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Miller EM, Bazrgari B, Nussbaum MA, Madigan ML.
J Biomech. 2013 Feb 22;46(4):801-5.
PMID: 23182221
The purpose of this study was to (1) compare trunk neuromuscular behavior between individuals with no history of low back pain (LBP) and individuals who experience exercise-induced LBP (eiLBP) when pain free, and (2) investigate changes in trunk neuromuscular behavior with eiLBP. Seventeen young adult males participated including eight reporting recurrent, acute eiLBP and nine control participants reporting no history of LBP. Intrinsic trunk stiffness and paraspinal muscle reflex delay were determined in both groups using sudden trunk flexion position perturbations 1-2 days following exercise when the eiLBP participants were experiencing an episode of LBP (termed post-exercise) and 4-5 days following exercise when eiLBP had subsided (termed post-recovery). Post-recovery, when the eiLBP group was experiencing minimal LBP, trunk stiffness was 26% higher in the eiLBP group compared to the control group (p=0.033) and reflex delay was not different (p=0.969) between groups. Trunk stiffness did not change (p=0.826) within the eiLBP group from post-exercise to post-recovery, but decreased 22% within the control group (p=0.002). Reflex delay decreased 11% within the eiLBP group from post-exercise to post-recovery (p=0.013), and increased 15% within the control group (p=0.006). Although the neuromuscular mechanisms associated with eiLBP and chronic LBP may differ, these results suggest that previously-reported differences in trunk neuromuscular behavior between individuals with chronic LBP and healthy controls reflect a combination of inherent differences in neuromuscular behavior between these individuals as well as changes in neuromuscular behavior elicited by pain.
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Langfitt MK, Halvorson JJ, Scott AT, Smith BP, Russell GB, Jinnah RH, Miller AN, Carroll EA.
J Orthop Trauma. 2013 Feb 20. [Epub ahead of print]
PMID: 23429175
OBJECTIVES:: To compare the efficacy of distal interlocking during intramedullary nailing using a freehand technique versus an electromagnetic field real time system (EFRTS). DESIGN:: Prospective, randomized controlled trial SETTING:: Level I academic trauma center PATIENTS/PARTICIPANTS:: Patients over the age of 18 who sustained a femoral or tibial shaft fracture amenable to antegrade intramedullary nailing were prospectively enrolled between August 2010 and November 2011. Exclusion criteria included injuries requiring retrograde nailing, and open wounds near the location of the distal interlocks (distal third of the femur, knee, or distal tibia). INTERVENTION:: Each patient had two distal interlocking screws placed: one utilizing the free-hand method and one utilizing EFRTS. MAIN OUTCOME MEASUREMENT:: Techniques were compared on procedural time and number of interlocking screw misses. Two time points were measured: time 1 (time to find perfect circles/time from wand placement to drill initiation); time 2 (drill initiation until completion of interlocking placement). RESULTS:: Twenty-four tibia and twenty-four femur fractures were studied. EFRTS proved faster at time 1 and 2 (p<0.0001 and p<0.0002), and total time (p<0.0001). This difference was larger for junior residents, though reached statistical significance for senior residents. Senior residents were faster with the freehand technique compared to junior residents (p<0.004), but the two were similar utilizing EFRTS (p=0.41). The number of misses was higher with freehand compared to EFRTS (p=0.02). CONCLUSION:: These results suggest that EFRTS is faster than the traditional freehand technique and results in fewer screw misses. LEVEL OF EVIDENCE:: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.
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Peiffer AM, Leyrer CM, Greene-Schloesser DM, Shing E, Kearns WT, Hinson WH, Tatter SB, Ip EH, Rapp SR, Robbins ME, Shaw EG, Chan MD.
Neurology. 2013 Feb 19;80(8):747-53.
PMID: 23390169
In a retrospective review to assess neuroanatomical targets of radiation-induced cognitive decline, dose volume histogram (DVH) analyses of specific brain regions of interest (ROI) are correlated to neurocognitive performance in 57 primary brain tumor survivors.
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Bowton DL, Hite RD, Martin RS, Sherertz R.
Respir Care. 2013 Feb 19. [Epub ahead of print]
PMID: 23431308
Background:Aspiration of colonized oropharyngeal secretions is a major factor in the pathogenesis of VAP. A tapered-cuff endotracheal tube has been demonstrated to reduce aspiration around the cuff.([1]) Whether these properties are efficacious in reducing VAP is not known.Methods:This two-period investigator-initiated observational study was designed to assess the efficacy of a tapered-cuff endotracheal tube to reduce the rate of VAP. All intubated, mechanically ventilated patients over the age of 18 were included. During the baseline period, a standard barrel cuff ETT (Mallinkrodt(™) Hi-Lo cuff, Covidien LLC, Mansfield, MA) was used. All endotracheal tubes throughout the hospital were then replaced with a tapered cuff ETT (TaperGuard(™) cuff, Covidien LLC, Mansfield, MA). The primary outcome variable was the incidence of VAP per 1,000 ventilator days.Results:2,849 patients, encompassing 15,250 ventilator days, were included. The mean monthly VAP rate (mean ± SD) was 3.29 ± 1.79/1000 ventilator days in the Standard Group and 2.77 ± 2.00/1000 ventilator days in the Taper Group (p=0.65). While compliance with the VAP prevention bundle was high throughout the study, bundle compliance was significantly higher during the Standard Group period than in the Taper Group period, 96.5±2.7% and 90.3±3.5% respectively (p=0.01).Conclusion:In the setting of a rate of VAP very near the average of ICUs in the United States and where there was high compliance with a VAP prevention bundle, the use of a tapered cuff endotracheal tube was not associated with a reduction in the rate of VAP.
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Plate JF, Mofidi A, Mannava S, Smith BP, Lang JE, Poehling GG, Conditt MA, Jinnah RH.
Adv Orthop. 2013;2013():837167.
PMID: 23634304
Unicompartmental knee arthroplasty (UKA) allows replacement of a single compartment in patients with limited disease. However, UKA is technically challenging and relies on accurate component positioning and restoration of natural knee kinematics. This study examined the accuracy of dynamic, real-time ligament balancing using a robotic-assisted UKA system. Surgical data obtained from the computer system were prospectively collected from 51 patients (52 knees) undergoing robotic-assisted medial UKA by a single surgeon. Dynamic ligament balancing of the knee was obtained under valgus stress prior to component implantation and then compared to final ligament balance with the components in place. Ligament balancing was accurate up to 0.53 mm compared to the preoperative plan, with 83% of cases within 1 mm at 0°, 30°, 60°, 90°, and 110° of flexion. Ligamentous laxity of 1.31 ± 0.13 mm at 30° of flexion was corrected successfully to 0.78 ± 0.17 mm (P < 0.05). Robotic-assisted UKA allows accurate and precise reproduction of a surgical balance plan using dynamic, real-time soft-tissue balancing to help restore natural knee kinematics, potentially improving implant survival and functional outcomes.
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Hayes AR, Gayzik FS, Moreno DP, Martin RS, Stitzel JD.
Comput Math Methods Med. 2013;2013():419821.
PMID: 23606901
The location and morphology of abdominal organs due to postural changes have implications in the prediction of trauma via computational models. The purpose of this study is to use data from a multimodality image set to devise a method for examining changes in organ location, morphology, and rib coverage from the supine to seated postures. Medical images of a male volunteer (78.6 ± 0.77 kg, 175 cm) in three modalities (Computed Tomography, Magnetic Resonance Imaging (MRI), and Upright MRI) were used. Through image segmentation and registration, an analysis between organs in each posture was conducted. For the organs analyzed (liver, spleen, and kidneys), location was found to vary between postures. Increases in rib coverage from the supine to seated posture were observed for the liver, with a 9.6% increase in a lateral projection and a 4.6% increase in a frontal projection. Rib coverage area was found to increase 11.7% for the spleen. Morphological changes in the organs were also observed. The liver expanded 7.8% cranially and compressed 3.4% and 5.2% in the anterior-posterior and medial-lateral directions, respectively. Similar trends were observed in the spleen and kidneys. These findings indicate that the posture of the subject has implications in computational human body model development.
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Ross CL, Harrison BS.
J Inflamm Res. 2013;6():45-51.
PMID: 23576877
In the treatment of bacterial infections, antibiotics have proven to be very effective, but the way in which antibiotics are dosed can create a lag time between the administration of the drug and its absorption at the site of insult. The time it takes an antibiotic to reach therapeutic levels can often be significantly increased if the vascular system is compromized. Bacteria can multiply pending the delivery of the drug, therefore, developing treatments that can inhibit the inflammatory response while waiting for antibiotics to take effect could help prevent medical conditions such as septic shock. The aim of this study was to examine the effect of a pulsed electromagnetic field on the production of inflammatory markers tumor necrosis factor (TNF), transcription factor nuclear factor kappa B (NFkB), and the expression of the A20 (tumor necrosis factor-alpha-induced protein 3), in an inflamed-cell model. Lipopolysaccharide-challenged cells were exposed to a pulsed electromagnetic field at various frequencies in order to determine which, if any, frequency would affect the TNF-NFkB-A20 inflammatory response pathway. Our study revealed that cells continuously exposed to a pulsed electromagnetic field at 5 Hz demonstrated significant changes in the downregulation of TNF-α and NFkB and also showed a trend in the down regulation of A20, as compared with controls. This treatment could be beneficial in modulating the immune response, in the presence of infection.
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Pareta RA, Farney AC, Opara EC.
Pathobiology. 2013;80(4):194-202.
PMID: 23652283
Islet transplantation has been shown to be a viable treatment option for patients afflicted with type 1 diabetes. However, the lack of availablity of human pancreases and the need to use risky immunosuppressive drugs to prevent transplant rejection remain two major obstacles to the routine use of islet transplantation in diabetic patients. Successful development of a bioartificial pancreas using the approach of microencapsulation with perm-selective coating of islets in hydrogels for graft immunoisolation holds tremendous promise for diabetic patients because it has great potential to overcome these two barriers. In this review article, we will discuss the need for a bioartificial pancreas, provide a detailed description of the microencapsulation process, and review the status of the technology in clinical development. We will also critically review the various factors that will need to be taken into consideration in order to achieve the ultimate goal of routine clinical application.
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Soland MA, Bego M, Colletti E, Zanjani ED, St Jeor S, Porada CD, Almeida-Porada G.
PLoS One. 2013;8(3):e60461.
PMID: 23555976
Mesenchymal stem cells (MSC) preferentially migrate to damaged tissues and, due to their immunomodulatory and trophic properties, contribute to tissue repair. Although MSC express molecules, such as membrane cofactor protein (CD46), complement decay-accelerating factor (CD55), and protectin (CD59), which confer protection from complement-mediated lysis, MSC are recruited and activated by anaphylatoxins after transplantation, potentially causing MSC death and limiting therapeutic benefit. We have previously demonstrated that transduction of MSC with a retrovirus encoding HCMV-US proteins resulted in higher levels of MSC engraftment due to decreased HLA-I expression. Here, we investigate whether engineering MSC to express US2 (MSC-US2), US3 (MSC-US3), US6 (MSC-US6), or US11 (MSC-US11) HCMV proteins can alter complement recognition, thereby better protecting MSC from complement attack and lysis. HCMV-US proteins increased MSC CD59 expression at different levels as determined by flow cytometric evaluation of the median fluorescence intensity ratio (MFI). A significant increase in CD59 expression was seen in MSC-US2, MSC-US3, and MSC-US6, but not in MSC-US11. Only MSC-US2 displayed increased expression of CD46, while US2 and US3 proteins were both able to augment the percentage of MSC expressing this molecule. Regardless of the HCMV protein expressed, none changed CD55 MFI; however, expression of US6, US11, and US2 each increased the percentage of MSC that were positive for this molecule. Because US2 protein was the most efficient in up-regulating all three complement regulatory proteins, we used a functional complement-mediated cytotoxicity assay to investigate whether MSC-US2 were protected from complement-mediated lysis. We demonstrated that over-expression of the US2 protein reduced complement lysis by 59.10±12.89% when compared to untransduced MSC. This is the first report, to our knowledge, describing a role of HCMV-US proteins in complement evasion, and our data shows that over-expression of US2 protein on MSC could serve as a strategy to protect these cells from complement lysis.
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Walker SJ, Fortunato J, Gonzalez LG, Krigsman A.
PLoS One. 2013;8(3):e58058.
PMID: 23520485
Gastrointestinal symptoms are common in children with autism spectrum disorder (ASD) and are often associated with mucosal inflammatory infiltrates of the small and large intestine. Although distinct histologic and immunohistochemical properties of this inflammatory infiltrate have been previously described in this ASD(GI) group, molecular characterization of these lesions has not been reported. In this study we utilize transcriptome profiling of gastrointestinal mucosal biopsy tissue from ASD(GI) children and three non-ASD control groups (Crohn's disease, ulcerative colitis, and histologically normal) in an effort to determine if there is a gene expression profile unique to the ASD(GI) group. Comparison of differentially expressed transcripts between the groups demonstrated that non-pathologic (normal) tissue segregated almost completely from inflamed tissue in all cases. Gene expression profiles in intestinal biopsy tissue from patients with Crohn's disease, ulcerative colitis, and ASD(GI), while having significant overlap with each other, also showed distinctive features for each group. Taken together, these results demonstrate that ASD(GI) children have a gastrointestinal mucosal molecular profile that overlaps significantly with known inflammatory bowel disease (IBD), yet has distinctive features that further supports the presence of an ASD-associated IBD variant, or, alternatively, a prodromal phase of typical inflammatory bowel disease. Although we report qPCR confirmation of representative differentially expressed transcripts determined initially by microarray, these findings may be considered preliminary to the extent that they require further confirmation in a validation cohort.
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Ma L, Murea M, Snipes JA, Marinelarena A, Krüger J, Hicks PJ, Langberg KA, Bostrom MA, Cooke JN, Suzuki D, Babazono T, Uzu T, Tang SC, Mondal AK, Sharma NK, Kobes S, Antinozzi PA, Davis M, Das SK, Rasouli N, Kern PA, Shores NJ, Rudel LL, Blüher M, Stumvoll M, Bowden DW, Maeda S, Parks JS, Kovacs P, Hanson RL, Baier LJ, Elbein SC, Freedman BI.
PLoS One. 2013;8(2):e56193.
PMID: 23460794
Acetyl coenzyme A carboxylase B gene (ACACB) single nucleotide polymorphism (SNP) rs2268388 is reproducibly associated with type 2 diabetes (T2DM)-associated nephropathy (DN). ACACB knock-out mice are also protected from obesity. This study assessed relationships between rs2268388, body mass index (BMI) and gene expression in multiple populations, with and without T2DM. Among subjects without T2DM, rs2268388 DN risk allele (T) associated with higher BMI in Pima Indian children (n = 2021; p-additive = 0.029) and African Americans (AAs) (n = 177; p-additive = 0.05), with a trend in European Americans (EAs) (n = 512; p-additive = 0.09), but not Germans (n = 858; p-additive = 0.765). Association with BMI was seen in a meta-analysis including all non-T2DM subjects (n = 3568; p-additive = 0.02). Among subjects with T2DM, rs2268388 was not associated with BMI in Japanese (n = 2912) or EAs (n = 1149); however, the T allele associated with higher BMI in the subset with BMI≥30 kg/m(2) (n = 568 EAs; p-additive = 0.049, n = 196 Japanese; p-additive = 0.049). Association with BMI was strengthened in a T2DM meta-analysis that included an additional 756 AAs (p-additive = 0.080) and 48 Hong Kong Chinese (p-additive = 0.81) with BMI≥30 kg/m(2) (n = 1575; p-additive = 0.0033). The effect of rs2268388 on gene expression revealed that the T risk allele associated with higher ACACB messenger levels in adipose tissue (41 EAs and 20 AAs with BMI>30 kg/m(2); p-additive = 0.018) and ACACB protein levels in the liver tissue (mixed model p-additive = 0.03, in 25 EA bariatric surgery patients with BMI>30 kg/m(2) for 75 exams). The T allele also associated with higher hepatic triglyceride levels. These data support a role for ACACB in obesity and potential roles for altered lipid metabolism in susceptibility to DN.
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Eckman DM, Stacey RB, Rowe R, D'Agostino R, Kock ND, Sane DC, Torti FM, Yeboah J, Workman S, Lane KS, Hundley WG.
PLoS One. 2013;8(2):e57554.
PMID: 23437398
Doxorubicin (DOX) is associated with premature cardiovascular events including myocardial infarction. This study was performed to determine if the weekly administration of DOX influenced coronary arteriolar medial and/or adventitial wall thickening.
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Andersson KE.
Ther Clin Risk Manag. 2013;9():161-70.
PMID: 23637536
In the last few years, much new information has been generated on the pathophysiology, possible therapeutic targets, and pharmacologic treatment of overactive bladder (OAB). Antimuscarinic drugs are still first-line pharmacologic treatment for OAB and often have good initial response rates, but adverse effects and decreasing efficacy cause long-term compliance problems, prompting a search for new therapeutic alternatives. Mirabegron and onabotulinumtoxinA, two drugs with different mechanisms of action, and with adverse effect profiles different from those of antimuscarinics, were recently approved for treatment of OAB. However, their place in the treatment of this disorder has not yet been established. In this short review, the mechanisms of action, clinical efficacy, and safety profiles of these drugs are discussed and compared with those of the current gold standard, antimuscarinic agents.
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