Malnutrition is a major contributor to mortality and is increasingly recognized as a cause of potentially lifelong functional disability. Yet, a rate-limiting step in achieving normal nutrition may ...be impaired absorptive function due to multiple repeated enteric infections. This is especially problematic in children whose diets are marginal. In malnourished individuals, the infections are even more devastating. This review documents the evidence that intestinal infections lead to malnutrition and that malnutrition worsens intestinal infections. The clinical data presented here derive largely from long-term cohort studies that are supported by controlled animal studies. Also reviewed are the mechanisms by which enteric infections lead to undernutrition and by which malnutrition worsens enteric infections, with implications for potential novel interventions. Further intervention studies are needed to document the relevance of these mechanisms and, most importantly, to interrupt the vicious diarrhea-malnutrition cycle so children may develop their full potential.
Understanding the complex relationship between early childhood infectious diseases, nutritional status, poverty, and cognitive development is significantly hindered by the lack of studies that ...adequately address confounding between these variables. This study assesses the independent contributions of early childhood diarrhea (ECD) and malnutrition on cognitive impairment in later childhood. A cohort of 131 children from a shantytown community in northeast Brazil was monitored from birth to 24 months for diarrhea and anthropometric status. Cognitive assessments including Test of Nonverbal Intelligence (TONI), coding tasks (WISC-III), and verbal fluency (NEPSY) were completed when children were an average of 8.4 years of age (range = 5.6-12.7 years). Multivariate analysis of variance models were used to assess the individual as well as combined effects of ECD and stunting on later childhood cognitive performance. ECD, height for age (HAZ) at 24 months, and weight for age (WAZ) at 24 months were significant univariate predictors of the studies three cognitive outcomes: TONI, coding, and verbal performance (P < 0.05). Multivariate models showed that ECD remained a significant predictor, after adjusting for the effect of 24 months HAZ and WAZ, for both TONI (HAZ, P = 0.029 and WAZ, P = 0.006) and coding (HAZ, P = 0.025 and WAZ, P = 0.036) scores. WAZ and HAZ were also significant predictors after adjusting for ECD. ECD remained a significant predictor of coding (WISC III) after number of household income was considered (P = 0.006). This study provides evidence that ECD and stunting may have independent effects on children's intellectual function well into later childhood.
Docosahexaenoic acid (DHA) and neuroprotectin D1 (NPD1) are neuroprotective after experimental ischemic stroke. To explore underlying mechanisms, SD rats underwent 2 h of middle cerebral artery ...occlusion (MCAo) and treated with DHA (5 mg/kg, IV) or NPD1 (5 μg/per rat, ICV) and vehicles 1 h after. Neuro-behavioral assessments was conducted on days 1, 2, and 3, and on week 1, 2, 3, or 4. BrdU was injected on days 4, 5, and 6, immunohistochemistry was performed on week 2 or 4, MRI on day 7, and lipidomic analysis at 4 and 5 h after onset of stroke. DHA improved short- and long-term behavioral functions and reduced cortical, subcortical, and total infarct volumes (by 42, 47, and 31%, respectively) after 2 weeks and reduced tissue loss by 50% after 4 weeks. DHA increased the number of BrdU
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and potentiated NPD1 synthesis in the penumbra at 5 h after MCAo. NPD1 improved behavior, reduced lesion volumes, protected ischemic penumbra, increased NeuN, GFAP, SMI-71-positive cells and vessels, axonal regeneration in the penumbra, and attenuated blood-brain barrier (BBB) after MCAo. We conclude that docosanoid administration increases neurogenesis and angiogenesis, activates NPD1 synthesis in the penumbra, and diminishes BBB permeability, which correlates to long-term neurobehavioral recovery after experimental ischemic stroke.
Hypotheses regarding the developmental origins of health and disease postulate that developing fetuses – and potentially young children – undergo adaptive epigenetic changes that have longstanding ...effects on metabolism and other processes. Ongoing research explores whether these adaptations occur during early life following early childhood malnutrition. In the developing world, there remains a high degree of nutritional stunting, defined as linear growth failure caused by inadequate caloric intake, which may be exacerbated by inflammation from ongoing infections. In areas with poor sanitation, children experience vicious cycles of enteric infections and malnutrition, resulting in poor nutrient absorption as a result of changes in the intestinal mucosa, now termed “environmental enteropathy.” Emerging evidence links early childhood diarrhea and/or growth failure with an increased occurrence of risk factors for cardiovascular disease in later life, including dyslipidemia, hypertension, and glucose intolerance. The mechanisms for these associations remain poorly understood and may relate to epigenetic responses to poor nutrition, increased inflammation, or both. Given the increased incidence of cardiovascular disease in developing areas of the world, associations between childhood malnutrition, early‐life infections, and the increased occurrence of risk factors for cardiovascular disease underscore further reasons to improve nutrition and infection‐related outcomes for young children worldwide.
Economic transitions in the era of globalization warrant a fresh look at the neurological risks associated with environmental change. These are driven by industrial expansion, transfer and mobility ...of goods, climate change and population growth. In these contexts, risk of infectious and non-infectious diseases are shared across geographical boundaries. In low- and middle-income countries, the risk of environmentally mediated brain disease is augmented several fold by lack of infrastructure, poor health and safety regulations, and limited measures for environmental protection. Neurological disorders may occur as a result of direct exposure to chemical and/or non-chemical stressors, including but not limited to, ultrafine particulate matters. Individual susceptibilities to exposure-related diseases are modified by genetic, epigenetic and metagenomic factors. The existence of several uniquely exposed populations, including those in the areas surrounding the Niger Delta or north western Amazon oil operations; those working in poorly regulated environments, such as artisanal mining industries; or those, mostly in sub-Saharan Africa, relying on cassava as a staple food, offers invaluable opportunities to advance the current understanding of brain responses to environmental challenges. Increased awareness of the brain disorders that are prevalent in low- and middle-income countries and investments in capacity for further environmental health-related research are positive steps towards improving human health.
Methylmercury (MeHg) toxicity is a major environmental concern. In the aquatic reservoir, MeHg bioaccumulates along the food chain until it is consumed by riverine populations. There has been much ...interest in the neurotoxicity of MeHg due to recent environmental disasters. Studies have also addressed the implications of long-term MeHg exposure for humans. The central nervous system is particularly susceptible to the deleterious effects of MeHg, as evidenced by clinical symptoms and histopathological changes in poisoned humans. In vitro and in vivo studies have been crucial in deciphering the molecular mechanisms underlying MeHg-induced neurotoxicity. A collection of cellular and molecular alterations including cytokine release, oxidative stress, mitochondrial dysfunction, Ca
and glutamate dyshomeostasis, and cell death mechanisms are important consequences of brain cells exposure to MeHg. The purpose of this review is to organize an overview of the mercury cycle and MeHg poisoning events and to summarize data from cellular, animal, and human studies focusing on MeHg effects in neurons and glial cells. This review proposes an up-to-date compendium that will serve as a starting point for further studies and a consultation reference of published studies.
A substantial number of zoonotic diseases are caused by viral pathogens, representing a significant menace to public health, particularly to susceptible populations, such as pregnant women, the ...elderly, and immunocompromised individuals. Individuals who have undergone solid organ transplantation frequently experience immunosuppression, to prevent organ rejection, and, thus are more prone to opportunistic infections. Furthermore, the reactivation of dormant viruses can threaten transplant recipients and organ viability. This mini-review examines the up-to-date literature covering potential zoonotic and organ rejection-relevant viruses in solid organ transplant recipients. A comprehensive list of viruses with zoonotic potential is highlighted and the most important clinical outcomes in patients undergoing transplantation are described. Moreover, this mini-review calls attention to complex multifactorial events predisposing viral coinfections and the need for continuous health surveillance and research to understand better viral pathogens' transmission and pathophysiology dynamics in transplanted individuals.
Cryptosporidiosis is a waterborne protozoal infection that may cause life-threatening diarrhea in undernourished children living in unsanitary environments. The aim of this study is to identify new ...biomarkers that may be related to gut-brain axis dysfunction in children suffering from the malnutrition/infection vicious cycle, necessary for better intervention strategies. Myeloperoxidase (MPO) is a well-known neutrophil-related tissue factor released during enteropathy that could drive gut-derived brain inflammation. We utilized a model of environmental enteropathy in C57BL/6 weanling mice challenged by Cryptosporidium and undernutrition. Mice were fed a 2%-Protein Diet (dPD) for eight days and orally infected with 107-C. parvum oocysts. C. parvum oocyst shedding was assessed from fecal and ileal-extracted genomic DNA by qRT-PCR. Ileal histopathology scores were assessed for intestinal inflammation. Prefrontal cortex samples were snap-frozen for MPO ELISA assay and NF-kb immunostaining. Blood samples were drawn by cardiac puncture after anesthesia and sera were obtained for serum amyloid A (SAA) and MPO analysis. Brain samples were also obtained for Iba-1 prefrontal cortex immunostaining. C. parvum-infected mice showed sustained stool oocyst shedding for six days post-infection and increased fecal MPO and inflammation scores. dPD and cryptosporidiosis led to impaired growth and weight gain. C. parvum-infected dPD mice showed increased serum MPO and serum amyloid A (SAA) levels, markers of systemic inflammation. dPD-infected mice showed greater MPO, NF-kB expression, and Iba-1 immunolabeling in the prefrontal cortex, an important brain region involved in executive function. Our findings suggest MPO as a potential biomarker for intestinal-brain axis dysfunction due to environmental enteropathy.
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