Top-down projections of the prefrontal cortex to the ventral tegmental area, laterodorsal tegmental nucleus, and median raphe nucleus.

Anatomical and functional evidence suggests that the PFC is fairly unique among all cortical regions, as it not only receives input from, but also robustly projects back to mesopontine monoaminergic and cholinergic cell groups. Thus, the PFC is in position to exert a powerful top-down control over several state-setting modulatory transmitter systems that are critically involved in the domains of arousal, motivation, reward/aversion, working memory, mood regulation, and stress processing. Regarding this scenario, the origin of cortical afferents to the ventral tegmental area (VTA), laterodorsal tegmental nucleus (LDTg), and median raphe nucleus (MnR) was here compared in rats, using the retrograde tracer cholera toxin subunit b (CTb). CTb injections into VTA, LDTg, or MnR produced retrograde labeling in the cortical mantle, which was mostly confined to frontal polar, medial, orbital, and lateral PFC subdivisions, along with anterior- and mid-cingulate areas. Remarkably, in all of the three groups, retrograde labeling was densest in layer V pyramidal neurons of the infralimbic, prelimbic, medial/ventral orbital and frontal polar cortex. Moreover, a lambda-shaped region around the apex of the rostral pole of the nucleus accumbens stood out as heavily labeled, mainly after injections into the lateral VTA and LDTg. In general, retrograde PFC labeling was strongest following injections into MnR and weakest following injections into VTA. Altogether, our findings reveal a fairly similar set of prefrontal afferents to VTA, LDTg, and MnR, further supporting an eminent functional role of the PFC as a controller of major state-setting mesopontine modulatory transmitter systems.

Habenular connections with the dopaminergic and serotonergic system and their role in stress-related psychiatric disorders.

The habenula (Hb) is a phylogenetically old epithalamic structure differentiated into two nuclear complexes, the medial (MHb) and lateral habenula (LHb). After decades of search for a great unifying function, interest in the Hb resurged when it was demonstrated that LHb plays a major role in the encoding of aversive stimuli ranging from noxious stimuli to the loss of predicted rewards. Consistent with a role as an anti-reward center, aberrant LHb activity has now been identified as a key factor in the pathogenesis of major depressive disorder. Moreover, both MHb and LHb emerged as new players in the reward circuitry by primarily mediating the aversive properties of distinct drugs of abuse. Anatomically, the Hb serves as a bridge that links basal forebrain structures with monoaminergic nuclei in the mid- and hindbrain. So far, research on Hb has focused on the role of the LHb in regulating midbrain dopamine release. However, LHb/MHb are also interconnected with the dorsal (DR) and median (MnR) raphe nucleus. Hence, it is conceivable that some of the habenular functions are at least partly mediated by the complex network that links MHb/LHb with pontomesencephalic monoaminergic nuclei. Here, we summarize research about the topography and transmitter phenotype of the reciprocal connections between the LHb and ventral tegmental area-nigra complex, as well as those between the LHb and DR/MnR. Indirect MHb outputs via interpeduncular nucleus to state-setting neuromodulatory networks will also be commented. Finally, we discuss the role of specific LHb-VTA and LHb/MHb-raphe circuits in anxiety and depression.

Connections of the laterodorsal tegmental nucleus with the habenular-interpeduncular-raphe system.

The laterodorsal tegmental nucleus (LDTg) is a hindbrain cholinergic cell group thought to be involved in mechanisms of arousal and the control of midbrain dopamine cells. Nowadays, there is increasing evidence that LDTg is also engaged in mechanisms of anxiety/fear and promotion of emotional arousal under adverse conditions. Interestingly, LDTg appears to be connected with other regulators of aversive motivational states, including the lateral habenula (LHb), medial habenula (MHb), interpeduncular nucleus (IP), and median raphe nucleus (MnR). However, the circuitry between these structures has hitherto not been systematically investigated. Here, we placed injections of retrograde or anterograde tracers into LDTg, LHb, IP, and MnR. We also examined the transmitter phenotype of LDTg afferents to IP by combining retrograde tracing with immunofluorescence and in situ hybridization techniques. We found LHb inputs to LDTg mainly emerging from the medial division of the LHb (LHbM), which also receives axonal input from LDTg. The bidirectional connections between IP and LDTg displayed a lateralized organization, with LDTg inputs to IP being predominantly GABAergic or cholinergic and mainly directed to the contralateral IP. Moreover, we disclosed reciprocal LDTg connections with structures involved in the modulation of hippocampal theta rhythm including MnR, nucleus incertus, and supramammillary nucleus. Our findings indicate that the habenula is linked with LDTg either by direct reciprocal projections from/to LHbM or indirectly via the MHb-IP axis, supporting a functional role of LDTg in the regulation of aversive behaviors, and further characterizing LHb as a master controller of ascending brainstem state-setting modulatory projection systems.

Effectiveness and Safety of Contrast Cryolipolysis for Subcutaneous-Fat Reduction.

Cryolipolysis is the noninvasive treatment of localized fat through cold-induced panniculitis. The purpose of the present study was to evaluate the safety and efficacy of contrast cryolipolysis for subcutaneous-fat reduction. Contrast cryolipolysis mixes the principles of conventional cryolipolysis and periods of heating in accordance with the contrast lipocryolysis process. Twenty-one subjects aged 34 ± 9 years were treated with contrast cryolipolysis in the regions of abdomen and flanks through the Polarys® device. Anthropometry, standardized photographs, measurements with a skinfold caliper, and diagnostic ultrasounds were performed at the baseline and during follow-ups at 30, 60, and 90 days after the treatment. The safety assessments included laboratory testing and monitoring of the adverse events. The level of significance for all tests was set at P < 0.05. No significant differences in weight and body mass index were found. The waist measurements at the baseline and 30-day follow-up had significant differences, as did the measurements at the 30-day and 60-day follow-ups. The skinfold and ultrasound measurements were significantly reduced in the treated areas in all the time points compared to the baseline. The laboratory results showed no significant changes from baseline. Temporary adverse effects were resolved spontaneously. This study confirmed that contrast cryolipolysis is safe and effective in reducing the fat layer and improving body contouring.

SOCS3 expression in SF1 cells regulates adrenal differentiation and exercise performance.

Many hormones/cytokines are secreted in response to exercise and cytokine signaling may play a pivotal role in the training adaptations. To investigate the importance of cytokine signaling during vertical ladder climbing, a resistance exercise model, we produced mice lacking SOCS3 protein exclusively in steroidogenic factor-1 (SF1) cells (SF1 Socs3 KO mice). SF1 expression is found in steroidogenic cells of the adrenal cortex and gonads, as well as in neurons of the ventromedial nucleus of the hypothalamus. Histological markers of the fetal adrenal zone (or X-zone in rodents) were still present in adult males and postpartum SF1 Socs3 KO females, suggesting a previously unrecognized effect of SOCS3 on the terminal differentiation of the adrenal gland. This change led to a distinct distribution of lipid droplets along the adrenal cortex. Under basal conditions, adult SF1 Socs3 KO mice exhibited similar adrenal weight, and plasma ACTH and corticosterone concentrations. Nonetheless, SF1 Socs3 KO mice exhibited a blunted ACTH-induced corticosterone secretion. The overall metabolic responses induced by resistance training remained unaffected in SF1 Socs3 KO mice, including changes in body adiposity, glucose tolerance and energy expenditure. However, training performance and glucose control during intense resistance exercise were impaired in SF1 Socs3 KO mice. Furthermore, a reduced counter-regulatory response to 2-deoxy-d-glucose was observed in mutant mice. These findings revealed a novel participation of SOCS3 regulating several endocrine and metabolic aspects. Therefore, cytokine signaling in SF1 cells exerts an important role to sustain training performance possibly by promoting the necessary metabolic adjustments during exercise.

The lateral habenula and the serotonergic system.

The habenula (Hb) is an epithalamic structure differentiated into two nuclear complexes, medial (MHb) and lateral habenula (LHb). After decades of relative neglect, interest in the Hb resurged when it was demonstrated that LHb neurons play a key role in encoding disappointments and expectation of punishments. Consistent with such a role, the LHb has been implicated in a broad array of functions and pathologic conditions, notably in mechanisms of stress and pain, as well as in the pathophysiology of mood disorders. So far, the vast majority of research involving the LHb has focused on its role in regulating midbrain dopamine release. However, the LHb is also robustly interconnected in a reciprocal manner with a set of rostral serotonin (5-HT) nuclei. Thus, there is increasing evidence that the LHb is amply linked to the dorsal (DR) and median raphe nucleus (MnR) by a complex network of parallel topographically organized direct and indirect pathways. Here, we summarize research about the interconnections of the LHb with different subregions of the DR and MnR, as well as findings about 5-HT-dependent modulation of LHb neurons. Finally, we discuss the contribution of distinct LHb-raphe loops to stress and stress-related psychiatric disorders including anxiety and depression.

Afferent and efferent connections of the interpeduncular nucleus with special reference to circuits involving the habenula and raphe nuclei.

The habenula is an epithalamic structure differentiated into two nuclear complexes, medial (MHb) and lateral habenula (LHb). Recently, MHb together with its primary target, the interpeduncular nucleus (IP), have been identified as major players in mediating the aversive effects of nicotine. However, structures downstream of the MHb-IP axis, including the median (MnR) and caudal dorsal raphe nucleus (DRC), may contribute to the behavioral effects of nicotine. The afferent and efferent connections of the IP have hitherto not been systematically investigated with sensitive tracers. Thus, we placed injections of retrograde or anterograde tracers into different IP subdivisions or the MnR and additionally examined the transmitter phenotype of major IP and MnR afferents by combining retrograde tract tracing with immunofluorescence and in situ hybridization techniques. Besides receiving inputs from MHb and also LHb, we found that IP is reciprocally interconnected mainly with midline structures, including the MnR/DRC, nucleus incertus, supramammillary nucleus, septum, and laterodorsal tegmental nucleus. The bidirectional connections between IP and MnR proved to be primarily GABAergic. Regarding a possible topography of IP outputs, all IP subnuclei gave rise to descending projections, whereas major ascending projections, including focal projections to ventral hippocampus, ventrolateral septum, and LHb originated from the dorsocaudal IP. Our findings indicate that IP is closely associated to a distributed network of midline structures that modulate hippocampal theta activity and forms a node linking MHb and LHb with this network, and the hippocampus. Moreover, they support a cardinal role of GABAergic IP/MnR interconnections in the behavioral response to nicotine.

Amputação de membros inferiores em pacientes diabéticos ­ qual é o controle dos fatores de risco? / Lower extremity amputation in diabetic patients: what is the control of risk factors?

Introdução: Define-se pé diabético como "infecção, ulceração e ou destruição dos tecidos profundos, associados a anormalidades neurológicas e vários graus de doença vascular periférica nos membros inferiores", que é a principal causa de amputações não traumá- ticas. Este estudo objetiva identificar fatores de risco para amputação de pé diabético dos portadores de diabetes. Métodos: Trata-se de um estudo do tipo caso-controle, transversal, observacional e prospectivo, realizado através da coleta de dados por aplicação de questionário e pesquisa de outras informações no sistema de registro eletrônico de prontuários do Hospital Santa Isabel (HSI) e do Núcleo de Atenção ao Diabético (NAD) em Blumenau/SC. As variáveis analisadas nos prontuários foram: complicações microvasculares e macrovasculares, valor de HbA1c, perfil lipídico, cálculo de IMC (índice de massa corporal), realização prévia de arteriografia, presença de pulsos arteriais e classificação de Wagner. Resultados: Verificou-se que o tempo de diagnóstico da doença foi fator de risco e o HDL-C foi considerado fator protetor para o desfecho. Entre as demais variáveis, não possuir amputações prévias, neuropatia, doença vascular periférica e complicações cardiovasculares, não se consultar no NAD, não realizar arteriografia e ausência de pulsos distais bilaterais foram considerados significativos (p<0.05). Apesar da variável HbA1c não ter apresentado valor significativo, é de suma importância o seu controle. Conclusões: Através do estudo, conclui-se que os pacientes amputados apresentam maior proporção de fatores de risco não controlados. Estudos, com delineamento longitudinal e amostras maiores, são necessários para se estabelecer as correlações significativas entre essas variáveis e os desfechos de amputação de membros inferiores nos pacientes diabéticos(AU)

Introduction: Diabetic foot is defined as "infection, ulceration and/or destruction of deep tissues associated with neurological abnormalities and various degrees of peripheral vascular disease of the lower limbs", which is the leading cause of nontraumatic amputations. This study aims to identify risk factors for diabetic foot amputation in patients with diabetes. Methods: This is a case-control, cross-sectional, observational and prospective study conducted by collecting data through questionnaire administration and research on other information in the electronic registration system of medical records of Hospital Santa Isabel (HSI) and the Diabetic Care Center (NAD) in Blumenau, SC. The variables analyzed in the medical records were microvascular and macrovascular complications, HbA1c value, lipid profile, BMI (body mass index) calculation, previous performance of arteriography, presence of arterial pulses, and Wagner's classification. Results: The time of disease diagnosis was found to be a risk factor, and HDL-C was considered as a protective factor for the outcome. Among the other variables, not having previous amputations, neuropathy, peripheral vascular disease and cardiovascular complications, not consulting the NAD, not performing arteriography, and absence of bilateral distal pulses were considered as significant (p<0.05). Although the HbA1c variable did not present significant value, its control is extremely important. Conclusions: Amputee patients have a higher proportion of uncontrolled risk factors. Studies with a longitudinal design and larger samples are needed to establish significant correlations between these variables and the outcomes of lower limb amputation in diabetic patients(AU)

Reading and writing: psychoanalytical treatment in a case of paranoia.

Difficulties encountered in clinical work with psychoses require psychoanalytical approaches different from those used for treating neurosis. The authors use a clinical case of a paranoiac patient to highlight the role played by writing, drawing, and painting in the psychoanalytical treatment of psychosis. They also discuss the role of the reader-analyst in this patient's transferential process, which led to the emergence of a new subjectivity.

Sobre a situação analítica: a experiência de psicoterapia psicanalítica no hospital universitário da Unicamp / On the analytic situation: the experience of psychoanalytic psychotherapy in a university hospital

Este artigo descreve a experiência de implantação e funcionamento de um serviço ambulatorial de psicoterapia psicanalítica em um hospital universitário. Apresentam-se algumas dificuldades e alternativas para tornar possível a instalação da situação analítica em contextos clínicos muito diversos daqueles originalmente pensados por Freud, num esforço de elaboração metapsicológica do tratamento proposto. Em relação aos desafios que se colocam neste processo de fundação de uma proposta clínica, destacam-se as questões ligadas à transferência, ao setting e à direção do tratamento

Sobre a situação analítica: a experiência de psicoterapia psicanalítica no hospital universitário da Unicamp / On the analytic situation: the experience of psychoanalytic psychotherapy in a university hospital

Este artigo descreve a experiência de implantação e funcionamento de um serviço ambulatorial de psicoterapia psicanalítica em um hospital universitário. Apresentam-se algumas dificuldades e alternativas para tornar possível a instalação da situação analítica em contextos clínicos muito diversos daqueles originalmente pensados por Freud, num esforço de elaboração metapsicológica do tratamento proposto. Em relação aos desafios que se colocam neste processo de fundação de uma proposta clínica, destacam-se as questões ligadas à transferência, ao setting e à direção do tratamento(AU)