Unhealthy Days and Quality of Life in Irish Patients with Diabetes

Objectives

To study the determinants of health-related quality of life (HRQoL) in Irish patients with diabetes using the Centres for Disease Controls'' (CDC''s) ‘Unhealthy Days’ summary measure and to assesses the agreement between this generic HRQoL measure and the disease-specific Audit of Diabetes Dependant Quality of Life (ADDQoL) measure.

Research Design and Methods

Data were analysed from the Diabetes Quality of Life Study, a cross-sectional study of 1,456 people with diabetes in Ireland (71% response rate). Unhealthy days were assessed using the CDC''s ‘Unhealthy days’ summary measure. Quality of life (QoL) was also assessed using the ADDQoL measure. Analyses were conducted primarily using logistic regression. The agreement between the two QoL instruments was measured using the kappa co-efficient.

Results

Participants reported a median of 2 unhealthy days per month. In multivariate analyses, female gender (P = 0.001), insulin use (P = 0.030), diabetes complications (P = <0.001) were significantly associated with more unhealthy days. Older patients had fewer unhealthy days per month (P = 0.003). Agreement between the two measures of QoL (unhealthy days measure and ADDQoL) was poor, Kappa = 0.234

Conclusions

The findings highlight the determinants of HRQoL in patients with diabetes using a generic HRQoL summary measure. The ‘Unhealthy Days’ and the ADDQoL have poor agreement, therefore the ‘Unhealthy Days’ summary measure may be assessing a different construct. Nonetheless, this study demonstrates that the generic ‘Unhealthy Days’ summary measure can be used to detect determinants of HRQoL in patients with diabetes.     

Minimal Erythema Dose (MED) Testing

Ultraviolet radiation (UV) therapy is sometimes used as a treatment for various common skin conditions, including psoriasis, acne, and eczema. The dosage of UV light is prescribed according to an individual''s skin sensitivity. Thus, to establish the proper dosage of UV light to administer to a patient, the patient is sometimes screened to determine a minimal erythema dose (MED), which is the amount of UV radiation that will produce minimal erythema (sunburn or redness caused by engorgement of capillaries) of an individual''s skin within a few hours following exposure. This article describes how to conduct minimal erythema dose (MED) testing. There is currently no easy way to determine an appropriate UV dose for clinical or research purposes without conducting formal MED testing, requiring observation hours after testing, or informal trial and error testing with the risks of under- or over-dosing. However, some alternative methods are discussed.     

β-Globin Sleeping Beauty Transposon Reduces Red Blood Cell Sickling in a Patient-Derived CD34+-Based In Vitro Model

The ultimate goal of gene therapy for sickle cell anemia (SCA) is an improved phenotype for the patient. In this study, we utilized bone marrow from a sickle cell patient as a model of disease in an in vitro setting for the hyperactive Sleeping Beauty transposon gene therapy system. We demonstrated that mature sickle red blood cells containing hemoglobin-S and sickling in response to metabisulfite can be generated in vitro from SCA bone marrow. These cells showed the characteristic morphology and kinetics of hemoglobin-S polymerization, which we quantified using video microscopy and imaging cytometry. Using video assessment, we showed that delivery of an IHK-β^T87Q antisickling globin gene by Sleeping Beauty via nucleofection improves metrics of sickling, decreasing percent sickled from 53.2 ± 2.2% to 43.9 ± 2.0%, increasing the median time to sickling from 8.5 to 9.6 min and decreasing the maximum rate of sickling from 2.3 x 10^-3 sickling cells/total cells/sec in controls to 1.26 x 10^-3 sickling cells/total cells/sec in the IHK-β^T87Q-globin group (p < 0.001). Using imaging cytometry, the percentage of elongated sickled cells decreased from 34.8 ± 4.5% to 29.5 ± 3.0% in control versus treated (p < 0.05). These results support the potential use of Sleeping Beauty as a clinical gene therapy vector and provide a useful tool for studying sickle red blood cells in vitro.     

Effect of Polymer Crystallinity in P3HT:PCBM Solar Cells on Band Gap Trap States and Apparent Recombination Order

The non‐geminate recombination of charge carriers in polymer‐fullerene solar cells has been modeled in the last few years with a trap‐assisted recombination model, which states that the apparent recombination order depends on the concentration of trapped charges tailing into the band gap. Higher concentrations of trapped charges lead to higher apparent recombination orders. In this work, the mass fraction f of highly crystalline nanofibrillar P3HT to the total P3HT content in P3HT:PCBM solar cells is consistently varied, controlling the temperature of a nanofibers‐P3HT casting dispersion. A systematic study of the apparent recombination order, measured with a transient photovoltage technique, as a function of f is presented. A correlation is shown between the apparent recombination order, the P3HT crystallinity, and the trap concentration in the band gap measured with an admittance spectroscopy technique.     

Memory T cells are uniquely resistant to melanoma-induced suppression

We have previously observed that in vivo exposure to growing melanoma tumors fundamentally alters activated T cell homeostasis by suppressing the ability of naïve T cells to undergo antigen-driven proliferative expansion. We hypothesized that exposure of T cells in later stages of differentiation to melanoma would have similar suppressive consequences. C57BL/6 mice were inoculated with media or syngeneic B16F10 melanoma tumors 8 or 60 days after infection with lymphocytic choriomeningitis virus (LCMV), and splenic populations of LCMV-specific T cells were quantified using flow cytometry 18 days after tumor inoculation. Inoculation with melanoma on post-infection day 8 potentiated the contraction of previously activated T cells. This enhanced contraction was associated with increased apoptotic susceptibility among T cells from tumor-bearing mice. In contrast, inoculation with melanoma on post-infection day 60 did not affect the ability of previously established memory T cells to maintain themselves in stable numbers. In addition, the ability of previously established memory T cells to respond to LCMV challenge was unaffected by melanoma. Following adoptive transfer into melanoma-bearing mice, tumor-specific memory T cells were significantly more effective at controlling melanoma growth than equivalent numbers of tumor-specific effector T cells. These observations suggest that memory T cells are uniquely resistant to suppressive influences exerted by melanoma on activated T cell homeostasis; these findings may have implications for T cell–based cancer immunotherapy.     

Niche Partition of Bacteriovorax Operational Taxonomic Units Along Salinity and Temporal Gradients in the Chesapeake Bay Reveals Distinct Estuarine Strains

The predatory Bacteriovorax are Gram-negative bacteria ubiquitous in saltwater systems that prey upon other Gram-negative bacteria in a similar manner to the related genus Bdellovibrio. Among the phylogenetically defined clusters of Bacteriovorax, cluster V has only been isolated from estuaries suggesting that it may be a distinct estuarine phylotype. To assess this hypothesis, the spatial and temporal distribution of cluster V and other Bacteriovorax phylogenetic assemblages along the salinity gradient of Chesapeake Bay were determined. Cluster V was expected to be found in significantly greater numbers in low to moderate salinity waters compared to high salinity areas. The analyses of water and sediment samples from sites in the bay revealed cluster V to be present at the lower salinity and not high salinity sites, consistent with it being an estuarine phylotype. Cluster IV had a similar distribution pattern and may also be specifically adapted to estuaries. While the distribution of clusters V and IV were similar for salinity, they were distinct on temperature gradients, being found in cooler and in warmer temperatures, respectively. The differentiation of phylotype populations along the salinity and temporal gradients in Chesapeake Bay revealed distinct niches inhabited by different phylotypes of Bacteriovorax and unique estuarine phylotypes.     

Selecting subsets of genotyped experimental populations for phenotyping to maximize genetic diversity

Selective phenotyping is a way of capturing the benefits of large population sizes without the need to carry out large-scale phenotyping and hence is a cost-effective means of capturing information about gene–trait relationships within a population. The diversity within the sample gives an indication of the efficiency of this information capture; less diversity implies greater redundancy of the genetic information. Here, we propose a method to maximize genetic diversity within the selected samples. Our method is applicable to general experimental designs and robust to common problems such as missing data and dominant markers. In particular, we discuss its application to multi-parent advanced generation intercross (MAGIC) populations, where, although thousands of lines may be genotyped as a large population resource, only hundreds may need to be phenotyped for individual studies. Through simulation, we compare our method to simple random sampling and the minimum moment aberration method. While the gain in power over simple random sampling for all tested methods is not large, our method results in a much more diverse sample of genotypes. This diversity can be applied to improve fine mapping resolution once a QTL region has been detected. Further, when applied to two wheat datasets from doubled haploid and MAGIC progeny, our method detects known QTL for small sample sizes where other methods fail.     

Current methods for molecular typing of Campylobacter species

Campylobacter remains one of the most common bacterial causes of gastroenteritis worldwide. Tracking sources of this organism is challenging due to the large numbers of human cases, and the prevalence of this organism throughout the environment due to growth in a wide range of animal species. Many molecular subtyping methods have been developed to characterize Campylobacter species, but only a few are commonly used in molecular epidemiology studies. This review examines the applicability of these methods, as well as the role that emerging whole genome sequencing technologies will play in tracking sources of Campylobacter spp. infection.     

Effects of wood removal on stream habitat and nitrate uptake in two northeastern US headwater streams

Forested headwater streams play an important role in watershed nutrient dynamics, and wood is thought to be a key factor influencing habitat structure and nitrate-nitrogen dynamics in many forested streams. Because wood in streams can promote nitrogen uptake through denitrification, we hypothesized that nitrate uptake velocities would decrease following wood removal. We measured stream characteristics and nitrate uptake velocities before and after wood manipulation experiments conducted at Hubbard Brook Experimental Forest, NH, and the Sleepers River watershed, VT. The mean size of stream substrates and the amount of riffle habitat increased following wood removal. In contrast to our expectations, summer nitrate uptake velocities increased in the wood removal treatments relative to the reference treatments, possibly because wood removal increased the availability of stable substrates for periphyton growth, therefore increasing nitrate demand in these streams. Our results highlight that effects of wood on stream ecosystems occur through multiple pathways and suggest that the relative importance of these pathways may vary seasonally.