Analysing practice for prosthetic restoration among Major lower Limb Amputees with diabetes:from Northern Borneo Perspective

Diabetes is high in the agenda of public health issues with significant prevalence of diabetic-related amputations. Prosthetic restoration post-amputation is imperative to reduce disability, but its success is influenced by several factors. This study analysed the practice, and the determining factors affecting prosthetic restoration among major lower limb amputees with diabetes in Sabah. Methods: Retrospective cross-sectional study among 65 major lower limb amputees with diabetes referred for rehabilitation medicine services at Queen Elizabeth Hospital from0 1st January 2015 to 31st December 2017. Demographics data, pre-morbid diseases, levels of amputation and practice on prosthetic restoration (suitability for restoration, duration from prosthetic application to restoration, funding issue) are primary evaluated factors. Results: Forty-nine, fifteen and one amputees had below knee amputation, above knee amputation and hip disarticulation respectively. Forty-three amputees (66.2%) were deemed suitable for prosthetic restoration but only 27 were prosthetically restored, with mean duration from prosthetic application to restoration of 5.92±2.189 months. Having additional pre-morbid diseases did not reduced the likelihood of suitability for prosthetic restoration compared to those only with diabetes (p=0.082). Funding issue is the key factor affecting prosthetic restoration with higher likelihood for restoration among those eligible through governmental agencies funding (p=0.027). Conclusion: In Sabah, low rate of suitability for prosthetic restoration is observed among major lower limb amputees with diabetes. A larger study is warranted to investigate causes of such low rate of suitability for prosthetic restoration among this specific population in the effort to reduce public health burden from major lower limb amputation-related disability

Layer thickness dependence of the current induced effective field vector in Ta|CoFeB|MgO

The role of current induced effective magnetic field in ultrathin magnetic heterostructures is increasingly gaining interest since it can provide efficient ways of manipulating magnetization electrically. Two effects, known as the Rashba spin orbit field and the spin Hall spin torque, have been reported to be responsible for the generation of the effective field. However, quantitative understanding of the effective field, including its direction with respect to the current flow, is lacking. Here we show vector measurements of the current induced effective field in Ta|CoFeB|MgO heterostructrures. The effective field shows significant dependence on the Ta and CoFeB layers' thickness. In particular, 1 nm thickness variation of the Ta layer can result in nearly two orders of magnitude difference in the effective field. Moreover, its sign changes when the Ta layer thickness is reduced, indicating that there are two competing effects that contribute to the effective field. The relative size of the effective field vector components, directed transverse and parallel to the current flow, varies as the Ta thickness is changed. Our results illustrate the profound characteristics of just a few atomic layer thick metals and their influence on magnetization dynamics

Shifting the Paradigm: The Putative Mitochondrial Protein ABCB6 Resides in the Lysosomes of Cells and in the Plasma Membrane of Erythrocytes

ABCB6, a member of the adenosine triphosphate–binding cassette (ABC) transporter family, has been proposed to be responsible for the mitochondrial uptake of porphyrins. Here we show that ABCB6 is a glycoprotein present in the membrane of mature erythrocytes and in exosomes released from reticulocytes during the final steps of erythroid maturation. Consistent with its presence in exosomes, endogenous ABCB6 is localized to the endo/lysosomal compartment, and is absent from the mitochondria of cells. Knock-down studies demonstrate that ABCB6 function is not required for de novo heme biosynthesis in differentiating K562 cells, excluding this ABC transporter as a key regulator of porphyrin synthesis. We confirm the mitochondrial localization of ABCB7, ABCB8 and ABCB10, suggesting that only three ABC transporters should be classified as mitochondrial proteins. Taken together, our results challenge the current paradigm linking the expression and function of ABCB6 to mitochondria

Screening the Expression of ABCB6 in Erythrocytes Reveals an Unexpectedly High Frequency of Lan Mutations in Healthy Individuals

Lan is a high-incidence blood group antigen expressed in more than 99.9% of the population. Identification of the human ABC transporter ABCB6 as the molecular basis of Lan has opened the way for studies assessing the relation of ABCB6 function and expression to health and disease. To date, 34 ABCB6 sequence variants have been described in association with reduced ABCB6 expression based on the genotyping of stored blood showing weak or no reactivity with anti-Lan antibodies. In the present study we examined the red blood cell (RBC) surface expression of ABCB6 by quantitative flow cytometry in a cohort of 47 healthy individuals. Sequencing of the entire coding region of the ABCB6 gene in low RBC ABCB6 expressors identified a new allele (IVS9+1G>A, affecting a putative splice site at the boundary of exon 9) and two nonsynonymous SNPs listed in the SNP database (R192Q (rs150221689) and G588 S (rs145526996)). The R192Q mutation showed co-segregation with reduced RBC ABCB6 expression in a family, and we found the G588 S mutation in a compound heterozygous individual with undetectable ABCB6 expression, suggesting that both mutations result in weak or no expression of ABCB6 on RBCs. Analysis of the intracellular expression pattern in HeLa cells by confocal microscopy indicated that these mutations do not compromise overall expression or the endolysosomal localization of ABCB6. Genotyping of two large cohorts, containing 235 and 1039 unrelated volunteers, confirmed the high allele frequency of Lan-mutations. Our results suggest that genetic variants linked to lower or absent cell surface expression of ABCB6/Langereis may be more common than previously thought.This work was supported by the Lendulet Program of the Hungarian Academy of Sciences (GS), OTKA 83533 and by the Polish POIG grant 01.01.02-10-005/08 TESTOPLEK, supported by the EU through the European Regional Development Fund. Hajnalka Andrikovics is a recipient of the Janos Bolyai Research Scholarship from the Hungarian Academy of Sciences. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Dr. Camilo Toro and Dr. William Gahl of the NIH Undiagnosed Diseases Program for an affected patient specimen; that work was supported by the Intramural Research Program of the National Human Genome Research Institute and the Office of the Director of the NIH. We thank Lionel Arnaud (National Institute of Blood Transfusion (INTS), Paris, France) for helpful discussions