A Study of Bridge House, New York City Bureau of Alcoholic Therapy, 1943-1948

The understanding, care and treatment of the alcoholic has from time immemorial been a problem. Communities have handled this problem in various ways - in some, alcoholics are merely fined, incarcerated or both, in others they may be sent to a hospital and, if sick or weak enough, retained. Some are sent to private sanitariums if financial conditions permit; still others are sent to public institutions. In May 1943, Mr. McGoldrick, Jr., the director of the New York City Bureau of Alcoholic Therapy, persuaded Mayor LaGuardia to permit him to operate a place to treat alcoholics. Thus Bridge House was founded. Bridge House has given a number of alcoholic men an opportunity to remain in the House for a period of three weeks, receiving food and shelter, consistent individual interviews, the choice to accept or refuse companionship and job opportunities, if necessary. Of most importance, the Bureau has given these men the opportunity to become rehabilitated. Bridge House has, with individual therapy, given a number of alcoholics confidence in themselves and their abilities; has specifically helped the men to assume anew their responsibilities and obligations and has returned them to Society either as useful citizens or well on the road to becoming useful citizens. This dissertation will discuss Bridge House as the only publicly operated agency available to alcoholics, the need for Bridge House, its aim and purpose

Metabolic Pathways and Ion Channels Involved in Skeletal Muscle Atrophy: A Starting Point for Potential Therapeutic Strategies

Skeletal muscle tissue has the important function of supporting and defending the organism. It is the largest apparatus in the human body, and its function is important for contraction and movements. In addition, it is involved in the regulation of protein synthesis and degradation. In fact, inhibition of protein synthesis and/or activation of catabolism determines a pathological condition called muscle atrophy. Muscle atrophy is a reduction in muscle mass resulting in a partial or complete loss of function. It has been established that many physiopathological conditions can cause a reduction in muscle mass. Nevertheless, it is not well known the molecular mechanisms and signaling processes causing this dramatic event. There are multiple concomitant processes involved in muscle atrophy. In fact, the gene transcription of some factors, oxidative stress mechanisms, and the alteration of ion transport through specific ion channels may contribute to muscle function impairment. In this review, we focused on the molecular mechanisms responsible for muscle damage and potential drugs to be used to alleviate this disabling condition

Therapeutic Targets in Amyotrophic Lateral Sclerosis: Focus on Ion Channels and Skeletal Muscle

Amyotrophic Lateral Sclerosis is a neurodegenerative disease caused by progressive loss of motor neurons, which severely compromises skeletal muscle function. Evidence shows that muscle may act as a molecular powerhouse, whose final signals generate in patients a progressive loss of voluntary muscle function and weakness leading to paralysis. This pathology is the result of a complex cascade of events that involves a crosstalk among motor neurons, glia, and muscles, and evolves through the action of converging toxic mechanisms. In fact, mitochondrial dysfunction, which leads to oxidative stress, is one of the mechanisms causing cell death. It is a common denominator for the two existing forms of the disease: sporadic and familial. Other factors include excitotoxicity, inflammation, and protein aggregation. Currently, there are limited cures. The only approved drug for therapy is riluzole, that modestly prolongs survival, with edaravone now waiting for new clinical trial aimed to clarify its efficacy. Thus, there is a need of effective treatments to reverse the damage in this devastating pathology. Many drugs have been already tested in clinical trials and are currently under investigation. This review summarizes the already tested drugs aimed at restoring muscle-nerve cross-talk and on new treatment options targeting this tissue

Temas en debate, sección de la revista Quimán –UnTER, 1987-1989

Este artículorepresenta un nuevo avance sobre el contenido del discurso de la prensa escrita de un gremio docente, la Unión de Trabajadores de la Educación de Río Negro, durante el último trienio del gobierno de Raúl Alfonsín.Se intenta dilucidar la urdiembre discursiva a través de las once revistas denominadas“Quimán”, editadas en forma regular y sistemática durante los años 1987-1989.El análisis se focalizaen una de las secciones titulada “Temas en debate”, que aparece con mayor recurrencia en diez ejemplares. Para desentrañar la trama textual e iconográfica, en primer lugar, se identifican las problemáticas y las tensiones que se ponen de manifiesto en cada uno de los artículos. En segundo lugar, se organizantres ejes de los cuales en esta ocasión se presentael relacionado con la política de descentralización educativa en la provincia de Río Negro. Este tipo de prensase constituye en una herramienta de poder político,generadora de debates y un medio de presión que viabiliza la apropiación y la defensa de derechos y distintas formas de resistencia ante el avance neoliberal que se consolidará en los noventaThis article represents a new advance on the content of the written press discourse of a teacher’s union, the Union of Education Workers of Río Negro, during the last three years of the government of Raúl Alfonsín. An attempt is made to elucidate the discursive warping through the eleven journals called "Quimán", published regularly and systematically during the years 1987-1989. The analysis focuses on one of the sections entitled"Topics in debate", whichappearswith greater recurrence in ten copies. To unravel the textual and iconographic plot, in the first place, the problems and tensions that are revealed in each of the articles are identified. In the second place, three axes are organized, of which on this occasion the one related to the educational decentralization policy in the province of Río Negro is presented. This type of press is a tool of political power, generating debates and a means of pressure that enables the appropriation and defense of rights and different forms of resistance to the neoliberal advance that will be consolidated in the nineties.Fil: Salerno, Nancy Liliana. Universidad Nacional de Comahue. Neuquén; ArgentinaFil: Silva, Nora Antonia. Universidad Nacional de Comahue. Neuquén; ArgentinaFil: Tarantino, Susana Ana María. Universidad Nacional de Comahue. Neuquén; Argentin

Artefactos culturales de la prensa gremial docente de la provincia de Rio Negro (1990-2000)

El presente trabajo constituye una aproximación al contenido del discurso de la prensa gremial escrita en relación con el campo educativo, específicamente de un gremio docente provincial, la Unión de Trabajadores de la Educación de Río Negro (Un TER) durante la década del noventa bajo los gobiernos sucesivos de Carlos Saúl Menem (1989-1999). Este período se caracterizó por el recrudecimiento de las medidas neoliberales. Se busca significar la trama discursiva en el periódico “La escuela en marcha”, las “Memorias”; los cuadernos de capacitación y divulgación llamados “La Un TER en la escuela”; y en tres ejemplares anuales de las revistas “Quimán”.El análisis de estos artefactos culturales permite indagar sobre su conceptualización, funciones y relevancia que lograron en un arco temporal que abarcó desde 1993 a 1999. Se intentará dilucidar, por un lado, si se constituyeron en soportes de información, reflexión y formación, para contra-argumentar el discurso hegemónico y por el otro, si actuaron como herramientas valiosas de lucha y resistencia, frente al avance de políticas de ajuste y descentralización de la educación públicaThe present work constitutes an approach to the content of the speech of the written trade union press in relation to the educational field; specifically of a provincial educational union, the Union of Workers of the Education of Río Negro (UnTER) during the nineties under the Carlos Saúl Menem successive governments (1989-1999). This period was distinguish due to the increase of neoliberal measures.The aim of this article is to signify the discursive plot in the newspaper "La Escuela en marcha” "Memorias"; the training and dissemination notebooks called “La UnTER en la escuela”; and in three annual copies of the “Quimán” magazines.The analysis of these cultural devices allows us to inquire about their conceptualization, functions and relevance that they achieved in a time arc that spanned from 1993 to 1999. An attempt will be made to elucidate, on the one hand, to elucidate if these cultural mechanisms acted as supports for information, reflection and training, to counter -to argue the hegemonic discourse and, on the other hand, if they acted as valuable tools of struggle and resistance, in the presence of the advancement of policies of adjustment and decentralization of public education.Fil: Salerno, Nancy Liliana. Universidad Nacional del Comahue. Neuquén; ArgentinaFil: Silva, Nora Antonia. Universidad Nacional del Comahue. Neuquén; ArgentinaFil: Tarantino, Susana Ana María. Universidad Nacional del Comahue. ISFD Nº 12. Neuquén; Argentin

Statin-Induced Myopathy: Translational Studies from Preclinical to Clinical Evidence

Statins are the most prescribed and effective drugs to treat cardiovascular diseases (CVD). Nevertheless, these drugs can be responsible for skeletal muscle toxicity which leads to reduced compliance. The discontinuation of therapy increases the incidence of CVD. Thus, it is essential to assess the risk. In fact, many studies have been performed at preclinical and clinical level to investigate pathophysiological mechanisms and clinical implications of statin myotoxicity. Consequently, new toxicological aspects and new biomarkers have arisen. Indeed, these drugs may affect gene transcription and ion transport and contribute to muscle function impairment. Identifying a marker of toxicity is important to prevent or to cure statin induced myopathy while assuring the right therapy for hypercholesterolemia and counteracting CVD. In this review we focused on the mechanisms of muscle damage discovered in preclinical and clinical studies and highlighted the pathological situations in which statin therapy should be avoided. In this context, preventive or substitutive therapies should also be evaluated

Ovariectomy results in inbred strain-specific increases in anxiety-like behavior in mice.

Women are at an increased risk for developing affective disorders during times of hormonal flux, including menopause when the ovaries cease production of estrogen. However, while all women undergo menopause, not all develop an affective disorder. Increased vulnerability can result from genetic predisposition, environmental factors and gene by environment interactions. In order to investigate interactions between genetic background and estrogen depletion, we performed bilateral ovariectomy, a surgical procedure that results in estrogen depletion and is thought to model the post-menopausal state, in a genetically defined panel of 37 inbred mouse strains. Seventeen days post-ovariectomy, we assessed behavior in two standard rodent assays of anxiety- and depressive-like behavior, the open field and forced swim tests. We detected a significant interaction between ovariectomy and genetic background on anxiety-like behavior in the open field. No strain specific effects of ovariectomy were observed in the forced swim assay. However, we did observe significant strain effects for all behaviors in both the open field and forced swim tests. This study is the largest to date to look at the effects of ovariectomy on behavior and provides evidence that ovariectomy interacts with genetic background to alter anxiety-like behavior in an animal model of menopause. Physiol Behav 2016 Sep 29; 167:404-41

Long-term treatment with romiplostim and treatment-free platelet responses in children with chronic immune thrombocytopenia

Children with immune thrombocytopenia for ≥6 months completing a romiplostim study received weekly subcutaneous romiplostim (1- 10 μg/kg targeting platelet counts of 50-200×10/L) in this extension to examine romiplostim's long-term safety and efficacy. Sixty-five children received romiplostim for a median of 2.6 years (range: 0.1-7.0 years). Median baseline age was 11 years (range: 3-18 years) and platelet count was 28×10/L (range: 2-458×10/L). No patient discontinued treatment for an adverse event. Median average weekly dose was 4.8 mg/kg (range: 0.1-10 mg/kg); median platelet counts remained >50×10/L, starting at week 2. Nearly all patients (94%) had ≥1 platelet response (≥50×10/L, no rescue medication in the previous 4 weeks), 72% had responded at ≥75% of visits, and 58% had responded at ≥90% of visits. Treatment-free response (platelets ≥50×10/L ≥24 weeks without immune thrombocytopenia treatment) was seen in 15 of 65 patients while withholding romiplostim doses. At onset of treatment-free response, the nine girls and six boys had a median immune thrombocytopenia duration of four years (range: 1-12 years) and had received romiplostim for two years (range: 1-6 years). At last observation, treatment-free responses lasted for a median of one year (range: 0.4- 2.1 years), with 14 of 15 patients still in treatment-free response. Younger age at first dose and platelet count >200×10/L in the first four weeks were associated with treatment-free responses. In this 7-year open-label extension, three-quarters of the patients responded ≥75% of the time, and romiplostim was well tolerated, with no substantial treatment-related adverse events. Importantly, 23% of children maintained treatment-free platelet responses while withholding romiplostim and all other immune thrombocytopenia medications for ≥6 months

Elucidating the Contribution of Skeletal Muscle Ion Channels to Amyotrophic Lateral Sclerosis in search of new therapeutic options

The discovery of pathogenetic mechanisms is essential to identify new therapeutic approaches in Amyotrophic Lateral Sclerosis (ALS). Here we investigated the role of the most important ion channels in skeletal muscle of an ALS animal model (MLC/SOD1 G93A ) carrying a mutated SOD1 exclusively in this tissue, avoiding motor-neuron involvement. Ion channels are fundamental proteins for muscle function, and also to sustain neuromuscular junction and nerve integrity. By a multivariate statistical analysis, using machine learning algorithms, we identified the discriminant genes in MLC/SOD1 G93A mice. Surprisingly, the expression of ClC-1 chloride channel, present only in skeletal muscle, was reduced. Also, the expression of Protein Kinase-C, known to control ClC-1 activity, was increased, causing its inhibition. The functional characterization confirmed the reduction of ClC-1 activity, leading to hyperexcitability and impaired relaxation. The increased expression of ion channel coupled AMPA-receptor may contribute to sustained depolarization and functional impairment. Also, the decreased expression of irisin, a muscle-secreted peptide protecting brain function, may disturb muscle-nerve connection. Interestingly, the in-vitro application of chelerythrine or acetazolamide, restored ClC-1 activity and sarcolemma hyperexcitability in these mice. These findings show that ion channel function impairment in skeletal muscle may lead to motor-neuron increased vulnerability, and opens the possibility to investigate on new compounds as promising therapy