Yoga therapy DYADS: A novel approach to chronic pain management in underserved populations.

Yoga therapy is an emerging integrative health approach that applies the practices and teachings of yoga for individuals with clinical concerns. It is generally offered as individual sessions between a yoga therapist and client or in a small group setting with several clients who share a clinical concern. Here we describe a third model for consideration- the yoga therapy dyad. A dyad includes two clients working simultaneously with a single yoga therapist and differs from both individual and small group sessions in the potential benefits and challenges. The yoga therapy dyad model that is detailed here was implemented as part of a feasibility trial along with group acupuncture therapy for chronic pain in an underserved population. Underserved populations are at risk for pain and reduced access to care. This pilot may inform future research, policy, education, and clinical practice.

Markers of muscle atrophy and impact of treatment with pergolide in horses with pituitary pars intermedia dysfunction and muscle atrophy.

Pituitary pars intermedia dysfunction (PPID) is a common endocrine disorder of aged horses, with muscle atrophy as one of the clinical signs. We sought to compare muscle mass and regulation of skeletal muscle proteolysis between horses with PPID and muscle atrophy to older horses without PPID, and to assess the impact of treatment with pergolide (dopaminergic agonist) on PPID horses. We hypothesized that PPID-associated muscle atrophy is a result of increased proteolysis, and that markers of muscle atrophy and proteolysis would improve over time with pergolide treatment. Markers of muscle atrophy, adiposity, insulin regulation, skeletal muscle composition, and proteolysis (muscle atrophy F- box/atrogin 1 [MAFbx1], muscle RING finger 1 [MuRF1], Bcl2/adenovirus EIV 19kD interacting protein 3 [Bnip3], and microtubule-associated light chain 3 [LC3]) were compared between PPID and control horses. PPID horses were treated for 12 weeks with either pergolide or placebo. Dose of pergolide was adjusted based upon monthly measurement of adrenocorticotropin, and markers of muscle atrophy, adiposity, insulin regulation, skeletal muscle composition, and proteolysis were compared after 12 weeks of treatment. Horses with PPID exhibited increased transcript abundance of MuRF1 (P= 0.04) compared to control. However, no difference was observed in transcript abundance of markers of proteolysis with treatment (P ≥ 0.25). Pergolide treated horses lost weight (P = 0.02) and improved fasting insulin (P = 0.02), while placebo treated horses gained weight and rump fat thickness (P = 0.02). Findings from this study suggest that treatment with pergolide may promote weight loss and improve insulin regulation in horses with PPID, but does not impact muscle mass or markers of muscle proteolysis.

Novel Osteogenic Ti-6Al-4V Device For Restoration Of Dental Function In Patients With Large Bone Deficiencies: Design, Development And Implementation.

Custom devices supporting bone regeneration and implant placement are needed for edentulous patients with large mandibular deficiencies where endosteal implantation is not possible. We developed a novel subperiosteal titanium-aluminum-vanadium bone onlay device produced by additive manufacturing (AM) and post-fabrication osteogenic micro-/nano-scale surface texture modification. Human osteoblasts produced osteogenic and angiogenic factors when grown on laser-sintered nano-/micro-textured surfaces compared to smooth surfaces. Surface-processed constructs caused higher bone-to-implant contact, vertical bone growth into disk pores (microCT and histomorphometry), and mechanical pull-out force at 5 and 10 w on rat calvaria compared to non surface-modified constructs, even when pre-treating the bone to stimulate osteogenesis. Surface-modified wrap-implants placed around rabbit tibias osseointegrated by 6 w. Finally, patient-specific constructs designed to support dental implants produced via AM and surface-processing were implanted on edentulous mandibular bone. 3 and 8 month post-operative images showed new bone formation and osseointegration of the device and indicated stability of the dental implants.

"An aristocracy of talent": the South Carolina physician-naturalists and their times.

During the natural history movement of the 18th and early 19th centuries, Charleston as a center was rivaled in the United States only by Philadelphia, New York, and Boston. Prominent physician-naturalists included Alexander Garden (for whom the gardenia is named), John Edwards Holbrook ("father of American herpetology"), and Francis Peyre Porcher (whose Resources of Southern Fields and Forests helped Confederates compensate for drug shortages). The Charleston physician-naturalists belonged to an "aristocracy of talent" as distinguished from the "aristocracy of wealth" of lowcountry planters, who probably did more than any other group to perpetuate slavery and propel the South toward a disastrous civil war. None of the physician-naturalists actively opposed slavery or secession, a reminder that we are all prisoners of the prevailing paradigms and prejudices of our times.

Minimally-invasive fetal autopsy using magnetic resonance imaging and percutaneous organ biopsies: clinical value and comparison to conventional autopsy.

OBJECTIVES: Autopsy is an important investigation following fetal death or termination for fetal abnormality. Postmortem magnetic resonance imaging (MRI) can provide macroscopic information of comparable quality to that of conventional autopsy in the event of perinatal death. It does not provide tissue for histological examination, which may limit the quality of counseling for recurrence risks and elucidation of the cause of death. We sought to examine the comparability and clinical value of a combination of postmortem MRI and percutaneous fetal organ biopsies (minimally invasive autopsy (MIA)) with conventional fetal autopsy. METHODS: Forty-four fetuses underwent postmortem MRI and attempted percutaneous biopsy (using surface landmarks) of major fetal organs (liver, lung, heart, spleen, kidney, adrenal and thymus) following fetal death or termination for abnormality, prior to conventional autopsy, which was considered the 'gold standard'. We compared significant findings of the two examinations for both diagnostic information and clinical significance. Ancillary investigations (such as radiographs and placental histology) were regarded as common to the two forms of autopsy. RESULTS: In 21 cases conventional autopsy provided superior diagnostic information to that of MIA. In two cases the MIA provided superior diagnostic information to that of conventional autopsy, when autolysis prevented detailed examination of the fetal brain. In the remaining 21 cases, conventional autopsy and MIA provided equivalent diagnostic information. With regard to clinical significance, however, in 32 (72.7%) cases, the MIA provided information of at least equivalent clinical significance to that of conventional autopsy. In no case did the addition of percutaneous biopsies reveal information of additional clinical significance. CONCLUSIONS: Although in some cases MRI may provide additional information, conventional perinatal autopsy remains the gold standard for the investigation of fetal death. The utility of adding percutaneous organ biopsies, without imaging guidance, to an MRI-based fetal autopsy remains unproven. Postmortem MRI, combined with ancillary investigations such as placental histology, external examination by a pathologist, cytogenetics and plain radiography provided information of equivalent clinical significance in the majority of cases.

The transcobalamin (TCN2) 776C>G polymorphism affects homocysteine concentrations among subjects with low vitamin B(12) status.

BACKGROUND/OBJECTIVES: Methionine synthase catalyzes the conversion of 5-methyltetrahydrofolate to tetrahydrofolate and homocysteine (Hcy) to methionine using vitamin B(12) as a cofactor. Transcobalamin is the main transporter of vitamin B(12) from blood into cells. This study was undertaken to assess the relationship between the transcobalamin P259R (TCN2 776C>G) polymorphism and both serum vitamin B(12) and total Hcy (tHcy) levels. SUBJECTS/METHODS: The population comprised 613 men from Northern Ireland, aged 30-49 years, for whom tHcy, serum vitamin B(12) and serum folate concentrations were available. TCN2 776C>G genotypes were determined using a TaqMan 5' nuclease Real-Time PCR assay. Standard statistical tests of association were applied to assess the relationships between the polymorphism and phenotypic variables. RESULTS: The TCN2 776CC homozygous genotype was associated with lower serum vitamin B(12) concentrations compared with the 776CG (P(unadjusted)=0.01; P(adjusted)=0.03) and 776GG genotypes (P(unadjusted)=0.015; P(adjusted)=0.045). Among individuals with vitamin B(12) concentrations in the lower half of the distribution, tHcy concentrations were higher in TCN2 776GG homozygotes than in individuals with the other genotypes (P(unadjusted)=0.015; P(adjusted)=0.06). CONCLUSIONS: These data suggest that, relative to transcobalamin with arginine at position 259 (776G), transcobalamin with proline at this position (776C) is either more efficient at vitamin B(12) transport from blood to tissues or has higher affinity for vitamin B(12). Furthermore, vitamin B(12) status influences the relationship between TCN2 776C>G genotype and tHcy concentrations. Thus, the TCN2 776C>G polymorphism may contribute to the risk of pathologies associated with a low B(12), and high tHcy phenotype.

Comparative transcriptomics implicates mechanisms of evolved pollution tolerance in a killifish population.

Wild populations of the killifish Fundulus heteroclitus resident in heavily contaminated North American Atlantic coast estuaries have recently and independently evolved dramatic, heritable, and adaptive pollution tolerance. We compared physiological and transcriptome responses to embryonic polychlorinated biphenyl (PCB) exposures between one tolerant population and a nearby sensitive population to gain insight into genomic, physiological and biochemical mechanisms of evolved tolerance in killifish, which are currently unknown. The PCB exposure concentrations at which developmental toxicity emerged, the range of developmental abnormalities exhibited, and global as well as specific gene expression patterns were profoundly different between populations. In the sensitive population, PCB exposures produced dramatic, dose-dependent toxic effects, concurrent with the alterations in the expression of many genes. For example, PCB-mediated cardiovascular system failure was associated with the altered expression of cardiomyocyte genes, consistent with sarcomere mis-assembly. In contrast, genome-wide expression was comparatively refractory to PCB induction in the tolerant population. Tolerance was associated with the global blockade of the aryl hydrocarbon receptor (AHR) signalling pathway, the key mediator of PCB toxicity, in contrast to the strong dose-dependent up-regulation of AHR pathway elements observed in the sensitive population. Altered regulation of signalling pathways that cross-talk with AHR was implicated as one candidate mechanism for the adaptive AHR signalling repression and the pollution tolerance that it affords. In addition to revealing mechanisms of PCB toxicity and tolerance, this study demonstrates the value of comparative transcriptomics to explore molecular mechanisms of stress response and evolved adaptive differences among wild populations.

BELFAST centenarians: a case of optimised cardiovascular risk?

INTRODUCTION: Centenarians are reservoirs of genetic and environmental information to successful ageing and local centenarian groups may help us to understand some of these secrets. The current centenarian cohort in Belfast survived the 1970s epidemic of death from coronary heart disease in Northern Ireland, where cardiovascular mortality was almost highest in the world. These centenarians provided an opportunity to assess biological and genetic factors important in cardiovascular risk and ageing. METHODS: Thirty-five (27 female, 8 male) centenarians, participants of the Belfast Elderly Longitudinal Free-living Ageing STudy (BELFAST), were community-living and of good cognition at enrollment. RESULTS: Centenarians showed median Body Mass Index (BMI) at 25.7, systolic blood pressure 140 mmHg and diastolic blood pressure 90 mmHg respectively, and fasting glucose of 5.54 mmol/l with no sex-related difference. Lipoproteins showed median cholesterol 5.3, High Density Lipoprotein (HDL) 1.10 and Low Density Lipoprotein (LDL) 3.47 micromol/l respectively. Centenarian smokers showed no different blood pressure or lipid measurements compared with non-smokers. Malondialdehyde, a measure of lipid peroxidation, was low at 1.19, and measures of antioxidant status showed variable results. Male centenarians did not carry any of the vascular risk genotypes studied-Apolipoprotein E (ApoE), Angiotensin-Converting Enzyme (ACE) and Methylenetetrafolatedehydrogenase reductase (MTFHR), though this was not true for female centenarians. CONCLUSIONS: This small local study shows, apart from age, that Belfast centenarians carry a reasonably optimized risk profile with respect to cardiovascular disease. There is also some evidence suggesting that vascular risk factors and genotypes may be tolerated differently between the male and female centenarians. Maintaining an optimized cardiovascular risk profile seems likely to improve the chance of becoming a centenarian, especially for males.

Chemical vapour deposition synthetic diamond: materials, technology and applications.

Substantial developments have been achieved in the synthesis of chemical vapour deposition (CVD) diamond in recent years, providing engineers and designers with access to a large range of new diamond materials. CVD diamond has a number of outstanding material properties that can enable exceptional performance in applications as diverse as medical diagnostics, water treatment, radiation detection, high power electronics, consumer audio, magnetometry and novel lasers. Often the material is synthesized in planar form; however, non-planar geometries are also possible and enable a number of key applications. This paper reviews the material properties and characteristics of single crystal and polycrystalline CVD diamond, and how these can be utilized, focusing particularly on optics, electronics and electrochemistry. It also summarizes how CVD diamond can be tailored for specific applications, on the basis of the ability to synthesize a consistent and engineered high performance product.

Concept, design and implementation of a cardiovascular gene-centric 50 k SNP array for large-scale genomic association studies.

A wealth of genetic associations for cardiovascular and metabolic phenotypes in humans has been accumulating over the last decade, in particular a large number of loci derived from recent genome wide association studies (GWAS). True complex disease-associated loci often exert modest effects, so their delineation currently requires integration of diverse phenotypic data from large studies to ensure robust meta-analyses. We have designed a gene-centric 50 K single nucleotide polymorphism (SNP) array to assess potentially relevant loci across a range of cardiovascular, metabolic and inflammatory syndromes. The array utilizes a "cosmopolitan" tagging approach to capture the genetic diversity across approximately 2,000 loci in populations represented in the HapMap and SeattleSNPs projects. The array content is informed by GWAS of vascular and inflammatory disease, expression quantitative trait loci implicated in atherosclerosis, pathway based approaches and comprehensive literature searching. The custom flexibility of the array platform facilitated interrogation of loci at differing stringencies, according to a gene prioritization strategy that allows saturation of high priority loci with a greater density of markers than the existing GWAS tools, particularly in African HapMap samples. We also demonstrate that the IBC array can be used to complement GWAS, increasing coverage in high priority CVD-related loci across all major HapMap populations. DNA from over 200,000 extensively phenotyped individuals will be genotyped with this array with a significant portion of the generated data being released into the academic domain facilitating in silico replication attempts, analyses of rare variants and cross-cohort meta-analyses in diverse populations. These datasets will also facilitate more robust secondary analyses, such as explorations with alternative genetic models, epistasis and gene-environment interactions.

Alcohol increases homocysteine and reduces B vitamin concentration in healthy male volunteers--a randomized, crossover intervention study.

BACKGROUND: Few studies have examined the effect of alcohol consumption on total homocysteine (tHcy) concentrations. AIM: To assess the effect of an 8-week intervention with vodka or red wine on plasma tHcy and B vitamin concentrations in healthy male volunteers. To assess the effect on tHcy according to methylenetetrahydrofolate reductase (MTHFR) 677C>T genotype. DESIGN AND METHODS: A randomized controlled crossover intervention study measuring tHcy and serum folate and vitamin B(12) concentrations was conducted in 78 male subjects (21-70 years). Following a 2-week washout period during which no alcohol was consumed, all subjects consumed 24 g alcohol (either 240 ml red wine or 80 ml vodka)/day for a 2-week period. Following a further 2-week washout, participants consumed the alternate intervention for 2 weeks. RESULTS: A significant increase in plasma tHcy was observed after the 2-week red wine intervention (5%, P = 0.03), and a non-significant increase in tHcy with vodka intervention (3%, P = 0.09). When the two interventions were compared, the change in tHcy did not differ between the vodka and red wine interventions (P = 0.57). There were significant decreases in serum vitamin B(12) and folate concentrations, and this decrease did not differ between interventions. The increase in tHcy observed in both interventions did not vary by MTHFR 677C>T genotype. CONCLUSION: A 2-week alcohol intervention resulted in a decrease in folate and vitamin B(12) status and an increase in plasma tHcy. The effect of alcohol intervention on tHcy, folate and vitamin B(12) concentrations did not differ between the red wine and vodka intervention groups.

Dosing algorithms to predict warfarin maintenance dose in Caucasians and African Americans.

The objective of this study was to determine whether warfarin dosing algorithms developed for Caucasians and African Americans on the basis of clinical, environmental, and genetic factors will perform better than an empirical starting dose of 5 mg/day. From April 2002 through December 2005, 259 subjects (Caucasians and African Americans) who started using warfarin were prospectively followed until they reached maintenance dose. The Caucasian algorithm included 11 variables (R(2) = 0.43). This model (which predicted 51% of the doses to within 1 mg of the observed dose) performed better than 5 mg/day (which predicted 29% of the doses to within 5 +/- 1 mg). The African-American algorithm included 10 variables (R(2) = 0.28). This model predicted 37% of the doses to within 1 mg of the observed dose, representing a small improvement compared with 5 mg/day (which predicted 34% of the doses to within 1 mg of 5 mg/day). These results were similar to the results we obtained from testing other published algorithms. The dosing algorithms explained <45% of the observed variability in Caucasians, and the algorithms performed only marginally better for African Americans when compared with giving 5 mg empirically.

Feasibility of percutaneous organ biopsy as part of a minimally invasive perinatal autopsy.

To determine the feasibility of percutaneous fetal organ biopsies in the context of a 'minimally invasive' perinatal autopsy after stillbirth and termination for abnormality is the aim of this study. We assessed successful biopsy rate and the proportion adequate for histological examination in 30 fetuses undergoing organ sampling before autopsy. The relationship between gestational age, body weight, death-biopsy interval, operator experience and successful biopsy rate was investigated. Significant findings from conventional block histology were compared with corresponding percutaneous biopsies. Of 210 organ biopsies attempted from seven target organs, 107 were obtained, of which 94 were adequate for pathological comment. The median delivery-autopsy interval was 4 (range 2-11) days. Adequate samples were obtained from the lung in 86% cases (95% CI 68, 96%), liver 76% (95% CI 56, 90%) and less frequently for the myocardium, kidney, adrenal, thymus and spleen. There was no relationship between biopsy success and time to biopsy, gestational age, body weight and user experience. No histological abnormalities found at autopsy were diagnosed from needle biopsies. Although targeted percutaneous biopsies appear feasible for some organs, fewer than 50% of all biopsies are adequate for histological examination. This technique cannot be considered to provide useful clinical information as part of a 'minimally invasive' perinatal autopsy.

Apolipoprotein E genotype and warfarin dosing among Caucasians and African Americans.

Warfarin sodium is a vitamin K antagonist that is plagued by large variability in patient response, including higher dose requirements among African Americans. Polymorphisms in the gene encoding apolipoprotein E (APOE) may partly explain this variability by altering transport of vitamin K to the liver. In a prospective cohort study of 232 individuals (52.2% Caucasian and 47.8% African American) initiating warfarin therapy, the weekly maintenance dose was significantly higher for African Americans than for Caucasians (mean 42.9 versus mean 36.9 mg, P=0.018), and the epsilon4 allele was more common among African Americans (37.8 versus 26.4% for Caucasians). In multivariable analyses, the presence of the epsilon4 allele was associated with a statistically significantly higher warfarin dose among African Americans (median 45.0 mg in epsilon4 carriers versus 35.0 mg in non-epsilon4 carriers, P=0.014) but not Caucasians (38.1 versus 35.0 mg, P=0.60). In addition, warfarin maintenance dose increased among African Americans according to genotype previously associated with differential hepatic chylomicron clearance (epsilon2/epsilon2 or epsilon2/epsilon3: 30.0 mg; epsilon3/epsilon3: 35.0 mg; epsilon3/epsilon4 or epsilon4/epsilon4: 45.0 mg; P=0.012), although the epsilon4/epsilon4 genotype was rare and not clearly associated with higher doses. The association of APOE with warfarin dosing was independent of CYP2C9 and VKORC1 polymorphisms. APOE polymorphisms thus may be important determinants of warfarin maintenance dose and could explain at least some of the observed racial differences in dose requirements.

Warfarin response and vitamin K epoxide reductase complex 1 in African Americans and Caucasians.

The objective of this study was to determine whether two vitamin K epoxide reductase complex 1 (VKORC1) polymorphisms contribute to the variability in warfarin response, particularly in African Americans. The effect of the VKORC1 1173C/T and -1639G/A polymorphisms was examined in a prospective cohort study of 338 warfarin users. Subjects carrying an 1173T allele had a lower warfarin maintenance dose compared with subjects with the CC genotype in African Americans (-12.10 mg/week+/-4.93; P=0.02) and Caucasians (-14.41 mg/week+/-3.28; P<0.001). Before reaching maintenance dose, only Caucasians with the T allele had significantly increased risk of international normalized ratio >3 (odds ratio=3.10; 95% confidence interval: 1.73-5.55) compared with Caucasians with the CC genotype. Polymorphisms in the VKORC1 gene are associated with warfarin maintenance dose requirements among both African Americans and Caucasians. However, these polymorphisms may not be as useful in predicting over-anticoagulation among African Americans.