Melatonin protects rats from radiotherapy-induced small intestine toxicity

Radiotherapy-induced gut toxicity is among the most prevalent dose-limiting toxicities following radiotherapy. Prevention of radiation enteropathy requires protection of the small intestine. However, despite the prevalence and burden of this pathology, there are currently no effective treatments for radiotherapy-induced gut toxicity, and this pathology remains unclear. The present study aimed to investigate the changes induced in the rat small intestine after external irradiation of the tongue, and to explore the potential radio-protective effects of melatonin gel. Male Wistar rats were subjected to irradiation of their tongues with an X-Ray YXLON Y.Tu 320-D03 irradiator, receiving a dose of 7.5 Gy/day for 5 days. For 21 days post-irradiation, rats were treated with 45 mg/day melatonin gel or vehicle, by local application into their mouths. Our results showed that mitochondrial oxidative stress, bioenergetic impairment, and subsequent NLRP3 inflammasome activation were involved in the development of radiotherapy-induced gut toxicity. Oral treatment with melatonin gel had a protective effect in the small intestine, which was associated with mitochondrial protection and, consequently, with a reduced inflammatory response, blunting the NF-κB/NLRP3 inflammasome signaling activation. Thus, rats treated with melatonin gel showed reduced intestinal apoptosis, relieving mucosal dysfunction and facilitating intestinal mucosa recovery. Our findings suggest that oral treatment with melatonin gel may be a potential preventive therapy for radiotherapy-induced gut toxicity in cancer patients.This study was partially supported by grant no. SAF2009-14037 from the Spanish Ministry of Economy and Competitivity (MINECO), GREIB.PT_2010_04 from the CEIBiotic Program of the University of Granada, Spain, and CTS-101 from the Consejería de Innovación, Ciencia y Empresa, Junta de Andalucía, Spain

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

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 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 https://researchonline.ljmu.ac.uk/images/research_banner_face_lab_290.jpgunderweight 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 obesity

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

AbstractOptimal 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 &lt;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.</jats:p

Lipids: A Suitable Therapeutic Target in Diabetic Neuropathy?

Diabetic polyneuropathy (DPN) encompasses multiple syndromes with a common pathogenesis. Glycemic control shows a limited correlation with DPN, arguing in favor of major involvement of other factors, one of which is alterations of lipid and lipoprotein metabolism. Consistent associations have been found between plasma triglycerides/remnant lipoproteins and the risk of DPN. Studies in cultured nerve tissue or in murine models of diabetes have unveiled mechanisms linking lipid metabolism to DPN. Deficient insulin action increases fatty acids flux to nerve cells, inducing mitochondrial dysfunction, anomalous protein kinase C signaling, and perturbations in the physicochemical properties of the plasma membrane. Oxidized low-density lipoproteins bind to cellular receptors and promote generation of reactive oxygen species, worsening mitochondrial function and altering the electrical properties of neurons. Supplementation with specific fatty acids has led to prevention or reversal of different modalities of DPN in animal models. Post hoc and secondary analyses of clinical trials have found benefits of cholesterol reducing (statins and ezetimibe), triglyceride-reducing (fibrates), or lipid antioxidant (thioctic acid) therapies over the progression and severity of DPN. However, these findings are mostly hypothesis-generating. Randomized trials are warranted in which the impact of intensive plasma lipids normalization on DPN outcomes is specifically evaluated

Melatonin enhances neural stem cell differentiation and engraftment by increasing mitochondrial function

Mendivil-Perez, Miguel et al.Neural stem cells (NSCs) are regarded as a promising therapeutic approach to protecting and restoring damaged neurons in neurodegenerative diseases (NDs) such as Parkinson's disease and Alzheimer's disease (PD and AD, respectively). However, new research suggests that NSC differentiation is required to make this strategy effective. Several studies have demonstrated that melatonin increases mature neuronal markers, which reflects NSC differentiation into neurons. Nevertheless, the possible involvement of mitochondria in the effects of melatonin during NSC differentiation has not yet been fully established. We therefore tested the impact of melatonin on NSC proliferation and differentiation in an attempt to determine whether these actions depend on modulating mitochondrial activity. We measured proliferation and differentiation markers, mitochondrial structural and functional parameters as well as oxidative stress indicators and also evaluated cell transplant engraftment. This enabled us to show that melatonin (25 μM) induces NSC differentiation into oligodendrocytes and neurons. These effects depend on increased mitochondrial mass/DNA/complexes, mitochondrial respiration, and membrane potential as well as ATP synthesis in NSCs. It is also interesting to note that melatonin prevented oxidative stress caused by high levels of mitochondrial activity. Finally, we found that melatonin enriches NSC engraftment in the ND mouse model following transplantation. We concluded that a combined therapy involving transplantation of NSCs pretreated with pharmacological doses of melatonin could efficiently restore neuronal cell populations in PD and AD mouse models depending on mitochondrial activity promotion.This study was partially funded by the following grants: SAF2009-14037 from the Spanish Ministry of Economy and Competitivity (MINECO), CB/10/00238 from the Carlos III Health Institute, GREIB.PT_2010_04 from the CEIBiotic Program of the University of Granada, Spain, and CTS-101 from the Innovation, Science and Business Council, Junta de Andalucía, Spain. The study was carried out within the framework of the “Convenio Marco 206-2012” agreement between the University of Antioquia in Colombia and the University of Granada in Spain. MJ-Del-Rio and CV-P were supported by Colciencias grants #1115-657-740786 (contract 623-2014). MM-P and V-SM are associate researchers. MM-P is funded by the Colciencias, Enlaza-Mundos, and AUIP mobility programs. VS-M was funded by the AUIP mobility program.Peer Reviewe

Effect of oxidation temperature on the properties of NiOx layers for application in optical sensors

Thin NiOx layers were prepared by oxidation at 400, 500 and 600 °C of metallic Ni deposited by electron beam evaporation. The bandgap of NiOx determined from optical measurements increases from 3.6 to 3.7 eV with the increase of oxidation temperature from 400 to 500°C. Higher temperature leads to larger grain sizes, 12.6 nm at 400 °C, 15.3 nm at 500 °C and 16.1 nm 600 °C. Photodiodes based on NiOx/Si heterostructure were fabricated by evaporation of semitransparent Au top contacts. The structures with NiOx obtained at 500 °C showed superior diode characteristics compared to the other two types of devices with dark current < 3.5 × 10-8 A (current density J < 3.9 × 10−4 A/cm2) for reverse biases between 0 and -2 V and forward current of 3.3 × 10−5 A (J = 0.36 A/cm2) at bias of 1.5 V. The responsivity of these devices at 0 V is between 0.85 and 0.55 A/W for wavelengths in the 365 – 635 nm range, values higher than those previously reported for self-powered NiOx/Si photodiodes. The responsivity at reverse bias of -1.5 V increases more than 60 times to values of 33, 32, 50 and 59 A/W for red, green, blue, and ultraviolet light, values among the highest reported for broadband photodetectors. The excellent properties of the photodiodes with NiOx obtained at 500 °C are the result of a higher quality of the Si/NiOx interfacial region, which leads to lower recombination rate of the photogenerated carriers.JRC gratefully acknowledges the National Council for Science and Technology (CONACYT), Mexico for a Ph.D. fellowship. MB acknowledges Fundación Iberdrola España, CIBER-BBN, the ICTS “NANBIOSIS”, and Agencia Estatal de Investigación-AEI (PID2019-107893RB-I00) for financial support. This work was partially supported by Proyecto Bilateral Conacyt-AFOSR CC0015-2016-05-279915 “Single Crystal and Thin Film Hybrid Perovskite Materials for Optoelectornic Applications”.Peer reviewe

Cost savings associated with 10 years of road safety policies in Catalonia, Spain

OBJECTIVE: To determine whether the road safety policies introduced between 2000 and 2010 in Catalonia, Spain, which aimed primarily to reduce deaths from road traffic collisions by 50% by 2010, were associated with economic benefits to society. METHODS: A cost analysis was performed from a societal perspective with a 10-year time horizon. It considered the costs of: hospital admissions; ambulance transport; autopsies; specialized health care; police, firefighter and roadside assistance; adapting to disability; and productivity lost due to institutionalization, death or sick leave of the injured or their caregivers; as well as material and administrative costs. Data were obtained from a Catalan hospital registry, the Catalan Traffic Service information system, insurance companies and other sources. All costs were calculated in euros (€) at 2011 values. FINDINGS: A substantial reduction in deaths from road traffic collisions was observed between 2000 and 2010. Between 2001 and 2010, with the implementation of new road safety policies, there were 26 063 fewer road traffic collisions with victims than expected, 2909 fewer deaths (57%) and 25 444 fewer hospitalizations. The estimated total cost savings were around €18 000 million. Of these, around 97% resulted from reductions in lost productivity. Of the remaining cost savings, 63% were associated with specialized health care, 15% with adapting to disability and 8.1% with hospital care. CONCLUSION: The road safety policies implemented in Catalonia in recent years were associated with a reduction in the number of deaths and injuries from traffic collisions and with substantial economic benefits to society