Background: We explored the association of anemia severity in patients with chronic kidney disease (CKD) and anemia treatment with work productivity in China. Methods: Cross-sectional survey data from Chinese physicians and their CKD patients were collected in 2015. Physicians recorded demographics, disease characteristics, and treatment. Patients completed the Work Productivity and Activity Impairment questionnaire. Data were stratified by dialysis-dependence, hemoglobin (Hb) level, and anemia treatment. Results: Based on data from 1,052 patients (704 non-dialysis-dependent [NDD] and 348 dialysis-dependent [DD] patients), prescribed anemia treatment differed significantly across Hb levels (P < 0.001). In NDD patients, anemia treatment also differed significantly by on-treatment Hb level (P < 0.001). In treated NDD patients with Hb < 10 g/ dL, Hb 10 to 12 g/dL, and Hb > 12 g/dL, 31%, 59%, and 38% of patients, respectively, were prescribed oral iron, and 34%, 19%, and 0% of patients, respectively, were prescribed oral iron with erythropoiesis-stimulating agents (ESA). NDD patients were less likely to be prescribed any anemia treatment, and ESA specifically, than DD patients. When treated, 67% and 45% of NDD and DD patients, respectively, had Hb ≥ 10 g/dL (P < 0.001). Overall work and activity impairment differed significantly across Hb levels in NDD and DD patients, with the least impairment observed at the highest Hb level. Conclusion Approximately 40% of NDD patients and 60% of DD patients receiving anemia treatment had Hb < 10 g/dL. Compared with mild anemia patients, severe anemia patients were more likely to be treated for anemia and have impaired work productivity. Chinese CKD patients could benefit from improved anemia treatment.

BACKGROUND: Several different patterns of wavebreak have been described by mapping of the tissue surface during fibrillation. However, it is not clear whether these surface patterns are caused by multiple distinct mechanisms or by a single mechanism. METHODS: To determine the mechanism by which wavebreaks are generated during ventricular fibrillation, we conducted optical mapping studies and single cell transmembrane potential recording in 6 isolated swine right ventricles. RESULTS: Among 763 episodes of wavebreak (0.75 times/sec/cm2), optical maps showed 3 patterns: 80% due to a wavefront encountering the refractory waveback of another wave, 11.5% due to wavefronts passing perpendicularly each other and 8.5% due to a new (target) wave arising just beyond the refractory tail of a previous wave. Computer simulations of scroll waves in 3-D tissue showed that these surface patterns could be attributed to two fundamental mechanisms: head-to-tail interactions and filament break. CONCLUSION: We conclude that during sustained ventricular fibrillation in swine RV, surface patterns of wavebreak are produced by two fundamental mechanisms: head-to-tail interaction between waves and filament break.
Computer Simulation ; Heart Ventricles* ; Membrane Potentials ; Swine* ; Ventricular Fibrillation*

OBJECTIVE: Computed tomography (CT), rather than conventional 2-dimensional radiography, was used to scan and measure pelvic parameters. The results were compared with measurements using X-ray. METHODS: Pelvic parameters were measured using both CT and X-ray in 254 patients who underwent both abdomino-pelvic CT and X-ray at the pelvic site. We assessed the similarity of the pelvic parameters between the 2 exams, as well as the correlations of pelvic parameters with sex and age. RESULTS: The mean values of the subjects’ pelvic parameters measured on X-ray were: sacral slope (SS), 31.6°; pelvic tilt (PT), 18.6°; and pelvic incidence (PI), 50.2°. The mean values measured on CT were: SS, 35.1°; PT, 11.9°; and PI, 47.0°. PT was found to be 4.07° higher on X-ray and 2.98° higher on CT in women, with these differences being statistically significant (p < 0.001, p < 0.001). PI was 4.10° higher on X-ray and 2.78° higher on CT in women, with these differences also being statistically significant (p < 0.001, p=0.009). We also observed a correlation between age and PI. For men, this correlation coefficient was 0.199 measured using X-ray and 0.184 measured using CT. For women, this correlation coefficient was 0.423 measured using X-ray and 0.372 measured using CT. CONCLUSION: When measured using CT compared to X-ray, SS increased by 3.5°, PT decreased by 6.7°, and PI decreased by 3.2°. There were also statistically significant differences in PT and PI between male and female subjects, while PI was found to increase with age.
Age Factors ; Female ; Humans ; Incidence* ; Male ; Posture* ; Radiography ; Sex Factors

Mitochondria are the powerhouses of the cell as well as the primary site of hematopoiesis, which also occurs in the cytoplasm. Hematopoietic stem cells (HSCs) are characterized by a very high turnover rate, and are thus considered to be relatively free from the age-related insults generated by mitochondria. However, HSCs are also subject to these age-related insults, including the incidence of myeloid proliferative diseases, marrow failure, hematopoietic neoplasms, and deterioration of the adaptive human immune system. Recently, NAD⁺ dietary supplements, known as niacin or vitamin B₃, including tryptophan, nicotinic acid, nicotinamide, and the newly identified NAD⁺ precursor nicotinamide riboside, have been shown to play a role in restoring adult stem cell function through the amelioration of mitochondrial dysfunction. This insight motivated a study that focused on reversing aging-related cellular dysfunction in adult mouse muscle stem cells by supplementing their diet with nicotinamide riboside. The remedial effect of nicotinamide riboside enhanced mitochondrial function in these muscle stem cells in a SIRT1-dependent manner, affecting cellular respiration, membrane potential, and production of ATP. Accordingly, numerous studies have demonstrated that sirtuins, under nuclear/mitochondrial control, have age-specific effects in determining HSC phenotypes. Based on the evidence accumulated thus far, we propose a clinical intervention for the restoration of aged HSC function by improving mitochondrial function through NAD⁺ precursor supplementation.
Adenosine Triphosphate ; Adult ; Adult Stem Cells ; Aging ; Animals ; Bone Marrow ; Cell Respiration ; Cytoplasm ; Diet ; Dietary Supplements ; Hematologic Neoplasms ; Hematopoiesis ; Hematopoietic Stem Cells* ; Humans ; Immune System ; Incidence ; Membrane Potentials ; Mice ; Mitochondria ; Niacin ; Niacinamide ; Phenotype ; Sirtuins ; Stem Cells ; Tryptophan ; Vitamins

Dystrophinopathy is the commonest form of muscular dystrophy and comprises clinically recognized forms, Duchenne dystrophy and Becker dystrophy. Mutations in the dystrophin gene which consist of large gene deletions (65%), duplications (5%) and point mutations (30%) are responsible for reducing the amount of functional dystrophin protein in skeletal muscle fi bres leading to fi bre destruction and disease. The aims of this study are to investigate the detection rate, types and distribution of large gene deletions in Malaysian dystrophinopathy patients using the multiplex polymerase chain reaction (MPCR). MPCR of 18 “hot-spot deletion” regions along the dystrophin gene was performed on DNA from 48 muscle biopsy-confi rmed cases of dystrophinopathy. A positive detection rate of 58% (28/48) was observed, where 84% (16/19) Indian, 35% (6/17) Chinese and 50% (6/12) Malay ethnic groups showed deletions in their dystrophin genes. The Malaysian Indians appear to have a higher prevalence for large gene deletions compared to the Chinese and Malays. Further analyses of 42 confi rmed positive cases (present 28 plus previous 14 cases) by MPCR showed the majority of deletions were in the mid-distal region of the dystrophin gene (81% in exons 45-60). The MPCR is a specifi c and sensitive method for confi rmation of gene deletions responsible for dystrophinopathy.

STUDY DESIGN: In vitro and in vivo studies to determine the anabolic effects of intervertebral disc (IVD) to adenovirus-mediated therapeutic gene transfer. OBJECTIVES: To quantify the anabolic effect of human IVD cells in vitro and rabbit IVD in vivo to therapeutic gene transfer. SUMMARY OF LITERATURE REVIEW: An alternative possibility to delivery of growth factors, in continuous manner, is the genetic modification of disc cells through gene transfer. Contemplating to extend this approach to treatment of disc degeneration, it is necessary to demonstrate anabolic effect of human IVD cells and rabbit disc to therapeutic gene transfer. MATERIALS AND METHODS: In vitro: IVD tissue was obtained from twelve patients. IVD cells were then isolated, cultured, and transduced with Ad/TGF-beta1. Genetically modified disc cells were incorporated into alginate beads and cultured. In vivo: Fifteen skeletally mature New Zealand white rabbit were used. 15ul of saline containing Ad/TGF-beta1 were injected into the nucleus pulposus of the disc in six rabbits. All rabbits were sacrificed 6 weeks after surgery. Nucleus pulposus tissues were harvested, weighted, and cultured. Conditioned medium of alginate bead and rabbit disc tissue cultures were subjected to ELISA to detect TGF-beta1 production. Newly synthesized proteoglycan were analyzed using chromatography on Sephadex G-25 in PD-10 columns after S35-sulfate incorporation. RESULTS: Concentration of TGF-beta1 increased over time in alginate beads cultures transduced with Ad/TGF- beta1. At 6 weeks nucleus pulposus tissue from the disc injected with Ad/TGF-beta1 exhibited 200% (p<0.05) increase in TGF- beta1 production. There was statistically significant 290% increase in newly synthesized proteoglycan in alginate cultures transduced with Ad/TGF- beta1 (p<0.05) compared to control. At 6 weeks nucleus pulposus tissue from the disc injected with Ad/TGF- beta1 exhibited 85% increase in proteoglycan synthesis (p<0.05) over that of intact control. CONCLUSION: In this study, we observed the robust upregulation of proteoglycan synthesis in gene transferred disc cells in vitro and in vivo - indicating good prospects for biologic effects of therapeutic gene therapy in the disc using adenovirus-mediated approach.
Anabolic Agents ; Chromatography ; Culture Media, Conditioned ; Enzyme-Linked Immunosorbent Assay ; Genetic Therapy* ; Humans ; Intercellular Signaling Peptides and Proteins ; Intervertebral Disc ; Intervertebral Disc Degeneration ; New Zealand ; Proteoglycans ; Rabbits ; Transforming Growth Factor beta1 ; Up-Regulation

STUDY DESIGN: In vitro experiment to determine the matrix synthesis of intervertebral disc (IVD) cell to various biologic interventions and conditions. OBJECTIVES: To elucidate biologic responses in terms of matrix synthesis of human IVD cells in vitro to various factors i.e. concentration of adenoviral vector and exogenous growth factor, duration of incubation, and type of culture methods. SUMMARY OF LITERATURE REVIEW: Sophisticated method to delivery of growth factors, in continuous manner, is the genetic modification of disc cells through gene transfer. Direct comparison of gene transfer and exogenous growth factor on matrix synthesis has not been reported. MATERIALS AND METHODS: IVD tissue was obtained from twenty three patients. Isolation and preparation of disc cells in monolayer (D) and alginate beads (3D) culture were performed. Disc cells in 2D and 3D were treated with either Ad/TGF-beta1 or exogenous TGF-beta1. Control cultures were treated with either saline or Ad/luciferase. Matrix synthesis (newly synthesized proteoglycan) was measured in various conditions (concentration of adenoviral vector and exogenous growth factor, duration of incubation, and type of culture methods). Newly synthesized proteoglycan were analyzed using chromatography on Sephadex G-25 in PD-10 columns after S35-sulfate incorporation. RESULTS: Ad/TGF-beta1 showed increase in proteoglycan synthesis (plateau at 75MOI) in 3D culture, (plateau at 25MOI) in 2D culture. In 3D culture, Ad/TGF-beta1 showed significant increase in proteoglycan synthesis on day 1, 2, and 3 of incubation. In 2D culture, Ad/TGF-beta1 showed significant increase in proteoglycan synthesis on day 2 of incubation with significant loss of anabolic effect on day 3. In 3D culture, exogenous TGF-beta1 showed increase in proteoglycan synthesis (plateau at 2ng/ml) while in 2D culture, there is no synthetic response to exogenous TGF-beta1 CONCLUSION: Therapeutic gene transfer provided sustained and increased anabolic responses than exogenous growth factor.
Anabolic Agents ; Chromatography ; Genetic Therapy ; Humans* ; Intercellular Signaling Peptides and Proteins ; Intervertebral Disc* ; Proteoglycans ; Transforming Growth Factor beta1

PURPOSE: To elucidate host immune responses to intradiscal gene transfer. MATERIALS AND METHODS: Twenty rabbits were utilized. Ad/luciferase (adenovirus construct) were injected into nucleus pulposus of lumbar vertebrae. Group 1 received intradiscal injection of Ad/luciferase only, Group 2 received subcutaneous and intradiscal injection simultaneously, Group 3 received subcutaneous injection then intradiscal injection with 2 weeks interval. Blood samples were obtained serially after injection. Animals were sacrificed at 7 weeks. Antibody to adenovirus in peripheral blood was measured with ELISA and transgene expression was measured with standard luciferase kits. RESULTS: All rabbits in the Group 2 and 3 exhibited increased production of neutralizing antibody. There were clearly two subgroups in Group 1, three rabbits exhibited production of antibody but remaining three rabbits showed little or no production of antibody. All rabbits showed robust increase in transgene expression regardless of titer of neutralizing antibody. CONCLUSION: The intervertebral disc is favorable site for adenovirus-mediated gene transfer escaping from systemic immunity.
Adenoviridae ; Animals ; Antibodies, Neutralizing ; Enzyme-Linked Immunosorbent Assay ; Injections, Subcutaneous ; Intervertebral Disc ; Luciferases ; Lumbar Vertebrae ; Rabbits ; Transgenes ; United Nations

The infusion and persistence in a transplant recipient of donor-derived bone marrow cells (DBMC) of multi-lineage can lead to a state of permanent chimerism. In solid vascular organ transplantation, the donor bone marrow lineage cells can even be derived from the transplant organ, and these cells can be detected in very small numbers in the recipient. This has been called microchimerism. Much controversy has developed with respect to the function of chimeric cells in organ transplantation. One idea is that the occurrence of these donor cells found in microchimerism in the recipient are coincidental and have no long-term beneficial effect on engraftment. A second and opposing view, is that these donor cells have immunoregulatory function that affect both the acute and chronic phases of the recipient anti-donor responses. It follows that detecting quantitative changes in chimerism might serve as an indication of the donor-specific alloimmune or regulatory response that could occur in concert with or independent of other adaptive immune responses. The latter, including autoimmune native disease, need to be controlled in the transplant organ. The safety and immune tolerance potential of DBMC infusion with deceased and living donor renal transplants was evaluated in a non-randomized trial at this center and compared with non-infused controls given identical immunosuppression. Overall DBMC infusions were well tolerated by the recipients. There were no complications from the infusion (s), no episodes of graft-vs-host disease (GVHD) and no increase infections or other complications. In the deceased DBMC- kidney trial, actuarial graft survival at 5 years was superior especially when graft survival was censored for recipient death. Acute rejections were significant reduced in patients given two DBMC infusions, and chronic rejection was dramatically reduced in all DBMC treated patients. The most interesting finding was that the degree of microchimerism slowly increased over the years the DBMC group that had exhibited no rejection episodes. In the DBMC-living related trial, the incidence of acute rejection did not differ between groups. However, DBMC chimerism in recipient iliac crest marrow had increased more rapidly than might be predicted from results previously seen in the cadaver group, despite four times fewer DBMC infused, with the generation of T- regulartory cells in-vitro assays.
*Bone Marrow Transplantation ; Humans ; *Kidney Transplantation ; *Living Donors ; *Tissue Donors ; *Transplantation Chimera ; *Transplantation Tolerance

BACKGROUND: Whole blood viscosity (WBV) refers to the internal resistance that occurs when blood flows through blood vessels. WBV is known to be related to many diseases including cardiovascular and neurovascular diseases. We have investigated the analytical performance and established reference intervals for a newly developed microfluidic viscometer, Viscore-300 (NanoBiz, Korea), used for the measurement of WBV. METHODS: We performed a precision test of 240 measurements over 20 days using three control materials. For evaluation of repeatability, a total of 60 WBV measurements were made in 3 whole blood samples 20 times a day. A total of 100 whole blood samples were used to evaluate the accuracy of the Viscore-300 in comparison to a rotating viscometer, DV3T (Brookfield, USA), in accordance with the the Clinical and Laboratory Standards Institute's guidelines. To establish the reference intervals, 122 healthy individuals were enrolled in this study. RESULTS: The precision and repeatability results showed that the CV was less than 5% for three samples and two shear rates. In the accuracy test, the mean differences between two viscometers were 0.09 cP (0.9%) and −0.07 cP (−1.4%) at shear rates of 10 s−1 and 300 s−1, respectively. The reference intervals of WBV for men were 6.88–13.52 cP at 10 s−1 and 4.32–6.43 cP at 300 s−1; those of women were 5.74–13.29 cP at 10 s−1 and 3.60–6.12 cP at 300 s−1. CONCLUSIONS: Viscore-300 showed excellent precision and accuracy and it might be a good instrument for reporting WBV quickly and accurately.
Blood Vessels ; Blood Viscosity ; Female ; Humans ; Male ; Microfluidics