Insulin resistance in type 1 diabetes: what is ‘double diabetes’ and what are the risks?

In this review, we explore the concept of ‘double diabetes’, a combination of type 1 diabetes with features of insulin resistance and type 2 diabetes. After considering whether double diabetes is a useful concept, we discuss potential mechanisms of increased insulin resistance in type 1 diabetes before examining the extent to which double diabetes might increase the risk of cardiovascular disease (CVD). We then go on to consider the proposal that weight gain from intensive insulin regimens may be associated with increased CV risk factors in some patients with type 1 diabetes, and explore the complex relationships between weight gain, insulin resistance, glycaemic control and CV outcome. Important comparisons and contrasts between type 1 diabetes and type 2 diabetes are highlighted in terms of hepatic fat, fat partitioning and lipid profile, and how these may differ between type 1 diabetic patients with and without double diabetes. In so doing, we hope this work will stimulate much-needed research in this area and an improvement in clinical practice

Development of a longitudinal integrated clerkship at an academic medical center

In 2005, medical educators at the University of California, San Francisco (UCSF), began developing the Parnassus Integrated Student Clinical Experiences (PISCES) program, a year-long longitudinal integrated clerkship at its academic medical center. The principles guiding this new clerkship were continuity with faculty preceptors, patients, and peers; a developmentally progressive curriculum with an emphasis on interdisciplinary teaching; and exposure to undiagnosed illness in acute and chronic care settings. Innovative elements included quarterly student evaluation sessions with all preceptors together, peer-to-peer evaluation, and oversight advising with an assigned faculty member. PISCES launched with eight medical students for the 2007/2008 academic year and expanded to 15 students for 2008/2009. Compared to UCSF's traditional core clerkships, evaluations from PISCES indicated significantly higher student satisfaction with faculty teaching, formal didactics, direct observation of clinical skills, and feedback. Student performance on discipline-specific examinations and United States Medical Licensing Examination step 2 CK was equivalent to and on standardized patient examinations was slightly superior to that of traditional peers. Participants' career interests ranged from primary care to surgical subspecialties. These results demonstrate that a longitudinal integrated clerkship can be implemented successfully at a tertiary care academic medical center

A Dynamic and Complex Network Regulates the Heterosis of Yield-Correlated Traits in Rapeseed (Brassica napus L.)

Although much research has been conducted, the genetic architecture of heterosis remains ambiguous. To unravel the genetic architecture of heterosis, a reconstructed F2 population was produced by random intercross among 202 lines of a double haploid population in rapeseed (Brassica napus L.). Both populations were planted in three environments and 15 yield-correlated traits were measured, and only seed yield and eight yield-correlated traits showed significant mid-parent heterosis, with the mean ranging from 8.7% (branch number) to 31.4% (seed yield). Hundreds of QTL and epistatic interactions were identified for the 15 yield-correlated traits, involving numerous variable loci with moderate effect, genome-wide distribution and obvious hotspots. All kinds of mode-of-inheritance of QTL (additive, A; partial-dominant, PD; full-dominant, D; over-dominant, OD) and epistatic interactions (additive × additive, AA; additive × dominant/dominant × additive, AD/DA; dominant × dominant, DD) were observed and epistasis, especially AA epistasis, seemed to be the major genetic basis of heterosis in rapeseed. Consistent with the low correlation between marker heterozygosity and mid-parent heterosis/hybrid performance, a considerable proportion of dominant and DD epistatic effects were negative, indicating heterozygosity was not always advantageous for heterosis/hybrid performance. The implications of our results on evolution and crop breeding are discussed

NGF Is an Essential Survival Factor for Bronchial Epithelial Cells during Respiratory Syncytial Virus Infection

Background: Overall expression of neurotrophins in the respiratory tract is upregulated in infants infected by the respiratory syncytial virus (RSV), but it is unclear where (structural vs. inflammatory cells, upper vs. lower airways) and why, these changes occur. We analyzed systematically the expression of neurotrophic factors and receptors following RSV infection of human nasal, tracheal, and bronchial epithelial cells, and tested the hypothesis that neurotrophins work as innate survival factors for infected respiratory epithelia. Methodology: Expression of neurotrophic factors (nerve growth factor, NGF; brain-derived neurotrophic factor, BDNF) and receptors (trkA, trkB, p75) was analyzed at the protein level by immunofluorescence and flow cytometry and at the mRNA level by real-time PCR. Targeted siRNA was utilized to blunt NGF expression, and its effect on virus-induced apoptosis/ necrosis was evaluated by flow cytometry following annexin V/7-AAD staining. Principal Findings: RSV infection was more efficient in cells from more distal (bronchial) vs. more proximal origin. In bronchial cells, RSV infection induced transcript and protein overexpression of NGF and its high-affinity receptor trkA, with concomitant downregulation of the low-affinity p75 NTR. In contrast, tracheal cells exhibited an increase in BDNF, trkA and trkB, and nasal cells increased only trkA. RSV-infected bronchial cells transfected with NGF-specific siRNA exhibited decreased trkA and increased p75 NTR expression. Furthermore, the survival of bronchial epithelial cells was dramaticall

The Complex Genetic Architecture of the Metabolome

Discovering links between the genotype of an organism and its metabolite levels can increase our understanding of metabolism, its controls, and the indirect effects of metabolism on other quantitative traits. Recent technological advances in both DNA sequencing and metabolite profiling allow the use of broad-spectrum, untargeted metabolite profiling to generate phenotypic data for genome-wide association studies that investigate quantitative genetic control of metabolism within species. We conducted a genome-wide association study of natural variation in plant metabolism using the results of untargeted metabolite analyses performed on a collection of wild Arabidopsis thaliana accessions. Testing 327 metabolites against >200,000 single nucleotide polymorphisms identified numerous genotype–metabolite associations distributed non-randomly within the genome. These clusters of genotype–metabolite associations (hotspots) included regions of the A. thaliana genome previously identified as subject to recent strong positive selection (selective sweeps) and regions showing trans-linkage to these putative sweeps, suggesting that these selective forces have impacted genome-wide control of A. thaliana metabolism. Comparing the metabolic variation detected within this collection of wild accessions to a laboratory-derived population of recombinant inbred lines (derived from two of the accessions used in this study) showed that the higher level of genetic variation present within the wild accessions did not correspond to higher variance in metabolic phenotypes, suggesting that evolutionary constraints limit metabolic variation. While a major goal of genome-wide association studies is to develop catalogues of intraspecific variation, the results of multiple independent experiments performed for this study showed that the genotype–metabolite associations identified are sensitive to environmental fluctuations. Thus, studies of intraspecific variation conducted via genome-wide association will require analyses of genotype by environment interaction. Interestingly, the network structure of metabolite linkages was also sensitive to environmental differences, suggesting that key aspects of network architecture are malleable

Screening for Posttraumatic Stress Disorder among Somali ex-combatants: A validation study

In Somalia, a large number of active and former combatants are affected by psychological problems such as Posttraumatic Stress Disorder (PTSD), that impairs their ability to re-integrate into civilian life. This study reports on development and validation of a screening tool for PTSD in Somali language with a sample of ex-combatants.Waxaa Soomaaliya ka jira tiro badan oo askartii hore ah oo dhimirka wax ka gaaray, sida cudurka la yiraahdo "Posttraumatic Stress Disorder (PTSD)", kaaso isbeddel ku sameeyo qofka dad ladhaqankiisa. Darasaadkanina wuxuu horumarinayaa qalabka baaritaanka caafimaadka cudurka DPTS oo loo adeegsanayo Af-soomaaliga.In Somalia, un gran numero di soldati o ex-soldati sono affetti da problemi psicologici come il Disturbo Post-Traumatico da Stress (DPTS), che altera la capacità di re-integrarsi nella vita civile. Questo studio riporta sullo sviluppo di uno strumento di screening per il DPTS in lingua somala

Avian Influenza Viruses Infect Primary Human Bronchial Epithelial Cells Unconstrained by Sialic Acid α2,3 Residues

Avian influenza viruses (AIV) are an important emerging threat to public health. It is thought that sialic acid (sia) receptors are barriers in cross-species transmission where the binding preferences of AIV and human influenza viruses are sias α2,3 versus α2,6, respectively. In this study, we show that a normal fully differentiated, primary human bronchial epithelial cell model is readily infected by low pathogenic H5N1, H5N2 and H5N3 AIV, which primarily bind to sia α2,3 moieties, and replicate in these cells independent of specific sias on the cell surface. NHBE cells treated with neuraminidase prior to infection are infected by AIV despite removal of sia α2,3 moieties. Following AIV infection, higher levels of IP-10 and RANTES are secreted compared to human influenza virus infection, indicating differential chemokine expression patterns, a feature that may contribute to differences in disease pathogenesis between avian and human influenza virus infections in humans

Induction of autophagy by spermidine promotes longevity.

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