Undernutrition Affects Cell Survival,Oxidative Stress,Ca2+ Handling and Signaling Pathways in Vas Deferens,Crippling Reproductive Capacity

Background

The aim of this work was to investigate the mechanisms by which chronic malnutrition (CM) affects vas deferens function, leading to compromised reproductive capacity. Previous studies have shown that maternal malnutrition affects the reproductive tracts of adult male offspring. However, little is known about the effects of CM, a widespread life-long condition that persists from conception throughout growth to adult life.

Methodology/Principal Findings

Young adult male rats, which were chronically malnourished from weaning, presented decreased total and haploid cells in the vas deferens, hypertrophy of the muscle layer in the epididymal portion of the vas deferens and intense atrophy of the muscular coat in its prostatic portion. At a molecular level, the vas deferens tissue of CM rats exhibited a huge rise in lipid peroxidation and protein carbonylation, evidence of an accentuated increase in local reactive oxygen species levels. The kinetics of plasma membrane Ca²⁺-ATPase activity and its kinase-mediated phosphorylation by PKA and PKC in the vas deferens revealed malnutrition-induced modifications in velocity, Ca²⁺ affinity and regulation of Ca²⁺ handling proteins. The severely crippled content of the 12-kDa FK506 binding protein, which controls passive Ca²⁺ release from the sarco(endo) plasmic reticulum, revealed another target of malnutrition related to intracellular Ca²⁺ handling, with a potential effect on forward propulsion of sperm cells. As a possible compensatory response, malnutrition led to enhanced sarco(endo) plasmic reticulum Ca²⁺-ATPase activity, possibly caused by stimulatory PKA-mediated phosphorylation.

Conclusions/Significance

The functional correlates of these cellular and molecular hallmarks of chronic malnutrition on the vas deferens were an accentuated reduction in fertility and fecundity.     

Physical Activity versus Sedentary Behavior: Associations with Lipoprotein Particle Subclass Concentrations in Healthy Adults

Background

Physical activity (PA) and sedentary behavior (SED) may have independent effects on health and disease. This might be due to PA and SED having distinct effects on lipoprotein metabolism. The aim of this study was to determine associations between lipoprotein subclass particle concentrations (-P) and accelerometer-measured SED and moderate-to-vigorous PA (MVPA) in a sample of healthy adult subjects.

Methods

Lipoprotein subclass particle concentrations were determined by proton nuclear magnetic resonance spectroscopy, whereas SED and MVPA were measured using Agtigraph GT1M and GT3X+ accelerometers. We obtained valid data in 73 subjects (30 men and 43 women, age 40.5 ± 10.6 years; body mass index 24.0 ± 2.8). Multiple regression analysis was used to determine associations (partial correlations) with lipoproteins.

Results

Positive associations were detected between SED and small VLDL-P, large LDL-P and TG (partial r = 0.24 to 0.25, p < .047). Corresponding associations were non-significant for MVPA (partial r = -0.12 to 0.04, p > .355). On the contrary, MVPA was positively associated with large HDL-P, average HDL size, Apo A1 and HDL-cholesterol (partial r = 0.28 to 0.50, p < .027), whereas SED was not (partial r = -0.06 to 0.07, p > .607).

Conclusion

There might be a specific effect of SED versus MVPA on lipoprotein metabolism. However, our results must be interpreted carefully due to possible effect-modification by gender and a low sample size. Thus, our findings should be viewed as preliminary.     

Effects of a Novel, Low-Molecular Weight Inhibitor of Lipid Peroxidation on Ischemia–Reperfusion Injury in Isolated Rat Hearts and in Cultured Cardiomyocytes

We investigated the effect of H290/51, a novel, low-molecular-weight inhibitor of lipid peroxidation, on cardiac ischemia–reperfusion injury. Lactate dehydrogenase (LD) release from cultured cardiomyocytes exposed to 1 h hypoxia and 4 h reoxygenation was measured after pretreatment with different concentrations of H290/51. In another series, Langendorff-perfused rat hearts were exposed to 30 min global ischemia and 60 min reperfusion (n = minimum 10 in each group): 1. Control ischemia–reperfusion. 2. Vehicle throughout the experiment. 3. Vehicle during stabilization, and H290/51 (10⁻⁶ mol/l) during reperfusion. 4. H290/51 throughout the experiments. During reoxygenation of isolated cardiomyocytes, H290/51 dose dependently inhibited LD release with an pIC₅₀ value of 7.2 ± 0.4 (mean ± SEM), with 10⁻⁶ mol/l as the lowest efficient concentration. In isolated hearts ischemia–reperfusion induced severe reperfusion arrhythmias, reduced left ventricular developed pressure (LVDP) and coronary flow (CF), and increased LV end-diastolic pressure (LVEDP). LD activity in the effluent increased. H290/51 throughout perfusion (group 4) reduced the occurrence of severe reperfusion arrhythmias (p < .0001), attenuated the decrease of LVDP (p < .008), and CF (p < .006), the increase of LVEDP (p < .008), and the release of LD (p < .002). Tissue contents of thiobarbituric acid-reactive substances did not increase during reperfusion in controls, but was reduced in group 4 (p < .004). H290/51 given only during reperfusion (group 3) tended to improve cardiac function, but significantly so only for increase of CF (p < .01). The lipid peroxidation inhibitor H290/51 attenuated cardiac injury induced by ischemia–reperfusion.     

The Andersen Aerobic Fitness Test: Reliability and Validity in 10-Year-Old Children

Background

High aerobic fitness is consistently associated with a favorable metabolic risk profile in children. Direct measurement of peak oxygen consumption (VO_2peak) is often not feasible, thus indirect tests such as the Andersen test are required in many settings. The present study seeks to determine the reliability and validity of the Andersen test in 10-year-old children.

Methods

A total of 118 10-year-old children (67 boys and 51 girls) were recruited from one school and performed four VO_2peak tests over three weeks: three Andersen tests (indirect) and one continuous progressive treadmill test (direct). Of these, 104 children provided valid data on all Andersen tests and 103 children also provided valid data on the direct treadmill test. Reliability and validity were assessed using Bland Altman plots and linear regression analysis.

Results

Bias (mean change) and random error (limits of agreement) were 26.7±125.2 m for test 2 vs. test 1 (p<.001 for mean difference) and 3.9±88.8 m for test 3 vs. test 2 (p = .514 for mean difference). The equation to estimate VO_2peak suggested by Andersen et al. (2008) showed a poor fit in the present sample; thus, we suggest a new equation: VO_2peak = 23.262+0.050*Andersen distance –3.858*gender –0.376*body weight (R² = 0.61, standard error of the estimate = 5.69, p<.001, boys = 0, girls = 1).

Conclusions

The Andersen test provided reliable and valid data on a group level. However, a substantial degree of individual variability was found for estimates of VO_2peak. Researchers should be aware of the amount of noise in indirect tests that estimate aerobic fitness.     

Tailored Implementation of Evidence-Based Practice for Patients with Chronic Diseases

Background

When designing interventions and policies to implement evidence based healthcare, tailoring strategies to the targeted individuals and organizations has been recommended. We aimed to gather insights into the ideas of a variety of people for implementing evidence-based practice for patients with chronic diseases, which were generated in five European countries.

Methods

A qualitative study in five countries (Germany, Netherlands, Norway, Poland, United Kingdom) was done, involving overall 115 individuals. A purposeful sample of four categories of stakeholders (healthcare professionals, quality improvement officers, healthcare purchasers and authorities, and health researchers) was involved in group interviews in each of the countries to generate items for improving healthcare in different chronic conditions per country: chronic obstructive pulmonary disease, cardiovascular disease, depression in elderly people, multi-morbidity, obesity. A disease-specific standardized list of determinants of practice in these conditions provided the starting point for these groups. The content of the suggested items was categorized in a pre-defined framework of 7 domains and specific themes in the items were identified within each domain.

Results

The 115 individuals involved in the study generated 812 items, of which 586 addressed determinants of practice. These largely mapped onto three domains: individual health professional factors, patient factors, and professional interactions. Few items addressed guideline factors, incentives and resources, capacity of organizational change, or social, political and legal factors. The relative numbers of items in the different domains were largely similar across stakeholder categories within each of the countries. The analysis identified 29 specific themes in the suggested items across countries.

Conclusion

The type of suggestions for improving healthcare practice was largely similar across different stakeholder groups, mainly addressing healthcare professionals, patient factors and professional interactions. As this study is one of the first of its kind, it is important that more research is done on tailored implementation strategies.     

Molecular Evidence that Only Two Opsin Subfamilies,the Blue Light- (SWS2) and Green Light-Sensitive (RH2), Drive Color Vision in Atlantic Cod (Gadus morhua)

Teleosts show a great variety in visual opsin complement, due to both gene duplication and gene loss. The repertoire ranges from one subfamily of visual opsins (scotopic vision) including rod opsin only retinas seen in many deep-sea species to multiple subfamilies of visual opsins in some pelagic species. We have investigated the opsin repertoire of Atlantic cod (Gadus morhua) using information in the recently sequenced cod genome and found that despite cod not being a deep sea species it lacks visual subfamilies sensitive towards the most extreme parts of the light spectra representing UV and red light. Furthermore, we find that Atlantic cod has duplicated paralogs of both blue-sensitive SWS2 and green-sensitive RH2 subfamilies, with members belonging to each subfamily linked in tandem within the genome (two SWS2-, and three RH2A genes, respectively). The presence of multiple cone opsin genes indicates that there have been duplication events in the cod ancestor SWS2 and RH2 opsins producing paralogs that have been retained in Atlantic. Our results are supported by expressional analysis of cone opsins, which further revealed an ontogenetic change in the array of cone opsins expressed. These findings suggest life stage specific programs for opsin regulation which could be linked to habitat changes and available light as the larvae is transformed into an early juvenile. Altogether we provide the first molecular evidence for color vision driven by only two families of cone opsins due to gene loss in a teleost.     

The Oral Commensal Streptococcus mitis Shows a Mixed Memory Th Cell Signature That Is Similar to and Cross-Reactive with Streptococcus pneumoniae

Background

Carriage of and infection with Streptococcus pneumoniae is known to predominantly induce T helper 17 (Th17) responses in humans, but the types of Th cells showing reactivity towards commensal streptococci with low pathogenic potential, such as the oral commensals S. mitis and S. salivarius, remain uncharacterized.

Methods

Memory CD4⁺ T helper (Th) cell subsets were isolated from healthy human blood donors according to differential expression of chemokine receptors, expanded in vitro using polyclonal stimuli and characterized for reactivity against different streptococcal strains.

Results

Th cells responding to S. mitis, S. salivarius and S. pneumoniae were predominantly in a CCR6⁺CXCR3⁺ subset and produced IFN-γ, and in a CCR6⁺CCR4⁺ subset and produced IL-17 and IL-22. Frequencies of S. pneumoniae-reactive Th cells were higher than frequencies of S. mitis- and S. salivarius-specific Th cells. S. mitis and S. pneumoniae isogenic capsule knock-out mutants and a S. mitis mutant expressing the serotype 4 capsule of S. pneumoniae showed no different Th cell responses as compared to wild type strains. S. mitis-specific Th17 cells showed cross-reactivity with S. pneumoniae.

Conclusions

As Th17 cells partly control clearance of S. pneumoniae, cross-reactive Th17 cells that may be induced by commensal bacterial species may influence the immune response, independent of capsule expression.