Leptin Regulates Nutrient Reward via Galanin and Orexin Neurons

Obesity has become a widespread concern to human health largely over the past three decades. It is thought that obesity is associated with the over consumption of calorically dense diets. The rewarding value of food is mediated through the mesolimbic dopamine system, though is less understood how appetitive control circuits relay information to existing reward circuitry. The adiposity signaling hormone, leptin, is a critical mediator of food intake and fat storage. Leptin signaling, via the long form of the leptin receptor (LepRb), is predominantly carried out within the hypothalamus. Leptin action specific to the lateral hypothalamus area (LHA) modulates reward function via direct and indirect inhibition of reward circuitry. Here, I have identified a novel leptin receptor population within the LHA that co-expresses the inhibitory neuropeptide galanin (termed Gal-LepRb neurons). To investigate the physiological function of leptin through Gal-LepRb neurons, we selectively deleted LepRb in galanin neurons (referred to as Gal-LepRbKO mice). In a two-bottle-choice paradigm, I assessed nutrient selection for isocaloric lipid and sucrose solutions. Interestingly, Gal-LepRbKO mice demonstrated a significant preference for the sucrose solution and decreased lipid intake compared to controls. Moreover, Gal-LepRbKO mice displayed stronger motivation to work for a sucrose treat. My data further indicate that Gal-LepRb neurons are inhibitory acting neurons that are stimulated by leptin. Gal-LepRb neurons strongly innervate local orexin neurons and noradrenergic neurons in the locus coeruleus (LC). Intriguingly, orexin neurons also strongly innervate the LC, and activation of orexin neurons correlates with motivational and food-seeking behaviors. My data also show that orexin neurons express the Gi-coupled GPCR galanin 1-receptor (GalR1), validating the cellular ability of orexin neurons to respond to galanin. In summary, we have characterized a novel population of LHA LepRb neurons and propose that leptin-mediated inhibition of orexin neurons, possibly via inhibitory galanin-GalR1 signaling, regulates the reward value of nutrients

A Study of the Decarboxylation of Trichloroacetic Acid in Solutions of Water and Dimethylsulfoxide

Author Institution: Department of Physical Science, Denison University, Granville, OhioThe decarboxylation of trichloroacetic acid has been found to occur readily at temperatures as low as 25.0°C in the presence of dimethylsulfoxide in water solutions, a fact not previously reported in chemical literature. The reaction rate is dependent upon the concentration of the dimethylsulfoxide. The reaction rate constant increases about sixty percent as the concentration of dimethylsulfoxide (DMSO) is increased from c. 50 percent to c. 86 percent. The reaction is first order and the rate is also influenced by the actual concentration of the trichloroacetate ion. An effect of the DMSO is to increase the concentration of this ion. The paper presents density curves at 20.00°C and 25.00°C (each±0.05 °C) for solutions of DMSO in water

Online, Mobile, and Text Food Ordering in the U.S. Restaurant Industry

A survey of the top 326 U.S. restaurant chains in all categories finds the industry gradually adopting electronic ordering, in the form of online, mobile, and text orders. Quick-service chains, most notably those selling pizza, and fast-casual chains are far ahead of other segments in adopting electronic ordering, particularly using online approaches. Mobile apps are less common, although their use is growing. Although order-placing functionality is limited for mobile apps, the fast-casual chains are leading the way in allowing customers to place orders. Nearly all restaurant chains have a Facebook presence, but just 3 percent allowed ordering through that channel. The advantages of electronic ordering include increased sales, particularly through automatic upselling and by storing order information so that customers are encouraged to repeat their previous orders with a single click. Other than the cost of installation and operation, the chief disadvantage of electronic ordering is the potential for amplifying rush time volume, with the potential of overwhelming the kitchen. Creating a separate line for electronic orders and pickups is one way to address that problem

Habilidades sociales y desempeño docente en una institución educativa de Moquegua, 2016

La presente investigación, tiene como objetivo Conocer la relación que existe entre habilidades sociales y desempeño docente según los estudiantes de secundaria de la Institución educativa los Ángeles de Moquegua, 2016 y se planteó la hipótesis: Las habilidades sociales se relacionan significativamente con el desempeño docente según los estudiantes de secundaria de la Institución educativa los Ángeles de Moquegua, 2016. Desde la perspectiva de su justificación práctica la realización de esta investigación posibilita la construcción de instrumentos de recolección de datos; estos instrumentos fueron validados y confiabilizados ya que su construcción siguió una ruta metodológica que garantice estas características, por tanto, dichos instrumentos podrán ser utilizados en el ejercicio de la práctica docente en las Instituciones educativas de la región y el país. Este estudio corresponde al tipo de investigación no experimental, descriptivo correlacional, con diseño transeccional correlacional porque nos permite demostrar si existe relación entre las variables de estudio. La muestra estuvo integrada por 55 estudiantes de educación secundaria de la institución educativa Los Ángeles de Moquegua. La técnica de recolección de datos fue la encuesta y los instrumentos utilizados fueron el cuestionario sobre habilidades sociales y el cuestionario sobre desempeño docente. Los resultados de esta investigación demuestran que existe una relación directa y significativa al aplicar la prueba de coeficiente de correlación alcanza un valor de rho = 0,794 y (p = 0,000), que es mucho menor que el nivel de significancia elegido (0,05) Se verifica entonces, una relación directa alta entre las variables. Por lo tanto, se rechaza la hipótesis nula, Ho y se acepta la hipótesis general, propuesta, Ha. Se concluye que: Las habilidades sociales se relacionan significativamente con el desempeño docente según los estudiantes de secundaria de la Institución educativa los Ángeles de Moquegua, 2016

For Dallas from Kansas, the Badass

Poe

Estrés laboral y desempeño laboral de los trabajadores de la Asociación de Productores de Muebles de Madera, Melamine y Metal “SAN JOSÉ” de la ciudad de Juliaca, 2019

La investigación tuvo por objetivo, determinar la influencia del estrés laboral sobre el desempeño laboral de los trabajadores de la Asociación. La metodología aplicada es de tipo cuantitativo, correlacional causal, no experimental de corte transversal, cuya herramienta de análisis es la encuesta a 56 trabajadores que cumplen la responsabilidad de ventas y atención al cliente; se utilizó el coeficiente de Spearman para determinar la relación de varibles. Los resultados obtenidos nos indican una correlación indirecta de magnitud alta con un valor de (Rho = -.604) que resulta ser muy significativo con un nivel del 1%. Se concluye que a mayor estrés laboral menor será el desempeño laboral de los trabajadores de la Asociación de productores de muebles de madera, melamine y metal “San José” de la ciudad de Juliaca, 2019.JULIACAEscuela Profesional de AdministraciónComportamiento organizaciona

La reparación civil en el ámbito penal dentro del primer juzgado de investigación preparatoria de Lima según el Código Procesal Penal

En esta investigación, se estudia con detalle la falta de eficacia del derecho al resarcimiento del daño sufrido por la víctima, en relación al Nuevo Código Procesal Penal del Perú, con la finalidad de describir como la víctima no logra alcanzar la justicia anhelada y por medio de esta el resarcimiento del daño ocasionado, y a la vez también identificar las causas por las que se vulnera este derecho. Se han analizado algunos artículos tanto del Código Penal, como del Nuevo Código Procesal Penal. Se tuvo en cuenta las opiniones de los Fiscales Jueces y de las víctimas recogidas en una encuesta. En esta investigación se toman como factor a la variable que es: La Reparación Civil, la cual será estudiada y analizada. Con esta investigación quiero demostrar como la Reparación Civil impuesta por la comisión de un Delito no hace justicia a la víctima en el Primer Juzgado de Investigación Preparatoria en los años 2014

Letrozole-induced necrotising leukocytoclastic small vessel vasculitis: First report of a case in the UK.

INTRODUCTION: Letrozole, an aromatase inhibitor, is a commonly used neo-adjuvant drug to treat hormone-sensitive breast cancer. There have been a few cases of aromatase inhibitor induced vasculitis but the first case of letrozole-induced vasculitis was reported from Switzerland in 2014 (Digklia et al.) [1]. PRESENTATION OF CASE: We report the case of a 72-year-old woman with a small breast cancer. She was started on pre-operative letrozole (2.5mg/d) whilst awaiting surgery. Ten days later she presented with burning pain and purpuric skin lesions which progressed to extensive ischaemic superficial necrosis of the lower limb skin, resolving over 3-4 months after local and systemic steroids. Histologically, it showed leucocytoclasis with evidence of eosinophilia consistent with a diagnosis of cutaneous leukocytoclastic small vessel vasculitis. DISCUSSION: The initial clinical presentation was severe burning pain around the ankles and a spreading violaceous rash. Letrozole was stopped. Wide local excision (lumpectomy) and sentinel node biopsy were postponed because of the accompanying pneumonitis and gastrointestinal upset, and were carried out 3.5 months later. Fortunately, the tumour size did not increase, but appeared to reduce, and axillary lymph nodes remained negative, i.e., this patient's cancer outcome does not seem to have been jeopardized. CONCLUSION: Leukocytoclastic vasculitis is a hypersensitivity reaction that is usually self-resolving, though our case needed systemic steroid treatment. Letrozole is a commonly used drug in clinical practice and prescribers should be aware of this rare side effect, which in our case delayed treatment without any apparent harm and possibly reduced tumour size

Tocilizumab in refractory Caucasian Takayasu’s arteritis: a multicenter study of 54 patients and literature review

Arteritis de Takayasu; Tocilizumab; Teràpia biològicaArteritis de Takayasu; Tocilizumab; Terapia biológicaTakayasu’s arteritis; Tocilizumab; Biological therapyObjective: To assess the efficacy and safety of tocilizumab (TCZ) in Caucasian patients with refractory Takayasu’s arteritis (TAK) in clinical practice. Methods: A multicenter study of Caucasian patients with refractory TAK who received TCZ. The outcome variables were remission, glucocorticoid-sparing effect, improvement in imaging techniques, and adverse events. A comparative study between patients who received TCZ as monotherapy (TCZMONO) and combined with conventional disease modifying anti-rheumatic drugs (cDMARDs) (TCZCOMBO) was performed. Results: The study comprised 54 patients (46 women/8 men) with a median [interquartile range (IQR)] age of 42.0 (32.5–50.5) years. TCZ was started after a median (IQR) of 12.0 (3.0–31.5) months since TAK diagnosis. Remission was achieved in 12/54 (22.2%), 19/49 (38.8%), 23/44 (52.3%), and 27/36 (75%) patients at 1, 3, 6, and 12 months, respectively. The prednisone dose was reduced from 30.0 mg/day (12.5–50.0) to 5.0 (0.0–5.6) mg/day at 12 months. An improvement in imaging findings was reported in 28 (73.7%) patients after a median (IQR) of 9.0 (6.0–14.0) months. Twenty-three (42.6%) patients were on TCZMONO and 31 (57.4%) on TCZCOMBO: MTX (n = 28), cyclosporine A (n = 2), azathioprine (n = 1). Patients on TCZCOMBO were younger [38.0 (27.0–46.0) versus 45.0 (38.0–57.0)] years; difference (diff) [95% confidence interval (CI) = -7.0 (-17.9, -0.56] with a trend to longer TAK duration [21.0 (6.0–38.0) versus 6.0 (1.0–23.0)] months; diff 95% CI = 15 (-8.9, 35.5), and higher c-reactive protein [2.4 (0.7–5.6) versus 1.3 (0.3–3.3)] mg/dl; diff 95% CI = 1.1 (-0.26, 2.99). Despite these differences, similar outcomes were observed in both groups (log rank p = 0.862). Relevant adverse events were reported in six (11.1%) patients, but only three developed severe events that required TCZ withdrawal. Conclusion: TCZ in monotherapy, or combined with cDMARDs, is effective and safe in patients with refractory TAK of Caucasian origin.The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was partially supported by RETICS Programs, RD08/0075 (RIER), RD12/0009/0013 and RD16/0012 from “Instituto de Salud Carlos III” (ISCIII) (Spain). However, this research did not receive any specific grant from funding agencies in the commercial or not-for-profit sectors