Specialized Pro-Resolving Lipid Mediators: The Future of Chronic Pain Therapy?

Chronic pain (CP) is a severe clinical entity with devastating physical and emotional consequences for patients, which can occur in a myriad of diseases. Often, conventional treatment approaches appear to be insufficient for its management. Moreover, considering the adverse effects of traditional analgesic treatments, specialized pro-resolving lipid mediators (SPMs) have emerged as a promising alternative for CP. These include various bioactive molecules such as resolvins, maresins, and protectins, derived from ω-3 polyunsaturated fatty acids (PUFAs); and lipoxins, produced from ω-6 PUFAs. Indeed, SPMs have been demonstrated to play a central role in the regulation and resolution of the inflammation associated with CP. Furthermore, these molecules can modulate neuroinflammation and thus inhibit central and peripheral sensitizations, as well as long-term potentiation, via immunomodulation and regulation of nociceptor activity and neuronal pathways. In this context, preclinical and clinical studies have evidenced that the use of SPMs is beneficial in CP-related disorders, including rheumatic diseases, migraine, neuropathies, and others. This review integrates current preclinical and clinical knowledge on the role of SPMs as a potential therapeutic tool for the management of patients with CP

Hemoglobin Mass, Blood Volume and VO₂max of Trained and Untrained Children and Adolescents Living at Different Altitudes

Introduction: To a considerable extent, the magnitude of blood volume (BV) and hemoglobin mass (Hbmass) contribute to the maximum O(2)-uptake (VO(2)max), especially in endurance-trained athletes. However, the development of Hbmass and BV and their relationships with VO(2)max during childhood are unknown. The aim of the present cross-sectional study was to investigate Hbmass and BV and their relationships with VO(2)max in children and adolescents. In addition, the possible influence of endurance training and chronic hypoxia was evaluated. Methods: A total of 475 differently trained children and adolescents (girls n = 217, boys n = 258; untrained n = 171, endurance trained n = 304) living at two different altitudes (∼1,000 m, n = 204, ∼2,600 m, n = 271) and 9–18 years old participated in the study. The stage of puberty was determined according to Tanner; Hbmass and BV were determined by CO rebreathing; and VO(2)max was determined by cycle ergometry and for runners on the treadmill. Results: Before puberty, there was no association between training status and Hbmass or BV. During and after puberty, we found 7–10% higher values in the trained groups. Living at a moderate altitude had a uniformly positive effect of ∼7% on Hbmass in all groups and no effect on BV. The VO(2)max before, during and after puberty was strongly associated with training (pre/early puberty: boys +27%, girls +26%; mid puberty: +42% and +45%; late puberty: +43% and +47%) but not with altitude. The associated effects of training in the pre/early pubertal groups were independent of Hbmass and BV, while in the mid- and late pubertal groups, 25% of the training effect could be attributed to the elevated Hbmass. Conclusions: The associated effects of training on Hbmass and BV, resulting in increased VO(2)max, can only be observed after the onset of puberty

Diplomado de profundización en farmacovigilancia

El diplomado de profundización en farmacovigilancia hace parte del campo de formación disciplinar y se realiza como opción de grado para obtener el título de tecnólogo en regencia de farmacia. Para la elaboración de este documento se hace un resumen de los temas de mayor relevancia que se trabajaron a lo largo del curso, donde se obtuvo conocimientos sobre temas de gran importancia para el desempeño como futuros regentes de farmacia ya que no se debe desconocer la importancia de la farmacovigilancia como herramienta para prevenir y disminuir los diferentes problemas asociados al uso de medicamentos y de esta manera reducir los riesgos que se pueden producir por el uso inadecuado de los medicamentos; Algunos de los temas más relevantes fueron las generalidades de la farmacovigilancia, eventos adversos asociados al uso de medicamentos haciendo un reconocimiento de los estos, para de esta manera tratar de prevenirlos; el quehacer del farmacéutico profundizando en la descripción de los procesos del servicio farmacéutico y la relación con la farmacovigilancia y por último se hace un reconocimiento de la evaluación y efectividad de los tratamientos farmacológicos en las enfermedades de mayor incidencia en el país que son la hipertensión arterial, diabetes mellitus, enfermedad renal crónica, enfermedad cerebrovascular y dislipidemia.The in-depth diploma in pharmacovigilance is part of the disciplinary training field and is carried out as a degree option to obtain the title of technologist in pharmacy regency. For the preparation of this document, a summary of the most relevant topics that were worked on throughout the course is made, where knowledge was obtained on topics of great importance for the performance as future pharmacy regents since the importance should not be ignored of pharmacovigilance as a tool to prevent and reduce the different problems associated with the use of drugs and in this way reduce the risks that can be produced by the inappropriate use of drugs; Some of the most relevant topics were the generalities of pharmacovigilance, adverse events associated with the use of drugs, making a recognition of these, in order to try to prevent them; the work of the pharmacist deepening in the description of the processes of the pharmaceutical service and the relationship with pharmacovigilance and finally a recognition is made of the evaluation and effectiveness of pharmacological treatments in the diseases with the highest incidence in the country, which are arterial hypertension , diabetes mellitus, chronic kidney disease, cerebrovascular disease, and dyslipidemia

Nuevos enfoques moleculares en la regulación de la adipogénesis. El papel de la Conexina 43

La prevalencia de la obesidad a nivel mundial se ha incrementadorápidamente durante los últimos años debido principalmentea los cambios en el estilo de vida de la poblacióncon un aumento significativo en el consumo de energía y disminuciónde los niveles de actividad física. Es por esto quela comunidad científica está interesada en comprender deforma más profunda los mecanismos que regulan la fisiopatologíade la obesidad. Dentro de los diferentes blancos deestudio se encuentra la adipogénesis, cuyo entendimiento esfundamental para comprender el desarrollo de la obesidad ylas patologías asociadas a esta. Recientemente ha surgidoimportantes evidencias que involucran a la proteína de canalesde “Gap Junction” conexina 43 (Cx43) en la regulaciónde los procesos relacionados con adipogénesis, cuyo papeles básicamente anti-adipogénico, sin embargo, nuevas funcionesde Cx43 en la regulación de la formación del tejidoadiposo siguen descubriéndose

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.Peer reviewe