Congenital intestinal diarrhoeal diseases: A diagnostic and therapeutic challenge

Congenital diarrhoeal disorders are a heterogeneous group of inherited malabsorptive or secretory diseases typically appearing in the first weeks of life, which may be triggered by the introduction of distinct nutrients. However, they may also be unrecognised for a while and triggered by exogenous factors later on. In principle, they can be clinically classified as osmotic, secretory or inflammatory diarrhoea. In recent years the disease-causing molecular defects of these congenital disorders have been identified. According to the underlying pathophysiology they can be classified into four main groups:1) Defects of digestion, absorption and transport of nutrients or electrolytes2) Defects of absorptive enterocyte differentiation or polarisation3) Defects of the enteroendocrine cells4) Defects of the immune system affecting the intestineHere, we describe the clinical presentation of congenital intestinal diarrhoeal diseases, the diagnostic work-up and specific treatment aspects.     

From the Cover: A simple nutrient-dependence mechanism for predicting the stoichiometry of marine ecosystems

It is widely recognized that the stoichiometry of nutrient elements in phytoplankton varies within the ocean. However, there are many conflicting mechanistic explanations for this variability, and it is often ignored in global biogeochemical models and carbon cycle simulations. Here we show that globally distributed particulate P:C varies as a linear function of ambient phosphate concentrations, whereas the N:C varies with ambient nitrate concentrations, but only when nitrate is most scarce. This observation is consistent with the adjustment of the phytoplankton community to local nutrient availability, with greater flexibility of phytoplankton P:C because P is a less abundant cellular component than N. This simple relationship is shown to predict the large-scale, long-term average composition of surface particles throughout large parts of the ocean remarkably well. The relationship implies that most of the observed variation in N:P actually arises from a greater plasticity in the cellular P:C content, relative to N:C, such that as overall macronutrient concentrations decrease, N:P rises. Although other mechanisms are certainly also relevant, this simple relationship can be applied as a first-order basis for predicting organic matter stoichiometry in large-scale biogeochemical models, as illustrated using a simple box model. The results show that including variable P:C makes atmospheric CO₂ more sensitive to changes in low latitude export and ocean circulation than a fixed-stoichiometry model. In addition, variable P:C weakens the relationship between preformed phosphate and atmospheric CO₂ while implying a more important role for the nitrogen cycle.Nutrient elements are used by phytoplankton to synthesize molecules, in order to accomplish biochemical functions. Some of these molecules are absolutely necessary, and the nutrient elements have no substitutes. Examples are P in nucleic acids, N in amino acids, and Fe in the photosynthetic apparatus (1). However, there is a degree of plasticity in the molecular assemblage required per phytoplankton cell, which varies between species and between clades (2, 3). Furthermore, there is a capacity for plasticity in molecular composition of even a given species, as shown in culture experiments (4, 5). Such plasticity leads to variability in the elemental ratios of nutrients in marine phytoplankton, widely documented in laboratory and field measurements (2, 6, 7). Recent analyses of global nutrient and particulate observations have shown that N:P, the most commonly discussed ratio, varies regionally, including low N:P in the high-latitude Southern Ocean and high N:P in the oligotrophic regions (7–9). Explanations of high N:P in oligotrophic waters have often invoked an enhanced reliance on N-rich proteins for gathering scarce resources (1, 10), whereas low N:P in the Southern Ocean has been variously attributed to the abundance of P-rich molecules in cold, fast-growing plankton (11), or to the availability of Si, which supports P-rich diatom communities (8, 12).Despite an abundant literature on stoichiometric variability and its potential causes, no simple predictive relationship has been widely adopted in global biogeochemical models. Instead, the vast majority of global biogeochemical models assumes fixed C:N:P in organic matter, including most participants in the recent Coupled Model Intercomparison Project, CMIP5 (13). Thus, the potential impact of changes in organic matter stoichiometry on ocean carbon storage and oxygen consumption remain largely unexplored. The neglect of stoichiometric variability is due, at least in part, to the lack of a clear predictive framework.Here, it is argued that the concentration of a nutrient element in seawater can provide a suitable predictive framework, because it is a critical determinant of the rate at which that element will tend to be taken up by the organisms in the local community. This hypothesis builds on classic resource competition theory (14), which argues that if the concentration of an element is low, such that uptake is difficult, the community will be dominated by organisms that are well adapted to a low cellular quota of that nutrient (10). If, on the other hand, the concentration is high, facilitating high uptake rates, the community will be dominated by organisms that are capable of taking advantage of that nutrient to grow faster. This suggestion leads to clear predictions with significant biogeochemical consequences, as outlined below.     

Food or nutrient pattern assessment using the principal component analysis applied to food questionnaires. Pitfalls,tips and tricks

We considered the Blom’s transformation, a statistical method aimed to normalise and standardise food intakes before principal component analysis. A simulation study was performed to evaluate the eigenvalue distribution of a correlation matrix under common conditions in food questionnaire analysis. The scree plot visual inspection and the Guttman–Kaiser (GK) criterion were compared to Horn’s parallel analysis to evaluate their efficacy in food pattern identification. The scree plot results as a monotone continuous series when no food patterns are present. In this situation, about 50% of the eigenvalues assume a value higher than one, showing a first fallacy of the GK. When three food patterns are simulated a clear discontinuity appears after the third eigenvalue, showing that the scree-plot visual inspection is a suitable method to identify food patterns. Finally, according to the present work it appears that the GK generates a number of false-positive food patterns.     

Mycobacterial genes essential for the pathogen's survival in the host

Mycobacterium tuberculosis (Mtb) has evolved within the human immune system as both host and reservoir. The study of genes required for its growth and persistence in vivo thus offers linked insights into its pathogenicity and host immunity. Studies of Mtb mutants have implicated metabolic adaptation (consisting of carbon, nitrogen, vitamin, and cofactor metabolism), intrabacterial pH homeostasis, and defense against reactive oxygen and reactive nitrogen species, as key determinants of its pathogenicity. However, the mechanisms of host immunity are complex and often combinatorial. Growing evidence has thus begun to reveal that the determinants of Mtb's pathogenicity may serve a broader and more complex array of functions than the isolated experimental settings in which they were initially found. Here, we review select examples, which exemplify this complexity, highlighting the distinct phases of Mtb's life cycle and the diverse microenvironments encountered therein.     

Nutrient-based dietary patterns and nasopharyngeal cancer: evidence from an exploratory factor analysis

Background:

To our knowledge, no study assessed the association between dietary patterns and nasopharyngeal carcinoma (NPC) in low-incidence areas.

Methods:

We examined this association in a hospital-based case–control study carried out in Italy between 1992 and 2008, including 198 incident NPC cases and 594 controls. A posteriori dietary patterns were identified through principal component factor analysis performed on 28 nutrients and minerals derived from a 78-item food-frequency questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional multiple logistic regression models on tertiles of factor scores.

Results:

We identified five dietary patterns named Animal products, Starch-rich, Vitamins and fibre, Animal unsaturated fatty acids (AUFAs), and Vegetable unsaturated fatty acids (VUFAs). The Animal product (OR=2.62, 95% CI=1.67–4.13, for the highest vs lowest score tertile), Starch-rich (OR=2.05, 95% CI=1.27–3.33), and VUFA (OR=1.90, 95% CI=1.22–2.96) patterns were positively associated with NPC. The AUFA pattern showed a positive association of borderline significance, whereas the Vitamins and fibre pattern was nonsignificantly but inversely associated with NPC.

Conclusions:

These findings suggest that diets rich in animal products, starch, and fats are positively related to NPC risk in this low-incidence country.     

Higher Dietary Energy Density is Associated with Stunting but not Overweight and Obesity in a Sample of Urban Malaysian Children

Although diets with high energy density are associated with increased risk of overweight and obesity, it is not known whether such diets are associated with undernutrition. This study assessed the relationship between dietary energy density (ED) and nutritional status of 745 urban 1- to 10-year-old children. Dietary intakes were obtained using food recall and record for two days. Dietary energy density was based on food and caloric beverages. Higher dietary ED was associated with lower intakes of carbohydrate, sugar, vitamins C and D, and calcium but higher fat, fiber, iron, and folate intakes. While intakes of fruits and milk/dairy products decreased, meat, fish, and legume intakes increased with higher dietary ED. Stunting, but not other growth problems, was associated with higher dietary ED. Future studies should confirm the cause-and-effect relationship between higher dietary ED and stunting.