Weight loss, glycemic control, and cardiovascular disease risk factors in response to differential diet composition in a weight loss program in type 2 diabetes: a randomized controlled trial.

ObjectiveTo test whether a weight loss program promotes greater weight loss, glycemic control, and improved cardiovascular disease risk factors compared with control conditions and whether there is a differential response to higher versus lower carbohydrate intake.Research design and methodsThis randomized controlled trial at two university medical centers enrolled 227 overweight or obese adults with type 2 diabetes and assigned them to parallel in-person diet and exercise counseling, with prepackaged foods in a planned menu during the initial phase, or to usual care (UC; two weight loss counseling sessions and monthly contacts).ResultsRelative weight loss was 7.4% (95% CI 5.7-9.2%), 9.0% (7.1-10.9%), and 2.5% (1.3-3.8%) for the lower fat, lower carbohydrate, and UC groups (P < 0.001 intervention effect). Glycemic control markers and triglyceride levels were lower in the intervention groups compared with UC group at 1 year (fasting glucose 141 [95% CI 133-149] vs. 159 [144-174] mg/dL, P = 0.023; hemoglobin A1c 6.9% [6.6-7.1%] vs. 7.5% [7.1-7.9%] or 52 [49-54] vs. 58 [54-63] mmol/mol, P = 0.001; triglycerides 148 [134-163] vs. 204 [173-234] mg/dL, P < 0.001). The lower versus higher carbohydrate groups maintained lower hemoglobin A1c (6.6% [95% CI 6.3-6.8%] vs. 7.2% [6.8-7.5%] or 49 [45-51] vs. 55 [51-58] mmol/mol) at 1 year (P = 0.008).ConclusionsThe weight loss program resulted in greater weight loss and improved glycemic control in type 2 diabetes

P2X receptors: epithelial ion channels and regulators of salt and water transport.

When the results from electrophysiological studies of renal epithelial cells are combined with data from in vivo tubule microperfusion experiments and immunohistochemical surveys of the nephron, the accumulated evidence suggests that ATP-gated ion channels, P2X receptors, play a specialized role in the regulation of ion and water movement across the renal tubule and are integral to electrolyte and fluid homeostasis. In this short review, we discuss the concept of P2X receptors as regulators of salt and water salvage pathways, as well as acknowledging their accepted role as ATP-gated ion channels

Plasma membrane recovery kinetics of a microfluidic intracellular delivery platform

Intracellular delivery of materials is a challenge in research and therapeutic applications. Physical methods of plasma membrane disruption have recently emerged as an approach to facilitate the delivery of a variety of macromolecules to a range of cell types. We use the microfluidic CellSqueeze delivery platform to examine the kinetics of plasma membrane recovery after disruption and its dependence on the calcium content of the surrounding buffer (recovery time ~5 min without calcium vs. ~30 s with calcium). Moreover, we illustrate that manipulation of the membrane repair kinetics can yield up to 5× improvement in delivery efficiency without significantly impacting cell viability. Membrane repair characteristics initially observed in HeLa cells are shown to translate to primary naïve murine T cells. Subsequent manipulation of membrane repair kinetics also enables the delivery of larger materials, such as antibodies, to these difficult to manipulate cells. This work provides insight into the membrane repair process in response to mechanical delivery and could potentially enable the development of improved delivery methods.National Institutes of Health (U.S.) (Grant RC1 EB011187-02)National Institutes of Health (U.S.) (Grant R01GN101420-01A1)Kathy and Curt Marble Cancer Research FundNational Cancer Institute (U.S.) (Cancer Center Support (Core) Grant P30-CA14051)National Cancer Institute (U.S.) (Cancer Center Support (Core) Grant MPP-09Call-Langer-60

Resource utilization and outcome at a university versus a community teaching hospital in tPA treated stroke patients: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Comparing patterns of resource utilization between hospitals is often complicated by biases in community and patient populations. Stroke patients treated with tissue plasminogen activator (tPA) provide a particularly homogenous population for comparison because of strict eligibility criteria for treatment. We tested whether resource utilization would be similar in this homogenous population between two hospitals located in a single Midwestern US community by comparing use of diagnostic testing and associated outcomes following treatment with t-PA.</p> <p>Methods</p> <p>Medical records from 206 consecutive intravenous t-PA-treated stroke patients from two teaching hospitals (one university, one community-based) were reviewed. Patient demographics, clinical characteristics and outcome were analyzed, as were the frequency of use of CT, MRI, MRA, echocardiography, angiography, and EEG.</p> <p>Results</p> <p>Seventy-nine and 127 stroke patients received t-PA at the university and community hospitals, respectively. The two patient populations were demographically similar. There were no differences in stroke severity. All outcomes were similar at both hospitals. Utilization of CT scans, and non-invasive carotid and cardiac imaging studies were similar at both hospitals; however, brain MR, TEE, and catheter angiography were used more frequently at the university hospital. EEG was obtained more often at the community hospital.</p> <p>Conclusions</p> <p>Utilization of advanced brain imaging and invasive diagnostic testing was greater at the university hospital, but was not associated with improved clinical outcomes. This could not be explained on the basis of stroke severity or patient characteristics. This variation of practice suggests substantial opportunities exist to reduce costs and improve efficiency of diagnostic resource use as well as reduce patient exposure to risk from diagnostic procedures.</p

A major genetic locus in <i>Trypanosoma brucei</i> is a determinant of host pathology

The progression and variation of pathology during infections can be due to components from both host or pathogen, and/or the interaction between them. The influence of host genetic variation on disease pathology during infections with trypanosomes has been well studied in recent years, but the role of parasite genetic variation has not been extensively studied. We have shown that there is parasite strain-specific variation in the level of splenomegaly and hepatomegaly in infected mice and used a forward genetic approach to identify the parasite loci that determine this variation. This approach allowed us to dissect and identify the parasite loci that determine the complex phenotypes induced by infection. Using the available trypanosome genetic map, a major quantitative trait locus (QTL) was identified on T. brucei chromosome 3 (LOD = 7.2) that accounted for approximately two thirds of the variance observed in each of two correlated phenotypes, splenomegaly and hepatomegaly, in the infected mice (named &lt;i&gt;TbOrg1&lt;/i&gt;). In addition, a second locus was identified that contributed to splenomegaly, hepatomegaly and reticulocytosis (&lt;i&gt;TbOrg2&lt;/i&gt;). This is the first use of quantitative trait locus mapping in a diploid protozoan and shows that there are trypanosome genes that directly contribute to the progression of pathology during infections and, therefore, that parasite genetic variation can be a critical factor in disease outcome. The identification of parasite loci is a first step towards identifying the genes that are responsible for these important traits and shows the power of genetic analysis as a tool for dissecting complex quantitative phenotypic traits

AMI observations of Lynds Dark Nebulae: further evidence for anomalous cm-wave emission

Observations at 14.2 to 17.9 GHz made with the AMI Small Array towards fourteen Lynds Dark Nebulae with a resolution of 2' are reported. These sources are selected from the SCUBA observations of Visser et al. (2001) as small angular diameter clouds well matched to the synthesized beam of the AMI Small Array. Comparison of the AMI observations with radio observations at lower frequencies with matched uv-plane coverage is made, in order to search for any anomalous excess emission which can be attributed to spinning dust. Possible emission from spinning dust is identified as a source within a 2' radius of the Scuba position of the Lynds dark nebula, exhibiting an excess with respect to lower frequency radio emission. We find five sources which show a possible spinning dust component in their spectra. These sources have rising spectral indices in the frequency range 14.2--17.9 GHz. Of these five one has already been reported, L1111, we report one new definite detection, L675, and three new probable detections (L944, L1103 and L1246). The relative certainty of these detections is assessed on the basis of three criteria: the extent of the emission, the coincidence of the emission with the Scuba position and the likelihood of alternative explanations for the excess. Extended microwave emission makes the likelihood of the anomalous emission arising as a consequence of a radio counterpart to a protostar or a proto-planetary disk unlikely. We use a 2' radius in order to be consistent with the IRAS identifications of dark nebulae (Parker 1988), and our third criterion is used in the case of L1103 where a high flux density at 850 microns relative to the FIR data suggests a more complicated emission spectrum.Comment: submitted MNRA

Vitamin D receptor ChIP-seq in primary CD4+ cells: relationship to serum 25-hydroxyvitamin D levels and autoimmune disease

PMCID: PMC3710212This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Relationships Between Cardiorespiratory Fitness, Physical Activity, and Psychosocial Variables in Overweight and Obese Breast Cancer Survivors

# The Author(s) 2010. This article is published with open access at Springerlink.com Background Breast cancer survivors not only experience distressing physical symptoms associated with treatments, but also are faced with psychosocial challenges. Despite growing scientific evidence that physical activity (PA) may mitigate psychosocial distress experienced by women treated for breast cancer, the literature is equivocal. Purpose This study investigated the relationships between cardiorespiratory fitness (CRF), PA, and psychosocial factors in breast cancer survivors. Method Data involving overweight or obese breast cancer survivors (N=260) were examined. CRF was determined by a submaximal graded exercise test. PA, depressive symptoms, total fatigue, and global self-esteem were assessed with selfreport measures. Pearson&apos;s correlations were conducted to determine associations among CRF, PA, depressive symptoms, total fatigue, and global self-esteem. Multiple regression models, with age and body mass index as covariates, were performed using continuous levels for CRF and PA. Results Bivariate correlations suggested that CRF and PA were unrelated to the psychosocial variables. One of the regression models identified a marginally significant (P=0.06) inverse association between depressive symptoms and PA. Conclusion CRF and PA were not associated with psychosocial factors in this sample of breast cancer survivors. However

Molecular Cloning and Characterization of Two Genes Encoding Dihydroflavonol-4-Reductase from Populus trichocarpa

Dihydroflavonol 4-reductase (DFR, EC 1.1.1.219) is a rate-limited enzyme in the biosynthesis of anthocyanins and condensed tannins (proanthocyanidins) that catalyzes the reduction of dihydroflavonols to leucoanthocyanins. In this study, two full-length transcripts encoding for PtrDFR1 and PtrDFR2 were isolated from Populus trichocarpa. Sequence alignment of the two PtrDFRs with other known DFRs reveals the homology of these genes. The expression profile of PtrDFRs was investigated in various tissues of P. trichocarpa. To determine their functions, two PtrDFRs were overexpressed in tobacco (Nicotiana tabacum) via Agrobacterium-mediated transformation. The associated color change in the flowers was observed in all 35S:PtrDFR1 lines, but not in 35S:PtrDFR2 lines. Compared to the wild-type control, a significantly higher accumulation of anthocyanins was detected in transgenic plants harboring the PtrDFR1. Furthermore, overexpressing PtrDFR1 in Chinese white poplar (P. tomentosa Carr.) resulted in a higher accumulation of both anthocyanins and condensed tannins, whereas constitutively expressing PtrDFR2 only improved condensed tannin accumulation, indicating the potential regulation of condensed tannins by PtrDFR2 in the biosynthetic pathway in poplars