Behavioral and Transcriptional Effects of Short or Prolonged Fasting on the Memory Performances of Lymnaea stagnalis

Introduction: The Garcia effect, a solid learning paradigm, was used to investigate the molecular and behavioral effects induced by different lengths of fasting on the cognitive functions in the pond snail Lymnaea stagnalis, a valid model systemMethods: Three experimental groups were used: Moderately hungry snails, food-deprived for 1 day (D1 snails), severely hungry snails (D5 snails), fasting for 5 days, and satiated snails with ad libitum access to food (AL snails). In the Garcia effect, a single pairing of an appetitive stimulus with a heat stressor results in a learned taste-specific negative hedonic shift. D5 snails were injected with bovine insulin and D1 snails with the insulin receptor antibody (Ab). As a control group, AL snails were injected with saline. Gene expression analyses were performed by Real-time PCR in snails' central nervous system (CNS).Results: AL snails are 'average learners', D1 snails are the best performers, whereas the D5 ones do not show the Garcia effect. Severely fasting snails injected with insulin 3h before the training procedure, show the Garcia effect, whereas injecting 1-day fasting snails with insulin receptor Ab blocks their ability to express memory. The differences in memory performances are associated with changes in the expression levels of selected targets involved in neuronal plasticity, energy homeostasis, and stress response.Discussion: Our results suggest that short-term fasting creates an optimal internal state in L. stagnalis' CNS, allowing a spike in insulin release and an upregulation of genes involved in neuroplasticity. Long-term fasting, instead, upregulates genes involved in energy homeostasis and animal survival

Transcriptional effect of serotonin in the ganglia of Lymnaea stagnalis

The serotonin system (5HT) is highly conserved in both vertebrates and invertebrates, and numerous evidence supports a biological link between 5HT and numerous animal function. In the present paper we evaluated the transcriptional effects of a serotonergic stimulation on selected targets involved in 5HT signalling and neurotransmission in the central nervous system of the great pond snail Lymnaea stagnalis. Adult snails were treated acutely (6 h) or chronically (48 h) with either 5-hydroxytrypthophan (5-HTP 1mM), the immediate precursor of serotonin, fluoxetine (FLX 1μM), a selective serotonin reuptake inhibitor, or a combination of two. The central ring ganglia were dissected and used for q-PCR gene expression analysis. Transcription was strongly induced following a chronic, but not an acute, exposure to 5-HTP in the ganglia of Lymnaea. In particular, LymCREB1 and LymP2X mRNA levels were decreased following a 6 h exposure and increased in snails receiving 5-hydroxytryptophan for 48 h. Interestingly, this effect was reduced when snails were exposed chronically to both 5-HTP and FLX, suggesting a role for SERT in mediating the effect of 5-hydroxytryptophan. These data suggest that L. stagnalis is suited to unravel the complexity of the serotonin signaling pathway

Molecular changes associated with escitalopram response in a stress-based model of depression

Converging evidence points at hypothalamus-pituitary-adrenal (HPA) axis hyperactivity and neuroinflammation as important factors involved in the etiopathogenesis of major depressive disorder (MDD) and in therapeutic efficacy of antidepressants. In this study, we examined the molecular effects associated with a response to a week-long treatment with escitalopram in the chronic escape deficit (CED) model, a validated model of depression based on the induction of an escape deficit after exposure of rats to an unavoidable stress. We confirmed our previous result that a treatment with escitalopram (10 mg/kg) was effective after 7 days in reverting the stress-induced escape deficit in approximately 50% of the animals, separating responders from non-responders. Expression of markers of HPA axis functionality as well as several inflammatory mediators were evaluated in the hypothalamus, a key structure integrating signals from the neuro, immune, endocrine systems. In the hypothalamus of responder animals we observed a decrease in the expression of CRH and its receptors and an increase in GR protein in total and nuclear extracts; this effect was accompanied by a significant decrease in circulating corticosterone in the same cohort. Hypothalamic IL-1\uce\ub2 and TNF\uce\ub1 expression were increased in stressed animals, while CXCL2, IL-6, and ADAM17 mRNA levels were decreased in escitalopram treated rats regardless of the treatment response. These data suggest that efficacy of a one week treatment with escitalopram may be partially mediated by a decrease HPA axis activity, while in the hypothalamus the drug-induced effects on the expression of immune modulators did not correlate with the behavioural outcome

Acidente do trabalho por material perfurocortante em trabalhadores de enfermagem

The purpose was to conduct a survey on work accidents which occur due to sharp cutting instruments. The population studied consisted of nursing personnel who had suffered work accidents. A sample of 22 female workers was selected and the individuals were interviewed. The average age of this sample was 38 years old and there were 59.1% nursing assistants, 22.7% nurses, 9.1% nursing technicians and 9.1%nursing attendants. The highest number of accidents occurred during the month of June and most of them around 3PM. Most of the accidents reported were from the neonatal unit. The hands were the most affected parts of the body and the majority of the accidents were due to perforating instruments. When the accidents occurred, 50% were wearing gloves and 86.4% were vaccinated.Este estudio tuvo por objetivo dimensionar la frecuencia de accidentes producidos por material perforante en el personal de enfermería. El universo fueron los profesionales de enfermería que tuvieron accidentes. Fueron entrevistados 22 trabajadores, del sexo femenino, con 38 años de edad en media, siendo que el 59,1% eran auxiliares de enfermería, el 22,7% enfermeras y el 9,1% atendientes de enfermería. Junio fue el mes de mayor ocurrencia. Las 15:00 hrs, fue el horario de mayor número de accidentes. La Neonatologia fue la enfermería que presentó más accidentes. Las manos fue la área corporal más afectada (86,4%), con heridas punzantes (63,6%). Cuando sucedieron los accidentes, el 50% estaba usando guantes, y el 86,4% tenían vacuna.O objetivo foi levantar a ocorrência de acidentes do trabalho por material perfurocortante. A população foi composta pelo universo dos trabalhadores de enfermagem que se acidentaram no trabalho. Dos 22 entrevistados, de sexo feminino e idade média de 38 anos, 59,1% eram auxiliares de enfermagem, 22,7% enfermeiras, 9,1% técnicas de enfermagem e 9,1% atendentes de enfermagem. O mês de maior ocorrência foi junho. O maior número de acidentes foi às 15 horas. A Neonatologia apresentou maior número de acidentes. As áreas mais atingidas foram as mãos, com ferimentos punctórios. No momento do acidente, 50% usavam luvas e 86,4% eram vacinados

Hypothalamic expression of inflammatory mediators in an animal model of binge eating

Binge eating episodes are characterized by uncontrollable, distressing eating of a large amount of highly palatable food and represent a central feature of bingeing related eating disorders. Research suggests that inflammation plays a role in the onset and maintenance of eating-related maladaptive behavior. Markers of inflammation can be selectively altered in discrete brain region where they can directly or indirectly regulate food intake. In the present study we measured expression levels of different components of cytokine systems (IL-1, IL-6, IL-18, TNF-\uf061 and IFN-&3) and related molecules (iNOS and COX2) in the preoptic and anterior-tuberal parts of the hypothalamus of a validated animal model of binge eating. In this animal model, based on the exposure to both food restriction and frustration stress, binge-like eating behavior for highly palatable food is not shown when animals are exposed to the frustration stress during the estrus phase. We found a characteristic down-regulation of the IL-18/ IL-18 receptor system (with increased expression of the inhibitor of the pro-inflammatory cytokine IL18, IL-18BP, together with a decreased expression of the binding chain of the IL-18 receptor) and a three-fold increase in the expression of iNOS specifically in the anterior- tuberal region of the hypothalamus of animals that develop a binge-like eating behavior. Differently, when food restricted animals were stressed during the estrus phase IL-18 expression increased while iNOS expression was not significantly affected. Considering the role of this region of the hypothalamus in controlling feeding related behavior, this can be relevant in eating disorders and obesity. Our data suggest that by targeting centrally selected inflammatory markers, we may prevent that disordered eating turns into a full blown eating disorder

Hub urbano de mobilidade: o caminho da estação central de Utrecht

Área de uma Estação pode ser base de tensões espaciais entre Nó de Transporte e Lugar, mas também pode ser considerada como um ponto estratégico para estruturação urbana e transformação espacial desse território: um Hub Urbano de Mobilidade. Ele é entendido como um Lugar que interconecta simultaneamente diversas escalas urbanas e modos de transporte sem ambivalências espaciais; concentra e irradia múltiplas atividades e funções urbanas e articula as partes interessadas no processo de planejamento. Assim, este artigo investiga as relações físico-espaciais entre um Nó de Transporte e Lugar, evidencia aspectos de Desenho Urbano a partir do estudo de caso da Estação Central de Utrecht, por meio de categorias elaboradas no âmbito do Transporte e do Urbano. Os resultados indicam, por um lado, os dilemas e desafios espaciais entre Nó e Lugar, por outro, relacionam um conjunto de diretrizes projetuais voltadas para potencializar as Áreas das Estações como um Hub Urbano de Mobilidade

Disease-induced neuroinflammation and depression

Progression of major depression, a multifactorial disorder with a neuroinflammatory signature, seems to be associated with the disruption of body allostasis. High rates of comorbidity between depression and specific medical disorders, such as, stroke, chronic pain conditions, diabetes mellitus, and human immunodeficiency virus (HIV) infection, have been extensively reported. In this review, we discuss how these medical disorders may predispose an individual to develop depression by examining the impact of these disorders on some hallmarks of neuroinflammation known to be impaired in depressed patients: altered permeability of the blood brain barrier, immune cells infiltration, activated microglia, increased cytokines production, and the role of inflammasomes. In all four pathologies, blood brain barrier integrity was altered, allowing the infiltration of peripheral factors, known to activate resident microglia. Evidence indicated morphological changes in the glial population, increased levels of circulating pro-inflammatory cytokines or increased production of these mediators within the brain, all fundamental in neuroinflammation, for the four medical disorders considered. Moreover, activity of the kynurenine pathway appeared to be enhanced. With respect to the inflammasome NLRP3, a new target whose role in neuroinflammation is emerging as being important, accumulating data suggest its involvement in the pathogenesis of brain injury following stroke, chronic pain conditions, diabetes mellitus or in HIV associated immune impairment. Finally, data gathered over the last 10 years, indicate and confirm that depression, stroke, chronic pain, diabetes, and HIV infection share a combination of underlying molecular, cellular and network mechanisms leading to a general increase in the neuroinflammatory burden for the individual

Lamivudine/dolutegravir dual therapy in HIV-infected, virologically suppressed patients

Background: Little is known about the applicability of dual treatments based on integrase inhibitors. We explored the combination of lamivudine + dolutegravir as an option when switching from standard cART in virologically suppressed patients. Methods: In this prospective cohort we enrolled patients previously switched to 3TC + DTG who were 18 years or older, with no previous resistance mutations to the used drugs, having a HIV-RNA 6 months) cART. Results: Ninety-four individuals were included. They were mostly men (77.7%) with a mean age of 53 years. They presented 159 co-morbidities including cardiovascular, bone, hepatic, kidney, and CNS diseases. Because of these pathologies, they took 207 non-ARV drugs (mean 2.2 per patient). Median duration of viral suppression was 77.5 months (IQR 61). All subjects were prospectively followed up to week 24 and all remained on dual therapy during the whole period. Neither virological failure, nor viral blip was detected. The median CD4 count rose from 658 cells/mcl (IQR 403) to 724 cells/mcl (IQR 401) (P = 0.006) without a significant (P = 0.44) change in the CD4/CD8 ratio. A significant (P < 0.0001) increment of median creatinine from 0.87 mg/dl (IQR 0.34) to 0.95 mg/dl (IQR 0.29) was observed in the first 2 months but thereafter leveled on these values (1.00 mg/dl; IQR 0.35) (P = 0.111 compared to 2 months). The lipid profile slightly improved. The daily cost of cART was significantly (P < 0.0001) reduced of 6.89 euros (SD 6.10). Discussion: Switching to a dual cART regimen based on lamivudine + dolutegravir maintains virological efficacy up to week 24, and is associated to slight improvements of the immunologic and metabolic status. The strategy allows to freely using concomitant medications for associated pathologies. The dual therapy is less expensive in economic terms. Conclusion: Although still limited evidence exists, a dolutegravir-based dual therapy in combination with lamivudine shows promising results to be confirmed in larger controlled trials