The transition from linear to highly branched poly(beta-amino ester)s: Branching matters for gene delivery

Nonviral gene therapy holds great promise but has not delivered treatments for clinical application to date. Lack of safe and efficient gene delivery vectors is the major hurdle. Among nonviral gene delivery vectors, poly(beta-amino ester)s are one of the most versatile candidates because of their wide monomer availability, high polymer flexibility, and superior gene transfection performance both in vitro and in vivo. However, to date, all research has been focused on vectors with a linear structure. A well-accepted view is that dendritic or branched polymers have greater potential as gene delivery vectors because of their three-dimensional structure and multiple terminal groups. Nevertheless, to date, the synthesis of dendritic or branched polymers has been proven to be a well-known challenge. We report the design and synthesis of highly branched poly(beta-amino ester)s (HPAEs) via a one-pot "A2 + B3 + C2"&-type Michael addition approach and evaluate their potential as gene delivery vectors. We find that the branched structure can significantly enhance the transfection efficiency of poly(beta-amino ester)s: Up to an 8521-fold enhancement in transfection efficiency was observed across 12 cell types ranging from cell lines, primary cells, to stem cells, over their corresponding linear poly(beta-amino ester)s (LPAEs) and the commercial transfection reagents polyethyleneimine, SuperFect, and Lipofectamine 2000...This work was funded by Science Foundation Ireland (SFI), a Technology Innovation and Development Award (14/TIDA/2367), an Industry Fellowship (15/IFA/3037), the Principal Investigator Program [10/IN.1/B2981(T)], an Investigator Award (12/IP/1688), the Health Research Board of Ireland (HRA-POR-2013-412), and the National Natural Science Foundation of China (130-0401180007). The atomic force microscope used for this work was funded by SFI (SFI07/IN1/B931

Tuberculosis vertebral

Introduction: tuberculosis is an infectious disease. It is a major cause of disability and death in many parts of the world. Pulmonary location is the most common, where a dissemination of the bacillus may occur and infect other organs and tissues, leading to extrapulmonary tuberculosis, including the spine. Clinical case: the case of a patient admitted in a closed-treatment unit in Pinar del Río city presented vertebral extrapulmonary tuberculosis, who initially presented respiratory symptoms and poor general status. A computed tomography [CT] of the mediastinum showed osseous lesions at vertebral level. Current treatment provided a favorable improvement. Conclusions: extrapulmonary clinical presentation is less common; however, its diagnosis is very important for this very vulnerable population group.Introducción: la tuberculosis es una enfermedad infecciosa. Es una importante causa de incapacidad y muerte en muchas zonas del mundo. Además de la localización pulmonar, que es la más frecuente, puede ocurrir una diseminación del bacilo hacia otros órganos, dando lugar a la llamada tuberculosis extrapulmonar, que puede afectar cualquier órgano o tejido, incluyendo la columna vertebral.Caso clínico: se presenta un caso con tuberculosis vertebral en un paciente de una institución cerrada de la ciudad de Pinar del Río; este debutó inicialmente con síntomas respiratorios y toma del estado general. Se le realizó una tomografía axial computarizada de mediastino que mostró lesiones óseas a nivel vertebral. El tratamiento actual resultó favorable. Conclusiones: la forma clínica extrapulmonar es de presentación menos frecuente, sin embargo, su diagnóstico es de mucha importancia en este grupo poblacional muy vulnerable

Spinal tuberculosis

Introducción: la tuberculosis es una enfermedad infecciosa. Es una importante causa de incapacidad y muerte en muchas zonas del mundo. Además de la localización pulmonar, que es la más frecuente, puede ocurrir una diseminación del bacilo hacia otros órganos, dando lugar a la llamada tuberculosis extrapulmonar, que puede afectar cualquier órgano o tejido, incluyendo la columna vertebral.Caso clínico: se presenta un caso con tuberculosis vertebral en un paciente de una institución cerrada de la ciudad de Pinar del Río; este debutó inicialmente con síntomas respiratorios y toma del estado general. Se le realizó una tomografía axial computarizada de mediastino que mostró lesiones óseas a nivel vertebral. El tratamiento actual resultó favorable. Conclusiones: la forma clínica extrapulmonar es de presentación menos frecuente, sin embargo, su diagnóstico es de mucha importancia en este grupo poblacional muy vulnerable.Introduction: tuberculosis is an infectious disease. It is a major cause of disability and death in many parts of the world. Pulmonary location is the most common, where a dissemination of the bacillus may occur and infect other organs and tissues, leading to extrapulmonary tuberculosis, including the spine. Clinical case: the case of a patient admitted in a closed-treatment unit in Pinar del Río city presented vertebral extrapulmonary tuberculosis, who initially presented respiratory symptoms and poor general status. A computed tomography [CT] of the mediastinum showed osseous lesions at vertebral level. Current treatment provided a favorable improvement. Conclusions: extrapulmonary clinical presentation is less common; however, its diagnosis is very important for this very vulnerable population group

Evaluación del Programa de Tuberculosis en instituciones cerradas

Introduction: assessments are vital to the success of any program to measure and analyze the fulfillment of the objectives. The most commonly used is based on the evaluation of three components: structure, process and results. Objective: to evaluate the national program for tuberculosis control in closed institutions of Pinar del Río. Material and method: an evaluative research was conducted with a retrospective study design. Criteria and variables, rating scale, operational description indicators and standards in the three components of the program were defined. The information was obtained from statistical records, histories and epidemiological picture. The evaluation of indicators was conducted by comparing the results obtained with the standards established in the national program for tuberculosis control of the Ministry of Public Health of Cuba and other closed institutions set by health, giving the categories of good, fair or wrong. Results: adequate coverage, training of human resources, materials and quality control in the component structure, treatment interruptions chemoprophylaxis of contacts made in late diagnosis and secondary health care in the process component identified , average age 36, increased incidence and prevalence in the provincial closed institution as the main component results. Conclusions: the program is evaluated regularly. The research identified gaps in the prevention and control actions carried out by providing objective and scientific operation thereof, useful in decision making evidence.Introducción: las evaluaciones son vitales para el éxito de cualquier programa al medir y analizar el cumplimiento de los objetivos trazados. La más utilizada se basa en la evaluación de los tres componentes: estructura, proceso y resultados. Objetivo: evaluar el programa nacional de control de la tuberculosis en instituciones cerradas de Pinar del Río. Material y método: se realizó una investigación evaluativa, con un diseño de estudio descriptivo retrospectivo. Se definieron criterios y variables, escala de clasificación, descripción operacional con indicadores y estándares en los tres componentes del programa. La información se obtuvo de registros estadísticos, historias y cuadro epidemiológico. Se realizó la evaluación de los indicadores, comparando el resultado obtenido con los estándares establecidos en el programa nacional de control de la tuberculosis del Ministerio de Salud Pública de Cuba y otros fijados por las instituciones cerradas de salud, otorgándoles las categorías de bien, regular o mal. Resultados: se identificó la adecuada cobertura, capacitación de recursos humanos, materiales y el control de calidad en el componente de estructura, interrupciones en el tratamiento de quimioprofilaxis de los contactos, diagnósticos tardíos y realizados en la atención secundaria de salud en el componente de proceso, media de edad de 36 años, incremento en la incidencia y predominio en la institución cerrada provincial como los principales del componente de resultados. Conclusiones: el programa se evaluó de regular. La investigación permitió identificar brechas existentes en las acciones de prevención y control realizadas, aportando evidencias objetivas y científicas del funcionamiento del mismo, útiles en la toma de decisiones

Evaluación del Programa de Tuberculosis en instituciones cerradas

Introduction: assessments are vital to the success of any program to measure and analyze the fulfillment of the objectives. The most commonly used is based on the evaluation of three components: structure, process and results. Objective: to evaluate the national program for tuberculosis control in closed institutions of Pinar del Río. Material and method: an evaluative research was conducted with a retrospective study design. Criteria and variables, rating scale, operational description indicators and standards in the three components of the program were defined. The information was obtained from statistical records, histories and epidemiological picture. The evaluation of indicators was conducted by comparing the results obtained with the standards established in the national program for tuberculosis control of the Ministry of Public Health of Cuba and other closed institutions set by health, giving the categories of good, fair or wrong. Results: adequate coverage, training of human resources, materials and quality control in the component structure, treatment interruptions chemoprophylaxis of contacts made in late diagnosis and secondary health care in the process component identified , average age 36, increased incidence and prevalence in the provincial closed institution as the main component results. Conclusions: the program is evaluated regularly. The research identified gaps in the prevention and control actions carried out by providing objective and scientific operation thereof, useful in decision making evidence.Introducción: las evaluaciones son vitales para el éxito de cualquier programa al medir y analizar el cumplimiento de los objetivos trazados. La más utilizada se basa en la evaluación de los tres componentes: estructura, proceso y resultados. Objetivo: evaluar el programa nacional de control de la tuberculosis en instituciones cerradas de Pinar del Río. Material y método: se realizó una investigación evaluativa, con un diseño de estudio descriptivo retrospectivo. Se definieron criterios y variables, escala de clasificación, descripción operacional con indicadores y estándares en los tres componentes del programa. La información se obtuvo de registros estadísticos, historias y cuadro epidemiológico. Se realizó la evaluación de los indicadores, comparando el resultado obtenido con los estándares establecidos en el programa nacional de control de la tuberculosis del Ministerio de Salud Pública de Cuba y otros fijados por las instituciones cerradas de salud, otorgándoles las categorías de bien, regular o mal. Resultados: se identificó la adecuada cobertura, capacitación de recursos humanos, materiales y el control de calidad en el componente de estructura, interrupciones en el tratamiento de quimioprofilaxis de los contactos, diagnósticos tardíos y realizados en la atención secundaria de salud en el componente de proceso, media de edad de 36 años, incremento en la incidencia y predominio en la institución cerrada provincial como los principales del componente de resultados. Conclusiones: el programa se evaluó de regular. La investigación permitió identificar brechas existentes en las acciones de prevención y control realizadas, aportando evidencias objetivas y científicas del funcionamiento del mismo, útiles en la toma de decisiones

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016

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

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

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries(1,2). However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world(3) and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health(4,5). However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol-which is a marker of cardiovascular riskchanged from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million-4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.Peer reviewe