Juvenile fibroadenoma arising in ectopic breast tissue presenting as an axillary mass

AbstractThe differential diagnosis of an axillary mass during childhood is extensive and malignant processes such as lymphoma or metastatic disease must be excluded. We describe an unusual case of a fibroadenoma growing within ectopic breast tissue located in the axilla in a 10 year old girl. The mass grew rapidly and was removed during an excisional biopsy. Histological evaluation revealed a diagnosis of fibroadenoma. Fibroadenoma of ectopic breast tissue has not previously been reported in the pediatric age group, and must be considered as part of the differential diagnosis for pediatric axillary masses

Visuospatial and Sensory Integration Tasks in Patients With Schizophrenia or Schizoaffective Disorder: Relationship to Body Mass Index and Smoking

Neurological soft signs (NSSs) are highly prevalent among patients with schizophrenia, but their pathophysiological significance remains unclear. The present study employed perceptual-motor and visuospatial processing tests that have not yet been attempted in this patient population. Patients with schizophrenia or schizoaffective disorder (n = 42) and mentally healthy subjects (n = 10) were administered Copy Figure Test, Detection and Recognition of an Object Test and Road Map Test. As compared to controls, schizophrenic and schizoaffective patients displayed significantly poorer ability to copy three-dimensional figures (namely, Necker- and hidden line elimination cubes) and to orient in space on a road-map test; group differences in copying two-dimensional figures and on objects' recognition against a background noise were not apparent. In the schizophrenia/schizoaffective group, more mistakes on the hidden line elimination cube was associated with greater body mass index and greater severity of nicotine dependence measured via the Fagerstrom Test of Nicotine Dependence. The above findings replicate those of prior reports and extend them to the tasks that do not involve motivational and attentional confounds. Furthermore, the present data support the hypothesis that subtle cerebral cortical abnormalities detected with specific NSSs tests may be related to some aspects of metabolic and motivational function in patients with schizophrenia/schizoaffective disorder

Biological and behavioral markers of pain following nerve injury in humans

The evolution of peripheral and central changes following a peripheral nerve injury imply the onset of afferent signals that affect the brain. Changes to inflammatory processes may contribute to peripheral and central alterations such as altered psychological state and are not well characterized in humans. We focused on four elements that change peripheral and central nervous systems following ankle injury in 24 adolescent patients and 12 age-sex matched controls. Findings include (a) Changes in tibial, fibular, and sciatic nerve divisions consistent with neurodegeneration; (b) Changes within the primary motor and somatosensory areas as well as higher order brain regions implicated in pain processing; (c) Increased expression of fear of pain and pain reporting; and (d) Significant changes in cytokine profiles relating to neuroinflammatory signaling pathways. Findings address how changes resulting from peripheral nerve injury may develop into chronic neuropathic pain through changes in the peripheral and central nervous system

Challenges of functional imaging research of pain in children

Functional imaging has revolutionized the neurosciences. In the pain field it has dramatically altered our understanding of how the brain undergoes significant functional, anatomical and chemical changes in patients with chronic pain. However, most studies have been performed in adults. Because functional imaging is non-invasive and can be performed in awake individuals, applications in children have become more prevalent, but only recently in the pain field. Measures of changes in the brains of children have important implications in understanding neural plasticity in response to acute and chronic pain in the developing brain. Such findings may have implications for treatments in children affected by chronic pain and provide novel insights into chronic pain syndromes in adults. In this review we summarize this potential and discuss specific concerns related to the imaging of pain in children

The reactive species interactome: evolutionary emergence, biological significance, and opportunities for redox metabolomics and personalized medicine

SIGNIFICANCE: Oxidative stress is thought to account for aberrant redox homeostasis and contribute to aging and disease. However, more often than not administration of antioxidants is ineffective, suggesting our current understanding of the underlying regulatory processes is incomplete. Recent Advances. Similar to reactive oxygen and nitrogen species (ROS, RNS), reactive sulfur species (RSS) are now emerging as important signaling molecules, targeting regulatory cysteine redox switches in proteins, affecting gene regulation, ion transport, intermediary metabolism and mitochondrial function. To rationalize the complexity of chemical interactions of reactive species with themselves and their targets and help define their role in systemic metabolic control, we here introduce a novel integrative concept coined the reactive species interactome (RSI). The RSI is a primeval multi-level redox-regulatory system whose architecture, together with the physicochemical characteristics of its constituents, allows efficient sensing and rapid adaptation to environmental changes and various other stresses to enhance fitness and resilience at the local and whole-organism level. CRITICAL ISSUES: To better characterise the RSI-related processes that determine fluxes through specific pathways and enable integration, it is necessary to disentangle the chemical biology and activity of reactive species (including precursors and reaction products), their targets, communication systems and effects on cellular, organ and whole-organism bioenergetics using systems-level/network analyses. FUTURE DIRECTIONS: Understanding the mechanisms through which the RSI operates will enable a better appreciation of the possibilities to modulate the entire biological system; moreover, unveiling molecular signatures that characterize specific environmental challenges or other stresses will provide new prevention/intervention opportunities for personalized medicine

Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons

The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions

Central modulation in cluster headache patients treated with occipital nerve stimulation: an FDG-PET study

Peer reviewe

Prefrontal Norepinephrine Determines Attribution of “High” Motivational Salience

Intense motivational salience attribution is considered to have a major role in the development of different psychopathologies. Numerous brain areas are involved in “normal” motivational salience attribution processes; however, it is not clear whether common or different neural mechanisms also underlie intense motivational salience attribution. To elucidate this a brain area and a neural system had to be envisaged that were involved only in motivational salience attribution to highly salient stimuli. Using intracerebral microdialysis, we found that natural stimuli induced an increase in norepinephrine release in the medial prefrontal cortex of mice proportional to their salience, and that selective prefrontal norepinephrine depletion abolished the increase of norepinephrine release in the medial prefrontal cortex induced by exposure to appetitive (palatable food) or aversive (light) stimuli independently of salience. However, selective norepinephrine depletion in the medial prefrontal cortex impaired the place conditioning induced exclusively by highly salient stimuli, thus indicating that prefrontal noradrenergic transmission determines approach or avoidance responses to both reward- and aversion-related natural stimuli only when the salience of the unconditioned natural stimulus is high enough to induce sustained norepinephrine outflow. This affirms that prefrontal noradrenergic transmission determines motivational salience attribution selectively when intense motivational salience is processed, as in conditions that characterize psychopathological outcomes

Negative Autoregulation by Fas Stabilizes Adult Erythropoiesis and Accelerates Its Stress Response

Erythropoiesis maintains a stable hematocrit and tissue oxygenation in the basal state, while mounting a stress response that accelerates red cell production in anemia, blood loss or high altitude. Thus, tissue hypoxia increases secretion of the hormone erythropoietin (Epo), stimulating an increase in erythroid progenitors and erythropoietic rate. Several cell divisions must elapse, however, before Epo-responsive progenitors mature into red cells. This inherent delay is expected to reduce the stability of erythropoiesis and to slow its response to stress. Here we identify a mechanism that helps to offset these effects. We recently showed that splenic early erythroblasts, ‘EryA’, negatively regulate their own survival by co-expressing the death receptor Fas, and its ligand, FasL. Here we studied mice mutant for either Fas or FasL, bred onto an immune-deficient background, in order to avoid an autoimmune syndrome associated with Fas deficiency. Mutant mice had a higher hematocrit, lower serum Epo, and an increased number of splenic erythroid progenitors, suggesting that Fas negatively regulates erythropoiesis at the level of the whole animal. In addition, Fas-mediated autoregulation stabilizes the size of the splenic early erythroblast pool, since mutant mice had a significantly more variable EryA pool than matched control mice. Unexpectedly, in spite of the loss of a negative regulator, the expansion of EryA and ProE progenitors in response to high Epo in vivo, as well as the increase in erythropoietic rate in mice injected with Epo or placed in a hypoxic environment, lagged significantly in the mutant mice. This suggests that Fas-mediated autoregulation accelerates the erythropoietic response to stress. Therefore, Fas-mediated negative autoregulation within splenic erythropoietic tissue optimizes key dynamic features in the operation of the erythropoietic network as a whole, helping to maintain erythroid homeostasis in the basal state, while accelerating the stress response