Gut microbiota drives age-related oxidative stress and mitochondrial damage in microglia via the metabolite N6-carboxymethyllysine.

Microglial function declines during aging. The interaction of microglia with the gut microbiota has been well characterized during development and adulthood but not in aging. Here, we compared microglial transcriptomes from young-adult and aged mice housed under germ-free and specific pathogen-free conditions and found that the microbiota influenced aging associated-changes in microglial gene expression. The absence of gut microbiota diminished oxidative stress and ameliorated mitochondrial dysfunction in microglia from the brains of aged mice. Unbiased metabolomic analyses of serum and brain tissue revealed the accumulation of N6-carboxymethyllysine (CML) in the microglia of the aging brain. CML mediated a burst of reactive oxygen species and impeded mitochondrial activity and ATP reservoirs in microglia. We validated the age-dependent rise in CML levels in the sera and brains of humans. Finally, a microbiota-dependent increase in intestinal permeability in aged mice mediated the elevated levels of CML. This study adds insight into how specific features of microglia from aged mice are regulated by the gut microbiota.

Degraded pastures in Brazil: improving livestock production and forest restoration.

Degraded pasture is a major liability in Brazilian agriculture, but restoration and recovery efforts could turn this area into a new frontier to both agricultural yield expansion and forest restoration. Currently, rural properties with larger degraded pasture areas are associated with higher levels of technical inefficiency in Brazil. The recovery of 12 million ha of degraded pastures could generate an additional production of 17.7 million bovines while reducing the need for new agricultural land. Regional identification of degraded pastures would facilitate the targeting of agricultural extension and advisory services and rural credit efforts aimed at fostering pasture recovery. Since only 1% of Brazilian municipalities contain 25% of degraded pastures, focusing pasture recovery efforts on this small group of municipalities could generate considerable benefits. More efficient allocation of degraded and native pastures for meat production and forest restoration could provide land enough to fully comply with its Forest Code requirements, while adding 9 million heads to the cattle inventory. Degraded pasture recovery and restoration is a win-win strategy that could boost livestock husbandry and avoid deforestation in Brazil and has to be the priority strategy of agribusiness sector.

Central nervous system, peripheral and hemodynamic effects of nanoformulated anandamide in hypertension.

PURPOSE: Hypertensive lesions induce alterations at hemodynamic, peripheral, and central levels. Anandamide (N-arachidonoylethanolamine; AEA) protects neurons from inflammatory damage, but its free administration may cause central adverse effects. AEA controlled release by nanoformulations could reduce/eliminate its side effects. The present study aimed to evaluate the effects of nanoformulated AEA (nf-AEA) on systolic blood pressure (SBP), behavior, and central/peripheral inflammatory, oxidative, and apoptotic state in spontaneously hypertensive rats (SHR). MATERIALS/METHODS: Male rats were used, both Wistar Kyoto (WKY) and SHR (n â€‹= â€‹10 per group), with/without treatment with nf-AEA (obtained by electrospraying) at a weekly dose of 5 â€‹mg/kg IP for 4 weeks. SBP was measured and behavioral tests were performed. Inflammatory/oxidative markers were quantified at the central (brain cortex) and peripheral (serum) level. RESULTS: SHR showed hyperactivity, low anxiety, and high concentrations of central/peripheral inflammatory/oxidative markers, also higher apoptosis of brain cortical cells compared to WKY. As opposed to this group, treatment with nf-AEA in SHR significantly reduced SBP, peripheral/central inflammatory/oxidative makers, and central apoptosis. Nf-AEA also increased neuroprotective mechanisms mediated by intracellular heat shock protein 70 (Hsp70), which were attenuated in untreated SHR. Additionally, nf-AEA reversed the abnormal behaviors observed in SHR without producing central adverse effects. CONCLUSIONS: Our results suggest protective properties of nf-AEA, both peripherally and centrally, through a signaling pathway that would involve the type I angiotensin II receptor, Wilms tumor transcription factor 1, Hsp70, and iNOS. Considering non-nf-AEA limitations, this nanoformulation could contribute to the development of new antihypertensive and behavioral disorder treatments associated with neuroinflammation.

Environmental Impacts and Policy Responses to Covid-19: A View from Latin America.

COVID-19 is currently having major short run effects with possible serious long run implications for the environment and the management of natural resources in Latin America. We discuss the possible effects of the pandemic on air pollution, deforestation and other relevant environmental dimensions across the region. With contributions from environmental economists from eight countries, we give an overview of the initial and expected environmental effects of this health crisis. We discuss potential effects on environmental regulations, possible policy interventions, and an agenda for future research for those interested in the design and evaluation of environmental policies relevant for the Latin American context.

Vitamin D-RAAS Connection: An Integrative Standpoint into Cardiovascular and Neuroinflammatory Disorders.

BACKGROUND: The neuroinflammatory process is associated with the pathogenesis of many cardiovascular disorders, particularly with hypertension. In this regard, the deficiency of vitamin D seems to increase the risk of cardiovascular pathologies related to neuroinflammation. Long-term lack of vitamin D leads to over-activation of the renin-angiotensin-aldosterone system (RAAS), one of the essential mechanisms of blood pressure regulation. PURPOSE OF REVIEW: This review summarizes the latest studies carried out to evaluate the primary mechanisms underlying the neuroprotective effect of vitamin D and its receptors (VDR) in the central nervous system. Besides, the present article condenses the evidence supporting the link between vitamin D and the RAAS in hypertension and neuroinflammation. Highlights Standpoints: Vitamin D deficiency is highly prevalent in the world, and the rising prevalence of neuroinflammatory diseases and associated pathologies such as hypertension around the world justifies the urgent need of searching new and more effective therapeutic methods that could be related to RAAS modulation and vitamin D levels management.

Melatonin and cannabinoids: mitochondrial-targeted molecules that may reduce inflammaging in neurodegenerative diseases.

Generally, the development and progression of neurodegenerative diseases are associated with advancing age, so they are usually diagnosed in late adulthood. A primary mechanism underlying the onset of neurodegenerative diseases is neuroinflammation. Based on this background, the concept of "neuroinflammaging" has emerged. In this deregulated neuroinflammatory process, a variety of immune cells participate, especially glial cells, proinflammatory cytokines, receptors, and subcellular organelles including mitochondria, which are mainly responsible for maintaining redox balance at the cellular level. Senescence and autophagic processes also play a crucial role in the neuroinflammatory disease associated with aging. Of particular interest, melatonin, cannabinoids, and the receptors of both molecules which are closely related, exert beneficial effects on the neuroinflammatory processes that precede the onset of neurodegenerative pathologies such as Parkinson's and Alzheimer's diseases. Some of these neuroprotective effects are fundamentally related to its anti-inflammatory and antioxidative actions at the mitochondrial level due to the strategic functions of this organelle. The aim of this review is to summarize the most recent advances in the study of neuroinflammation and neurodegeneration associated with age and to consider the use of new mitochondrial therapeutic targets related to the endocannabinoid system and the pineal gland.

Allicin pharmacology: Common molecular mechanisms against neuroinflammation and cardiovascular diseases.

According to investigations in phytomedicine and ethnopharmacology, the therapeutic properties of garlic (Allium sativum) have been described by ancestral cultures. Notwithstanding, it is of particular concern to elucidate the molecular mechanisms underlying this millenary empirical knowledge. Allicin (S-allyl prop-2-ene-1-sulfinothioate), a thioester of sulfenic acid, is one of the main bioactive compounds present in garlic, and it is responsible for the particular aroma of the spice. The pharmacological attributes of allicin integrate a broad spectrum of properties (e.g., anti-inflammatory, immunomodulatory, antibiotic, antifungal, antiparasitic, antioxidant, nephroprotective, neuroprotective, cardioprotective, and anti-tumoral activities, among others). The primary goal of the present article is to review and clarify the common molecular mechanisms by which allicin and its derivates molecules may perform its therapeutic effects on cardiovascular diseases and neuroinflammatory processes. The intricate interface connecting the cardiovascular and nervous systems suggests that the impairment of one organ could contribute to the dysfunction of the other. Allicin might target the cornerstone of the pathological processes underlying cardiovascular and neuroinflammatory disorders, like inflammation, renin-angiotensin-aldosterone system (RAAS) hyperactivation, oxidative stress, and mitochondrial dysfunction. Indeed, the current evidence suggests that allicin improves mitochondrial function by enhancing the expression of HSP70 and NRF2, decreasing RAAS activation, and promoting mitochondrial fusion processes. Finally, allicin represents an attractive therapeutic alternative targeting the complex interaction between cardiovascular and neuroinflammatory disorders.

Daily and seasonal mitochondrial protection: Unraveling common possible mechanisms involving vitamin D and melatonin.

From an evolutionary point of view, vitamin D and melatonin appeared very early and share functions related to defense mechanisms. In the current clinical setting, vitamin D is exclusively associated with phosphocalcic metabolism. Meanwhile, melatonin has chronobiological effects and influences the sleep-wake cycle. Scientific evidence, however, has identified new actions of both molecules in different physiological and pathological settings. The biosynthetic pathways of vitamin D and melatonin are inversely related relative to sun exposure. A deficiency of these molecules has been associated with the pathogenesis of cardiovascular diseases, including arterial hypertension, neurodegenerative diseases, sleep disorders, kidney diseases, cancer, psychiatric disorders, bone diseases, metabolic syndrome, and diabetes, among others. During aging, the intake and cutaneous synthesis of vitamin D, as well as the endogenous synthesis of melatonin are remarkably depleted, therefore, producing a state characterized by an increase of oxidative stress, inflammation, and mitochondrial dysfunction. Both molecules are involved in the homeostatic functioning of the mitochondria. Given the presence of specific receptors in the organelle, the antagonism of the renin-angiotensin-aldosterone system (RAAS), the decrease of reactive species of oxygen (ROS), in conjunction with modifications in autophagy and apoptosis, anti-inflammatory properties inter alia, mitochondria emerge as the final common target for melatonin and vitamin D. The primary purpose of this review is to elucidate the common molecular mechanisms by which vitamin D and melatonin might share a synergistic effect in the protection of proper mitochondrial functioning.

Hypertension linked to allostatic load: from psychosocial stress to inflammation and mitochondrial dysfunction.

Although a large number of available treatments and strategies, the prevalence of cardiovascular diseases continues to grow worldwide. Emerging evidence supports the notion of counteracting stress as a critical component of a comprehensive therapeutic strategy for cardiovascular disease. Indeed, an unhealthy lifestyle is a burden to biological variables such as plasma glucose, lipid profile, and blood pressure control. Recent findings identify allostatic load as a new paradigm for an integrated understanding of the importance of psychosocial stress and its impact on the development and maintenance of cardiovascular disease. Allostasis complement homeostasis and integrates behavioral and physiological mechanisms by which genes, early experiences, environment, lifestyle, diet, sleep, and physical exercise can modulate and adapt biological responses at the cellular level. For example, variability is a physiological characteristic of blood pressure necessary for survival and the allostatic load in hypertension can contribute to its related cardiovascular morbidity and mortality. Therefore, the current review will focus on the mechanisms that link hypertension to allostatic load, which includes psychosocial stress, inflammation, and mitochondrial dysfunction. We will describe and discuss new insights on neuroendocrine-immune effects linked to allostatic load and its impact on the cellular and molecular responses; the links between allostatic load, inflammation, and endothelial dysfunction; the epidemiological evidence supporting the pathophysiological origins of hypertension; and the biological embedding of allostatic load and hypertension with an emphasis on mitochondrial dysfunction.

Provider supply, utilization, and infant health: evidence from a physician distribution policy

We analyze a policy that substantially expanded the supply of primary care physicians in Brazil. The program is associated with a significant increase in doctor visits across all age groups, and greater utilization of doctors as source of prenatal care. However, this increased used of doctors was accompanied by significant reductions in prenatal care from nurses. As a result of this shift in the provider of care, there were no gains in widely-used metrics of infant health, including birth weight, gestation and infant mortality. These findings suggest that physicians and nurses may be good substitutes in terms of neonatal health.

Este estudo analisa uma política que ampliou substancialmente a oferta de médicos de atenção primária no Brasil. O programa está associado a um aumento significativo de consultas médicas em todas as faixas etárias e `a maior utilização de médicos como fonte de assistência pré-natal. No entanto, esse aumento no uso de médicos foi acompanhado por reduções significativas no número de consultas pré-natais fornecidas por enfermeiras. Como resultado dessa mudança no provedor da atenção, não houve ganhos em métricas amplamente utilizadas de saúde infantil, incluindo peso ao nascer, gestação e mortalidade infantil. Esses resultados sugerem que médicos e enfermeiras podem ser bons substitutos em termos de saúde neonatal.

[The impact of climate change on leishmaniasis in Brazil]. / Impacto das mudanças climáticas sobre a leishmaniose no Brasil.

This paper sought to assess how climate change will affect the proliferation of leishmaniasis in Brazil in three time frames: 2010-2039, 2040-2079 and 2080-2100, and with two climate change scenarios. The relation of temperature, precipitation and the number of hospital admissions due to leishmaniasis was estimated and projections were made using these results. Results show that precipitation has a strong relation with leishmaniasis incidence and projections show that by the end of the twenty-first century there will be a 15% growth in the annual number of hospital admissions due to leishmaniasis in Brazil, compared to the base scenario (1992-2002). In regional terms, projections indicate growth in every region, with the exception of the Mid-West. The highest relative growth will be in the South of the country, while the highest increase in absolute terms will be observed in the Northeast region. In general, the incidence of leishmaniasis will grow in Brazil due to climate change.

Impacto das mudanças climáticas sobre a leishmaniose no Brasil / The impact of climate change on leishmaniasis in Brazil

Resumo Este estudo buscou verificar como as mudanças climáticas podem afetar a proliferação das leishmanioses no Brasil, em três períodos, 2010-2039, 2040-2079 e 2080-2100 e dois cenários de mudanças climáticas. Realizou-se uma estimação da relação entre temperatura, precipitação e números de internações por leishmaniose e, posteriormente, a equação estimada foi utilizada para prever o impacto da mudança climática na proliferação da doença no Brasil até o fim do século XXI. Os resultados encontrados indicam que a precipitação possui forte relação com a incidência de leishmaniose e as projeções indicam que haverá uma elevação, para o final do século, da quantidade anual de internações por essa doença, em cerca de 15%, em relação a 1992-2002 (cenário base). Em termos regionais, as projeções indicam crescimento em todas as regiões, com exceção do Centro-Oeste. No Sul do país haverá o maior crescimento relativo no número de internações anuais, ao passo que no Nordeste haverá o maior aumento absoluto. No geral, verifica-se que a leishmaniose aumentará sua incidência no país com a mudança climática.

Abstract This paper sought to assess how climate change will affect the proliferation of leishmaniasis in Brazil in three time frames: 2010-2039, 2040-2079 and 2080-2100, and with two climate change scenarios. The relation of temperature, precipitation and the number of hospital admissions due to leishmaniasis was estimated and projections were made using these results. Results show that precipitation has a strong relation with leishmaniasis incidence and projections show that by the end of the twenty-first century there will be a 15% growth in the annual number of hospital admissions due to leishmaniasis in Brazil, compared to the base scenario (1992-2002). In regional terms, projections indicate growth in every region, with the exception of the Mid-West. The highest relative growth will be in the South of the country, while the highest increase in absolute terms will be observed in the Northeast region. In general, the incidence of leishmaniasis will grow in Brazil due to climate change.

A social and ecological assessment of tropical land uses at multiple scales: the Sustainable Amazon Network.

Science has a critical role to play in guiding more sustainable development trajectories. Here, we present the Sustainable Amazon Network (Rede Amazônia Sustentável, RAS): a multidisciplinary research initiative involving more than 30 partner organizations working to assess both social and ecological dimensions of land-use sustainability in eastern Brazilian Amazonia. The research approach adopted by RAS offers three advantages for addressing land-use sustainability problems: (i) the collection of synchronized and co-located ecological and socioeconomic data across broad gradients of past and present human use; (ii) a nested sampling design to aid comparison of ecological and socioeconomic conditions associated with different land uses across local, landscape and regional scales; and (iii) a strong engagement with a wide variety of actors and non-research institutions. Here, we elaborate on these key features, and identify the ways in which RAS can help in highlighting those problems in most urgent need of attention, and in guiding improvements in land-use sustainability in Amazonia and elsewhere in the tropics. We also discuss some of the practical lessons, limitations and realities faced during the development of the RAS initiative so far.

Impactos das mudanças climáticas sobre o bem-estar relacionado à saúde no Brasil / Climate change impacts on health-related welfare in Brazil

Este estudo tem por objetivo avaliar o impacto das mudanças climáticas sobre o bem-estar relacionado à saúde no Brasil, por meio de equações estimadas para dados em painel e de projeções climáticas. Os resultados indicam que as mudanças climáticas afetam principalmente a mortalidade de crianças e mulheres. A análise procurou também incorporar aos custos de bem-estar o gasto decorrente do consumo adicional de energia para manutenção do conforto térmico e da redução de riscos à saúde. O aumento do consumo residencial anual de energia com as mudanças climáticas foi estimado em aproximadamente 6%. Os resultados sugerem que a perda de bem-estar relacionada à saúde poderá chegar a 4,7% do Produto Interno Bruto (PIB).

Is CK-MB isoenzyme useful for diagnosis of cardiac involvement in icteric leptospirosis?

Na ausencia de insuficiencia cardiaca ou choque cardiogenico, o diagnostico de envolvimento cardiaco na leptospirose icterica pode ser baseado em alteracoes eletrocardiograficas. Devido ao frequente comprometimento multisistemico da doenca, algumas dessas alteracoes podem ser secundarias a disturbios metabolicos ou eletroliticos. Realizou-se um estudo para avaliacao do significado da enzima CK-MB elevada em casos suspeitos de envolvimento cardiaco. Sessenta e nove pacientes com leptospirose icterica foram estudados prospectivamente. Dez dos 16 casos com envolvimento cardiaco e 25 dos 53 pacientes sem envolvimento cardiaco CK-MB elevada (p>0,05). O valor medio de CK-MB foi maior no grupo com envolvimento cardiaco (p<0,05). Nossa analise indica que a presenca de CK-MB elevada no curso de leptospirose icterica nao e indicadora de envolvimento cardiaco.

Estenose supraaórtica em dois pacientes da raça negra / Supravalvular aortic stenosis in two black patients

Dois pacientes negro, de 18 e 12 anos e do sexo masculino, com retardo mental e facies características de elfo, apresentavam severa estenose aórtica supravalvular, caracterizando a síndrome de Williams, ou da estenose supravalvar aórtica. Ambos foram submetidos a correçäo cirúrgica da estenose, com boa evoluçäo em seguimento de um e quatro anos. Pela primenra vez esta forma clássica da síndrome é descrita em pacientes negros

Two male black patients, 18 and 12-year-old, with mental retardation and typical elfin face, presented with severe supravalvular aortic stenosis, thus characterizing Williamss or aortic supravalvular stenosis syndrome. Both were submitted to surgical treatment of the stenosis, and are assymptomatic after a one and four years follow-up. For the first time this syndrome, in its classical form, is described in black patients