Chitosan Glutamate-Coated Niosomes: a proposal for Nose-to-Brain delivery

The aim of this in vitro study is to prepare and characterize drug free and pentamidine loaded chitosan glutamate coated niosomes for intranasal drug delivery to reach the brain through intranasal delivery. Mucoadhesive properties and stability testing in various environments were evaluated to examine the potential of these formulations to be effective drug delivery vehicles for intranasal delivery to the brain. Samples were prepared using thin film hydration method. Changes in size and ζ-potential of coated and uncoated niosomes with and without loading of pentamidine in various conditions were assessed by dynamic light scattering (DLS), while size and morphology were also studied by atomic force microscopy (AFM). Bilayer properties and mucoadhesive behavior were investigated by fluorescence studies and DLS analyses, respectively. Changes in vesicle size and ζ-potential values were shown after addition of chitosan glutamate to niosomes, and when in contact with mucin solution. In particular, interactions with mucin were observed in both drug free and pentamidine loaded niosomes regardless of the presence of the coating. The characteristics of the proposed systems, such as pentamidine entrapment and mucin interaction, show promising results to deliver pentamidine or other possible drugs to the brain via nasal administration

When neglected species gain global interest: Lessons learned from quinoa's boom and bust for teff and minor millet

Until recently, many so-called neglected and underutilized species (NUS) were not present in global markets despite playing a pivotal role in the local livelihoods in their places of origin. Today, some NUS receive substantial global interest and face growing global demands. Sudden increases in consumer demand trigger prices to rise; land-use change at the farm and national levels results in a rapid production increase. This phenomenon is known as “boom” and is usually followed by a “bust”, a rapid decrease in prices, and subsequently, production. This review elaborates on the boom-and-bust phases of two NUS: quinoa from the Andes and teff from Ethiopia. We explored the potential upcoming boom of minor millets in India. Our study proposes a generic framework for exploring cross-scale interactions and rethinking sustainability pathways for future NUS booms.EEA FamailláFil: Andreotti, Federico. Wageningen University & Research. Laboratory of Geo-information Science and Remote Sensing; Países BajosFil: Andreotti, Federico. CIRAD; FranciaFil: Andreotti, Federico. Université Paul Valery Montpellier; FranciaFil: Bazile, Didier. CIRAD; FranciaFil: Bazile, Didier. Université Paul Valery Montpellier; FranciaFil: Biaggi, Maria Cristina. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Famaillá; ArgentinaFil: Callo-Concha, Daniel. University of Bonn. Center for Development Research (ZEF); AlemaniaFil: Callo-Concha, Daniel. University of Koblenz-Landau. Institute for Environmental Sciences (iES); AlemaniaFil: Jacquet, Julie. University Paris Ouest-Nanterre (LAVUE); FranciaFil: Jacquet, Julie. French Institute of Pondicherry; IndiaFil: Jemal, Omarsherif M. Arsi University. College of Agriculture and Veterinary Science. Department of Forestry; EtiopíaFil: King, Oliver I. M.S. Swaminathan Research Foundation; IndiaFil: Mbosso, C. Bioversity International; ItaliaFil: Padulosi, Stefano. Bioversity International; ItaliaFil: Speelman, Erika N. Wageningen University & Research. Laboratory of Geo-information Science and Remote Sensing; Países BajosFil: van Noordwijk, Meine. World Agroforestry (ICRAF); IndonesiaFil: van Noordwijk, Meine. Wageningen University & Research. Plant Production Systems; Países Bajo

Resistance to wheat rusts identified in wheat/Amblyopyrum muticum chromosome introgressions

© 2020 The Authors. Crop Science © 2020 Crop Science Society of America Wheat (Triticum aestivum L.) rusts are a worldwide production problem. Plant breeders have used genetic resistance to combat these fungi. However, single-gene resistance is rapidly overcome as a result of frequent occurrence of new virulent fungal strains. Thus, a supply of new resistance sources is continually needed, and new resistance sources are limited within hexaploid wheat genetic stocks. Wild relatives are able to be a resource for new resistance genes but are hindered because of chromosome incapability with domesticated wheats. Twenty-eight double-haploid hexaploid wheat/Amblyopyrum muticum (Boiss.) Eig introgression lines, with introgressions covering the majority of the T genome, were evaluated for resistance to Puccinia triticina Erikss., P. graminis Pers.:Pers. f.sp. tritici Erikss. & E. Henning, and P. striiformis Westend. f.sp. tritici Erikss. At the seedling level, four lines were resistant to races of P. triticina, six lines were resistant to P. graminis, and 15 lines were resistant to P. striiformis. At the adult stage, 16 lines were resistant to P. triticina. Line 355 had resistance to all three rusts and line 161 had resistance to all tested races of P. triticina. Some of these lines will require further work to reduce the size of the introgressed segment; however, lines 92 and 355 have very small fragments and can be used directly as new resistance donors

MicroRNA-155 negatively affects blood-brain barrier function during neuroinflammation.

Blood-brain barrier (BBB) dysfunction is a hallmark of neurological conditions such as multiple sclerosis (MS) and stroke. However, the molecular mechanisms underlying neurovascular dysfunction during BBB breakdown remain elusive. MicroRNAs (miRNAs) have recently emerged as key regulators of pathogenic responses, although their role in central nervous system (CNS) microvascular disorders is largely unknown. We have identified miR-155 as a critical miRNA in neuroinflammation at the BBB. miR-155 is expressed at the neurovascular unit of individuals with MS and of mice with experimental autoimmune encephalomyelitis (EAE). In mice, loss of miR-155 reduced CNS extravasation of systemic tracers, both in EAE and in an acute systemic inflammation model induced by lipopolysaccharide. In cultured human brain endothelium, miR-155 was strongly and rapidly upregulated by inflammatory cytokines. miR-155 up-regulation mimicked cytokine-induced alterations in junctional organization and permeability, whereas inhibition of endogenous miR-155 partially prevented a cytokine-induced increase in permeability. Furthermore, miR-155 modulated brain endothelial barrier function by targeting not only cell-cell complex molecules such as annexin-2 and claudin-1, but also focal adhesion components such as DOCK-1 and syntenin-1. We propose that brain endothelial miR-155 is a negative regulator of BBB function that may constitute a novel therapeutic target for CNS neuroinflammatory disorders

Multicenter, Observational Cohort Study Evaluating Third-Generation Cephalosporin Therapy for Bloodstream Infections Secondary to Enterobacter, Serratia, and Citrobacter Species

Objectives: There is debate on whether the use of third-generation cephalosporins (3GC) increases the risk of clinical failure in bloodstream infections (BSIs) caused by chromosomally-mediated AmpC-producing Enterobacterales (CAE). This study evaluates the impact of definitive 3GC therapy versus other antibiotics on clinical outcomes in BSIs due to Enterobacter, Serratia, or Citrobacter species. Methods: This multicenter, retrospective cohort study evaluated adult hospitalized patients with BSIs secondary to Enterobacter, Serratia, or Citrobacter species from 1 January 2006 to 1 September 2014. Definitive 3GC therapy was compared to definitive therapy with other non-3GC antibiotics. Multivariable Cox proportional hazards regression evaluated the impact of definitive 3GC on overall treatment failure (OTF) as a composite of in-hospital mortality, 30-day hospital readmission, or 90-day reinfection. Results: A total of 381 patients from 18 institutions in the southeastern United States were enrolled. Common sources of BSIs were the urinary tract and central venous catheters (78 (20.5%) patients each). Definitive 3GC therapy was utilized in 65 (17.1%) patients. OTF occurred in 22/65 patients (33.9%) in the definitive 3GC group vs. 94/316 (29.8%) in the non-3GC group (p = 0.51). Individual components of OTF were comparable between groups. Risk of OTF was comparable with definitive 3GC therapy vs. definitive non-3GC therapy (aHR 0.93, 95% CI 0.51–1.72) in multivariable Cox proportional hazards regression analysis. Conclusions: These outcomes suggest definitive 3GC therapy does not significantly alter the risk of poor clinical outcomes in the treatment of BSIs secondary to Enterobacter, Serratia, or Citrobacter species compared to other antimicrobial agents

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500

National and subnational mortality effects of metabolic risk factors and smoking in Iran: a comparative risk assessment

<p>Abstract</p> <p>Background</p> <p>Mortality from cardiovascular and other chronic diseases has increased in Iran. Our aim was to estimate the effects of smoking and high systolic blood pressure (SBP), fasting plasma glucose (FPG), total cholesterol (TC), and high body mass index (BMI) on mortality and life expectancy, nationally and subnationally, using representative data and comparable methods.</p> <p>Methods</p> <p>We used data from the Non-Communicable Disease Surveillance Survey to estimate means and standard deviations for the metabolic risk factors, nationally and by region. Lung cancer mortality was used to measure cumulative exposure to smoking. We used data from the death registration system to estimate age-, sex-, and disease-specific numbers of deaths in 2005, adjusted for incompleteness using demographic methods. We used systematic reviews and meta-analyses of epidemiologic studies to obtain the effect of risk factors on disease-specific mortality. We estimated deaths and life expectancy loss attributable to risk factors using the comparative risk assessment framework.</p> <p>Results</p> <p>In 2005, high SBP was responsible for 41,000 (95% uncertainty interval: 38,000, 44,000) deaths in men and 39,000 (36,000, 42,000) deaths in women in Iran. High FPG, BMI, and TC were responsible for about one-third to one-half of deaths attributable to SBP in men and/or women. Smoking was responsible for 9,000 deaths among men and 2,000 among women. If SBP were reduced to optimal levels, life expectancy at birth would increase by 3.2 years (2.6, 3.9) and 4.1 years (3.2, 4.9) in men and women, respectively; the life expectancy gains ranged from 1.1 to 1.8 years for TC, BMI, and FPG. SBP was also responsible for the largest number of deaths in every region, with age-standardized attributable mortality ranging from 257 to 333 deaths per 100,000 adults in different regions.</p> <p>Discussion</p> <p>Management of blood pressure through diet, lifestyle, and pharmacological interventions should be a priority in Iran. Interventions for other metabolic risk factors and smoking can also improve population health.</p

Measuring Under-Five Mortality: Validation of New Low-Cost Methods

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Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Participant engagement with a UK community-based preschool childhood obesity prevention programme: : a focused ethnography study

Background Children’s centres in the UK provide a setting for public health programmes; offering support to families living in the most disadvantaged areas where obesity prevalence is at its highest. Health, Exercise and Nutrition in the Really Young (HENRY) is an eight-week obesity prevention programme currently delivered in children’s centres across the UK. However, low participant engagement in some local authorities threatens its potential reach and impact. This study aimed to explore the factors influencing participant engagement with HENRY to describe where local intervention may support engagement efforts. Method A focused ethnography study was undertaken in five children’s centres delivering HENRY across the UK. One hundred and ninety hours of field observations, 22 interviews with staff (commissioners, HENRY co-ordinators, managers and facilitators) and six focus groups (36 parents), took place over five consecutive days in each centre. The Consolidated Framework for Implementation Research (CFIR) was used to guide the observations and analysis of the data. Results Three overarching themes described the factors influencing participant engagement with HENRY: local authority decision making around children’s centre programmes; children’s centre implementation of HENRY; and the participant experience of HENRY. The results indicate that factors influencing participant engagement with public health programmes begin at the commissioning body level, influencing children’s centre implementation and subsequently the experience of participants. Local authority funding priorities and constraints influence availability of places and who these places are offered to, with funding often targeted towards those deemed most at need. This was perceived to have a detrimental effect on participant experience of the programme. Conclusion In summary, participant engagement is affected by multiple factors, working at different levels of the children’s centre and local authority hierarchy, most of which are at play even before participants decide whether or not they choose to enrol and maintain attendance. For programmes to achieve their optimal reach and impact, factors at the commissioning and local implementation level need to be addressed prior to addressing participant facing issues