Anti-Acanthamoeba Activity of Brominated Sesquiterpenes from Laurencia johnstonii

Focusedonourinteresttodevelopnovelantiparasisticagents,thepresentstudywasaimed to evaluate the biological activity of an extract of Laurencia johnstonii collected in Baja California Sur, Mexico, against an Acantamoeba castellanii Neff strain. Bioassay-guided fractionation allowed us to identify the amoebicidal diastereoisomers α-bromocuparane (4) and α-isobromocuparane (5). Furthermore, bromination of the inactive laurinterol (1) and isolaurinterol (2) yielded four halogenated derivatives, (6)–(9), which improved the activity of the natural sesquiterpenes. Among them, the most active compound was 3α-bromojohnstane (7), a sesquiterpene derivative which possesses a novel carbon skeleton johnstane

Bactericide, Antioxidant and Cytotoxic Activities from Marine Algae of Genus Laurencia Collected in Baja California Sur, Mexico

Abstract Background and Objective: Marine environment represents countless and diverse resource for new drugs to combat major diseases. Extracts from four Laurencia species ( L. johnstonii, L. pacifica, L. gardneri and L. papillosa) from Baja California Sur, México were evaluated for their antioxidant, antibacterial and cytotoxic activity. Methodology: The antioxidants activity of Laurencia sp. were evaluated using the radical scavenging activity in three in vitro radicals: 1,1-Diphenyl-2-picrylhydrazyl (DPPH), 2,2'-Azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) and nitric oxide (NO). The antibacterial activity was evaluated by the broth microdilution method to determinate the Minimum Inhibitory Concentrations (MIC) against Staphylococcus aureus, Bacillus subtilis, Enterococcus faecalis, Micrococcus luteus, Pseudomonas aerugi nosa and Klebsiella pneumoniae . The cytotoxicity was analyzed on HeLa (cervix adenocarcinoma) and Vero (kidney epithelial) cells, using the reduction of tetrazolium salt WST-1. Results: The seaweed of genus Laurencia demonstrated an overall low activity, with half maximal effective concentration (EC50) values >1.5 mg mLG1. Laurencia pacifica showed the best biocide effects with MIC of 6.25 µg mLG1 against Gram positive bacterial and cytotoxic potential with half inhibitory concentration (IC50) <30 µg mLG1 against Vero and HeLa cells. Conclusion: Some Laurencia species have a great antibacterial and cytotoxic activity which could be considered for future studies

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Impacts of the Tropical Pacific/Indian Oceans on the Seasonal Cycle of the West African Monsoon

The current consensus is that drought has developed in the Sahel during the second half of the twentieth century as a result of remote effects of oceanic anomalies amplified by local land–atmosphere interactions. This paper focuses on the impacts of oceanic anomalies upon West African climate and specifically aims to identify those from SST anomalies in the Pacific/Indian Oceans during spring and summer seasons, when they were significant. Idealized sensitivity experiments are performed with four atmospheric general circulation models (AGCMs). The prescribed SST patterns used in the AGCMs are based on the leading mode of covariability between SST anomalies over the Pacific/Indian Oceans and summer rainfall over West Africa. The results show that such oceanic anomalies in the Pacific/Indian Ocean lead to a northward shift of an anomalous dry belt from the Gulf of Guinea to the Sahel as the season advances. In the Sahel, the magnitude of rainfall anomalies is comparable to that obtained by other authors using SST anomalies confined to the proximity of the Atlantic Ocean. The mechanism connecting the Pacific/Indian SST anomalies with West African rainfall has a strong seasonal cycle. In spring (May and June), anomalous subsidence develops over both the Maritime Continent and the equatorial Atlantic in response to the enhanced equatorial heating. Precipitation increases over continental West Africa in association with stronger zonal convergence of moisture. In addition, precipitation decreases over the Gulf of Guinea. During the monsoon peak (July and August), the SST anomalies move westward over the equatorial Pacific and the two regions where subsidence occurred earlier in the seasons merge over West Africa. The monsoon weakens and rainfall decreases over the Sahel, especially in August.Peer reviewe

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Ansiedad, depresión, afecto negativo y positivo asociados con el consumo de tabaco en universitarias

Introduction: In recent years the prevalence of tobacco consumption in women has increased significantly, which results in high costs at economic, family and health. Particularly, university women is a sector of the population in which is essential to carry out research on the factors associated with tobacco consumption, in order to develop prevention and intervention strategies to stop smoking. Objective: determine the association between tobacco consumption and nicotine dependence with anxiety, depression and negative and positive affect in female university students. Method: 72 female university smokers who voluntarily attended to a smoking cessation treatment in the Center of Attention and Orientation for Students (CAOPE) of the Iztacala School of Higher Studies, UNAM. Different instruments were applied to assess the pattern of consumption, the levels of dependence, depressive and anxiety symptoms, and positive and negative affect levels. Results: all emotional factors (anxiety, depression, positive and negative affect) incorporated in a model, adequately predicted both the consumption pattern and the level of dependence. In female university smokers, anxiety increased the risk of tobacco consumption and nicotine dependence. Discussion and conclusions: these results should be considered when designing prevention and treatment strategies to stop smoking in female university students, including cognitive-behavioral strategies. It is recommended to consider strategies for emotional self-control, problem solution and anxiety coping when working with smoking prevention.----------------------- Introducción: en los últimos años, la prevalencia del consumo de tabaco en mujeres se ha incrementado de manera significativa a nivel nacional e internacional. Esto genera altos costos a nivel económico, familiar y de salud. Un sector de la población en el que resulta particularmente indispensable realizar investigación sobre los factores asociados con el consumo de tabaco es el de mujeres universitarias, a fin de incidir en el desarrollo de estrategias de prevención y en las intervenciones para dejar de fumar. Objetivo: determinar la asociación, entre el consumo de tabaco, la dependencia de la nicotina y enfermedades como ansiedad, depresión y afecto negativo y positivo en universitarias. Método: 72 universitarias fumadoras que asistieron de manera voluntaria a solicitar tratamiento para dejar de fumar al Centro de Atención y Orientación para Estudiantes (CAOPE) de la Facultad de Estudios Superiores Iztacala, de la Universidad Autónoma de México; se aplicaron diferentes instrumentos para conocer el patrón de consumo, el nivel de dependencia, la sintomatología depresiva y de ansiedad, y los afectos positivo y negativo. Resultados: todos los factores emocionales (ansiedad, depresión, afectos positivo y negativo) integrados en un modelo son predictores, tanto del patrón del consumo como del nivel de dependencia en universitarias; la ansiedad, en específico, aumenta el riesgo de consumo de tabaco y de presentar dependencia de la nicotina. Discusión y conclusiones: dichos resultados se deben considerar para diseñar estrategias de prevención y tratamiento para dejar de fumar en mujeres universitarias, en las que se incluyan técnicas cognitivo-conductuales. En cuanto a la prevención, es indispensable incluir estrategias enfocadas al autocontrol de emociones, a la solución de problemas y al afrontamiento para el manejo de la ansiedad

Anti-<i>Acanthamoeba</i> Activity of Brominated Sesquiterpenes from <i>Laurencia johnstonii</i>

Focused on our interest to develop novel antiparasistic agents, the present study was aimed to evaluate the biological activity of an extract of Laurencia johnstonii collected in Baja California Sur, Mexico, against an Acantamoeba castellanii Neff strain. Bioassay-guided fractionation allowed us to identify the amoebicidal diastereoisomers &#945;-bromocuparane (4) and &#945;-isobromocuparane (5). Furthermore, bromination of the inactive laurinterol (1) and isolaurinterol (2) yielded four halogenated derivatives, (6)&#8315;(9), which improved the activity of the natural sesquiterpenes. Among them, the most active compound was 3&#945;-bromojohnstane (7), a sesquiterpene derivative which possesses a novel carbon skeleton johnstane

Aplicación práctica de la resolución 2003 de 2014 y sus estándares de habilitación: en servicios prestados por la ese hospital Santa Margarita del municipio de Copacabana.

El Sistema Obligatorio de Garantía de Calidad tiene como objetivo proveer de servicios de salud a los usuarios individuales y colectivos de manera accesible y equitativa, a través de un nivel profesional óptimo, teniendo en cuenta el balance entre beneficio, riesgo y costo, con el propósito de disminuir el riesgo en la atención en salud y garantizar un servicio con calidad. Las Entidades Departamentales y Distritales de Salud deben contar con un equipo humano de carácter interdisciplinario, responsable de la administración del Registro Especial de Prestadores de Servicios de Salud y de la verificación del cumplimiento de las condiciones para la habilitación, así como de las demás actividades relacionadas con este proceso; la formación académica de dicho personal está a cargo de instituciones educativas de nivel superior con el fin de alcanzar los objetivos planteados por la norma. La verificación de los estándares que plantea la Resolución 2003 de 2014, constituye un beneficio tanto para los estudiantes de la Universidad Cooperativa de Colombia, como para la ESE Hospital Santa Margarita de Copacabana; como producto de esta actividad académica se genera un informe que le permite a los estudiantes aplicar sus conocimientos a la práctica profesional y para la institución se convierte en oportunidades de mejora.1. Tabla de contenido. -- 2. Introducción. -- 3. Justificación. -- 4. Antecedentes. -- 5. Objetivo general. -- a. Objetivos específicos. -- 6. Producto. -- 7. Alcance. -- 8. Metodología. -- a. Cronograma de actividades. -- i. Planeación de la auditoria. -- ii. Ejecución de la auditoria. -- iii. Finalización de auditoria. -- 9. Diagnóstico. -- 10. Limitaciones y fortalezas. -- a. Fortalezas. -- b. Limitaciones y oportunidades de mejora. -- 11. Conclusiones y recomendaciones. -- 12. Bibliografía. -- 13. Anexos. -- Anexo A. Informe de visita de verificación de las condiciones del sistema único de habilitación a los prestadores de servicios de salud. [email protected]@[email protected]@[email protected]@[email protected]@[email protected]

Laurequinone, a Lead Compound against <i>Leishmania</i>

Among neglected tropical diseases, leishmaniasis is one of the leading causes, not only of deaths but also of disability-adjusted life years. This disease, caused by protozoan parasites of the genus Leishmania, triggers different clinical manifestations, with cutaneous, mucocutaneous, and visceral forms. As existing treatments for this parasitosis are not sufficiently effective or safe for the patient, in this work, different sesquiterpenes isolated from the red alga Laurencia johnstonii have been studied for this purpose. The different compounds were tested in vitro against the promastigote and amastigote forms of Leishmania amazonensis. Different assays were also performed, including the measurement of mitochondrial potential, determination of ROS accumulation, and chromatin condensation, among others, focused on the detection of the cell death process known in this type of organism as apoptosis-like. Five compounds were identified that displayed leishmanicidal activity: laurequinone, laurinterol, debromolaurinterol, isolaurinterol, and aplysin, showing IC50 values against promastigotes of 1.87, 34.45, 12.48, 10.09, and 54.13 µM, respectively. Laurequinone was the most potent compound tested and was shown to be more effective than the reference drug miltefosine against promastigotes. Different death mechanism studies carried out showed that laurequinone appears to induce programmed cell death or apoptosis in the parasite studied. The obtained results underline the potential of this sesquiterpene as a novel anti-kinetoplastid therapeutic agent