Therapeutic Action and Gene Therapy for Parkinson’s Disease

La enfermedad de Parkinson (EP) cuenta en la actualidad con un gran número de alternativas terapéuticas, pero ninguna de ellas es capaz de llegar a la curación por sí misma, aunque sí tienen una importante repercusión sintomática. Así surge el interés por nuevas alternativas terapéuticas como el trasplante celular, la infusión del Factor Neurotrópico Derivado de la Glía (GDNF), la terapia celular o la terapia génica. En esta revisión se pretende dar una mirada general tanto de las terapias que actualmente existen como de las presentes y futuras líneas de investigación, destacando el papel de la terapia génica. Posteriormente, se revisan las diferentes variantes que podemos encontrar dentro de la terapia génica aplicada a la EP, tanto una terapia génica sintomática, aumentando la cantidad de dopamina en el cerebro, como una terapia génica centrada en la modificación de la enfermedad, para la que es fundamental la familia de ligandos de las células gliales. Debemos dejar claro, también, que estas líneas de investigación están aún muy lejos de aplicación clínica.There are numerous therapeutic alternatives for the treatment of Parkinson’s disease (PD). However, none of this can stop the progression of this disease, although they do have major symptomatic benefit. Thus, interest arises in new therapeutic alternatives such as cell transplantation, glial cell line-derived neurotrophic factor (GDNF) infusion, cell therapy or gene therapy. This review presents a general overview of current therapies used for PD and future lines of research, highlighting the role of gene therapy. The different gene therapy approaches for PD are revised. These include a symptomatic gene therapy, which aims to restore dopamine levels in the brain, and a therapy focused on the modification of the disease, for which the glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) plays a fundamental role. Finally, the authors conclude that these lines of research are still far from clinical application

Intentional Storytelling to Sustain Low-cost/Free Breast Cancer Services: A Latina Example of Community-driven Advocacy

Background: Community-based public health advocacy efforts are crucial to sustaining the low-cost/free breast cancer services that support underserved populations. Objectives: We introduce two ways in which narrative theory may be a useful tool for developing advocacy materials and provide an example, using a community–academic partnership to promote Latina breast health in Chicago, Illinois. Methods: Community and academic partners 1) engaged 25 Spanish-speaking Latinas in an advocacy workshop, 2) leveraged narrative theory to develop multi-media advocacy materials, and 3) disseminated materials to policymakers. Lessons Learned: Our project highlights 1) that narrative theory may be useful to describe how Latinas engage policy-makers in relation to their needs and cultural norms, 2) the importance of flexibility and offering community members multiple options to engage policymakers, and 3) the importance of leveraging partners’ complementary strengths. Conclusions: Narrative theory may be a useful tool for developing advocacy materials in community–academic partnerships

Effects of Cover Whitening Concentrations on the Microclimate and on the Development and Yield of Tomato (Lycopersicon esculentum Mill.) Inside Mediterranean Greenhouses

This work analyzes the influence of whitening a greenhouse roof on the microclimate and yield of a tomato crop. In the west sectors of two multi-span greenhouses, a whitening concentration of 0.250 kg L−1 was used as a control. In an autumn–winter cycle, a lower (0.125 kg L−1) and an increased (0.500 kg L−1) concentration were used in the east sectors of greenhouses 1 and 2. In a spring–summer cycle, the whitening concentrations in the east were varied depending on outside temperature. The effect of whitening on photosynthetic activity, production, plants’ morphological parameters, and the quality of the fruits were also analyzed. To evaluate the effect on microclimate, solar and photosynthetically active (PAR) radiations, air and soil temperatures, and heat flux in the soil were measured in greenhouse 1. Results show that excessive whitening leads to reductions of inside PAR radiation that decreases photosynthesis and crop yield. A whitening concentration of 0.500 kg L−1 is proposed at the beginning of the autumn–winter crop cycle, washing the cover when inside temperature drops to 35 °C. At the end of the spring–summer cycle, a concentration of 0.125 kg L−1 is recommended when inside temperature increases to 35 °C

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Mujer y enfermedades cardiovasculares

Las enfermedades cardiovasculares (ECV) son desde hace muchos años una de las principales causas de mortalidad en el mundo, de ahí que hayan sido el foco de numerosos estudios en la medicina. Sin embargo, ni el diagnóstico ni el tratamiento han tenido siempre la misma importancia en hombres que en mujeres. Por lo general, todos estos estudios se han basado en la fisiopatología y en la clínica masculinas, realizándose ensayos con un número poco significativo de mujeres y sin tener en cuenta las múltiples diferencias que estas enfermedades presentan según el sexo. Una de estas patologías y, sin duda una de las más importantes, es la cardiopatía isquémica (CI). En esta enfermedad encontramos un gran número de características propias de la mujer que hasta hace relativamente pocos años habían pasado desapercibidas. Entre ellas, podemos destacar el importante papel que la aterosclerosis presenta en la fisiopatología femenina, así como la diabetes, que es uno de los principales factores de riesgo. No obstante, uno de los datos más relevantes es la protección hormonal que existe en la mujer, que desaparece en la menopausia, fomentando el padecimiento de esta y muchas otras ECV. Todo esto, entre muchos otros factores, desemboca en una clínica diferente en la mujer que debe conocerse y reconocerse para dar un diagnóstico y un tratamiento adecuados a las características de la patología

Effects of Cover Whitening Concentrations on the Microclimate and on the Development and Yield of Tomato (Lycopersicon esculentum Mill.) Inside Mediterranean Greenhouses

This work analyzes the influence of whitening a greenhouse roof on the microclimate and yield of a tomato crop. In the west sectors of two multi-span greenhouses, a whitening concentration of 0.250 kg L−1 was used as a control. In an autumn–winter cycle, a lower (0.125 kg L−1) and an increased (0.500 kg L−1) concentration were used in the east sectors of greenhouses 1 and 2. In a spring–summer cycle, the whitening concentrations in the east were varied depending on outside temperature. The effect of whitening on photosynthetic activity, production, plants’ morphological parameters, and the quality of the fruits were also analyzed. To evaluate the effect on microclimate, solar and photosynthetically active (PAR) radiations, air and soil temperatures, and heat flux in the soil were measured in greenhouse 1. Results show that excessive whitening leads to reductions of inside PAR radiation that decreases photosynthesis and crop yield. A whitening concentration of 0.500 kg L−1 is proposed at the beginning of the autumn–winter crop cycle, washing the cover when inside temperature drops to 35 °C. At the end of the spring–summer cycle, a concentration of 0.125 kg L−1 is recommended when inside temperature increases to 35 °C

Angiotensin II Inhibits Insulin Receptor Signaling in Adipose Cells

Angiotensin II (Ang II) is a critical regulator of insulin signaling in the cardiovascular system and metabolic tissues. However, in adipose cells, the regulatory role of Ang II on insulin actions remains to be elucidated. The effect of Ang II on insulin-induced insulin receptor (IR) phosphorylation, Akt activation, and glucose uptake was examined in 3T3-L1 adipocytes. In these cells, Ang II specifically inhibited insulin-stimulated IR and insulin receptor substrate-1 (IRS-1) tyrosine-phosphorylation, Akt activation, and glucose uptake in a time-dependent manner. These inhibitory actions were associated with increased phosphorylation of the IR at serine residues. Interestingly, Ang II-induced serine-phosphorylation of IRS was not detected, suggesting that Ang II-induced desensitization begins from IR regulation itself. PKC inhibition by BIM I restored the inhibitory effect of Ang II on insulin actions. We also found that Ang II promoted activation of several PKC isoforms, including PKCα/βI/βII/δ, and its association with the IR, particularly PKCβII, showed the highest interaction. Finally, we also found a similar regulatory effect of Ang II in isolated adipocytes, where insulin-induced Akt phosphorylation was inhibited by Ang II, an effect that was prevented by PKC inhibitors. These results suggest that Ang II may lead to insulin resistance through PKC activation in adipocytes

De la libertad y la abolición

La libertad, antónimo de la esclavitud, fue el objectivo esencial de vida de aquellos seres humanos sometidos a tan aberrante práctica. Distintas fueron las formas que, tanto ellos y quienes por motivos diversos los alentaron, usaron para obtener su propósito, que a fin de cuentas era ineludible. Esta recopilación es muestra de algunas de las vías por las que los esclavos lograron sus fines. El itinerario seguido para obtener la libertad habría de ser difícil, los obstáculos, muchas veces vistos como insalvables, sin embargo fueron vencidos con acciones de participación directa que involucraba la violencia, hasta la sutil intervención que con ingenio y astucia desplegaron quienes carentes de todo pusieron en este propósito toda su imaginación e ingenio. Acciones comunes que se repiten sin límites fronterizos con fines similares, pero que a pesar de ello adquieren rasgos propios de su entorno, entre otros muchos: las formas de dominio y la cohabitación étnica. En esta breve muestra se recogen experiencias iberoamericanas acaecidas en periodos diferentes que cubren desde los tempranos destellos de rebelión del siglo XVI hasta las luchas sistematizadas del siglo XVIII. Juan Manuel de la Serna H., investigador de la Universidad Nacional Autónoma de México, asignado al Centro de Investigaciones sobre América Latina y el Caribe tiene como líneas de investigación la historia social regional de México y el Caribe. Ha trabajado sobre la esclavitud de los africanos y sus descendientes desde varias perspectivas

Plan Andaluz de Atención Integrada a Pacientes con Enfermedades Crónicas

Vigencia del plan 2012-2016. Publicado en la página web de la Consejería de Salud y Bienestar Social: www.juntadeandalucia.es/salud (Consejería de Salud y Bienestar Social / Ciudadanía / Quiénes somos / Planes y Estrategias)YesEl envejecimiento natural de la población y el aumento de las enfermedades crónicas en los últimos años está obligando a que los sistemas sanitarios adapten sus recursos y los reorienten para ofrecer una atención integral a estos pacientes. De hecho, las patologías crónicas son, en la actualidad, responsables del 59% de las muertes en el mundo y copan más del 70% del gasto sanitario, y ésto nos obliga a continuar emprendiendo nuevas actuaciones. El Sistema Sanitario Público de Andalucía tiene una orientación, desde hace años, hacia los pacientes con enfermedades crónicas. Esto se refleja, tanto en la cartera de servicio de Atención Primaria, como en la puesta en marcha de herramientas orientadas a facilitar la accesibilidad, la continuidad asistencial y el automanejo de la propia situación de salud. También ha dado respuesta a las nuevas necesidades de la ciudadanía, impulsando el desarrollo de nuevas competencias profesionales y favoreciendo nuevos espacios asistenciales más cercanos y accesibles, que favorezcan el que cada paciente con enfermedad crónica y sus cuidadores, se sientan únicos

Discovering HIV related information by means of association rules and machine learning

Acquired immunodeficiency syndrome (AIDS) is still one of the main health problems worldwide. It is therefore essential to keep making progress in improving the prognosis and quality of life of affected patients. One way to advance along this pathway is to uncover connections between other disorders associated with HIV/AIDS-so that they can be anticipated and possibly mitigated. We propose to achieve this by using Association Rules (ARs). They allow us to represent the dependencies between a number of diseases and other specific diseases. However, classical techniques systematically generate every AR meeting some minimal conditions on data frequency, hence generating a vast amount of uninteresting ARs, which need to be filtered out. The lack of manually annotated ARs has favored unsupervised filtering, even though they produce limited results. In this paper, we propose a semi-supervised system, able to identify relevant ARs among HIV-related diseases with a minimal amount of annotated training data. Our system has been able to extract a good number of relationships between HIV-related diseases that have been previously detected in the literature but are scattered and are often little known. Furthermore, a number of plausible new relationships have shown up which deserve further investigation by qualified medical experts