Anaerobe-enriched gut microbiota predicts pro-inflammatory responses in pulmonary tuberculosis

BACKGROUND: The relationship between tuberculosis (TB), one of the leading infectious causes of death worldwide, and the microbiome, which is critical for health, is poorly understood. METHODS: To identify potential microbiome-host interactions, profiling of the oral, sputum and stool microbiota [n = 58 cases, n = 47 culture-negative symptomatic controls (SCs)] and whole blood transcriptome were done in pre-treatment presumptive pulmonary TB patients. This was a cross-sectional study. Microbiota were also characterised in close contacts of cases (CCCs, n = 73) and close contacts of SCs (CCSCs, n = 82) without active TB. FINDINGS: Cases and SCs each had similar α- and β-diversities in oral washes and sputum, however, β-diversity differed in stool (PERMANOVA p = 0•035). Cases were enriched with anaerobes in oral washes, sputum (Paludibacter, Lautropia in both) and stool (Erysipelotrichaceae, Blautia, Anaerostipes) and their stools enriched in microbial genes annotated as amino acid and carbohydrate metabolic pathways. In pairwise comparisons with their CCCs, cases had Megasphaera-enriched oral and sputum microbiota and Bifidobacterium-, Roseburia-, and Dorea-depleted stools. Compared to their CCSCs, SCs had reduced α-diversities and many differential taxa per specimen type. Cases differed transcriptionally from SCs in peripheral blood (PERMANOVA p = 0•001). A co-occurrence network analysis showed stool taxa, Erysipelotrichaceae and Blautia, to negatively co-correlate with enriched "death receptor" and "EIF2 signalling" pathways whereas Anaerostipes positively correlated with enriched "interferon signalling", "Nur77 signalling" and "inflammasome" pathways; all of which are host pathways associated with disease severity. In contrast, none of the taxa enriched in SCs correlated with host pathways. INTERPRETATION: TB-specific microbial relationships were identified in oral washes, induced sputum, and stool from cases before the confounding effects of antibiotics. Specific anaerobes in cases' stool predict upregulation of pro-inflammatory immunological pathways, supporting the gut microbiota's role in TB. FUNDING: European & Developing Countries Clinical Trials Partnership, South African-Medical Research Council, National Institute of Allergy and Infectious Diseases

The trajectory of land reform in Zimbabwe: Post-independence era 1980-2000

There is a general consensus that land reform in post settler colonies fits like a glove. Since extensive land alienation occurred in Zimbabwe, which resulted in the occupation of larger, more fertile, arable healthy pieces of land by minority whites and occupation of the unproductive, crowded, marginal and deteriorating lands by blacks, independence has given the land question a new force. Going through available literature on Zimbabwe’s land reform progress, there is the impression that, during the liberation struggle, the land question was more of a political issue than anything else. It was about fighting exploitative governmental agrarian policies, fighting for ancestral land, fighting for the power with which land ownership came. With the advent of independence, the land question, as Moyo opines, has been popularized within the “growth with equity” parameters set out by the new regime allowing for a significant amount of land redistribution.3 Thus, through reading library sources and literature in private collections, as well as carrying out interviews, this article seeks to demonstrate the essentiality and centrality of the land question in post independence Zimbabwe. Also to register that the land question presently has grown bigger and wider to entail, among other things, land redistribution, solutions to promote rural development of communal lands, political stability of a nation as well as the economics that goes with land utilization, land tenure, grazing schemes, population control, restitution, gender issues and the list goes on

Development, Validity, and Cross-Context Equivalence of the Child Food Insecurity Experiences Scale for Assessing Food Insecurity of School-Age Children and Adolescents

BACKGROUND: Children ages 6 to 17 years can accurately assess their own food insecurity, whereas parents are inaccurate reporters of their children's experiences of food insecurity. No globally applicable scale to assess the food insecurity of children has been developed and validated. OBJECTIVES: We aimed to develop a globally applicable, experience-based measure of child and adolescent food insecurity and establish the validity and cross-contextual equivalence of the measure. METHODS: The 10-item Child Food Insecurity Experiences Scale (CFIES) was based on items previously validated from questionnaires from the United States, Venezuela, and Lebanon. Cognitive interviews were conducted to check understanding of the items. The questionnaire then was administered in 15 surveys in 13 countries. Other items in each survey that assessed the household socioeconomic status, household food security, or child psychological functioning were selected as criterion variables to compare to the scores from the CFIES. To investigate accuracy (i.e., criterion validity), linear regression estimated the associations of the CFIES scores with the criterion variables. To investigate the cross-contextual equivalence (i.e., measurement invariance), the alignment method was used based on classical measurement theory. RESULTS: Across the 15 surveys, the mean scale scores for the CFIES ranged from 1.65 to 5.86 (possible range of 0 to 20) and the Cronbach alpha ranged from 0.88 to 0.94. The variance explained by a 1-factor model ranged from 0.92 to 0.99. Accuracy was demonstrated by expected associations with criterion variables. The percentages of equivalent thresholds and loadings across the 15 surveys were 28.0 and 5.33, respectively, for a total percentage of nonequivalent thresholds and loadings of 16.7, well below the guideline of <25%. That is, 83.3% of thresholds and loadings were equivalent across these surveys. CONCLUSIONS: The CFIES provides a globally applicable, valid, and cross-contextually equivalent measure of the experiences of food insecurity of school-aged children and adolescents, as reported by them

N-Acetyl cysteine ameliorates hyperglycemia-induced cardiomyocyte toxicity by improving mitochondrial energetics and enhancing endogenous Coenzyme Q9/10 levels

The diabetic heart has been linked with reduced endogenous levels of coenzyme Q9/10 (CoQ), an important antioxidant and component of the electron transport chain. Although CoQ has displayed cardioprotective potential in experimental models of diabetes, the impact of N-acetyl cysteine (NAC) on mitochondrial energetics and endogenous levels of CoQ remains to be clarified. To explore these effects, high glucose-exposed H9c2 cardiomyocytes were used as an experimental model of hyperglycemia-induced cardiac injury. The results showed that high glucose exposure caused an increased production of reactive oxygen species (ROS), which was associated with impaired mitochondrial energetics as confirmed by a reduction of maximal respiration rate and depleted ATP levels. These detrimental effects were consistent with significantly reduced endogenous CoQ levels and accelerated cell toxicity. Although metformin demonstrated similar effects on mitochondrial energetics and cell viability, NAC demonstrated a more pronounced effect in ameliorating cytosolic and mitochondrial ROS production. Interestingly, the ameliorative effects of NAC against hyperglycemia-induced injury were linked with its capability to enhance endogenous CoQ levels. Although such data are to be confirmed in other models, especially in vivo studies, the overall findings provide additional evidence on the therapeutic mechanisms by which NAC protects against diabetes-induced cardiac injury

The kinetic exclusion process: a tale of two fields

We introduce a general class of stochastic lattice gas models, and derive their fluctuating hydrodynamics description in the large size limit under a local equilibrium hypothesis. The model consists of energetic particles on a lattice subject to exclusion interactions, which move and collide stochastically with energy-dependent rates. The resulting fluctuating hydrodynamics equations exhibit nonlinear coupled particle and energy transport, including particle currents due to temperature gradients (Soret effect) and energy flow due to concentration gradients (Dufour effect). The microscopic dynamical complexity is condensed in just two matrices of transport coefficients: the diffusivity matrix (or equivalently the Onsager matrix) generalizing Fick Fourier's law, and the mobility matrix controlling current fluctuations. Both transport coefficients are coupled via a fluctuation-dissipation theorem, suggesting that the noise terms affecting the local currents have Gaussian properties. We further prove the positivity of entropy production in terms of the microscopic dynamics. The so-called kinetic exclusion process has as limiting cases two of the most paradigmatic models of nonequilibrium physics, namely the symmetric simple exclusion process of particle diffusion and the Kipnis Marchioro Presutti model of heat flow, making it the ideal testbed where to further develop modern theories of nonequilibrium behavior.We thank R Hurtado for many useful comments on the manuscript. Financial support from Spanish Ministry MINECO project FIS2017-84256-P is also acknowledged. This study has been partially financed by the Consejeria de Conocimiento, Investigacion y Universidad (Junta de Andalucia), and European Regional Development Fund (ERDF), ref. SOMM17/6105/UGR