Artificial Magnetic Bacteria: Living Magnets at Room Temperature

"This is the peer reviewed version of the following article: Martín Marcos, M.A.; et al. Artificial Magnetic Bacteria: Living Magnets at Room Temperature. Advanced Functional Materials, 24(23): 3489-3493 (2014), which has been published in final form at http://dx.doi.org/10.1002/adfm.201303754 . This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."Biogenic magnetite is a fascinating example of how nature can generate functional magnetic nanostructures. Inspired by the magnetic bacteria, an attempt is made to mimic their magnetic properties, rather than their structures, to create living magnets at room temperature. The non-magnetic probiotic bacteria Lactobacillus fermentum and Bifidobacteria breve are used as bioplatforms to densely arrange superparamagnetic nanoparticles on their external surfaces, thus obtaining the artificial magnetic bacteria. Magnetic probiotic bacteria can be produced by using superparamagnetic maghemite nanoparticles assembled at their surfaces. They present a collective ferromagnetic phase at room temperature. The blocking temperature of these maghemite nanoparticles increases more than 100 K when assembled at the artificial magnetic bacteria.This work was funded by Biosearch S. A. (POSTBIO project-Agency for Innovation and Development of Andalucia IDEA) and by MINECO and FEDER (project CTQ2012–32236)

COVID-19 Severity and Survival over Time in Patients with Hematologic Malignancies: A Population-Based Registry Study

Mortality rates for COVID-19 have declined over time in the general population, but data in patients with hematologic malignancies are contradictory. We identified independent prognostic factors for COVID-19 severity and survival in unvaccinated patients with hematologic malignancies, compared mortality rates over time and versus non-cancer inpatients, and investigated post COVID-19 condition. Data were analyzed from 1166 consecutive, eligible patients with hematologic malignancies from the population-based HEMATO-MADRID registry, Spain, with COVID-19 prior to vaccination roll-out, stratified into early (February–June 2020; n = 769 (66%)) and later (July 2020–February 2021; n = 397 (34%)) cohorts. Propensity-score matched non-cancer patients were identified from the SEMI-COVID registry. A lower proportion of patients were hospitalized in the later waves (54.2%) compared to the earlier (88.6%), OR 0.15, 95%CI 0.11–0.20. The proportion of hospitalized patients admitted to the ICU was higher in the later cohort (103/215, 47.9%) compared with the early cohort (170/681, 25.0%, 2.77; 2.01–3.82). The reduced 30-day mortality between early and later cohorts of non-cancer inpatients (29.6% vs. 12.6%, OR 0.34; 0.22–0.53) was not paralleled in inpatients with hematologic malignancies (32.3% vs. 34.8%, OR 1.12; 0.81–1.5). Among evaluable patients, 27.3% had post COVID-19 condition. These findings will help inform evidence-based preventive and therapeutic strategies for patients with hematologic malignancies and COVID-19 diagnosis.Depto. de MedicinaFac. de MedicinaTRUEFundación Madrileña de Hematología y HemoterapiaFundación Leucemia y LinfomaAsociación Madrileña de Hematología y Hemoterapiapu

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI <18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For schoolaged children and adolescents, we report thinness (BMI <2 SD below the median of the WHO growth reference) and obesity (BMI >2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesit

Analys av gynnsamma affärsammansättningar för bildäck

Abstract The average price of commodities has over the past years increased significantly and already erased the real price fall seen during the 20th century. Humanity is today consuming resources corresponding to 1,5 earths which puts pressure on manufacturers to develop more sustainable and resource conservative business models. The current market for car tires isstanding before a potential change in the tires conceptual design, which opens up for manufacturers to take advantage of the situation to develop a more sustainable proposition to customers. Research up until today has mainly focused on the supply chain without including the necessary business model. Lately the holistic concept Resource Conservative Manufacturing (ResCoM) has been developed to take the full grasp of the problem. This thesis therefore focuses on finding a range of favourable business model compositions for cartires from the perspective ResCoM. Initially, this thesis investigates the ResCoM model and its requirements on a business model. Furthermore the market for car tires and the product itself is investigated thoroughly to find elements that affect the business model composition. Afterwards a tool for evaluation of thejoint effect of the products as well as the markets individual effects on the business model composition is developed in the form of a key figure. The key figure is used as an indicatorfor favourable business model compositions to meet the products, the markets and theResCoM models requirements. Finally the key figure is analysed and a top and bottom border for the range of favourable business model compositions is defined. The result illustrates that the bottom border for favourable business model composition for car tires is located at rental, whereas the top boarder stretches to, but does not include, functional sales. The developed tool has someconstraints when used and therefore the conclusion is that the purpose of the thesis has beenfulfilled to a limited extent.Sammanfattning Det genomsnittliga priset på råvaror har under det senaste århundradet ökat signifikant och raderat ut den reella prissänkning som skedde under 1900-talet. Idag använder mänskligheten resurser som motsvarar 1,5 jordklot vilket sätter krav på tillverkare att utveckla mer hållbara och resurssnåla affärsmodeller. Marknaden för bildäck står idag inför en potentiell ändring av bildäckets konceptuella design vilket öppnar upp för tillverkare att dra nytta av denna situation och utveckla ett mer hållbart erbjudande till kunder. Forskning har fram till idag framförallt fokuserat på försörjningskedjor utan att inkludera lämpliga affärsmodeller. Det holistiska konceptet Resource Conservative Manufacturing (ResCoM) har den senaste tiden utvecklats genom att fullständigt angripa problemet och dess omfattning. Denna uppsats fokuserar således på att hitta gynnsamma affärssammansättningar för bildäck utifrån perspektivet ResCoM. Inledningsvis fokuserar uppsatsen på modellen ResCoM och dess krav på en affärsmodell. Vidare är marknaden för bildäck samt produkten i sig grundligt undersökt för att hitta element som påverkar affärs sammansättningen. Därefter utvecklas ett verktyg för evaluering av de sammanlagda effekterna av de produkt- samt marknadsrelaterade faktorerna på affärssammansättningen i form av ett nyckeltal. Nyckeltalet används som en indikator för gynnsamma affärssammansättningar i syfte att möta kraven från produkten, marknaden och även ResCoM. Slutligen analyseras nyckeltalet där en övre och undre gräns definierar ett spann av gynnsamma affärssammansättningar. Resultatet illustrerar att spannet för gynnsamma affärssammansättningar börjar vid uthyrning och sträcker sig till, men inkluderar inte, funktionsbaserad försäljning. Det utvecklade verktyget kan även konstateras ha vissa begränsningar varpå det slutligen kan fastslås att syftet med arbetet i viss utsträckning uppnåtts

Multifunctional nanostructures as trimodal MRI-OI-SPECT diagnosis agents

Número de publicación: ES2370359 B1. Número de solicitud: 200931146.Las nanoestructuras multifuncionales que consisten en una ferritina, caracterizada porque comprende al menos un quantum dot y al menos una molécula de un polímero biocompatible ambos unidos covalentemente a la superfice de la ferrtina. La invención también se refiere a un método para obtener dichas nanoestructuras, así como a su uso como medicamento y más preferiblemente para la diagnosis de cáncer o como agente de contraste.The invention relates to multifunctional nanostructures consisting of a ferritin characterised in that it comprises at least one quantum dot and at least one molecule of a biocompatible polymer, both of which are covalently bound to the surface of the ferritin. The invention also relates to a method for obtaining said nanostructures, and to the use thereof as a drug, preferably for the diagnosis of cancer or as a contrast agent.Universidad de GranadaUniversita Degli Studi di VeronaUniversidad de CádizUniversidad de Jaé

Epigenetic and proteomic expression changes promoted by eating addictive-like behavior

An increasing perspective conceptualizes obesity and overeating as disorders related to addictive-like processes that could share common neurobiological mechanisms. In the present study, we aimed at validating an animal model of eating addictive-like behavior in mice, based on the DSM-5 substance use disorder criteria, using operant conditioning maintained by highly palatable chocolate-flavored pellets. For this purpose, we evaluated persistence of food-seeking during a period of non-availability of food, motivation for food, and perseverance of responding when the reward was associated with a punishment. This model has allowed identifying extreme subpopulations of mice related to addictive-like behavior. We investigated in these subpopulations the epigenetic and proteomic changes. A significant decrease in DNA methylation of CNR1 gene promoter was revealed in the prefrontal cortex of addict-like mice, which was associated with an upregulation of CB1 protein expression in the same brain area. The pharmacological blockade (rimonabant 3 mg/kg; i.p.) of CB1 receptor during the late training period reduced the percentage of mice that accomplished addiction criteria, which is in agreement with the reduced performance of CB1 knockout mice in this operant training. Proteomic studies have identified proteins differentially expressed in mice vulnerable or not to addictive-like behavior in the hippocampus, striatum, and prefrontal cortex. These changes included proteins involved in impulsivity-like behavior, synaptic plasticity, and cannabinoid signaling modulation, such as alpha-synuclein, phosphatase 1-alpha, doublecortin-like kinase 2, and diacylglycerol kinase zeta, and were validated by immunoblotting. This model provides an excellent tool to investigate the neurobiological substrate underlying the vulnerability to develop eating addictive-like behavior.This work was supported by the DG Research of the European Commission FP7 (No. HEALTH-F2 2013-602891), the Spanish ‘RETICS-Instituto de Salud Carlos III’ (No. RD12/0028/0023), the Spanish ‘Ministerio de Ciencia e Innovación’ (No. SAF2011-29864), and the Catalan Government ‘AGAUR-Generalitat de Catalunya’ (Nos. 2009SGR00731 and 2014-SGR-1547). The FEDER funds support is also acknowledged. SM and AB were supported by FI predoctoral fellowships of the Catalan Government, and JG-C was supported by a ‘Juan de la Cierva’ postdoctoral fellowship from the Spanish ‘Ministerio de Ciencia e Innovación’. Also support by the Italian Ministry of University and Research under grants FIRB-RBFR12DELS to CDA and PRIN2010-11 to MM is gratefully acknowledged. The authors declare no conflict of interest

Diminishing benefits of urban living for children and adolescents’ growth and development

Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified