Common Ribs of Inhibitory Synaptic Dysfunction in the Umbrella of Neurodevelopmental Disorders

The term neurodevelopmental disorder (NDD) is an umbrella term used to group together a heterogeneous class of disorders characterized by disruption in cognition, emotion, and behavior, early in the developmental timescale. These disorders are heterogeneous, yet they share common behavioral symptomatology as well as overlapping genetic contributors, including proteins involved in the formation, specialization, and function of synaptic connections. Advances may arise from bridging the current knowledge on synapse related factors indicated from both human studies in NDD populations, and in animal models. Mounting evidence has shown a link to inhibitory synapse formation, specialization, and function among Autism, Angelman, Rett and Dravet syndromes. Inhibitory signaling is diverse, with numerous subtypes of inhibitory interneurons, phasic and tonic modes of inhibition, and the molecular and subcellular diversity of GABAA receptors. We discuss common ribs of inhibitory synapse dysfunction in the umbrella of NDD, highlighting alterations in the developmental switch to inhibitory GABA, dysregulation of neuronal activity patterns by parvalbumin-positive interneurons, and impaired tonic inhibition. Increasing our basic understanding of inhibitory synapses, and their role in NDDs is likely to produce significant therapeutic advances in behavioral symptom alleviation for interrelated NDDs. Highlights • Human studies and animal models need to be bridged in neurodevelopmental disorders • Inhibitory signaling emerges as a common contributor to neurodevelopmental disorders • Inhibitory signaling is diverse in mode, source, and target • Systematic evaluation of inhibitory diversity is lacking in neurodevelopment • Understanding of inhibitory signaling diversity will advance therapeutic strategie

Edificio para Cristalería Española

In the course of a series of lectures on the subject of curtain walls, held at the Higher Technical College of Architecture, in Madrid, the author described his own experience whilst constructing a building (designed by him and by Mr. Manuel Barbero) for the firm Cristalería Española, at San Andrés del Palomar, Barcelona. Mr. De la Joya summarised the advantages that foreign experts attribute to curtain walls. These advantages are: less weight of the materials of the enclosing walls; maximum use of the available building surface; cheaper foundations; better building time control; superior quality and accuracy; and greater maintenance facility. The lecturer then explained why, and in what aspects, he was in disagreement with the above supposed advantages. He dealt with these as follows: 1. In terms of present day construction, with concrete blocks and lightweight flooring structures, it is not easy to save much weight, owing to the number of special fittings that are necessary to support and keep the curtain wall in place.—2. Although in theory a. curtain wall may be only 4 or 5 cm thick, the truth is that unless heating or air conditioning is provided on a much larger scale, a special internal protection layer is necessary.—3. It is difficult to reduce the cost of the foundations by fitting curtain walls, and any calculated saving in cost in this aspect is more theoretical than real.—4. Building time estimates usually fail to work out in practice, and in addition to this, workmanship quality is not yet very satisfactory.—5. Curtain walls require periodic overhauls, so that they do not age too rapidly, and in this sense they are no better than traditional walls. The lecturer also made a number of additional points, one of them being that he did not advise the use of curtain walls in Spain (because of the cheapness of brickwalls, the climate, the high cost of air conditioning, etc. He also emphasized how important it is to make a very full and careful study of cost when preparing a project involving curtain walls, in order to evaluate correctly their advantages.<br><br>Dio a conocer—dentro del ciclo de conferencias sobre muros-cortina, celebrado en la Escuela Técnica Superior de Arquitectura, de Madrid—sus experiencias personales en la construcción de un edificio, proyectado por él y por Manuel Barbero, para Cristalería Española, en San Andrés del Palomar, de Barcelona. Enumeró las ventajas que exponen los técnicos de otros países sobre el muro-cortina: menor peso de los materiales que componen la fachada; máximo aprovechamiento de la superficie habitable; abaratamiento de la cimentación; mejor control del tiempo; calidad y precisión; y facilidad de conservación. A continuación, y en el mismo orden, explicó por qué y en qué puntos no estaba de acuerdo con dichas ventajas: 1.° Partiendo de la construcción actual, con elementos de hormigón y forjados de tipo aligerado, no es fácil obtener una gran economía debido a la serie de elementos que hay que emplear para colocar y mantener en su sitio el muro-cortina. 2.° Que aunque teóricamente el muro-cortina puede tener 4 ó 5 m de espesor, la realidad es que si no es a costa de un enorme aumento de la calefacción, o del acondicionamiento, precisan, además, un revestimiento interior. 3.° Es muy difícil que los cimientos puedan abaratarse por el empleo de este tipo de fachada, ya que dicho abaratamiento es más teórico que real. 4.° Que aparte de que el factor tiempo suele fallar, la calidad en la ejecución no está todavía muy lograda. 5.° Se necesita un entretenimiento periódico para que la vejez no se acentúe, al igual que en las fachadas de tipo tradicional. Se extendió en una serie de consideraciones, además de las puramente técnicas, que no aconsejan el empleo del muro-cortina en España (economía en la mano de obra de albañilería, factor clima, carestía de las instalaciones de acondicionamiento, etc.). A continuación, haciendo un estudio de precios del nuevo sistema, resaltó la importancia que para la perfección y economía del mismo tiene un adecuado y completo estudio del proyecto

Monoclonal antibody: a cell specific immunotherapy to treat cancer

Fundamentally, the therapy technique which is utilized in malignancy immunotherapy, monoclonal antibodies (mAb), is one of them, and it is used extensively as a treatment for the disease. To achieve more successful treatment, novel combination treatments and treatment procedures must be created. The purpose of this study is the improvement of mAb treatment and detail late advance and new limits, particularly in cancer therapy. With various keywords, we searched Google Scholar, PubMed, and Scopus for monoclonal antibody therapy as an alternate form of chemotherapy. The number of patients who received each therapy regimen, and the recovery rate are all displayed in this study, also a comparative study between monotherapy and chemotherapy. The result showed that rituximab had a greater overall response rate than other drugs, at 68%. In the combination treatment group (monotherapy+chemotherapy), 100% of patients had adverse events, compared to 84.2 percent in the monotherapy group. The pharmaceutical industry's fastest-growing medications, monoclonal antibodies are increasingly being examined in Clinical trials as stand-alone treatments or in conjunction with other therapies. It has a promising future since it will provide better tailored therapy and combination therapy for the treatment of cancer

Use of infrared thermography in the detection of superficial phlebitis in adult intensive care unit patients:A prospective single-center observational study

Common methods to detect phlebitis may not be sufficient for patients in the intensive care unit (ICU). The goal of this study was to investigate the feasibility of infrared (IR) thermography to objectively detect phlebitis in adult ICU patients. We included a total of 128 adult ICU-patients in a pilot and subsequent validation study. Median [interquartile range] age was 62 [54-71] years and 88 (69%) patients were male. Severity of phlebitis was scored using the visual infusion phlebitis (VIP)-score, ranging from 0 (no phlebitis) to 5 (thrombophlebitis). The temperature difference (ΔT) between the insertion site and a proximal reference point was measured with IR thermography. In 78 (34%) catheters early phlebitis and onset of moderate phlebitis was observed (VIP-score of 1-3). In both the pilot and the validation study groups ΔT was significantly higher when the VIP-score was ≥1 compared to a VIP-score of 0 (p<0.01 and p<0.001, respectively). Multivariate analysis identified ΔT (p<0.001) and peripheral venous catheter (PVC) dwell time (p = 0.001) as significantly associated with phlebitis. IR thermography may be a promising technique to identify phlebitis in the ICU. An increased ΔT as determined with thermography may be a risk factor for phlebitis

La evolución en la metodología de reclutamiento en las empresas argentinas desde 1990 a la actualidad

Trabajo final e práctica profesionalLa siguiente investigación se basa en la evolución de los procesos, herramientas y técnicas del reclutamiento del personal. A raíz de los avances tecnológicos se desplegaron relevantes desarrollos en el área de los recursos humanos, esto ha traído como consecuencia que el reclutamiento se haya tenido que adaptar al contexto actual. El crecimiento del tamaño de las empresas, la complejidad de los nuevos puestos de trabajo, originó nuevos sistemas de reclutamiento para poder atraer a las personas que debían cubrir esos puestos. En el desarrollo de dicha investigación se describe cómo ha evolucionado el departamento de Recursos Humanos, el capital humano en las organizaciones, la función de reclutamiento, su evolución en los procesos, técnicas, las nuevas tendencias, los cambios generacionales y su impacto en el mercado laboral. el marco metodológico se basa en entrevistas a responsables del sector de RRHH de empresas del sector IT, ya que son las que se tienen que adaptar más a los cambios tecnológicos, a la transformación digital de estos últimos años, tomando como representatividad a la provincia de Buenos Aires. En donde se indaga cómo se han tenido que adaptar a los cambios tecnológicos, generacionales, y cómo ha impactado al proceso de reclutamiento, cual es la herramienta más utilizada, si se siguen utilizando las herramientas tradicionales y si ha generado beneficios en temas de recursos invertido a la hora de reclutar personal con las nuevas metodologías. La entrevista será del tipo conversacional y mayormente informal, a pesar de seguir determinadas pautas elegidas por nosotros para guiar y orientar la charla sobre el tema que estudiamos, sin quitarle a la persona entrevistada la posibilidad de expresarse libremente y establecer sus prioridades acordes a sus conocimientos. Por otra parte, se investigará como impactan las nuevas generaciones en el mercado laboral.Fil: Garcilazo, Cyntia. Universidad Nacional de San Martín. Escuela de Economía y NegociosFil: Joya Galán, Oscar M. Universidad Nacional de San Martín. Escuela de Economía y Negocio

Therapeutic Strategies to Enhance the Anticancer Efficacy of Histone Deacetylase Inhibitors

Histone acetylation is a posttranslational modification that plays a role in regulating gene expression. More recently, other nonhistone proteins have been identified to be acetylated which can regulate their function, stability, localization, or interaction with other molecules. Modulating acetylation with histone deacetylase inhibitors (HDACi) has been validated to have anticancer effects in preclinical and clinical cancer models. This has led to development and approval of the first HDACi, vorinostat, for the treatment of cutaneous T cell lymphoma. However, to date, targeting acetylation with HDACi as a monotherapy has shown modest activity against other cancers. To improve their efficacy, HDACi have been paired with other antitumor agents. Here, we discuss several combination therapies, highlighting various epigenetic drugs, ROS-generating agents, proteasome inhibitors, and DNA-damaging compounds that together may provide a therapeutic advantage over single-agent strategies

Nucleotomía percutánea automatizada: experiencia en 425 casos

En el presente trabajo exponemos nuestra experiencia en el tratamiento de la hernia discal lumbar mediante Nucleotomía Percutánea Automatizada. El estudio comprende el periodo de Junio de 1988 a Diciembre de 1992. Se incluyen un total de 425 enfermos de edades comprendidas entre los 18 y 58 años. Los pacientes han sido evaluados a las 6 semanas, a los 3 y a los 6 meses tras la intervención. Los resultados han sido satisfactorios en el 71% de los casos. Solamente hubo una complicación de espondilodiscitis. En el 29% de los casos se obtuvieron malos resultados. Un porcentaje importante de los fracasos, se debieron a una mala selección de los pacientes desde el punto de vista de su perfil psicológico.Our experience using automated percutaneous nucleotomy for treatment for herniated disc is presented. A total of 42 5 patientes, aged between 18 and 58 years and operated from June 88 to December 1992, has been included. Patients were clinically assessed at 6 weeks, 3 months and 6 months after surgery. Satisfactory results were found in 71% of cases. As for complications, there was only a case of discitis. In 29% of patients, the outcome was poor. An important group of failures were due to bad selection of patients regadings psychological profile