Search

Fibromyalgia syndrome (FMS) is a complex disorder, with primary symptoms of sleep disturbances, pain, and fatigue. FMS is one of the most common reasons for patient visits to a rheumatologist. Previous studies have suggested that complementary and alternative medicine (CAM) use in patients with rheumatic diseases is common, but such data specific to FMS patients is limited. Objective: The following study sought to describe the prevalence of CAM use in a primary care practice of patients with FMS and assess whether these patients discuss CAM use with their physician, physician-extender, and/or pharmacist. Methods: A one-group cross-sectional survey design was implemented in a large, community-based, private physician practice of patients diagnosed with FMS. A self-administered questionnaire was distributed during clinic visits. It solicited information related to demographic characteristics; FMS-specific health background; whether CAM use had been discussed with a health care provider; and the “ever-use” of common types of CAM. Respondents returned the questionnaire via US mail in a postage-paid, self-addressed envelope. Results: A total of 115 surveys were distributed with 54 returned for analysis (47% completion rate). The sample was predominantly female, well educated and had a mean age of 55.6 years. All respondents were White. Most respondents (92.6%) reported using some type of CAM. Exercise (92.2%), chiropractic treatment (48.1%), lifestyle and diet (45.8%), relaxation therapy (44.9%), and dietary and herbal supplements (36.5%) were most commonly reported CAM therapies “ever-used” by respondents. Dietary and herbal supplements with the highest prevalence of “ever-use” were magnesium (19.2%), guaifenesin (11.5%), and methylsulfonylmethane (MSM) (9.6%). Respondents most commonly discussed CAM with the clinic rheumatologist and the primary care physician (53.7% and 38.9%, respectively). Only 14.8% of respondents discussed CAM with a pharmacist. However, a significantly higher proportion of respondents who “ever-used” dietary and herbal supplements discussed CAM with a pharmacist compared to those who never used dietary and herbal supplements [chi square=6.03, p=0.014]. Conclusion: This pilot study suggests that CAM use is common in patients diagnosed with FMS. Compared to other healthcare providers, respondents were least likely to discuss CAM with a pharmacist. However, respondents who used dietary and herbal supplements were more likely to discuss CAM with a pharmacist compared to those who did not, suggesting the potential influence of pharmacist intervention.

We have prepared recombinant fourteen subunit yeast SWR1 complex from insect cells using a modified MultiBac system. The 1.07 MDa recombinant protein complex has histone-exchange activity. Full exchange activity is realized with a single SWR1 complex bound to a nucleosome. We also prepared mutant complexes that lack a variety of subunits or combinations of subunits and these start to reveal roles for some of these subunits as well as indicating interactions between them in the full complex. Complexes containing a series of N-terminally and C-terminally truncated Swr1 subunits reveal further details about interactions between subunits as well as their binding sites on the Swr1 subunit. Finally, we present electron microscopy studies revealing the dynamic nature of the complex and a 21 Å resolution reconstruction of the intact complex provides details not apparent in previously reported structures, including a large central cavity of sufficient size to accommodate a nucleosome., (© The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.)

We have developed a novel system to facilitate the rapid and easy cloning of multiple genes (>10) in under a week. Using this system we have been able to successfully clone, overexpress, and purify a number of large multimeric proteins from insect cells, including the chromatin remodeling complexes SWR1 and INO80. Using Förster resonance energy transfer (FRET)-based assays we have demonstrated that our overexpressed enzymes have activities comparable to those purified from sources where the proteins are expressed under their endogenous promoters., (© 2017 Elsevier Inc. All rights reserved.)

Aims: Adenosine triphosphate (ATP) synthase uses chemiosmotic energy across the inner mitochondrial membrane to convert adenosine diphosphate and orthophosphate into ATP, whereas genetic deletion of Sirt3 decreases mitochondrial ATP levels. Here, we investigate the mechanistic connection between SIRT3 and energy homeostasis., Results: By using both in vitro and in vivo experiments, we demonstrate that ATP synthase F1 proteins alpha, beta, gamma, and Oligomycin sensitivity-conferring protein (OSCP) contain SIRT3-specific reversible acetyl-lysines that are evolutionarily conserved and bind to SIRT3. OSCP was further investigated and lysine 139 is a nutrient-sensitive SIRT3-dependent deacetylation target. Site directed mutants demonstrate that OSCP(K139) directs, at least in part, mitochondrial ATP production and mice lacking Sirt3 exhibit decreased ATP muscle levels, increased ATP synthase protein acetylation, and an exercise-induced stress-deficient phenotype., Innovation: This work connects the aging and nutrient response, via SIRT3 direction of the mitochondrial acetylome, to the regulation of mitochondrial energy homeostasis under nutrient-stress conditions by deacetylating ATP synthase proteins., Conclusion: Our data suggest that acetylome signaling contributes to mitochondrial energy homeostasis by SIRT3-mediated deacetylation of ATP synthase proteins.

The molecular description of the mechanism of F(1)-ATPase is based mainly on high-resolution structures of the enzyme from mitochondria, coupled with direct observations of rotation in bacterial enzymes. During hydrolysis of ATP, the rotor turns counterclockwise (as viewed from the membrane domain of the intact enzyme) in 120° steps. Because the rotor is asymmetric, at any moment the three catalytic sites are at different points in the catalytic cycle. In a "ground-state" structure of the bovine enzyme, one site (β(E)) is devoid of nucleotide and represents a state that has released the products of ATP hydrolysis. A second site (β(TP)) has bound the substrate, magnesium. ATP, in a precatalytic state, and in the third site (β(DP)), the substrate is about to undergo hydrolysis. Three successive 120° turns of the rotor interconvert the sites through these three states, hydrolyzing three ATP molecules, releasing the products and leaving the enzyme with two bound nucleotides. A transition-state analog structure, F(1)-TS, displays intermediate states between those observed in the ground state. For example, in the β(DP)-site of F(1)-TS, the terminal phosphate of an ATP molecule is undergoing in-line nucleophilic attack by a water molecule. As described here, we have captured another intermediate in the catalytic cycle, which helps to define the order of substrate release. In this structure, the β(E)-site is occupied by the product ADP, but without a magnesium ion or phosphate, providing evidence that the nucleotide is the last of the products of ATP hydrolysis to be released.

The structure of the complex between bovine mitochondrial F(1)-ATPase and a stator subcomplex has been determined at a resolution of 3.2 A. The resolved region of the stator contains residues 122-207 of subunit b; residues 5-25 and 35-57 of F(6); 3 segments of subunit d from residues 30-40, 65-74, and 85-91; and residues 1-146 and 169-189 of the oligomycin sensitivity conferral protein (OSCP). The stator subcomplex represents its membrane distal part, and its structure has been augmented with an earlier structure of a subcomplex containing residues 79-183, 3-123, and 5-70 of subunits b, d, and F(6), respectively, which extends to the surface of the inner membrane of the mitochondrion. The N-terminal domain of the OSCP links the stator with F(1)-ATPase via alpha-helical interactions with the N-terminal region of subunit alpha(E). Its C-terminal domain makes extensive helix-helix interactions with the C-terminal alpha-helix of subunit b from residues 190-207. Subunit b extends as a continuous 160-A long alpha-helix from residue 188 back to residue 79 near to the surface of the inner mitochondrial membrane. This helix appears to be stiffened by other alpha-helices in subunits d and F(6), but the structure can bend inward toward the F(1) domain around residue 146 of subunit b. The linker region between the 2 domains of the OSCP also appears to be flexible, enabling the stator to adjust its shape as it passes over the changing profile of the F(1) domain during a catalytic cycle. The structure of the membrane extrinsic part of bovine ATP synthase is now complete.

Background: Coronary angiography and angioplasty have to date been performed using digital angiography and fluoroscopic systems which incorporate an image intensifier (II). More recently flat-panel (FP) detectors have been introduced which are thought to improve spatial resolution. However, there is limited data on the effect of flat-panel detection on radiation exposure. We sought to determine the impact of flat-panel on cumulative radiation exposure in patients undergoing elective coronary angioplasty at our institution., Methods: Patients who underwent elective coronary angioplasty in the six months prior to and following upgrade of our Toshiba catheterisation laboratory from image intensifier to flat-panel were included. Demographic and radiation data were collected prospectively and the same five operators performed interventions during the 12-month period. Radiation data was obtained from the dose-area product meter intrinsic to the fluoroscopy system., Results: One hundred and thirty seven patients underwent elective angioplasty over the 12-month period (68 II, 69 FP). Cumulative radiation exposure was increased in flat-panel cases (99, 129 Gy cm(2) versus 71, 77 Gy cm(2), p=0.001). This increase was independent of patient weight (78+/-15 kg versus 78+/-17 kg, p=NS), screening time (19+/-12 min versus 18+/-13 min, p=NS) and total number of digital acquisitions (1475, 820 versus 1668, 1365, p=NS). The total amount of contrast dye did not differ between flat-panel and image intensifier cases (195+/-76 ml versus 194+/-79 ml, p=NS)., Conclusions: Adoption of flat-panel detector technology increases radiation exposure. This may have important safety implications for catheterisation laboratory staff and patients undergoing multiple interventional procedures.

A 60-year-old man experienced catastrophic haemodynamic decompensation 3 days following coronary artery bypass grafting (CABG). Aspiration thrombectomy to remove a left main coronary artery saddle embolus resulted in immediate haemodynamic improvement with no requirement for angioplasty or repeat bypass grafting. Coronary thromboembolism should be considered in the differential diagnosis of haemodynamic collapse post CABG. Urgent coronary angiography and aspiration thrombectomy may result in significant improvement for this condition.

The use of dietary omega 3 fatty acid capsules has been associated with a decrease in plasma triglyceride levels. In addition, populations consuming diets rich in fish appear to have a decreased incidence of cardiovascular disease. Eicosapentaenoic acid (EPA, 20:5 omega 3) and docosahexaenoic acid (DHA, 22:6 omega 3) are major fatty acids in fish oils. It is believed that fish oils exert their biologic effect through these fatty acids. Many individuals are currently taking fish oil capsules to lower lipids, increase bleeding time, and possibly decrease cardiovascular risk. These capsules also have been classified as food additives with less stringent controls on content. We assessed the fatty acid, cholesterol, and vitamin A and E content of eight commercially available capsules along with cod liver oil. The content of EPA was found to range from 8.7-26.4% (wt %) with a mean of 17.3% (82.4% of labeled content), and that of DHA from 8.9-17.4% with a mean of 11.5% (90.0% of labeled content) as assessed by capillary column gas-liquid chromatography. The mean content of the polyunsaturated omega 3 fatty acids was 31.9%, and that of the omega 6 fatty acids was 1.4%. The content of saturated fatty acids was 32.0%, and that of monounsaturated fatty acids was 25.1%. Cholesterol content was low, with a range of 0.7-8.3 mg/g, the alpha-tocopherol range was 0.62-2.24 mg/g, and the range of retinyl esters was 0.4-298.4 micrograms/g. Cod liver oil had substantially more retinyl esters (2450.1 micrograms/g) than did fish oil capsules.(ABSTRACT TRUNCATED AT 250 WORDS)