Project description:Background and aimsMalnutrition in lung transplantation (LT) candidates increases postoperative morbidity and mortality. Early diagnosis of malnutrition could attenuate adverse prognostic factors. This study aimed to assess the prevalence of nutritional risk and malnutrition using GLIM criteria in LT candidates and clinically characterize those with malnutrition.MethodsA prospective longitudinal study was conducted from 2000 to 2020 of LT candidates who underwent complete nutritional assessment (nutritional screening, anthropometry, bioelectrical impedance, blood laboratory tests and malnutrition diagnosis using GLIM criteria).ResultsObstructive diseases (45.6%), interstitial diseases (36.6%) and cystic fibrosis/non-cystic fibrosis bronchiectasis (15.4%) were the main conditions assessed for LT. Of the 1060 candidates evaluated, 10.6% were underweight according to BMI, 29% were at risk of malnutrition and 47% were diagnosed with malnutrition using GLIM criteria. Reduced muscle mass was the most frequent GLIM phenotypic criterion. Malnutrition was more prevalent in patients with cystic fibrosis/non-cystic fibrosis bronchiectasis (84.5%) and obstructive (45.4%) and interstitial (31.3%) diseases. GLIM criteria detected some degree of malnutrition in all diseases requiring LT and identified patients with higher CRP levels and worse respiratory function, anthropometric measurements and visceral protein and lipid profiles.ConclusionsLT candidates present a high prevalence of malnutrition using the GLIM algorithm. GLIM criteria detected malnutrition in all diseases requiring LT and defined patients with worse clinical-analytical profiles.
Project description:Gene regulatory networks exhibit complex, hierarchical features such as global regulation and network motifs. There is much debate about whether the evolutionary origins of such features are the results of adaptation, or the by-products of non-adaptive processes of DNA replication. The lack of availability of gene regulatory networks of ancestor species on evolutionary timescales makes this a particularly difficult problem to resolve. Digital organisms, however, can be used to provide a complete evolutionary record of lineages. We use a biologically realistic evolutionary model that includes gene expression, regulation, metabolism and biosynthesis, to investigate the evolution of complex function in gene regulatory networks. We discover that: (i) network architecture and complexity evolve in response to environmental complexity, (ii) global gene regulation is selected for in complex environments, (iii) complex, inter-connected, hierarchical structures evolve in stages, with energy regulation preceding stress responses, and stress responses preceding growth rate adaptations and (iv) robustness of evolved models to mutations depends on hierarchical level: energy regulation and stress responses tend not to be robust to mutations, whereas growth rate adaptations are more robust and non-lethal when mutated. These results highlight the adaptive and incremental evolution of complex biological networks, and the value and potential of studying realistic in silico evolutionary systems as a way of understanding living systems.
Project description:Severe acute malnutrition (SAM) is associated with increased severity of common infectious diseases, and death amongst children with SAM is almost always as a result of infection. The diagnosis and management of infection are often different in malnourished versus well-nourished children. The objectives of this brief are to outline the evidence underpinning important practical questions relating to the management of infectious diseases in children with SAM and to highlight research gaps. Overall, the evidence base for many aspects covered in this brief is very poor. The brief addresses antimicrobials; antipyretics; tuberculosis; HIV; malaria; pneumonia; diarrhoea; sepsis; measles; urinary tract infection; nosocomial Infections; soil transmitted helminths; skin infections and pharmacology in the context of SAM. The brief is structured into sets of clinical questions, which we hope will maximise the relevance to contemporary practice.
Project description:Pollinators contribute around 10% of the economic value of crop production globally, but the contribution of these pollinators to human nutrition is potentially much higher. Crops vary in the degree to which they benefit from pollinators, and many of the most pollinator-dependent crops are also among the richest in micronutrients essential to human health. This study examines regional differences in the pollinator dependence of crop micronutrient content and reveals overlaps between this dependency and the severity of micronutrient deficiency in people around the world. As much as 50% of the production of plant-derived sources of vitamin A requires pollination throughout much of Southeast Asia, whereas other essential micronutrients such as iron and folate have lower dependencies, scattered throughout Africa, Asia and Central America. Micronutrient deficiencies are three times as likely to occur in areas of highest pollination dependence for vitamin A and iron, suggesting that disruptions in pollination could have serious implications for the accessibility of micronutrients for public health. These regions of high nutritional vulnerability are understudied in the pollination literature, and should be priority areas for research related to ecosystem services and human well-being.
Project description:BackgroundLow- to middle-income countries (LMICs) are believed to be characterized by the coexistence of underweight and overweight. It has also been posited that such coexistence is appearing among the low socioeconomic status (SES) groups.MethodsWe conducted a cross-sectional analysis of nationally representative samples of 451,321 women aged 20-49 years drawn from 57 Demographic and Health Surveys conducted between 1994 and 2008. Body Mass Index (BMI in kg/m²), was used to define underweight and overweight following conventional cut-points. Covariates included age, household wealth, education, and residence. We estimated multinomial multilevel models to assess the extent to which underweight (BMI<18.5 kg/m²) and overweight (BM I≥ 25.0 kg/m²) correlate at the country-level, and at the neighborhood-level within each country.ResultsIn age-adjusted models, there was a strong negative correlation between likelihood of being underweight and overweight at country- (r = -0.79, p<0.001), and at the neighborhood-level within countries (r = -0.51, P<0.001). Negative correlations ranging from -0.11 to -0.90 were observed in 46 of the 57 countries at the neighborhood-level and 29/57 were statistically significant (p ≤ 0.05). Similar negative correlations were observed in analyses restricted to low SES groups. Finally, the negative correlations across countries, and within-countries, appeared to be stable over time in a sub-set of 36 countries.ConclusionThe explicitly negative correlations between prevalence of underweight and overweight at the country-level and at neighborhood-level suggest that the hypothesized coexistence of underweight and overweight has not yet occurred in a substantial manner in a majority of LMICs.
Project description:Dietary protein deficiency results in diminished capacity of the pancreas to secrete enzymes needed for macronutrient digestion. Previous work has suggested that modulation of the mammalian target of rapamycin (mTOR) pathway by the hormone cholecystokinin (CCK) plays an important role in normal digestive enzyme synthesis after feeding. The purpose of this study was to elucidate the role of mTOR in protein deficiency-induced pancreatic dysfunction.Wild-type and CCK-null mice were fed protein-deficient chow for 4 days and then allowed to recover on control chow in the presence or absence of the mTOR inhibitor rapamycin.The size and secretory capacity of the pancreas rapidly decreased after feeding protein-deficient chow. Refeeding protein-replete chow reversed these changes in both wild-type and CCK-null mice. Changes in the size of the pancreas were paralleled by changes in the content and secretion of digestive enzymes, as well as the phosphorylation of downstream targets of mTOR. Administration of the mTOR inhibitor rapamycin decreased regrowth of the pancreas but did not affect digestive enzyme content or secretory capacity.These studies demonstrate that dietary protein modulates pancreatic growth, but not digestive enzyme synthesis, via CCK-independent activation of the mTOR pathway.
Project description:Human noroviruses are the primary cause of severe childhood diarrhea in the United States, and they are of particular clinical importance in pediatric populations in the developing world. A major contributing factor to the general increased severity of infectious diseases in these regions is malnutrition-nutritional status shapes host immune responses and the composition of the host intestinal microbiota, both of which can influence the outcome of pathogenic infections. In terms of enteric norovirus infections, mucosal immunity and intestinal microbes are likely to contribute to the infection outcome in substantial ways. We probed these interactions using a murine model of malnutrition and murine norovirus infection. Our results reveal that malnutrition is associated with more severe norovirus infections as defined by weight loss, impaired control of norovirus infections, reduced antiviral antibody responses, loss of protective immunity, and enhanced viral evolution. Moreover, the microbiota is dramatically altered by malnutrition. Interestingly, murine norovirus infection also causes changes in the host microbial composition within the intestine but only in healthy mice. In fact, the infection-associated microbiota resembles the malnutrition-associated microbiota. Collectively, these findings represent an extensive characterization of a new malnutrition model of norovirus infection that will ultimately facilitate elucidation of the nutritionally regulated host parameters that predispose to more severe infections and impaired memory immune responses. In a broad sense, this model may provide insight into the reduced efficacy of oral vaccines in malnourished hosts and the potential for malnourished individuals to act as reservoirs of emergent virus strains. IMPORTANCE Malnourished children in developing countries are susceptible to more severe infections than their healthy counterparts, in particular enteric infections that cause diarrhea. In order to probe the effects of malnutrition on an enteric infection in a well-controlled system devoid of other environmental and genetic variability, we studied norovirus infection in a mouse model. We have revealed that malnourished mice develop more severe norovirus infections and they fail to mount effective memory immunity to a secondary challenge. This is of particular importance because malnourished children generally mount less effective immune responses to oral vaccines, and we can now use our new model system to probe the immunological basis of this impairment. We have also determined that noroviruses evolve more readily in the face of malnutrition. Finally, both norovirus infection and malnutrition independently alter the composition of the intestinal microbiota in substantial and overlapping ways.
Project description:BackgroundThe proposal of the global leadership initiative in malnutrition (GLIM) criteria has received great attention from clinicians. The criteria are mainly used in the research environment and have the potential to be widely used in the clinic in the future. However, the prevalence of malnutrition and risk of future malnutrition based on a current diagnosis of malnutrition are worth exploring.MethodsA systematic search of PubMed, Embase, and the Cochrane Library was performed from the earliest available date to 1 February 2023. According to the diagnostic criteria of the GLIM, we analysed the prevalence of malnutrition by directly adopting the GLIM criteria for diagnosis without a previous nutritional risk screening (one-step approach) and by adopting the GLIM criteria for diagnosis after a nutritional risk screening (two-step approach). The main outcome was the prevalence of malnutrition based on the one-and two-step approaches. Secondary outcomes were the future risk of malnutrition based on the GLIM diagnosis, including mortality within and beyond 1 year. primary outcomes were pooled using random-effects models, and secondary outcomes are presented as hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsA total of 64 articles were included in the study, including a total of 47,654 adult hospitalized patients and 15,089 malnourished patients based on the GLIM criteria. Malnutrition was diagnosed by the one-step approach in 18 studies and by the two-step approach in 46 studies. The prevalence of malnutrition diagnosed by the one-and two-step approaches was 53% (95% CI, 42%-64%) and 39% (95% CI, 0.35%-0.43%), respectively. The prevalence of malnutrition diagnosed by the GLIM criteria after a nutritional risk screening was quite different; the prevalence of malnutrition diagnosed by the Nutritional Risk Screening 2002 (NRS2002) GLIM tool was 35% (95% CI, 29%-40%); however, the prevalence of malnutrition diagnosed by the Mini Nutrition Assessment (MNA) GLIM tool was 48% (95% CI, 35%-62%). Among the disease types, the prevalence of malnutrition in cancer patients was 44% (95% CI, 36%-52%), while that in acute and critically ill patients was 44% (95% CI, 33%-56%). The prevalence in patients in internal medicine wards was 40% (95% CI, 34%-45%), while that in patients in surgical wards was 47% (95% CI, 30%-64%). In addition, the mortality risk within 1 year (HR, 2.62; 95% CI, 1.95-3.52; I2 = 77.1%) and beyond 1 year (HR, 2.04; 95% CI, 1.70-2.45; I2 = 59.9%) of patients diagnosed with malnutrition by the GLIM criteria was double that of patients with normal nutrition.ConclusionThe prevalence of malnutrition diagnosed by the GLIM criteria after a nutritional risk screening was significantly lower than the prevalence of malnutrition diagnosed directly by the GLIM criteria. In addition, the mortality risk was significantly greater among malnourished patients assessed by the GLIM criteria.Systematic review registration: identifier CRD42023398454.