Physiology and Pathology of Neuroimmunology: Role of Inflammation in Parkinson’s Disease

Parkinson’s disease (PD) is a neurodegenerative disease that affects 1% of the population aged 65 and over and is the second most common neurodegenerative disease next to Alzheimer’s disease. Interneuronal proteinaceous inclusions called Lewy bodies (LB) and a selective degeneration of dopaminergic neurons of the substantia nigra pars compacta (SNPC) are the main features of PD pathology. The most common clinical manifestations are rigidity, tremor, bradykinesia, postural instability, sleep disorders, alterations in gait, smell, memory, and dementia. Genetic and environmental factors are involved in PD, and, recently, oxidative stress, proteasome-mediated protein degradation, and inflammation have acquired relevance as major mechanisms of neuronal dysfunction. Increased levels of reactive oxygen and nitrogen species in the brain contribute to greater vulnerability of proteins to nitro-oxidative modification and to greater degrees of aggregation. These protein aggregates contain a variety of proteins of which α-synuclein appears to be the main structural component. Interestingly, α-synuclein can be secreted by neuronal cells and may lead the initiation and the maintenance of inflammatory events through the activation of microglia, which contributes to dopaminergic neuron depletion. New evidence also suggests that PD may be the result of an autoimmune response in which the immune cells recognize the neurons as foreign elements and would act against them, causing their death

Connections : safe spaces for women and youth in Latin America and The Caribbean

RESUMEN: Este libro se puede leer en muchos niveles. Uno de ellos puede no ser muy obvio para aquellos que están acostumbrados a leer sobre violencia e inseguridad en América Latina. Es el nivel que le da a este libro un estatus de originalidad y una contribución que va más allá de la región: el ser una forma de conocimiento destinada no solo a interpretar el mundo, sino a cambiarlo […], visibiliza la importancia de un proceso de investigación ajustado al tipo de conocimiento que produce. Aquí se conectan el proceso y el resultado, lo que debería propiciar un debate más amplio con respecto a cómo y qué sabemos de la naturaleza de la violencia y la agencia social para reducirla […]. Esta visión es particularmente relevante en contextos donde el Estado reproduce la violencia, con terribles impactos, en especial en periferias excluidas. […] El proceso de investigación abordado en este libro transgredió muchas fronteras. Hubo fronteras entre países, barreras lingüísticas, fronteras en torno a la educación, el conocimiento y la experiencia, y entre etnias, géneros y generaciones. […] este proceso reunió a académicos, activistas y líderes comunitarios de cinco países de América Latina y uno del Caribe, incluyendo comunidades indígenas en México y Guatemala […]. La violencia está en el tiempo y en el espacio y se reproduce entre las generaciones en diversos espacios de socialización. Este proceso de investigación que trasciende las fronteras, plantea una discusión que atraviesa los diferentes casos sobre cómo los déficits y las desigualdades materiales, las violencias estatales en nombre de la ‘seguridad’, las especificidades culturales, de género y generacionales de la experiencia y la comprensión de la violencia, así como las diversas formas de criminalidad, se cruzan y se reproducen a través del tiempo y el espacio. Jenny Pearce, investigadora y profesora en el Latin American and Caribbean Centre (LACC) de la London School of Economics and Political ScienceABSTRACT: This book can be read on many levels. One level may not be so obvious to those who are used to reading about violence and insecurity in Latin America. It is the level which gives this book a claim to true originality and a contribution beyond the region. This contribution is to form of scholarship aimed not only to interpret the world but to change it […], this text visibilizes the significance of the research process to the kind of knowledge that is produced. It connects process and outcome, and this should start a wider debate about how as well as what we know about the nature of violence and the social agency to reduce it […]. This is particularly relevant in contexts where the State reproduces violence, with terrible impacts on the margins. The research process discussed in this book transgressed many boundaries. There were intercountry borders, linguistic barriers, boundaries around education, knowledge and experience and between ethnicities, genders and generations. […] the research process brought together scholars and community activists and actors from five Latin American and one Caribbean country. And within Latin America there were indigenous communities in Mexico and Guatemala who participated […]. Violence is located in time and space. It is reproduced inter-generationally through varied socialisation spaces. The boundary crossing research process, raises cross case discussion about how material deficits and inequalities, state violences in the name of ‘security’, cultural, gender and generational specificities of experience and understanding of violence, and varied forms of criminality, intersect and reproduce through time and space. Professor Jenny Pearce. Latin American and Caribbean Centre (LACC), London School of Economics and Political Scienc

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

4to. Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad. Memoria académica

Este volumen acoge la memoria académica de la Cuarta edición del Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad, CITIS 2017, desarrollado entre el 29 de noviembre y el 1 de diciembre de 2017 y organizado por la Universidad Politécnica Salesiana (UPS) en su sede de Guayaquil. El Congreso ofreció un espacio para la presentación, difusión e intercambio de importantes investigaciones nacionales e internacionales ante la comunidad universitaria que se dio cita en el encuentro. El uso de herramientas tecnológicas para la gestión de los trabajos de investigación como la plataforma Open Conference Systems y la web de presentación del Congreso http://citis.blog.ups.edu.ec/, hicieron de CITIS 2017 un verdadero referente entre los congresos que se desarrollaron en el país. La preocupación de nuestra Universidad, de presentar espacios que ayuden a generar nuevos y mejores cambios en la dimensión humana y social de nuestro entorno, hace que se persiga en cada edición del evento la presentación de trabajos con calidad creciente en cuanto a su producción científica. Quienes estuvimos al frente de la organización, dejamos plasmado en estas memorias académicas el intenso y prolífico trabajo de los días de realización del Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad al alcance de todos y todas

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

Low CD36 and LOX-1 Levels and CD36 Gene Subexpression Are Associated with Metabolic Dysregulation in Older Individuals with Abdominal Obesity

Background. Obesity study in the context of scavenger receptors has been linked to atherosclerosis. CD36 and LOX-1 are important, since they have been associated with atherogenic and metabolic disease but not fat redistribution. The aim of our study was to determinate the association between CD36 and LOX-1 in presence of age and abdominal obesity. Methods. This is a cross-sectional study that included 151 healthy individuals, clinically and anthropometrically classified into two groups by age (<30 and ≥30 years old) and abdominal obesity (according to World Health Organization guidelines). We excluded individuals with any chronic and metabolic illness, use of medication, or smoking. Fasting blood samples were taken to perform determination of CD36 mRNA expression by real-time PCR, lipid profile and metabolic and low grade inflammation markers by routine methods, and soluble scavenger receptors (CD36 and LOX-1) by ELISA. Results. Individuals ≥30 years old with abdominal obesity presented high atherogenic index, lower soluble scavenger receptor levels, and subexpression of CD36 mRNA (54% less). On the other hand, individuals <30 years old with abdominal adiposity presented higher levels in the same parameters, except LOX-1 soluble levels. Conclusion. In this study, individuals over 30 years of age presented low soluble scavenger receptors levels pattern and CD36 gene subexpression, which suggest the chronic metabolic dysregulation in abdominal obesity

CCR2/CCL2 and CMKLR1/RvE1 chemokines system levels are associated with insulin resistance in rheumatoid arthritis.

Rheumatoid arthritis (RA) has been associated with insulin resistance (IR). Due to an excess in storage of white adipose tissue, IR has an inflammatory process that overlaps with RA. This is performed by the activation/migration of monocytes carried out by the CCR2/CCL2 and CMKLR1/RvE1 chemokines systems. Furthermore, these can potentiate chronic inflammation which is the central axis in the immunopathogenesis of RA. We evaluated the association between the relative expression of CCR2 and CMKLR1 and the serum levels of their ligands CCL2 and RvE1, in the context of adiposity status with IR as a comorbidity in RA. We studied 138 controls and 138 RA-patients classified with and without IR. We evaluated adiposity, RA activity, IR status and immunometabolic profiles by routine methods. Insulin, CCL2 and RvE1 serum levels were determined by ELISA. Relative expression of CCR2, CMKLR1 and RPS28 as constitutive gene by SYBR green RT-qPCR and 2-ΔΔCT method. Increased measurements were observed of body adiposity and metabolic status as follows: RA with IR>control group with IR>RA without IR> control group without IR. CCR2 and CMKLR1 relative expression was increased in RA without IR versus control without IR. CCR2: 2.3- and 1.3-fold increase and CMKLR1: 3.5- and 2.7-fold increase, respectively. Whereas, CCR2 expression correlates with CMKLR1 expression (rho = 0.331) and IR status (rho = 0.497 to 0.548). CMKLR1 expression correlates with inflammation markers (rho = 0.224 to 0.418). CCL2 levels were increased in the RA groups but levels of RvE1 were increased in RA without IR. We conclude that in RA with IR, the chemokine receptors expression pattern showed a parallel increase with their respective ligands. RA and IR in conjunction with the pathological distribution of body fat mass might exacerbate chronic inflammation. These results suggest that high CCL2 levels and compensatory RvE1 levels might not be enough to resolve the inflammation by themselves