A Rheumatoid Nodule at the Sternoclavicular Joint: An uncommon presentation of a common problem

Most rheumatoid nodules are found at joints or pressure points. They rarely require medical intervention and even fewer require surgery. A 78-year-old female developed a 7.2 x 3.2 x 2.8 cm rheumatoid nodule originating at the right sternoclavicular joint, a novel site for a common pathology. Management involved a complex differential diagnosis and surgical treatment was resection from adjacent vascular and neural structures. Following surgical excision, the patient maintained good mobility and sensation of the neck and surrounding areas

High-Altitude Cognitive Impairment Is Prevented by Enriched Environment Including Exercise via VEGF Signaling

Exposure to hypobaric hypoxia at high altitude (above 2500 m asl) causes cognitive impairment, mostly attributed to changes in brain perfusion and consequently neuronal death. Enriched environment and voluntary exercise has been shown to improve cognitive function, to enhance brain microvasculature and neurogenesis, and to be neuroprotective. Here we show that high-altitude exposure (3540 m asl) of Long Evans rats during early adulthood (P48-P59) increases brain microvasculature and neurogenesis but impairs spatial and visual memory along with an increase in neuronal apoptosis. We tested whether enriched environment including a running wheel for voluntary exercise (EE) can prevent cognitive impairment at high-altitude and whether apoptosis is prevented. We found that EE retained spatial and visual memory at high altitude, and prevented neuronal apoptosis. Further, we tested whether vascular endothelial growth factor (VEGF) signaling is required for the EE-mediated recovery of spatial and visual memory and the reduction in apoptosis. Pharmacological inhibition of VEGF signaling by oral application of a tyrosine kinase inhibitor (Vandetanib) prevented the recovery of spatial and visual memory in animals housed in EE, along with an increase in apoptosis and a reduction in neurogenesis. Surprisingly, inhibition of VEGF signaling also caused impairment in spatial memory in EE-housed animals reared at low altitude, affecting mainly dentate gyrus microvasculature but not neurogenesis. We conclude that EE-mediated VEGF signaling is neuroprotective and essential for the maintenance of cognition and neurogenesis during high-altitude exposure, and for the maintenance of spatial memory at low altitude. Finally, our data also underlines the potential risk of cognitive impairment and disturbed high altitude adaption from the use of VEGF-signaling inhibitors for therapeutic purposes.This research was supported by the Swiss National Science Foundation [Marie Heim-Vogtlin (MHV) - SNF grant PMPDP3_145480], the Institute of Veterinary Physiology and the Institute of Pharmacology and Toxicology at the University of Zurich, the Institute of Anatomy at the University of Freiburg, and the Institute of Neuroscience at the University of Basque, Spain

Valores de referencia para leptina, cortisol, insulina y glucosa entre los adolescentes europeos y su asociación con adiposidad: Estudio Helena

Background and Objective: Adequate concentrations of leptin, cortisol, and insulin are important for a suitable metabolism and development during adolescence. These hormones jointly with glucose play a major role in fat metabolism and development of childhood obesity. Our main objective was to quantify biomarkers as leptin, cortisol, insulin and glucose status in European adolescents to contribute to establish reference ranges. Methods: A representative sample of 927 adolescents (45% males, 14.9±1.2 years for the overall population) from ten European cities of the HELENA study was used to obtain fasting blood samples for these biomarkers. The percentile distributions were computed by sex and age and percentiles were associated with BMI classification. Results: Serum leptin concentration in adolescents varied significantly according to BMI, sex and age (all p<0.001). Cortisol presented a tendency to increase with age, both for females and males, while insulin and glucose were stable with age. Leptin and insulin were highest in obese adolescents (p<0.001), whilst cortisol and glucose did not vary with BMI. Percentiles 5, 25, 50, 75 and 95, 26.70 and 65.33 ng/ml for leptin; 5.00, 8.11, 11.14, 15.00 and 24.51 μg/dl for cortisol and 3.65, 6.15, 8.52, 11.90 and 20.53 μlU/ml for insulin. Conclusions: In adolescents, leptin, cortisol, insulin and glucose concentrations are differently affected by age, sex and BMI. Establishment of reference ranges (percentiles) of these biomarkers would be of great interest when pediatricians have to assess the trend of an adolescent to develop obesity years after.Objetivo: Concentraciones adecuadas de leptina, cortisol e insulina son importantes para un metabolismo normal durante la adolescencia, puesto que valores alterados de estas hormonas, junto con la glucosa, se asocian con el desarrollo de la obesidad infantil. Nuestro principal objetivo fue cuantificar estos marcadores en adolescentes europeos con el fin de establecer rangos de referencia. Métodos: Muestras de sangre procedentes de 927 adolescentes en ayunas (14,9 ± 1,2 años, 45% varones, estudio HELENA), fueron analizadas para cuantificar la leptina, cortisol, insulina y glucosa. Las distribuciones de percentiles se determinaron teniendo en cuenta el sexo y la edad. También se estudió la asociación entre percentiles y la clasificación del IMC. Resultados: La concentración de leptina en suero variaba significativamente con el IMC, el sexo y la edad (todos p<0,001). El cortisol presentó una tendencia a aumentar con la edad, tanto para varones como mujeres, mientras que la insulina y la glucosa eran estables con la edad. La leptina y la insulina fueron más altas en los adolescentes obesos (p <0,001), mientras que el cortisol y glucosa no variaron con el IMC. Los percentiles 5, 25, 50, 75 y 95, para los valores de hormonas fueron, respectivamente: 1.27, 4.06, 11.54, 26.70 y 65.33 ng/ml para la leptina; 5.00, 8.11, 11.14, 15.00 y 24.51 μg/dl para el cortisol y 3.65, 6.15, 8.52, 11.90 y 20.53 μlU/ml de insulina.The HELENA study has taken place with the financial support of the European Community Sixth RTD Framework Programme (Contract FOODCT- 2005-007034). This study was also supported by a grant from the Spanish Ministry of Science and Innovation AGL2007-29784-E

High-Altitude Cognitive Impairment Is Prevented by Enriched Environment Including Exercise via VEGF Signaling

Exposure to hypobaric hypoxia at high altitude (above 2500 m asl) causes cognitive impairment, mostly attributed to changes in brain perfusion and consequently neuronal death. Enriched environment and voluntary exercise has been shown to improve cognitive function, to enhance brain microvasculature and neurogenesis, and to be neuroprotective. Here we show that high-altitude exposure (3540 m asl) of Long Evans rats during early adulthood (P48–P59) increases brain microvasculature and neurogenesis but impairs spatial and visual memory along with an increase in neuronal apoptosis. We tested whether enriched environment including a running wheel for voluntary exercise (EE) can prevent cognitive impairment at high-altitude and whether apoptosis is prevented. We found that EE retained spatial and visual memory at high altitude, and prevented neuronal apoptosis. Further, we tested whether vascular endothelial growth factor (VEGF) signaling is required for the EE-mediated recovery of spatial and visual memory and the reduction in apoptosis. Pharmacological inhibition of VEGF signaling by oral application of a tyrosine kinase inhibitor (Vandetanib) prevented the recovery of spatial and visual memory in animals housed in EE, along with an increase in apoptosis and a reduction in neurogenesis. Surprisingly, inhibition of VEGF signaling also caused impairment in spatial memory in EE-housed animals reared at low altitude, affecting mainly dentate gyrus microvasculature but not neurogenesis. We conclude that EE-mediated VEGF signaling is neuroprotective and essential for the maintenance of cognition and neurogenesis during high-altitude exposure, and for the maintenance of spatial memory at low altitude. Finally, our data also underlines the potential risk of cognitive impairment and disturbed high altitude adaption from the use of VEGF-signaling inhibitors for therapeutic purposes

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics

Amylin/Calcitonin receptor–mediated signaling in POMC neurons influences energy balance and locomotor activity in chow-fed male mice

Amylin, a pancreatic hormone and neuropeptide, acts principally in the hindbrain to decrease food intake and has recently been shown to act as a neurotrophic factor to control the development of area postrema → nucleus of the solitary tract and arcuate hypothalamic nucleus→ paraventricular nucleus axonal fiber outgrowth. Amylin is also able to activate ERK signaling specifically in POMC neurons independently of leptin. For investigation of the physiological role of amylin signaling in POMC neurons, the core component of the amylin receptor, calcitonin receptor (CTR), was depleted from POMC neurons using an inducible mouse model. The loss of CTR in POMC neurons leads to increased body weight gain, increased adiposity, and glucose intolerance inmale knockoutmice, characterized by decreased energy expenditure (EE) and decreased expression of uncoupling protein 1 (UCP1) in brown adipose tissue. Furthermore, a decreased spontaneous locomotor activity and absent thermogenic reaction to the application of the amylin receptor agonist were observed in male and female mice. Together, these results show a significant physiological impact of amylin/calcitonin signaling in CTR-POMC neurons on energy metabolism and demonstrate the need for sex-specific approaches in obesity research and potentially treatment

Entry, entry-deterrence, and exit: a study of the market for CFCs

Summary in GermanSIGLEAvailable from Bibliothek des Instituts fuer Weltwirtschaft, ZBW, Duesternbrook Weg 120, D-24105 Kiel W 179 (96.23) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Erythropoietin stimulates GABAergic maturation in the mouse hippocampus

Several neurodevelopmental disabilities are strongly associated with alterations in GABAergic transmission, and therapies to stimulate its normal development are lacking. Erythropoietin (EPO) is clinically used in neonatology to mitigate acute brain injury, and to stimulate neuronal maturation. Yet it remains unclear whether EPO can stimulate maturation of the GABAergic system. Here, with the use of a transgenic mouse line that constitutively overexpresses neuronal EPO (Tg21), we show that EPO stimulates postnatal GABAergic maturation in the hippocampus. We show an increase in hippocampal GABA-immunoreactive neurons, and postnatal elevation of interneurons expressing parvalbumin (PV), somatostatin (SST), and neuropeptide Y (NPY). Analysis of perineuronal net (PNN) formation and innervation of glutamatergic terminals onto PV+ cells, shows to be enhanced early in postnatal development. Additionally, an increase in GABA$_{A}$ergic synapse density and IPSCs in CA1 pyramidal cells from Tg21 mice is observed. Detection of EPO receptor (EPOR) mRNA was observed to be restricted to glutamatergic pyramidal cells and increased in Tg21 mice at postnatal day (P)7, along with reduced apoptosis. Our findings show that EPO can stimulate postnatal GABAergic maturation in the hippocampus, by increasing neuronal survival, modulating critical plasticity periods, and increasing synaptic transmission. Our data supports EPO's clinical use to balance GABAergic dysfunction

Physical Activity Reduces Clinical Symptoms and Restores Neuroplasticity in Major Depression

Brüchle W, Schwarzer C, Berns C, et al. Physical Activity Reduces Clinical Symptoms and Restores Neuroplasticity in Major Depression. Frontiers in Psychiatry. 2021;12.Major depressive disorder (MDD) is the most common mental disorder and deficits in neuroplasticity are discussed as one pathophysiological mechanism. Physical activity (PA) enhances neuroplasticity in healthy subjects and improves clinical symptoms of MDD. However, it is unclear whether this clinical effect of PA is due to restoring deficient neuroplasticity in MDD. We investigated the effect of a 3-week PA program applied on clinical symptoms, motor excitability and plasticity, and on cognition in patients with MDD (N= 23), in comparison to a control intervention (CI;N= 18). Before and after the interventions, the clinical symptom severity was tested using self- (BDI-II) and investigator- (HAMD-17) rated scales, transcranial magnetic stimulation (TMS) protocols were used to test motor excitability and paired-associative stimulation (PAS) to test long-term-potentiation (LTP)-like plasticity. Additionally, cognitive functions such as attention, working memory and executive functions were tested. After the interventions, the BDI-II and HAMD-17 decreased significantly in both groups, but the decrease in HAMD-17 was significantly stronger in the PA group. Cognition did not change notably in either group. Motor excitability did not differ between the groups and remained unchanged by either intervention. Baseline levels of LTP-like plasticity in the motor cortex were low in both groups (PA: 113.40 ± 2.55%; CI: 116.83 ± 3.70%) and increased significantly after PA (155.06 ± 10.48%) but not after CI (122.01 ± 4.1%). Higher baseline BDI-II scores were correlated with lower levels of neuroplasticity. Importantly, the more the BDI-II score decreased during the interventions, the stronger did neuroplasticity increase. The latter effect was particularly strong after PA (r= −0.835;p&lt; 0.001). The level of neuroplasticity related specifically to the psychological/affective items, which are tested predominantly in the BDI-II. However, the significant clinical difference in the intervention effects was shown in the HAMD-17 which focuses more on somatic/neurovegetative items known to improve earlier in the course of MDD. In summary, PA improved symptoms of MDD and restored the deficient neuroplasticity. Importantly, both changes were strongly related on the individual patients' level, highlighting the key role of neuroplasticity in the pathophysiology and the clinical relevance of neuroplasticity-enhancing interventions for the treatment of MDD

Neurophysiology of the concurrent costs of manual actions on working memory processes

Gündüz R, Schack T, Koester D. Neurophysiology of the concurrent costs of manual actions on working memory processes. In: Bermeitinger C, Mojzisch A, Greve W, eds. Abstracts of the 57th Conference of Experimental Psychologists (TeaP 2015). Lengerich: Pabst Science Publishers; 2015: 101