Dopamine D1 receptor activation drives plasticity in the songbird auditory pallium.

Vocal learning species must form and extensively hone associations between sounds and social contingencies. In songbirds, dopamine signaling guides song motor-production, variability, and motivation, but it is unclear how dopamine regulates fundamental auditory associations for learning new sounds. We hypothesized that dopamine regulates learning in the auditory pallium, in part by interacting with local neuroestradiol signaling. Here, we show that zebra finch auditory neurons frequently coexpress D1 receptor (D1R) protein, neuroestradiol-synthase, GABA, and parvalbumin. Auditory classical conditioning increased neuroplasticity gene induction in D1R-positive neurons. In vitro, D1R pharmacological activation reduced the amplitude of GABAergic and glutamatergic currents and increased the latter's frequency. In vivo, D1R activation reduced the firing of putative interneurons, increased the firing of putative excitatory neurons, and made both neuronal types unable to adapt to novel stimuli. Together, these findings support the hypothesis that dopamine acting via D1Rs modulates auditory association in the songbird sensory pallium.SIGNIFICANCE STATEMENTOur key finding is that auditory forebrain D1 receptors modulate auditory plasticity, in support of the hypothesis that dopamine modulates the formation of associations between sounds and outcomes. Recent work in songbirds has identified roles for dopamine in driving reinforcement learning and motor variability in song production. This leaves open whether dopamine shapes the initial events that are critical for learning vocalizations, e.g., auditory learning. Our study begins to address this question in the songbird caudomedial nidopallium (NCM), an analogue of the mammalian secondary auditory cortex. Our findings indicate that dopamine receptors are important modulators of excitatory/inhibitory balance and sound association learning mechanisms in the NCM, a system that could be a fundamental feature of vertebrate ascending auditory pathways.

Auditory learning in an operant task with social reinforcement is dependent on neuroestrogen synthesis in the male songbird auditory cortex.

Animals continually assess their environment for cues associated with threats, competitors, allies, mates or prey, and experience is crucial for those associations. The auditory cortex is important for these computations to enable valence assignment and associative learning. The caudomedial nidopallium (NCM) is part of the songbird auditory association cortex and it is implicated in juvenile song learning, song memorization, and song perception. Like human auditory cortex, NCM is a site of action of estradiol (E2) and is enriched with the enzyme aromatase (E2-synthase). However, it is unclear how E2 modulates auditory learning and perception in the vertebrate auditory cortex. In this study we employ a novel, auditory-dependent operant task governed by social reinforcement to test the hypothesis that neuro-E2 synthesis supports auditory learning in adult male zebra finches. We show that local suppression of aromatase activity in NCM disrupts auditory association learning. By contrast, post-learning performance is unaffected by either NCM aromatase blockade or NCM pharmacological inactivation, suggesting that NCM E2 production and even NCM itself are not required for post-learning auditory discrimination or memory retrieval. Therefore, neuroestrogen synthesis in auditory cortex supports the association between sounds and behaviorally relevant consequences.

Norepinephrine enhances song responsiveness and encoding in the auditory forebrain of male zebra finches.

Norepinephrine (NE) can dynamically modulate excitability and functional connectivity of neural circuits in response to changes in external and internal states. Regulation by NE has been demonstrated extensively in mammalian sensory cortices, but whether NE-dependent modulation in sensory cortex alters response properties in downstream sensorimotor regions is less clear. Here we examine this question in male zebra finches, a songbird species with complex vocalizations and a well-defined neural network for auditory processing of those vocalizations. We test the hypothesis that NE modulates auditory processing and encoding, using paired extracellular electrophysiology recordings and pattern classifier analyses. We report that a NE infusion into the auditory cortical region NCM (caudomedial nidopallium; analogous to mammalian secondary auditory cortex) enhances the auditory responses, burst firing, and coding properties of single NCM neurons. Furthermore, we report that NE-dependent changes in NCM coding properties, but not auditory response strength, are transmitted downstream to the sensorimotor nucleus HVC. Finally, NE modulation in the NCM of males is qualitatively similar to that observed in females: in both sexes, NE increases auditory response strengths. However, we observed a sex difference in the mechanism of enhancement: whereas NE increases response strength in females by decreasing baseline firing rates, NE increases response strength in males by increasing auditory-evoked activity. Therefore, NE signaling exhibits a compensatory sex difference to achieve a similar, state-dependent enhancement in signal-to-noise ratio and coding accuracy in males and females. In summary, our results provide further evidence for adrenergic regulation of sensory processing and modulation of auditory/sensorimotor functional connectivity. NEW & NOTEWORTHY This study documents that the catecholamine norepinephrine (also known as noradrenaline) acts in the auditory cortex to shape local processing of complex sound stimuli. Moreover, it also enhances the coding accuracy of neurons in the auditory cortex as well as in the downstream sensorimotor cortex. Finally, this study shows that while the sensory-enhancing effects of norepinephrine are similar in males and females, there are sex differences in the mode of action.

Adult Neurogenesis Leads to the Functional Reconstruction of a Telencephalic Neural Circuit.

UNLABELLED: Seasonally breeding songbirds exhibit pronounced annual changes in song behavior, and in the morphology and physiology of the telencephalic neural circuit underlying production of learned song. Each breeding season, new adult-born neurons are added to the pallial nucleus HVC in response to seasonal changes in steroid hormone levels, and send long axonal projections to their target nucleus, the robust nucleus of the arcopallium (RA). We investigated the role that adult neurogenesis plays in the seasonal reconstruction of this circuit. We labeled newborn HVC neurons with BrdU, and RA-projecting HVC neurons (HVCRA) with retrograde tracer injected in RA of adult male white-crowned sparrows (Zonotrichia leucophrys gambelii) in breeding or nonbreeding conditions. We found that there were many more HVCRA neurons in breeding than nonbreeding birds. Furthermore, we observed that more newborn HVC neurons were back-filled by the tracer in breeding animals. Behaviorally, song structure degraded as the HVC-RA circuit degenerated, and recovered as the circuit regenerated, in close correlation with the number of new HVCRA neurons. These results support the hypothesis that the HVC-RA circuit degenerates in nonbreeding birds, and that newborn neurons reconstruct the circuit in breeding birds, leading to functional recovery of song behavior. SIGNIFICANCE STATEMENT: We investigated the role that adult neurogenesis plays in the seasonal reconstruction of a telencephalic neural circuit that controls song behavior in white-crowned sparrows. We showed that nonbreeding birds had a 36%-49% reduction in the number of projection neurons compared with breeding birds, and the regeneration of the circuit in the breeding season is due to the integration of adult-born projection neurons. Additionally, song structure degraded as the circuit degenerated and recovered as the circuit regenerated, in close correlation with new projection neuron number. This study demonstrates that steroid hormones can help reestablish functional neuronal circuits following degeneration in the adult brain and shows non-injury-induced degeneration and reconstruction of a neural circuit critical for producing a learned behavior.

Characterization of NADPH Diaphorase- and Doublecortin-Positive Neurons in the Lizard Hippocampal Formation.

The lizard cortex has remarkable similarities with the mammalian hippocampus. Both regions process memories, have similar cytoarchitectural properties, and are important neurogenic foci in adults. Lizards show striking levels of widespread neurogenesis in adulthood and can regenerate entire cortical areas after injury. Nitric oxide (NO) is an important regulatory factor of mammalian neurogenesis and hippocampal function. However, little is known about its role in nonmammalian neurogenesis. Here, we analyzed the distribution, morphology, and dendritic complexity (Neurolucida reconstructions) of NO-producing neurons through NADPH diaphorase (NADPHd) activity, and how they compare with the distribution of doublecortin-positive (DCX+) neurons in the hippocampal formation of the neotropical lizard Tropidurus hispidus. NADPHd-positive (NADPHd+) neurons in the dorsomedial cortex (DMC; putatively homologous to mammalian CA3) were more numerous and complex than the ones in the medial cortex (MC; putatively homologous to the dentate gyrus). We found that NADPHd+ DMC neurons send long projections into the MC. Interestingly, in the MC, NADPHd+ neurons existed in 2 patterns: small somata with low intensity of staining in the outer layer and large somata with high intensity of staining in the deep layer, a pattern similar to the mammalian cortex. Additionally, NADPHd+ neurons were absent in the granular cell layer of the MC. In contrast, DCX+ neurons were scarce in the DMC but highly numerous in the MC, particularly in the granular cell layer. We hypothesize that NO-producing neurons in the DMC provide important input to proliferating/migrating neurons in the highly neurogenic MC.

Orbitofrontal cortex modulates auditory cortical sensitivity and sound perception in Mongolian gerbils.

Sensory perception is dynamic, quickly adapting to sudden shifts in environmental or behavioral context. Although decades of work have established that these dynamics are mediated by rapid fluctuations in sensory cortical activity, we have a limited understanding of the brain regions and pathways that orchestrate these changes. Neurons in the orbitofrontal cortex (OFC) encode contextual information, and recent data suggest that some of these signals are transmitted to sensory cortices. Whether and how these signals shape sensory encoding and perceptual sensitivity remain uncertain. Here, we asked whether the OFC mediates context-dependent changes in auditory cortical sensitivity and sound perception by monitoring and manipulating OFC activity in freely moving Mongolian gerbils of both sexes under two behavioral contexts: passive sound exposure and engagement in an amplitude modulation (AM) detection task. We found that the majority of OFC neurons, including the specific subset that innervates the auditory cortex, were strongly modulated by task engagement. Pharmacological inactivation of the OFC prevented rapid context-dependent changes in auditory cortical firing and significantly impaired behavioral AM detection. Our findings suggest that contextual information from the OFC mediates rapid plasticity in the auditory cortex and facilitates the perception of behaviorally relevant sounds.

Social reinforcement guides operant behaviour and auditory learning in a songbird.

Motivation to seek social interactions is inherent to all social species. For instance, even with risk of disease transmission in a recent pandemic, humans sought out frequent in-person social interactions. In other social animals, socialization can be prioritized even over water or food consumption. Zebra finches, Taeniopygia guttata, are highly gregarious songbirds widely used in behavioural and physiological research. Songbirds, like humans, are vocal learners during development, which rely on intense auditory learning. Aside from supporting song learning, auditory learning further supports individual identification, mate choice and outcome associations in songbirds. To study auditory learning in a laboratory setting, studies often employ operant paradigms with food restriction and reinforcement and require complete social isolation, which can result in stress and other unintended physiological consequences for social species. Thus, in this work, we designed an operant behavioural method leveraging the sociality of zebra finches for goal-directed behaviours. Our approach relies on visual social reinforcement, without depriving the animals of food or social contact. Using this task, we found that visual social reinforcement was a strong motivational drive for operant behaviour. Motivation was sensitive to familiarity towards the stimulus animal and higher when engaging with a familiar versus a novel individual. We further show that this tool can be used to assess auditory discrimination learning using either songs or synthetic pure tones as stimuli. As birds gained experience in the task, they developed a strategy to maximize reward acquisition in spite of receiving more punishment, i.e. liberal response bias. Our operant paradigm provides an alternative to tasks using food reinforcement and could be applied to a variety of highly social species, such as rodents and nonhuman primates.

Acute Aromatase Inhibition Impairs Neural and Behavioral Auditory Scene Analysis in Zebra Finches.

Auditory perception can be significantly disrupted by noise. To discriminate sounds from noise, auditory scene analysis (ASA) extracts the functionally relevant sounds from acoustic input. The zebra finch communicates in noisy environments. Neurons in their secondary auditory pallial cortex (caudomedial nidopallium, NCM) can encode song from background chorus, or scenes, and this capacity may aid behavioral ASA. Furthermore, song processing is modulated by the rapid synthesis of neuroestrogens when hearing conspecific song. To examine whether neuroestrogens support neural and behavioral ASA in both sexes, we retrodialyzed fadrozole (aromatase inhibitor, FAD) and recorded in vivo awake extracellular NCM responses to songs and scenes. We found that FAD affected neural encoding of songs by decreasing responsiveness and timing reliability in inhibitory (narrow-spiking), but not in excitatory (broad-spiking) neurons. Congruently, FAD decreased neural encoding of songs in scenes for both cell types, particularly in females. Behaviorally, we trained birds using operant conditioning and tested their ability to detect songs in scenes after administering FAD orally or injected bilaterally into NCM. Oral FAD increased response bias and decreased correct rejections in females, but not in males. FAD in NCM did not affect performance. Thus, FAD in the NCM impaired neuronal ASA but that did not lead to behavioral disruption suggesting the existence of resilience or compensatory responses. Moreover, impaired performance after systemic FAD suggests involvement of other aromatase-rich networks outside the auditory pathway in ASA. This work highlights how transient estrogen synthesis disruption can modulate higher-order processing in an animal model of vocal communication.

Orbitofrontal Cortex Modulates Auditory Cortical Sensitivity and Sound Perception.

Sensory perception is dynamic, quickly adapting to sudden shifts in environmental or behavioral context. Though decades of work have established that these dynamics are mediated by rapid fluctuations in sensory cortical activity, we have a limited understanding of the brain regions and pathways that orchestrate these changes. Neurons in the orbitofrontal cortex (OFC) encode contextual information, and recent data suggest that some of these signals are transmitted to sensory cortices. Whether and how these signals shape sensory encoding and perceptual sensitivity remains uncertain. Here, we asked whether the OFC mediates context-dependent changes in auditory cortical sensitivity and sound perception by monitoring and manipulating OFC activity in freely moving animals under two behavioral contexts: passive sound exposure and engagement in an amplitude modulation (AM) detection task. We found that the majority of OFC neurons, including the specific subset that innervate the auditory cortex, were strongly modulated by task engagement. Pharmacological inactivation of the OFC prevented rapid context-dependent changes in auditory cortical firing, and significantly impaired behavioral AM detection. Our findings suggest that contextual information from the OFC mediates rapid plasticity in the auditory cortex and facilitates the perception of behaviorally relevant sounds. Significance Statement: Sensory perception depends on the context in which stimuli are presented. For example, perception is enhanced when stimuli are informative, such as when they are important to solve a task. Perceptual enhancements result from an increase in the sensitivity of sensory cortical neurons; however, we do not fully understand how such changes are initiated in the brain. Here, we tested the role of the orbitofrontal cortex (OFC) in controlling auditory cortical sensitivity and sound perception. We found that OFC neurons change their activity when animals perform a sound detection task. Inactivating OFC impairs sound detection and prevents task-dependent increases in auditory cortical sensitivity. Our findings suggest that the OFC controls contextual modulations of the auditory cortex and sound perception.

Time trends in breast cancer incidence and mortality in a mid-sized northeastern Brazilian city.

BACKGROUND: Breast cancer incidence within an area is usually proportional to the area's income level. High-income areas have shown the highest incidence rates and since 2003, negative trends. As for mortality, rates are often higher in low-income regions. The purpose of this study was to analyze trends in incidence and mortality in a capital city of a northeastern Brazilian state with an intermediate human development index. METHODS: Incidence data from the Population-Based Cancer Registry of Aracaju and mortality data from the Official State Database for the period 1996-2006 were used. Incidence and mortality crude and age-standardized rates were calculated. Time trends were obtained using the Joinpoint Regression Model. RESULTS: For the period studied, invasive breast cancer age-standardized incidence rates increased annually with an annual percentage change (APC) of 2.9 (95% CI: 1.2-4.6). Significant increasing trends were observed in groups aged 45-54 years (APC: 3.9, 95% CI: 1.4 to 6.6), and 55-64 years (APC: 5.6, 95% CI: 1.8 to 9.6). Age-standardized mortality rates did not show an increasing trend (APC: 3.0, (95% CI: -2.8 to9.1), except for the group aged 55-64 years (APC: 11.3, 95% CI: 1.1 to 22.4). CONCLUSIONS: In the study community, breast cancer showed increasing incidence among women in the peri- and postmenopausal periods. However, mortality did not present increasing overall trends, except for among the group aged 55-64 years. For better outcomes, screening policies should focus on the peri- and postmenopausal periods of women's lives to diagnose disease.

Structural organization of the cerebral cortex of the neotropical lizard Tropidurus hispidus.

Lizards belonging to the Tropiduridae family are "sit-and-wait" foragers, relying mainly on visual identification to catch prey that cross their visual fields. Little is known about the neurobiology of Tropiduridae lizards. We have used neurohistological techniques to study the structural organization of the telencephalon of the neotropical lizard Tropidurus hispidus, paying special attention to the cerebral cortex. As revealed by the Nissl technique and Golgi staining, the telencephalon of T. hispidus follows the squamate pattern, with some differences: the lateral cortex appears relatively atrophic, and most of the neuronal somata of the dorsal cortex are dispersed without forming a conspicuous cell layer. Golgi staining has revealed ten different neuronal types in the three cortical layers, based on somata shape and dendritic morphology: the granular (unipolar, bipolar, and multipolar), pyramidal (normal, inverted, open, bipyramidal, and horizontal), spherical horizontal, and fusiform neuronal types. The axon direction could be traced in five of the subtypes. We have also studied the distribution of zinc-enriched terminals in the telencephalon of T. hispidus by the Neo-Timm method. Some portions of the cortex, septum, striatum, and amygdaloid complex stain heavily, with patterns resembling those described for other lizard families. Thus, T. hispidus appears to be an interesting representative of the Tropiduridae family for further neurobiological comparative studies.

Dopamine Modulation of Motor and Sensory Cortical Plasticity among Vertebrates.

Goal-directed learning is a key contributor to evolutionary fitness in animals. The neural mechanisms that mediate learning often involve the neuromodulator dopamine. In higher order cortical regions, most of what is known about dopamine's role is derived from brain regions involved in motivation and decision-making, while significantly less is known about dopamine's potential role in motor and/or sensory brain regions to guide performance. Research on rodents and primates represents over 95% of publications in the field, while little beyond basic anatomy is known in other vertebrate groups. This significantly limits our general understanding of how dopamine signaling systems have evolved as organisms adapt to their environments. This review takes a pan-vertebrate view of the literature on the role of dopamine in motor/sensory cortical regions, highlighting, when available, research on non-mammalian vertebrates. We provide a broad perspective on dopamine function and emphasize that dopamine-induced plasticity mechanisms are widespread across all cortical systems and associated with motor and sensory adaptations. The available evidence illustrates that there is a strong anatomical basis-dopamine fibers and receptor distributions-to hypothesize that pallial dopamine effects are widespread among vertebrates. Continued research progress in non-mammalian species will be crucial to further our understanding of how the dopamine system evolved to shape the diverse array of brain structures and behaviors among the vertebrate lineage.

Genetically identified neurons in avian auditory pallium mirror core principles of their mammalian counterparts.

In vertebrates, advanced cognitive abilities are typically associated with the telencephalic pallium. In mammals, the pallium is a layered mixture of excitatory and inhibitory neuronal populations with distinct molecular, physiological, and network phenotypes. This cortical architecture is proposed to support efficient, high-level information processing. Comparative perspectives across vertebrates provide a lens to understand the common features of pallium that are important for advanced cognition. Studies in songbirds have established strikingly parallel features of neuronal types between mammalian and avian pallium. However, lack of genetic access to defined pallial cell types in non-mammalian vertebrates has hindered progress in resolving connections between molecular and physiological phenotypes. A definitive mapping of the physiology of pallial cells onto their molecular identities in birds is critical for understanding how synaptic and computational properties depend on underlying molecular phenotypes. Using viral tools to target excitatory versus inhibitory neurons in the zebra finch auditory association pallium (calmodulin-dependent kinase alpha [CaMKIIα] and glutamate decarboxylase 1 [GAD1] promoters, respectively), we systematically tested predictions derived from mammalian pallium. We identified two genetically distinct neuronal populations that exhibit profound physiological and computational similarities with mammalian excitatory and inhibitory pallial cells, definitively aligning putative cell types in avian caudal nidopallium with these molecular identities. Specifically, genetically identified CaMKIIα and GAD1 cell types in avian auditory association pallium exhibit distinct intrinsic physiological parameters, distinct auditory coding principles, and inhibitory-dependent pallial synchrony, gamma oscillations, and local suppression. The retention, or convergence, of these molecular and physiological features in both birds and mammals clarifies the characteristics of pallial circuits for advanced cognitive abilities.

Telencephalic distributions of doublecortin and glial fibrillary acidic protein suggest novel migratory pathways in adult lizards.

Adult neurogenesis has been reported in all major vertebrate taxa. However, neurogenic rates and the number of neurogenic foci vary greatly, and are higher in ancestral taxa. Our study aimed to evaluate the distribution of doublecortin (DCX) and glial fibrillary acidic protein (GFAP) in telencephalic areas of the adult tropical lizard Tropidurus hispidus. We describe evidence for four main neurogenic foci, which coincide anatomically with the ventricular sulci described by the literature. Based on neuronal morphology, we infer four migratory patterns/pathways. In the cortex, patterns of GFAP and DCX staining support radial migrations from ventricular zones into cortical areas and dorsoventricular ridge. Cells radiating from the sulcus septomedialis (SM) seemed to migrate to the medial cortex and dorsal cortex. From the sulcus lateralis (SL), they seemed to be bound for the lateral cortex, central amygdala and nucleus sphericus. We describe a DCX-positive stream originating in the caudal sulcus ventralis and seemingly bound for the olfactory bulb, resembling a rostral migratory stream. We provide evidence for a previously undescribed tangential dorso-septo-caudal migratory stream, with neuroblasts supported by DCX-positive fibers. Finally, we provide evidence for a commissural migration stream seemingly bound for the contralateral nucleus sphericus. Therefore, in addition to two previously known migratory streams, this study provides anatomical evidence in support for two novel migratory routes in amniotes.

A Membrane G-Protein-Coupled Estrogen Receptor Is Necessary but Not Sufficient for Sex Differences in Zebra Finch Auditory Coding.

Estradiol acts as a neuromodulator in brain regions important for cognition and sensory processing. Estradiol also shapes brain sex differences but rarely have these concepts been considered simultaneously. In male and female songbirds, estradiol rapidly increases within the auditory forebrain during song exposure and enhances local auditory processing. We tested whether G-protein-coupled estrogen receptor 1 (GPER1), a membrane-bound estrogen receptor, is necessary and sufficient for neuroestrogen regulation of forebrain auditory processing in male and female zebra finches (Taeniopygia guttata). At baseline, we observed that females had elevated single-neuron responses to songs vs males. In males, narrow-spiking (NS) neurons were more responsive to conspecific songs than broad-spiking (BS) neurons, yet cell types were similarly auditory responsive in females. Following acute inactivation of GPER1, auditory responsiveness and coding were suppressed in male NS yet unchanged in female NS and in BS of both sexes. By contrast, GPER1 activation did not mimic previously established estradiol actions in either sex. Lastly, the expression of GPER1 and its coexpression with an inhibitory neuron marker were similarly abundant in males and females, confirming anatomical similarity in the auditory forebrain. In this study, we found: (1) a role for GPER1 in regulating sensory processing and (2) a sex difference in auditory processing of complex vocalizations in a cell type-specific manner. These results reveal sex specificity of a rapid estrogen signaling mechanism in which neuromodulation accounts and/or compensates for brain sex differences, dependent on cell type, in brain regions that are anatomically similar in both sexes.

Sensory Coding and Sensitivity to Local Estrogens Shift during Critical Period Milestones in the Auditory Cortex of Male Songbirds.

Vocal learning occurs during an experience-dependent, age-limited critical period early in development. In songbirds, vocal learning begins when presinging birds acquire an auditory memory of their tutor's song (sensory phase) followed by the onset of vocal production and refinement (sensorimotor phase). Hearing is necessary throughout the vocal learning critical period. One key brain area for songbird auditory processing is the caudomedial nidopallium (NCM), a telencephalic region analogous to mammalian auditory cortex. Despite NCM's established role in auditory processing, it is unclear how the response properties of NCM neurons may shift across development. Moreover, communication processing in NCM is rapidly enhanced by local 17ß-estradiol (E2) administration in adult songbirds; however, the function of dynamically fluctuating E2 in NCM during development is unknown. We collected bilateral extracellular recordings in NCM coupled with reverse microdialysis delivery in juvenile male zebra finches (Taeniopygia guttata) across the vocal learning critical period. We found that auditory-evoked activity and coding accuracy were substantially higher in the NCM of sensory-aged animals compared to sensorimotor-aged animals. Further, we observed both age-dependent and lateralized effects of local E2 administration on sensory processing. In sensory-aged subjects, E2 decreased auditory responsiveness across both hemispheres; however, a similar trend was observed in age-matched control subjects. In sensorimotor-aged subjects, E2 dampened auditory responsiveness in left NCM but enhanced auditory responsiveness in right NCM. Our results reveal an age-dependent physiological shift in auditory processing and lateralized E2 sensitivity that each precisely track a key neural "switch point" from purely sensory (pre-singing) to sensorimotor (singing) in developing songbirds.

Solid pseudopapillary tumor of the pancreas: Clinical features, diagnosis and treatment.

INTRODUCTION:: Solid pseudopapillary tumor of the pancreas (SPTP) is a rare neoplasm of low malignant potential with uncertain behavior, diagnosed mainly in young women. METHOD:: Our report comprises a series of cases of SPTP reviewed retrospectively, highlighting clinical, tomographic and immunohistochemical features, treatment performed and outcomes. RESULTS:: Thirteen patients were found to have pancreatic [solid] masses on computed tomography scan measuring a mean diameter of 8.8 cm. All patients underwent complete surgical excision. Immunohistochemistry confirmed diagnosis in all cases. CONCLUSION:: SPTP occurs more frequently in young women. Diagnostic suspicion lies on the finding of a bulky, solid and cystic pancreatic mass. Imaging findings might provide diagnostic information before resection. Conservative approaches can be used in selected cases and survival rates are usually excellent following complete resection.

Essential Oil of Ocimum basilicum L. and (-)-Linalool Blocks the Excitability of Rat Sciatic Nerve.

The racemate linalool and its levogyrus enantiomer [(-)-LIN] are present in many essential oils and possess several pharmacological activities, such as antinociceptive and anti-inflammatory. In this work, the effects of essential oil obtained from the cultivation of the Ocimum basilicum L. (EOOb) derived from Germplasm Bank rich in (-)-LIN content in the excitability of peripheral nervous system were studied. We used rat sciatic nerve to investigate the EOOb and (-)-LIN effects on neuron excitability and the extracellular recording technique was used to register the compound action potential (CAP). EOOb and (-)-LIN blocked the CAP in a concentration-dependent way and these effects were reversible after washout. EOOb blocked positive amplitude of 1st and 2nd CAP components with IC50 of 0.38 ± 0.2 and 0.17 ± 0.0 mg/mL, respectively. For (-)-LIN, these values were 0.23 ± 0.0 and 0.13 ± 0.0 mg/mL. Both components reduced the conduction velocity of CAP and the 2nd component seems to be more affected than the 1st component. In conclusion EOOb and (-)-LIN inhibited the excitability of peripheral nervous system in a similar way and potency, revealing that the effects of EOOb on excitability are due to the presence of (-)-LIN in the essential oil.

Trends in prostate cancer incidence and mortality in a mid-sized Northeastern Brazilian city.

OBJECTIVE: International data have reported prostate cancer as the most frequent among men, and the third highest in mortality. A rise in incidence has been observed in the course of recent decades, probably influenced by early detection, mainly in asymptomatic men, through regular screening with prostate-specific antigen (PSA) testing. The purpose of this study was to contribute to information on trends in prostate cancer incidence and mortality using population-based data. METHODS: This was an exploratory ecological study of time trends, aiming at describing changes in prostate cancer incidence and mortality in Aracaju, Sergipe, Brazil, from 1996 to 2006. Rates were calculated from data of the Registro de Câncer de Base Populacional de Aracaju. Trends were calculated using the Joinpoint Regression Program. RESULTS: For the study period, 1,490 incident cases and 334 deaths were included. Incident cases were more common after 50 years of age, and deaths after 55 years. Age-standardized incidence rates of 46.6 and 50.0/100,000 were observed in the early years of the series, and then progressively increased, with rates higher than 100.0/100,000 in later years. For mortality, age-standardized rates varied from 21.6 and 16.6/100,000 to 24.1 and 28.9/100,000 in later years. Joinpoint analysis identified one joinpoint for the incidence series, resulting in two trends, the first with annual percent change of 34% and the second with 5.8%; for the mortality series no joinpoint was identified, and the annual percent change was 2.1%. CONCLUSION: There was a sharp increase in incidence rates during the study period, probably due to screening. Mortality rates had a small upward trend, and did not show major changes during the study period.

Solid pseudopapillary tumor of the pancreas: Clinical features, diagnosis and treatment / Tumor sólido pseudopapilífero do pâncreas: características clínicas, diagnóstico e tratamento

Summary Introduction: Solid pseudopapillary tumor of the pancreas (SPTP) is a rare neoplasm of low malignant potential with uncertain behavior, diagnosed mainly in young women. Method: Our report comprises a series of cases of SPTP reviewed retrospectively, highlighting clinical, tomographic and immunohistochemical features, treatment performed and outcomes. Results: Thirteen patients were found to have pancreatic [solid] masses on computed tomography scan measuring a mean diameter of 8.8 cm. All patients underwent complete surgical excision. Immunohistochemistry confirmed diagnosis in all cases. Conclusion: SPTP occurs more frequently in young women. Diagnostic suspicion lies on the finding of a bulky, solid and cystic pancreatic mass. Imaging findings might provide diagnostic information before resection. Conservative approaches can be used in selected cases and survival rates are usually excellent following complete resection.

Resumo Introdução: O tumor sólido pseudopapilífero do pâncreas é uma neoplasia rara de baixo potencial de malignidade e com comportamento incerto, diagnosticado principalmente em mulheres jovens. Método: Uma série de casos dessa patologia é revisada retrospectivamente, focalizando os aspectos clínicos, tomográficos e imuno-histoquímicos, o tratamento realizado e o desfecho. Resultados: Foram avaliadas 13 pacientes com massas pancreáticas, por meio de tomografia computadorizada, com diâmetro médio de 8,8 cm. Todas as pacientes submeteram-se a ressecção cirúrgica completa. A imuno-histoquímica confirmou o diagnóstico em todos os casos. Conclusão: Esses tumores ocorrem frequentemente em mulheres jovens. Suspeita-se do diagnóstico ao encontrar uma volumosa tumoração sólido-cística no pâncreas. As imagens podem fornecer informações diagnósticas antes da ressecção. Podem-se empregar abordagens conservadoras em pacientes selecionados, e a sobrevida geralmente é excelente com a ressecção completa.