A New Approach to Express Regional Adiposity and Its Association with Blood Lipids, Inflammation and Insulin Resistance Markers

Regional adiposity is classically related with inflammation, insulin resistance (IR) and an altered blood lipid profile. Traditionally, central adiposity expressed as a ratio (%FM) = fat mass/total mass of the region is the variable most used in research. However, this ratio does not account for total bodily fat mass (TFM). So, a great accumulation in a region, where lean mass is more important than fat, could be more associated with risk factors than other with less absolute fat (kg) but higher percentage (in instance abdomen). PURPOSE: To analyse the associations between the ratio (RW) = regional fat mass (kg) / TFM (kg) and blood lilid profile, IR and inflammation. METHODS: Sixty-two pre-menopausal and healthy women were recruited for this study (age, 39.6 ±7.2 years; BMI, 29.2 ±4.2 kg.m-2; total %TFM, 42.0 ±5.9%). Weight and height were measured to the nearest 0.1 kg and 0.1 cm respectively, and body composition was estimated with dual energy x-ray aborptiometry. RWF were calculated for trunk (RWT), lower limbs (RWLL) and upper limbs (RWUL). Insulin, glycaemia and insulin sensitivity (HOMA) were the IR markers. C-reactive protein (CRP) and Tumour Necrosis Factor (TNF-α) were the inflammation variables. Total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglycerides (TG) were also measured. Partial correlations adjusted to TFM between RW and blood markers were carried out. RESULTS: Significant correlations were found between RWUL and HOMA (r=0.276, P<0.05), TG (r=0.292, P<0.05) and insulin (r=0.271, P<0.05). RWT was also correlated with blood lipids: TG (r=0.278, P<0.05) and LDL (r=-0.318, P<0.05). Finally, RWLL was the ratio with more number of associations: HOMA (r=-0.274, P<0.05), TG (r=-0.342, P<0.01), LDL (r=0.317, P<0.05) and insulin (r=-0.253, P<0.05). Abdominal and trunk %FM were only correlated with HOMA (r=0.380, P<0.01) and LDL (r=0.264, P<0.05) respectively. CONCLUSION: In our sample, regional fat mass contribution (RW) for whole body FM showed more associations with blood markers than classical ratios (regional %FM). These findings highlighted RW ratios were well correlated with inflammatory and IR risk factors, which in turn could be useful to express positive or negative results in future studies. This issue requires further investigation.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Mucoid morphotype variation of Burkholderia multivorans during chronic cystic fibrosis lung infection is correlated with changes in metabolism, motility, biofilm formation and virulence

Burkholderia cepacia complex (Bcc) bacteria are opportunistic pathogens infecting hosts such as cystic fibrosis (CF) patients. Long-term Bcc infection of CF patients' airways has been associated with emergence of phenotypic variation. Here we studied two Burkholderia multivorans clonal isolates displaying different morphotypes from a chronically infected CF patient to evaluate trait development during lung infection. Expression profiling of mucoid D2095 and non-mucoid D2214 isolates revealed decreased expression of genes encoding products related to virulence-associated traits and metabolism in D2214. Furthermore, D2214 showed no exopolysaccharide production, lower motility and chemotaxis, and more biofilm formation, particularly under microaerophilic conditions, than the clonal mucoid isolate D2095. When Galleria mellonella was used as acute infection model, D2214 at a cell number of approximately 7×10(6) c.f.u. caused a higher survival rate than D2095, although 6 days post-infection most of the larvae were dead. Infection with the same number of cells by mucoid D2095 caused larval death by day 4. The decreased expression of genes involved in carbon and nitrogen metabolism may reflect lower metabolic needs of D2214 caused by lack of exopolysaccharide, but also by the attenuation of pathways not required for survival. As a result, D2214 showed higher survival than D2095 in minimal medium for 28 days under aerobic conditions. Overall, adaptation during Bcc chronic lung infections gave rise to genotypic and phenotypic variation among isolates, contributing to their fitness while maintaining their capacity for survival in this opportunistic human niche

Tissue Oxygenation in Response to Different Relative Levels of Blood-Flow Restricted Exercise

Blood flow restrictive (BFR) exercise elicits a localized hypoxic environment compatible with greater metabolic stress. We intended to compare the acute changes in muscle microvascular oxygenation following low-intensity knee extension exercise, combined with different levels of BFR. Thirteen active young men (age: 23.8 ± 5.4 years) were tested for unilateral knee extension exercise (30 + 15 + 15 + 15 reps at 20% one repetition maximum) on four different conditions: no-BFR (NOBFR), 40, 60, and 80% of arterial occlusion pressure (AOP). Deoxyhemoglobin+myoglobin concentration Deoxy[Hb+Mb], total hemoglobin [T(H+Mb)] and tissue oxygen saturation [TOI] were measured on the vastus lateralis muscle using near-infrared spectroscopy (NIMO, Nirox srl, Brescia, Italy). The magnitude of change in Deoxy[Hb+Mb]during exercise was similar between 60 and 80% AOP. Overall, compared to that seen during 60 and 80% AOP, NOBFR as well as 40% AOP resulted in a lower magnitude of change in Deoxy[Hb+Mb] (p &lt; 0.05). While the oxygen extraction decreased during each inter-set resting interval in NOBFR and 40% AOP, this was not the case for 60 or 80% AOP. Additionally, TOI values obtained during recovery from each set of exercise were similarly affected by all conditions. Finally, our data also show that, when performed at higher restrictive values (60 and 80%), BFR exercise increases total Deoxy[Hb+Mb] extraction (p &lt; 0.05). Taken together, we provide evidence that BFR is effective for increasing deoxygenation and reducing tissue oxygenation during low-intensity exercise. We also showed that when using low loads, a relative pressure above 40% of the AOP at rest is required to elicit changes in microvascular oxygenation compared with the same exercise with unrestricted conditions

Structure of a Burkholderia pseudomallei Trimeric Autotransporter Adhesin Head

Pathogenic bacteria adhere to the host cell surface using a family of outer membrane proteins called Trimeric Autotransporter Adhesins (TAAs). Although TAAs are highly divergent in sequence and domain structure, they are all conceptually comprised of a C-terminal membrane anchoring domain and an N-terminal passenger domain. Passenger domains consist of a secretion sequence, a head region that facilitates binding to the host cell surface, and a stalk region.Pathogenic species of Burkholderia contain an overabundance of TAAs, some of which have been shown to elicit an immune response in the host. To understand the structural basis for host cell adhesion, we solved a 1.35 A resolution crystal structure of a BpaA TAA head domain from Burkholderia pseudomallei, the pathogen that causes melioidosis. The structure reveals a novel fold of an intricately intertwined trimer. The BpaA head is composed of structural elements that have been observed in other TAA head structures as well as several elements of previously unknown structure predicted from low sequence homology between TAAs. These elements are typically up to 40 amino acids long and are not domains, but rather modular structural elements that may be duplicated or omitted through evolution, creating molecular diversity among TAAs.The modular nature of BpaA, as demonstrated by its head domain crystal structure, and of TAAs in general provides insights into evolution of pathogen-host adhesion and may provide an avenue for diagnostics

Garlic Revisited: Antimicrobial Activity of Allicin-Containing Garlic Extracts against Burkholderia cepacia Complex

The antimicrobial activities of garlic and other plant alliums are primarily based on allicin, a thiosulphinate present in crushed garlic bulbs. We set out to determine if pure allicin and aqueous garlic extracts (AGE) exhibit antimicrobial properties against the Burkholderia cepacia complex (Bcc), the major bacterial phytopathogen for alliums and an intrinsically multiresistant and life-threatening human pathogen. We prepared an AGE from commercial garlic bulbs and used HPLC to quantify the amount of allicin therein using an aqueous allicin standard (AAS). Initially we determined the minimum inhibitory concentrations (MICs) of the AGE against 38 Bcc isolates; these MICs ranged from 0.5 to 3% (v/v). The antimicrobial activity of pure allicin (AAS) was confirmed by MIC and minimum bactericidal concentration (MBC) assays against a smaller panel of five Bcc isolates; these included three representative strains of the most clinically important species, B. cenocepacia. Time kill assays, in the presence of ten times MIC, showed that the bactericidal activity of AGE and AAS against B. cenocepacia C6433 correlated with the concentration of allicin. We also used protein mass spectrometry analysis to begin to investigate the possible molecular mechanisms of allicin with a recombinant form of a thiol-dependent peroxiredoxin (BCP, Prx) from B. cenocepacia. This revealed that AAS and AGE modifies an essential BCP catalytic cysteine residue and suggests a role for allicin as a general electrophilic reagent that targets protein thiols. To our knowledge, we report the first evidence that allicin and allicin-containing garlic extracts possess inhibitory and bactericidal activities against the Bcc. Present therapeutic options against these life-threatening pathogens are limited; thus, allicin-containing compounds merit investigation as adjuncts to existing antibiotics

Genomic Expression Analysis Reveals Strategies of Burkholderia cenocepacia to Adapt to Cystic Fibrosis Patients' Airways and Antimicrobial Therapy

Pulmonary colonization of cystic fibrosis (CF) patients with Burkholderia cenocepacia or other bacteria of the Burkholderia cepacia complex (Bcc) is associated with worse prognosis and increased risk of death. During colonization, the bacteria may evolve under the stressing selection pressures exerted in the CF lung, in particular, those resulting from challenges of the host immune defenses, antimicrobial therapy, nutrient availability and oxygen limitation. Understanding the adaptive mechanisms that promote successful colonization and long-term survival of B. cenocepacia in the CF lung is essential for an improved therapeutic outcome of chronic infections. To get mechanistic insights into these adaptive strategies a transcriptomic analysis, based on DNA microarrays, was explored in this study. The genomic expression levels in two clonal variants isolated during long-term colonization of a CF patient who died from the cepacia syndrome were compared. One of the isolates examined, IST439, is the first B. cenocepacia isolate retrieved from the patient and the other isolate, IST4113, was obtained three years later and is more resistant to different classes of antimicrobials. Approximately 1000 genes were found to be differently expressed in the two clonal variants reflecting a marked reprogramming of genomic expression. The up-regulated genes in IST4113 include those involved in translation, iron uptake (in particular, in ornibactin biosynthesis), efflux of drugs and in adhesion to epithelial lung tissue and to mucin. Alterations related with adaptation to the nutritional environment of the CF lung and to an oxygen-limited environment are also suggested to be a key feature of transcriptional reprogramming occurring during long-term colonization, antibiotic therapy and the progression of the disease

A review of source tracking techniques for fine sediment within a catchment

Excessive transport of fine sediment, and its associated pollutants, can cause detrimental impacts in aquatic environments. It is therefore important to perform accurate sediment source apportionment to identify hot spots of soil erosion. Various tracers have been adopted, often in combination, to identify sediment source type and its spatial origin; these include fallout radionuclides, geochemical tracers, mineral magnetic properties and bulk and compound-specific stable isotopes. In this review, the applicability of these techniques to particular settings and their advantages and limitations are reviewed. By synthesizing existing approaches, that make use of multiple tracers in combination with measured changes of channel geomorphological attributes, an integrated analysis of tracer profiles in deposited sediments in lakes and reservoirs can be made. Through a multi-scale approach for fine sediment tracking, temporal changes in soil erosion and sediment load can be reconstructed and the consequences of changing catchment practices evaluated. We recommend that long-term, as well as short-term, monitoring of riverine fine sediment and corresponding surface and subsurface sources at nested sites within a catchment are essential. Such monitoring will inform the development and validation of models for predicting dynamics of fine sediment transport as a function of hydro-climatic and geomorphological controls. We highlight that the need for monitoring is particularly important for hilly catchments with complex and changing land use. We recommend that research should be prioritized for sloping farmland-dominated catchments

A review of source tracking techniques for fine sediment within a catchment

Excessive transport of fine sediment, and its associated pollutants, can cause detrimental impacts in aquatic environments. It is therefore important to perform accurate sediment source apportionment to identify hot spots of soil erosion. Various tracers have been adopted, often in combination, to identify sediment source type and its spatial origin; these include fallout radionuclides, geochemical tracers, mineral magnetic properties and bulk and compound-specific stable isotopes. In this review, the applicability of these techniques to particular settings and their advantages and limitations are reviewed. By synthesizing existing approaches, that make use of multiple tracers in combination with measured changes of channel geomorphological attributes, an integrated analysis of tracer profiles in deposited sediments in lakes and reservoirs can be made. Through a multi-scale approach for fine sediment tracking, temporal changes in soil erosion and sediment load can be reconstructed and the consequences of changing catchment practices evaluated. We recommend that long-term, as well as short-term, monitoring of riverine fine sediment and corresponding surface and subsurface sources at nested sites within a catchment are essential. Such monitoring will inform the development and validation of models for predicting dynamics of fine sediment transport as a function of hydro-climatic and geomorphological controls. We highlight that the need for monitoring is particularly important for hilly catchments with complex and changing land use. We recommend that research should be prioritized for sloping farmland-dominated catchments