treatment is instituted.

COVID-19 and obesity in childhood and adolescence: a clinical review / COVID-19 e obesidade na infância e adolescência: uma revisão clínica

Abstract Objective: To identify factors that contribute to the increased susceptibility and severity of COVID-19 in obese children and adolescents, and its health consequences. Sources: Studies published between 2000 and 2020 in the PubMed, MEDLINE, Scopus, SciELO, and Cochrane databases. Summary of findings: Obesity is a highly prevalent comorbidity in severe cases of COVID-19 in children and adolescents; social isolation may lead to increase fat accumulation. Excessive adipose tissue, deficit in lean mass, insulin resistance, dyslipidemia, hypertension, high levels of proinflammatory cytokines, and low intake of essential nutrients are factors that compromise the functioning of organs and systems in obese individuals. These factors are associated with damage to immune, cardiovascular, respiratory, and urinary systems, along with modification of the intestinal microbiota (dysbiosis). In severe acute respiratory syndrome coronavirus 2 infection, these organic changes from obesity may increase the need for ventilatory assistance, risk of thromboembolism, reduced glomerular filtration rate, changes in the innate and adaptive immune response, and perpetuation of the chronic inflammatory response. Conclusions: The need for social isolation can have the effect of causing or worsening obesity and its comorbidities, and pediatricians need to be aware of this issue. Facing children with suspected or confirmed COVID-19, health professionals should 1) diagnose excess weight; 2) advise on health care in times of isolation; 3) screen for comorbidities, ensuring that treatment is not interrupted; 4) measure levels of immunonutrients; 5) guide the family in understanding the specifics of the situation; and 6) refer to units qualified to care for obese children and adolescents when necessary.

Resumo Objetivo: Identificar fatores que contribuem para o aumento da suscetibilidade e gravidade da COVID-19 em crianças e adolescentes obesos e suas consequências para a saúde. Fontes de dados: Estudos publicados entre 2000 e 2020 nas bases de dados PubMed, Medline, Scopus, SciELO e Cochrane. Síntese dos dados: A obesidade é uma comorbidade altamente prevalente em casos graves de COVID-19 em crianças e adolescentes e o isolamento social pode levar ao aumento do acúmulo de gordura. Tecido adiposo excessivo, déficit de massa magra, resistência à insulina, dislipidemia, hipertensão, altos níveis de citocinas pró-inflamatórias e baixa ingestão de nutrientes essenciais são fatores que comprometem o funcionamento dos órgãos e sistemas no indivíduo obeso. Esses fatores estão associados a danos nos sistemas imunológico, cardiovascular, respiratório e urinário, juntamente com a modificação da microbiota intestinal (disbiose). Na infecção por SARS-CoV-2, essas alterações orgânicas causadas pela obesidade podem aumentar a necessidade de assistência ventilatória, risco de tromboembolismo, taxa de filtração glomerular reduzida, alterações na resposta imune inata e adaptativa e perpetuação da resposta inflamatória crônica. Conclusões: A necessidade de isolamento social pode ter o efeito de causar ou agravar a obesidade e suas comorbidades e pediatras precisam estar cientes desse problema. Diante de crianças com suspeita ou confirmação de COVID-19, os profissionais de saúde devem 1) diagnosticar o excesso de peso; 2) aconselhar sobre cuidados de saúde em tempos de isolamento; 3) fazer a triagem de comorbidades, garantindo que o tratamento não seja interrompido; 4) medir os níveis de imunonutrientes; 5) orientar a família respeitando as especificidades da situação; e 6) encaminhamento a unidades qualificadas para cuidar de crianças e adolescentes obesos, quando necessário.

COVID-19 and obesity in childhood and adolescence: a clinical review.

OBJECTIVE: To identify factors that contribute to the increased susceptibility and severity of COVID-19 in obese children and adolescents, and its health consequences. SOURCES: Studies published between 2000 and 2020 in the PubMed, MEDLINE, Scopus, SciELO, and Cochrane databases. SUMMARY OF FINDINGS: Obesity is a highly prevalent comorbidity in severe cases of COVID-19 in children and adolescents; social isolation may lead to increase fat accumulation. Excessive adipose tissue, deficit in lean mass, insulin resistance, dyslipidemia, hypertension, high levels of proinflammatory cytokines, and low intake of essential nutrients are factors that compromise the functioning of organs and systems in obese individuals. These factors are associated with damage to immune, cardiovascular, respiratory, and urinary systems, along with modification of the intestinal microbiota (dysbiosis). In severe acute respiratory syndrome coronavirus 2 infection, these organic changes from obesity may increase the need for ventilatory assistance, risk of thromboembolism, reduced glomerular filtration rate, changes in the innate and adaptive immune response, and perpetuation of the chronic inflammatory response. CONCLUSIONS: The need for social isolation can have the effect of causing or worsening obesity and its comorbidities, and pediatricians need to be aware of this issue. Facing children with suspected or confirmed COVID-19, health professionals should 1) diagnose excess weight; 2) advise on health care in times of isolation; 3) screen for comorbidities, ensuring that treatment is not interrupted; 4) measure levels of immunonutrients; 5) guide the family in understanding the specifics of the situation; and 6) refer to units qualified to care for obese children and adolescents when necessary.

Causal Link between n-3 Polyunsaturated Fatty Acid Deficiency and Motivation Deficits.

Reward-processing impairment is a common symptomatic dimension of several psychiatric disorders. However, whether the underlying pathological mechanisms are common is unknown. Herein, we asked if the decrease in the n-3 polyunsaturated fatty acid (PUFA) lipid species, consistently described in these pathologies, could underlie reward-processing deficits. We show that reduced n-3 PUFA biostatus in mice leads to selective motivational impairments. Electrophysiological recordings revealed increased collateral inhibition of dopamine D2 receptor-expressing medium spiny neurons (D2-MSNs) onto dopamine D1 receptor-expressing MSNs in the nucleus accumbens, a main brain region for the modulation of motivation. Strikingly, transgenically preventing n-3 PUFA deficiency selectively in D2-expressing neurons normalizes MSN collateral inhibition and enhances motivation. These results constitute the first demonstration of a causal link between a behavioral deficit and n-3 PUFA decrease in a discrete neuronal population and suggest that lower n-3 PUFA biostatus in psychopathologies could participate in the etiology of reward-related symptoms.

The Treatment of Acute Diaphyseal Long-bones Fractures with Orthobiologics and Pharmacological Interventions for Bone Healing Enhancement: A Systematic Review of Clinical Evidence.

BACKGROUND: The healing of long bones diaphyseal fractures can be often impaired and eventually end into delayed union and non-union. A number of therapeutic strategies have been proposed in combination with surgical treatment in order to enhance the healing process, such as scaffolds, growth factors, cell therapies and systemic pharmacological treatments. Our aim was to investigate the current evidence of bone healing enhancement of acute long bone diaphyseal fractures. METHODS: A systematic review was conducted by using Pubmed/MEDLINE; Embase and Ovid databases. The combination of the search terms "long-bones; diaphyseal fracture; bone healing; growth factors; cell therapies; scaffolds; graft; bone substitutes; orthobiologics; teriparatide". RESULTS: The initial search resulted in 4156 articles of which 37 papers fulfilled the inclusion criteria and were the subject of this review. The studies included 1350 patients (837 males and 513 females) with a mean age of 65.3 years old. CONCLUSIONS: General lack of high-quality studies exists on the use of adjuvant strategies for bone healing enhancement in acute shaft fractures. Strong evidence supports the use of bone grafts, while only moderate evidence demineralized bone matrix and synthetic ceramics. Conflicting results partially supported the use of growth factors and cell therapies in acute fractures. Teriparatide showed promising results, particularly for atypical femoral fractures and periprosthetic femoral fractures.

Operant, oral alcohol self-administration: Sex differences in Sardinian alcohol-preferring rats.

Sardinian alcohol-preferring (sP) rats have been selectively bred, over almost 40 years, for high alcohol preference and consumption. sP rats have served as an animal model for more than 120 published studies. With very few exceptions, however, these studies have always employed male sP rats, and little is known about alcohol-related behaviors in female sP rats. The present study was designed to fill, at least in part, this gap. Accordingly, alcohol self-administration under the fixed ratio 4 schedule of reinforcement was compared among male, intact female, and ovariectomized female sP rats. Additionally, it was investigated whether i) estrous cycle influenced alcohol self-administration, and ii) alcohol self-administration in the three sP rat groups differed in sensitivity to pharmacological manipulation. Lever-responding for alcohol was steadily higher in male than intact and ovariectomized female sP rats; conversely, because of large sex differences in rat body weight, estimated amount of self-administered alcohol (in g/kg) did not differ among the three sP rat groups or occasionally was higher in intact female than male and ovariectomized female sP rats. Blood alcohol levels derived from self-administered alcohol i) did not differ among the three sP rat groups and ii) were positively correlated with the number of lever-responses for alcohol and the estimated amount of self-administered alcohol. Treatment with the opioid receptor antagonist, naloxone (0, 0.3, 1, and 3 mg/kg, i.p. [intraperitoneally]), and the positive allosteric modulator of the GABAB receptor, GS39783 (0, 25, 50, and 100 mg/kg, i.g. [intragastrically]), reduced alcohol self-administration with comparable potency and efficacy in the three sP rat groups. The impact of the estrous cycle on alcohol self-administration was relatively modest, limited to a tendency toward a reduction in the number of lever-responses for alcohol and the estimated amount of self-administered alcohol in estrus and metestrus. Together, these results provide the first characterization of alcohol-seeking and -taking behavior in female sP rats.

Hippocampal CB1 Receptors Control Incidental Associations.

By priming brain circuits, associations between low-salience stimuli often guide future behavioral choices through a process known as mediated or inferred learning. However, the precise neurobiological mechanisms of these incidental associations are largely unknown. Using sensory preconditioning procedures, we show that type 1 cannabinoid receptors (CB1R) in hippocampal GABAergic neurons are necessary and sufficient for mediated but not direct learning. Deletion and re-expression of CB1R in hippocampal GABAergic neurons abolishes and rescues mediated learning, respectively. Interestingly, paired presentations of low-salience sensory cues induce a specific protein synthesis-dependent enhancement of hippocampal CB1R expression and facilitate long-term synaptic plasticity at inhibitory synapses. CB1R blockade or chemogenetic manipulations of hippocampal GABAergic neurons upon preconditioning affect incidental associations, as revealed by impaired mediated learning. Thus, CB1R-dependent control of inhibitory hippocampal neurotransmission mediates incidental associations, allowing future associative inference, a fundamental process for everyday life, which is altered in major neuropsychiatric diseases. VIDEO ABSTRACT.

Comparison between male and female rats in a model of self-administration of a chocolate-flavored beverage: Behavioral and neurochemical studies.

The existence of sex differences was studied in a rat model of operant self-administration of a chocolate-flavored beverage (CFB), which possesses strong reinforcing properties and is avidly consumed by rats. Whether these differences occurred concomitantly to changes in extracellular dopamine in the dialysate obtained from the nucleus accumbens, was assessed by intracerebral microdialysis. Male, ovariectomized and intact female rats showed similar self-administration profiles, with minor differences in both acquisition and maintenance phases. Intact females self-administered larger amounts of CFB, when expressed per body weight, than males and ovariectomized females, in spite of similar values of lever-responding, latency to the first lever-response and consumption efficiency (a measure of rat's licking effectiveness) in males, ovariectomized and intact females and no difference in breakpoint value and number of lever-responses emerged when males, ovariectomized and intact females were exposed to a progressive ratio schedule of reinforcement. Intracerebral microdialysis revealed a slight but significant increase in dopamine activity in the shell of the nucleus accumbens of male rats when compared to intact female rats during CFB self-administration. The above differences may be caused by the hormonal (mainly estradiol) fluctuations that occur during the estrus cycle in intact females. Accordingly, in intact females CFB self-administration and dopamine activity were found to fluctuate across the estrus cycle, with lower parameters of CFB self-administration and lower dopamine activity in the Proestrus and Estrus phases vs. the Metestrus and Diestrus phases of the cycle.

Microinjection of baclofen and CGP7930 into the ventral tegmental area suppresses alcohol self-administration in alcohol-preferring rats.

Systemic administration of the orthosteric agonist, baclofen, and several positive allosteric modulators (PAMs) of the GABAB receptor has repeatedly been reported to decrease operant oral alcohol self-administration in rats. The aim of the present study was to evaluate the contribution of the mesolimbic dopamine system to the reducing effect of baclofen and GABAB PAMs on the reinforcing properties of alcohol. To this end, baclofen or the GABAB PAM CGP7930 were microinjected into the ventral tegmental area (VTA) of selectively bred, Sardinian alcohol-preferring (sP) rats trained to self-administer alcohol. Baclofen (0, 0.03, 0.1, and 0.3 µg) or CGP7930 (0, 5, 10, and 20 µg) were microinjected via indwelling unilateral guide cannula aiming at the left hemisphere of the VTA. Treatment with baclofen resulted in a dose-related suppression of the number of lever-responses for alcohol and the amount of self-administered alcohol. No dose of baclofen altered rat motor-performance, evaluated by the inverted screen test immediately before the self-administration session. Treatment with CGP7930 halved the number of lever-responses for alcohol and amount of self-administered alcohol, with no effect on rat motor-performance. Site-specificity was investigated testing the effect of microinjection of baclofen and CGP7930 into the left hemisphere of deep mesencephalic nucleus: compared to vehicle, neither 0.3 µg baclofen nor 20 µg CGP7930 altered lever-responding for alcohol and amount of self-administered alcohol. Collectively, the results of the present study suggest the involvement of GABAB receptors located in the VTA in the mediation of alcohol reinforcing properties in sP rats. This article is part of the "Special Issue Dedicated to Norman G. Bowery".

Anxiety-like behaviors at the end of the nocturnal period in sP rats with a "history" of unpredictable, limited access to alcohol.

Recent research found that exposure of selectively bred, Sardinian alcohol-preferring (sP) rats to multiple alcohol concentrations (10%, 20%, and 30%, v/v), under the 4-bottle "alcohol vs. water" choice regimen, in daily 1-h drinking sessions with an unpredictable time schedule, promoted high intakes of alcohol (≥2 g/kg) when the drinking session occurred over the final hours of the dark phase of the light/dark cycle. The present study investigated whether these high intakes of alcohol (a) were associated with alterations in rats' emotional state (Experiment 1) and (b) were pharmacologically manipulable (Experiment 2). In both experiments, over a period of 12 days, sP rats were initially exposed daily to a 1-h drinking session during the dark phase; time of alcohol exposure was changed each day and was unpredictable to rats. The day after this 12-day drinking phase, rats were (a) exposed to the Social Interaction (SI) test at the 1st or 12th hour of the dark phase with no alcohol available (Experiment 1) or (b) treated with the positive allosteric modulator of the GABAB receptor, GS39783 (0, 25, 50, and 100 mg/kg, intragastrically [i.g.]), and exposed to a drinking session at the 12th hour of the dark phase (Experiment 2). In Experiment 1, rats exposed to the SI test during the 12th hour spent approximately 35% less time in "social" behaviors than rats exposed to the SI test during the 1st hour. No difference in "social" behaviors was observed between alcohol-naive sP rats exposed to the SI test at the 1st and 12th hour. In Experiment 2, all doses of GS39783 selectively reduced alcohol intake. These results suggest that (a) expectation of alcohol availability likely exacerbated the anxiety-like state of sP rats and (b) the GABAB receptor is part of the neural substrate underlying these exceptionally high intakes of alcohol in sP rats.

Role of dopamine D4 receptors in copulatory behavior: Studies with selective D4 agonists and antagonists in male rats.

Dopamine influences the anticipatory and consummatory phases of sexual behavior, by acting on receptors of the D2 family (D2, D3 and D4) and in particular of the D2 subtype, although evidence for a role of D4 receptors in erectile function and copulatory behavior is also available. In order to clarify such a role of D4 receptors, the effect of selective D4 receptor agonists and antagonists on copulatory behavior of sexually potent male rats in classic copulation tests with a receptive female, was compared with that of apomorphine and haloperidol, a classic dopamine receptor agonist and antagonist, respectively. PD-168,077 (0.05-0.2mg/kg) and ABT-724 (0.01-0.04mg/kg), two selective D4 receptor agonists, given subcutaneously, improved dose-dependently copulatory behavior as shown by the decrease of mount frequency and post ejaculatory interval induced by PD-168,077, and of mount frequency, ejaculation latency, post ejaculatory and inter intromission intervals induced by ABT-724, and by the increase of ejaculation frequency and copulatory efficacy induced by both drugs. Conversely, L-745,870 (1-5mg/kg), a selective D4 receptor antagonist, given intraperitoneally, impaired dose-dependently copulatory behavior, as shown by the increase in intromission and ejaculation latencies, mount frequency, post ejaculatory interval and the decrease in ejaculation frequency and copulatory efficacy induced by this drug. L-745,870 (5mg/kg) administered before PD-168,077 (0.2mg/kg) or ABT-724 (0.04mg/kg), also abolished completely the facilitatory effects of both PD-168,077 and ABT-724 on sexual behavior. These results confirm the involvement of D4 receptors in specific aspects of male rat copulatory behavior that overlap only partially with those influenced by apomorphine and haloperidol.

Elevated reinforcing and motivational properties of alcohol at the end of the nocturnal period in sP rats.

RATIONALE: Sardinian alcohol-preferring (sP) rats displayed high sensitivity to time schedule and consumed intoxicating amounts of alcohol during the last portion of the dark phase of the light/dark cycle when exposed to daily drinking sessions of 1 h, with concurrent availability of multiple alcohol concentrations and unpredictability of time of alcohol access. OBJECTIVES: The present study investigated whether sensitivity of sP rats to time schedule extended to operant procedures of alcohol self-administration. METHODS: In experiment 1, three different alcohol solutions (10, 20, and 30%, v/v) were concurrently available under a fixed ratio 4 schedule of reinforcement and with unpredictable time schedule; water was available uncontingently. Experiments 2 and 3 assessed the sensitivity of the motivational properties of alcohol to time schedule; rats were exposed to (a) self-administration sessions under the progressive ratio (PR) schedule of reinforcement and (b) sessions of alcohol seeking under the extinction responding (ER) schedule. RESULTS: In experiment 1, number of lever responses and amount of self-administered alcohol were positively correlated with time of alcohol access during the dark phase. When the self-administration session occurred at the first and latest hours of the dark phase, the amount of self-administered alcohol averaged 0.95-1.0 and 1.55-1.65 g/kg, respectively. In experiments 2 and 3, values of breakpoint and ER for alcohol were approximately 50% higher when the sessions occurred at the last than first hour of the dark phase. CONCLUSIONS: The reinforcing and motivational properties of alcohol were sensitive to time schedule and stronger at the end of the dark phase.

Acute aortic dissection: epidemiology and outcomes.

BACKGROUND: Little epidemiological information on acute aortic dissection (AAD) is available in the literature. The objective of the present study was to determine the incidence and mortality rates of AAD in the general population and to analyze its clinical features. METHODS: Data from the Emilia-Romagna regional database of hospital admissions was analyzed. Urgent admissions with the diagnosis of dissection of the aorta, dissection of the thoracic aorta and dissection of the thoracoabdominal aorta were selected. RESULTS: Between January 2000 and December 2008, 1499 Emilia-Romagna residents were hospitalized with a diagnosis of AAD. The patients were divided into three groups: Group A, 617 patients (41.2%) surgically treated for type A AAD; Group B, 93 complicated patients (6.2%) with type B AAD treated by endovascular stent-grafting and Group C, 789 patients (52.6%) suffering from any type of AAD medically treated. The overall annual incidence rate was 4.7%/100,000 people and was higher for men than for women (6.7% vs 2.9%).Two hundred ninety-six patients (19.8%) were 80 years of age or older.The overall in-hospital mortality rate was 27.7%, with mortality rates of 21.1%, 26.9% and 33% in Groups A, B and C, respectively. CONCLUSION: The incidence of AAD is not negligible and a notable rate of patients is ultra-octogenarian. A large number of patients with AAD had no surgery or interventional treatment. The results of surgical treatment for patients with type A dissection are acceptable but the results obtained in patients with complicated type B dissection who were treated with an endoprosthesis are dismal.