Voluntary wheel running prevents formation of membrane attack complexes and myelin degradation after peripheral nerve injury.

Regular aerobic activity is associated with a reduced risk of chronic pain in humans and rodents. Our previous studies in rodents have shown that prior voluntary wheel running can normalize redox signaling at the site of peripheral nerve injury, attenuating subsequent neuropathic pain. However, the full extent of neuroprotection offered by voluntary wheel running after peripheral nerve injury is unknown. Here, we show that six weeks of voluntary wheel running prior to chronic constriction injury (CCI) reduced the terminal complement membrane attack complex (MAC) at the sciatic nerve injury site. This was associated with increased expression of the MAC inhibitor CD59. The levels of upstream complement components (C3) and their inhibitors (CD55, CR1 and CFH) were altered by CCI, but not increased by voluntary wheel running. Since MAC can degrade myelin, which in turn contributes to neuropathic pain, we evaluated myelin integrity at the sciatic nerve injury site. We found that the loss of myelinated fibers and decreased myelin protein which occurs in sedentary rats following CCI was not observed in rats with prior running. Substitution of prior voluntary wheel running with exogenous CD59 also attenuated mechanical allodynia and reduced MAC deposition at the nerve injury site, pointing to CD59 as a critical effector of the neuroprotective and antinociceptive actions of prior voluntary wheel running. This study links attenuation of neuropathic pain by prior voluntary wheel running with inhibition of MAC and preservation of myelin integrity at the sciatic nerve injury site.

Disruption of polyhomeotic polymerization decreases nucleosome occupancy and alters genome accessibility.

Chromatin attains its three-dimensional (3D) conformation by establishing contacts between different noncontiguous regions. Sterile Alpha Motif (SAM)-mediated polymerization of the polyhomeotic (PH) protein regulates subnuclear clustering of Polycomb Repressive Complex 1 (PRC1) and chromatin topology. The mutations that perturb the ability of the PH to polymerize, disrupt long-range chromatin contacts, alter Hox gene expression, and lead to developmental defects. To understand the underlying mechanism, we combined the experiments and theory to investigate the effect of this SAM domain mutation on nucleosome occupancy and accessibility on a genome wide scale. Our data show that disruption of PH polymerization because of SAM domain mutation decreases nucleosome occupancy and alters accessibility. Polymer simulations investigating the interplay between distant chromatin contacts and nucleosome occupancy, both of which are regulated by PH polymerization, suggest that nucleosome density increases when contacts between different regions of chromatin are established. Taken together, it appears that SAM domain-mediated PH polymerization biomechanically regulates the organization of chromatin at multiple scales from nucleosomes to chromosomes and we suggest that higher order organization can have a top-down causation effect on nucleosome occupancy.

Isolation and Annotation of Xitlalli, a Cluster EK1 Actinobacteriophage Isolated Using Microbacterium foliorum.

Xitlalli is an actinobacteriophage that was isolated from soil using Microbacterium foliorum. Based on gene content similarity to phages in the Actinobacteriophage Database, Xitlalli is assigned to cluster EK1. The genome is 53,929 bp long and contains 52 protein-coding genes, of which 26% could be assigned functions.

Efficacy of Three-dimensional Locking Miniplates versus Three-dimensional Standard Miniplates in the Management of Mandibular Fractures - A Prospective Clinical Study.

Introduction: Fifty patients were included to compare the efficacy of three-dimensional (3D) locking miniplates versus 3D standard miniplates in the management of mandibular fractures. Materials and Methods: Fifty patients were randomly allocated to either 3D locking miniplate group or 3D standard miniplate group. All patients were followed for six months to compare post-operative occlusion, stability and associated clinical complications such as wound dehiscence, infection and plate/screw fracture and mental nerve paraesthesia. Results: All the fractures were adequately fixed when checked intraoperatively. Four patients in each group had mildly deranged occlusion, one patient in Group A and two patients in Group B had reduced stability. None of the patients had complications of non-union or malunion. In Group A, one out of 25 patients had mental nerve paraesthesia and two had wound dehiscence. Moreover, in Group B, two patients had mental nerve paraesthesia and two others had wound dehiscence. The data when compared were statistically significant (=0.05). Discussion: The overall result of our study led us to the conclusion that both the plating systems were satisfactory and there is no statistically significant difference when used for open reduction and fixation in mandibular fractures. Healing was satisfactory in both groups.

Evaluation of Shear Bond Strength of a Primer Incorporated Orthodontic Composite Resin: An In-Vitro Study.

Introduction Newer adhesive systems are available eliminating the separate priming step during the bonding procedure thereby reducing the chances of introduction of error during bonding. The purpose of this study was to compare the shear bond strength of a primer-incorporated adhesive with that of a self-etching primer system and conventional bonding system. Materials and method Sixty-six extracted human premolars were cleaned, mounted, and randomly divided into three groups. In group A (control), 22 teeth were bonded with stainless steel orthodontic brackets using the conventional bonding system; in group B, 22 teeth were bonded using a self-etching primer system (Transbond Plus SEP, 3M Unitek, Monrovia, CA) and in group C, 22 teeth were bonded using the new primer-incorporated adhesive system (GC Ortho Connect, GC Orthodontics, Breckerfeld, Germany). After bonding, the teeth were stored in artificial saliva at 37ºC for 24 hours and debonded with a universal testing machine. The adhesive remnant index (ARI) was also evaluated. Statistical analysis was done using one-way ANOVA to compare the shear bond strength values among the three groups and Kruskal Wallis test was used for comparison of ARI scores. Results The SBS values in group A (11.60 ± 2.95 MPa), group B (9.44 ± 4.46 MPa) and group C (12.68 ± 6.25 MPa) were found to be comparable with no statistically significant difference. The ARI scores were also similar among the tested groups with the predominant site of bond failure being the bracket-adhesive interface indicating a safe bond-failure site. Conclusion GC Ortho Connect was found have clinically acceptable shear bond strength values that are comparable with that of self-etching primer and conventional bonding system. Therefore, it can be used effectively for saving the clinician's chairside time by reduction in the number of steps during bonding without compromising on the bond strength.

Comparative Evaluation of Frictional Resistance Between Different Types of Ceramic Brackets and Stainless Steel Brackets With Teflon-Coated Stainless Steel and Stainless Steel Archwires: An In-Vitro Study.

Background Orthodontic tooth movement relies on sliding mechanics usually achieved by sliding the archwire through brackets. Sliding causes friction which is a force resisting the relative motion of two contacting objects. Frictional resistance is undesirable in orthodontic tooth movement because the archwire might bind with the bracket and prevent tooth movement. In addition, friction causes bending of the archwire leading to unwanted tooth movement or space loss through anchorage interference, prolonging the treatment time and root resorption. This study was performed to compare the frictional resistance produced by different types of ceramic brackets and stainless steel brackets with Teflon-coated stainless steel and stainless steel archwires. The surface texture of the wire before and after friction test was also evaluated using a scanning electron microscope (SEM). Methodology A total of 48 samples were tested. In total, 12 premolar brackets each of stainless steel (Ortho technology, Carlsbad, CA, USA), monocrystalline ceramic (Ortho technology, Carlsbad, CA, USA), polycrystalline ceramic (Ortho technology, Carlsbad, CA, USA), and ceramic bracket with a metal slot (Ortho technology, Carlsbad, CA, USA) having an 0.022-inch slot were coupled with 0.019 × 0.025-inch stainless steel and Teflon-coated stainless steel wires. Each bracket-wire assembly was vertically mounted and clamped to the jaws of the universal testing machine. The wire was pulled across the bracket with a cross head speed of 10 mm per minute. The readings obtained were recorded. To evaluate the surface roughness, wires were examined using an SEM (in four magnifications 250×, 500×, 1,000×, and 5,000×) before and after testing. Results Under the testing conditions, the stainless steel bracket-stainless steel wire combination produced the least frictional resistance, and the polycrystalline ceramic bracket-stainless steel wire combination produced the highest frictional resistance. Ceramic brackets with a metal slot generated lesser friction than other types of ceramic brackets but more friction than stainless steel brackets. Moreover, for all bracket-archwire combinations, Teflon-coated wires generated reduced frictional resistance compared to stainless steel wires. The surface examination of Teflon-coated stainless steel wire and conventional uncoated stainless steel wire revealed that Teflon-coated wire had a smoother surface compared to uncoated stainless steel wire. Conclusions Within the limitations of this study, it was concluded that the stainless steel bracket produced the lowest frictional resistance and the polycrystalline ceramic bracket produced the highest frictional resistance. Ceramic brackets with a metal slot showed a coefficient of friction that was more than but comparable to that of stainless steel brackets. Monocrystalline ceramic brackets generated lesser friction compared to polycrystalline ceramic brackets. Further, Teflon coating of stainless steel archwires can reduce frictional resistance compared to conventional uncoated stainless steel archwires. The surface of Teflon-coated stainless steel wires was found to be smoother than uncoated stainless steel wires.

Subnuclear distribution of proteins: Links with genome architecture.

Metazoan genomes have a hierarchal 3-dimensional (3D) organization scaling from nucleosomes, loops, topologically associating domains (TADs), compartments, to chromosome territories. The 3D organization of genome has been linked with development, differentiation and disease. However, the principles governing the 3D chromatin architecture are just beginning to get unraveled. The nucleus has very high concentration of proteins and these proteins are either diffusely distributed throughout the nucleus, or aggregated in the form of foci/bodies/clusters/speckles or in combination of both. Several evidences suggest that the distribution of proteins within the nuclear space is linked to the organization and function of genome. Here, we describe advances made in understanding the relationship between subnuclear distribution of proteins and genome architecture.

Subclinical cardiovascular disease in patients with chronic obstructive pulmonary disease: a systematic review.

BACKGROUND: Cardiovascular disease (CVD) accounts for a significant portion of deaths in patients with COPD; however, evidence for early detection strategies for CVD in this population remain limited. Our paper aims to summarize existing data regarding subclinical CVD in patients with COPD with a view to identifying screening strategies in these patients. METHODS: A systematic review of published literature was conducted for studies examining the relationship of COPD and markers of subclinical disease such as coronary artery calcification (CAC), carotid intima media thickness (cIMT), endothelial dysfunction, arterial stiffness as measured by pulse wave velocity (PWV) and augmentation indices (AIx). Both MEDLINE and EMBASE databases were searched till October 2015. RESULTS: A total of 22 studies were included in the review. Compared with control subjects, patients with COPD had significantly higher cIMT (SMD 0.53, 95% CI 0.16-0.90), PWV (SMD 0.91, 95% CI 0.67-1.16) and AIx (SMD 0.86, 95% CI 0.52-1.19). Additionally, an overall higher prevalence of subclinical CVD as assessed by CAC, ABI and FMD was noted in our review. CONCLUSION: Although our findings need further evaluation in prospective studies, our review presents significant evidence in support of increased subclinical CVD burden in COPD patients independent of smoking status. Further large-scale case-control studies are required to highlight the significance of subclinical CVD screening in COPD patients.

Prognostic value of a cell cycle progression signature for prostate cancer death in a conservatively managed needle biopsy cohort.

BACKGROUND: The natural history of prostate cancer is highly variable and it is difficult to predict. We showed previously that a cell cycle progression (CCP) score was a robust predictor of outcome in a conservatively managed cohort diagnosed by transurethral resection of the prostate. A greater need is to predict outcome in patients diagnosed by needle biopsy. METHODS: Total RNA was extracted from paraffin specimens. A CCP score was calculated from expression levels of 31 genes. Clinical variables consisted of centrally re-reviewed Gleason score, baseline prostate-specific antigen level, age, clinical stage, and extent of disease. The primary endpoint was death from prostate cancer. RESULTS: In univariate analysis (n=349), the hazard ratio (HR) for death from prostate cancer was 2.02 (95% CI (1.62, 2.53), P<10(-9)) for a one-unit increase in CCP score. The CCP score was only weakly correlated with standard prognostic factors and in a multivariate analysis, CCP score dominated (HR for one-unit increase=1.65, 95% CI (1.31, 2.09), P=3 × 10(-5)), with Gleason score (P=5 × 10(-4)) and prostate-specific antigen (PSA) (P=0.017) providing significant additional contributions. CONCLUSION: For conservatively managed patients, the CCP score is the strongest independent predictor of cancer death outcome yet described and may prove valuable in managing clinically localised prostate cancer.

Investigation on reconstruction methods applied to 3D terahertz computed tomography.

3D terahertz computed tomography has been performed using a monochromatic millimeter wave imaging system coupled with an infrared temperature sensor. Three different reconstruction methods (standard back-projection algorithm and two iterative analysis) have been compared in order to reconstruct large size 3D objects. The quality (intensity, contrast and geometric preservation) of reconstructed cross-sectional images has been discussed together with the optimization of the number of projections. Final demonstration to real-life 3D objects has been processed to illustrate the potential of the reconstruction methods for applied terahertz tomography.

Characterization and anti-microbial susceptibility of gram-negative bacteria isolated from bloodstream infections of cancer patients on chemotherapy in Pakistan.

PURPOSE: Bloodstream infection remains a major cause of morbidity and mortality in patients undergoing treatment for cancer. Severe infections due to Gram-negative bacilli & staphylococci are common in cancer patients. Altered gut flora because of frequent antibiotic administration and damage of epithelial surfaces contribute to the development of infection. To access the use of new potent antibiotics against bloodstream infection in cancer patients and to determine the cross resistance of Gram-negative bacterial strains. MATERIALS AND METHODS: We studied the bacterial spectrum & antimicrobial susceptibility pattern of cephalosporins, fluoroquinolones, carbapenems and aminoglycosides against Gram-negative bacterial strains in cancer patients. The susceptibility was determined by broth dilution method according to National Committee for Clinical Laboratory Standards (NCCLS) now called Clinical Laboratory Standards Institute (CLSI) during study period (July 2006 to Jan 2007). RESULTS: A total of 60 Gram-negative bacterial blood cultures were examined. Among these, Pseudomonas aeruginosa was the most common (38%). The Minimum Inhibitory Concentration at which 50% (MIC 50 ) and 90% (MIC 90 ) of Enterobacteriaceae and P. aeruginosa inhibited were found. Resistance in P.aeruginosa against cefepime, meropenem, ciprofloxacin, ceftriaxone, tobramycin, cefoperazone and imipenem was 60%, 13%, 80%, 67%, 40%, 90% and 10% respectively while for Enterobacteriaceae 80%, 20%, 88%, 72%, 20%, 90% and four per cent resistance was observed. Meropenem was found to be the most effective antimicrobial against Gram-negative bacteria. CONCLUSION: High resistance observed in this study warrants the needs of surveillance of resistant pattern of antimicrobial agents. Due to increased level of drug resistance, carbapenem would be a prudent choice in high- risk cases.

Antimicrobial susceptibility patterns and characterization of clinical isolates of Staphylococcus aureus in immunocompromised cancer patients undergoing chemotherapy in Pakistan.

Cancer patients undergoing chemotherapy are highly prone to infections because of suppression of their immune system. in the present study, the activity of fluoroquinolones, cephalosporins, glycopeptides and oxazolidinones was evaluated in Staphylococcus aureus strains by broth dilution method according to Clinical and laboratory Standards institute (ClSi), USA guidelines. the frequency of methicillin-resistant S. aureus (mRSA) and methicillin-sensitive S. aureus (mSSA) strains was 67% and 33% respectively. The MIC(50 )and MIC(90 )of isolates were ciprofloxacin 8 and 32 microg/ml for mRSA, 8 and 16 microg/ml for mSSA, levofloxacin 8 and 16 microg/ml for mRSA and mSSA, gatifloxacin 4 and 16 microg/ml for mRSA and 4 and 8 microg/ml for mSSA. MIC(50 )and MIC(90 )of vancomycin and linzolid were 1 and 2 microg/ml, 2 and 4 microg/ml for both mRSA and mSSA strains respectively. this study shows a high prevalence of and resistance in mRSA. However, vancomycin and linezolid were highly active and could be used for treating mRSA infections.