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Smith WK, Berry ZC.
Tree Physiol. 2013 Mar ;33(3):233-7.
PMID: 23438468
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Arcury TA, Grzywacz JG, Sidebottom J, Wiggins MF.
Am J Ind Med. 2013 Feb 28. [Epub ahead of print]
PMID: 23450742
BACKGROUND: Manual labor in the Agriculture, Forestry, and Fishing (AgFF) Sector is provided primarily by immigrant workers. Limited information is available that documents the demographic characteristics of these manual workers, the occupational illnesses, injuries and fatalities they experience; or the risk factors to which they are exposed. METHODS: A working conference of experts on occupational health in the AgFF Sector was held to address information limitations. This paper provides an overview of the conference. Other reports address organization of work, health outcomes, healthcare access, and safety policy. CONTENTS: This report addresses how best to define the population and the AgFF Sector, occupational exposures for the sector, data limitations, characteristics of immigrant workers, reasons for concern for immigrant workers in the AgFF Sector, regulations, a conceptual model for occupational health, and directions for research and intervention. Am. J. Ind. Med. © 2013 Wiley Periodicals, Inc.
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Quandt SA, Kucera KL, Haynes C, Klein BG, Langley R, Agnew M, Levin JL, Howard T, Nussbaum MA.
Am J Ind Med. 2013 Feb 28. [Epub ahead of print]
PMID: 23450720
BACKGROUND: Workers in the Agriculture, Forestry, and Fisheries (AgFF) sector experience exposures directly related to the work itself, as well as the physical environment in which the work occurs. Health outcomes vary from immediate to delayed, and from acute to chronic. METHODS: We reviewed existing literature on the health outcomes of work in the AgFF sector and identified areas where further research is needed to understand the impact of these exposures on immigrant Latino workers in the southeastern US. RESULTS: Outcomes related to specific body systems (e.g., musculoskeletal, respiratory) as well as particular exposure sources (e.g., pesticides, noise) were reviewed. The most extensive evidence exists for agriculture, with a particular focus on chemical exposures. Little research in the southeastern US has examined health outcomes of exposures of immigrant workers in forestry or fisheries. CONCLUSION: As the AgFF labor force includes a growing number of Latino immigrants, more research is needed to characterize a broad range of exposures and health outcomes experienced by this population, particularly in forestry and fisheries. Am. J. Ind. Med. © 2013 Wiley Periodicals, Inc.
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Young L, Kemper KJ.
J Altern Complement Med. 2013 Feb 28. [Epub ahead of print]
PMID: 23448120
Abstract Objectives: Although pediatric patients with chronic pain often turn to complementary therapies, little is known about patients who seek academic integrative pediatric care. Design: The study design comprised abstraction of intake forms and physician records from new patients whose primary concern was pain. Setting/location: The study setting was an academic pediatric clinic between January 2010 and December 2011. Subjects: Of the 110 new patients, 49 (45%) had a primary concern about headache (20), abdominal pain (18), or musculoskeletal pain (11). Results: The average age was 13±4 years, and 37% were male. Patients reported an average pain level of 6±3 on a 10-point scale, and most reported more than one kind of pain; parents had an average of 7±3 health concerns per child, including fatigue (47%), mood or anxiety (45%), constipation/diarrhea (41%), and/or sleep problems (35%). Most patients (57%) were referred by specialists; 71% were taking prescription medications; and 53% were taking one or more dietary supplements at intake. Of those tested, most (61%) had suboptimal vitamin D levels. All families wanted additional counseling about diet (76%), exercise (66%), sleep (58%), and/or stress management (81%). In addition to encouraging continued medical care (100%) and referral to other medical specialists (16%), frequent advice included continuing or initiating dietary supplements such as vitamins/minerals (80%), omega-3 fatty acids (67%), and probiotics (31%). Stress-reducing recommendations included biofeedback (33%), gratitude journals (16%), and yoga/t'ai chi (8%). Other referrals included acupuncture (24%) and massage (20%). Discussion: Patients who have chronic pain and who present to an integrative clinic frequently have complex conditions and care. They are interested in promoting a healthy lifestyle, reducing stress, and using selected complementary therapies. Conclusion: Patients with chronic pain who seek integrative care may benefit from the kind of coordinated, integrated, comprehensive care provided in a medical home.
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Liu J, Argenta L, Morykwas M, Wagner WD.
J Biomater Appl. 2013 Feb 28. [Epub ahead of print]
PMID: 23449680
Single nanofibers with chemical and functional properties consistent with artery extracellular matrix nanofibers were produced by electrospinning. Using weight ratios to mimic artery extracellular matrix, five materials were tested: (1) Collagen type I, (2) Collagen type I + Collagen type III, (3) Collagen type I + poly (diol citrate), (4) Collagen type I + Collagen type III + poly (diol citrate), and (5) Collagen type I + poly (diol citrate) + Decorin + Aggrecan. Fiber sizes for all materials ranged from 50 nm to 600 nm and random fiber mats had pore sizes from 21 to 40 = m(2) and porosities of 72-84%. Human embryonic palatal mesenchymal cells fibroblasts adhered to all fibers and proliferated over a 7-day study period. Mechanical properties of single fibers were investigated using a combined atomic force/optical microscope. Materials containing poly (diol citrate) showed elasticity increased 3.2 fold greater than composites without poly (diol citrate). Maximum stress was within functional range in comparison to decellularized artery extracellular matrix fibers. By incorporating poly (diol citrate) and proteoglycan along with collagen, a viscoelastic nanofibrous material was produced for use in tissues such as artery where viscoelasticity and tensile strength are required.
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Yang Q, Ayers K, Chen Y, Helderman J, Welch CD, O'Shea TM.
J Pediatr. 2013 Feb 28. [Epub ahead of print]
PMID: 23453547
OBJECTIVE: To test the hypothesis that in the premature infant with an enterostomy, early enteral supplementation with Microlipid (fat supplement) and fish oil increases enteral fat absorption and decreases the requirement for Intralipid (intravenous fat emulsion). STUDY DESIGN: Premature infants (<2 months old) with an enterostomy after surgical treatment for necrotizing enterocolitis or spontaneous intestinal perforation and tolerating enteral feeding at 20 mL/kg/day were randomized to usual care (control 18 infants) or early supplementing enteral fat and fish oil (treatment 18 infants). Intravenous fat emulsion was decreased as enteral fat intake was increased. Daily weight, ostomy output, and nutrition data were recorded. Weekly 24-hour ostomy effluent was collected until bowel reanastomosis, and fecal fat, fecal liquid, and dry feces were measured. Fat absorption (g/kg/d) was calculated by subtracting fecal fat from dietary fat. The fecal liquid and dry feces were reported as mg/g wet stool. Date were analyzed by using ANOVA and mixed-effects model. RESULTS: The interval from initial postoperative feeding to bowel reanastomosis varied from 2 to 10 weeks. The treatment group received more dietary fat and less intravenous fat emulsion and had higher enteral fat absorption, less fecal liquid, and drier feces than the control group. These effects were greater among infants with a high ostomy compared with those with a low ostomy. Enteral fat intake was significantly correlated with fat absorption. CONCLUSION: Early enteral fat supplement and fish oil increases fat absorption and decreases the requirement for intravenous fat emulsion. This approach could be used to promote bowel adaptation and reduce the use of intravenous fat emulsion in the premature infant with an enterostomy.
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Andersson KE, Martin N, Nitti V.
J Urol. 2013 Feb 28. [Epub ahead of print]
PMID: 23458471
BACKGROUND AND PURPOSE: Bladder effects of isoprenaline and selective β1- and β2-adrenoceptor (AR) agonists reported in early studies suggested that bladder β-ARs are "atypical". Since there is a lack of alternatives to antimuscarinics in the treatment of overactive bladder (OAB) symptoms, there has been an intensive search for new drug targets. The discovery of the β3-AR with high expression in the bladder, suggested that this receptor, mediating detrusor relaxation, could be a target for treatment of patients with OAB symptoms. METHODS: An overview of published literature on β-ARs and bladder (MEDLINE) was performed. The US Food and Drug Administration web site, clinicaltrials.gov, and controlled-trials.com online trial registries were searched for English-language articles containing the terms β3-ARs and β3-AR agonists. In addition, abstracts from recent international scientific meetings were searched for randomised controlled trials (RCTs) on β3-AR agonists. RESULTS: Stimulation of β3-ARs relaxes detrusor smooth muscle, decreases afferent signaling from the bladder, improves bladder compliance on filling, and increases bladder capacity. RCTs show that the selective β3-AR agonist, mirabegron, for which most information is available and which is approved in Japan, USA, and Europe, reduces the number of micturitions and incontinence episodes in a 24-h period compared with placebo. The most common adverse effects recorded are dry mouth (placebo level) and gastrointestinal disturbances rated as mild to moderate. Small rises in mean heart rate (1 beat /minute) and blood pressure (1 mm Hg) have been demonstrated in OAB patients. CONCLUSIONS: Available information suggests that β3-AR agonists may be a promising alternative to antimuscarinics in the treatment of OAB. However, further clinical experiences outside clinical trials, and information on the long-term use in terms of efficacy, safety, and tolerability are warranted to optimally characterize the position of β3-AR agonists in the treatment algorithm for OAB.
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Marchant B, Sheele JM.
J Emerg Med. 2013 Feb 27. [Epub ahead of print]
PMID: 23453428
BACKGROUND: Pneumocephalus is rare, mostly arising as a complication of surgery, trauma, infection, or neoplasm. OBJECTIVE: Our aim was to briefly discuss the etiology and Emergency Department evaluation of patients with pneumocephalus. CASE REPORT: We present a case of a spontaneous esophageal-arachnoid fistula in a patient with stage IV non-small cell carcinoma leading to spontaneous pneumocephalus with resulting meningitis and death. CONCLUSIONS: Although usually asymptomatic, pneumocephalus can lead to tension pneumocephalus, a potentially fatal condition, or septic meningitis, if it is the result of infection from gas-producing bacteria.
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Choi JS, Kim EY, Kim MJ, Khan FA, Giegengack M, D'Agostino R, Criswell T, Khang G, Soker S.
Cell Transplant. 2013 Feb 26. [Epub ahead of print]
PMID: 23461892
Corneal transplantation is a common transplant procedure used to improve visual acuity by replacing the opaque or distorted host tissue with clear healthy donor tissue. However, its clinical utility is limited due to a lack of donor supply of high quality corneas. Bioengineered neo-corneas, created using an expandable population of human donor-derived corneal endothelial cells (HCECs), could address this shortage. Thus, the objective of this study was to evaluate HCEC sourcing with various isolation methods, including enzymatic digestion, culture medium components, and adhesive proteins. HCECs were obtained from corneas obtained from various aged donors after endothelial keratoplasty. Under a dissection microscope, the Descemet's membrane, including the attached corneal endothelium was stripped from the stroma and the cells were isolated and expanded by explant culture or by enzymatic digestion with enzymes such as collagenase II, dispase, or trypsin. In order to improve the initial cell attachment, tissue culture plates were coated with collagen IV, fibronectin, or fibronectin-collagen combination coating mix (FNC) before cell plating. We were able to successfully HCECs from 32% (86/269) of donor corneas. Donor age and isolation method influenced the characteristics of the resulting in vitro HCEC culture. Under all conditions tested, FNC-coated plates showed higher quality cultures than the other coatings tested. These results suggested that donor age and HCEC isolation methodology are the two factors that most directly affect the quality of the resulting HCEC culture in vitro. These factors should guide the methodological development for the clinical expansion of HCECs for the generation of bioengineered neo-corneas.
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Ravish ME, Krowchuk DP, Zapadka M, Shetty AK.
J Emerg Med. 2013 Feb 26. [Epub ahead of print]
PMID: 23485263
BACKGROUND: Rocky Mountain spotted fever (RMSF) is a well-described, potentially lethal, tick-borne zoonotic infection and has very effective therapy. However, the diagnosis might not be made early enough, often leading to worse outcomes. OBJECTIVE: Our aim was to discuss the diagnostic dilemmas facing the physician when evaluating patients with suspected RMSF. METHODS: We report a case of RMSF in a 6-year-old girl who presented to our hospital with a 7-day history of fever, headache, and a petechial rash. After blood cultures were obtained, the patient was treated empirically with doxycycline, vancomycin, and ceftriaxone. During the next 24 h, her clinical status worsened, with acute onset of altered mental status, posturing, and fixed and dilated pupils. A computed tomography scan of the brain demonstrated diffuse cerebral edema with evidence of tonsillar herniation. She died 24 h after admission. A serum specimen tested positive for immunoglobulin G to Rickettsia rickettsii at a titer of 128 dilutions, confirming recent infection. CONCLUSIONS: We present this case to raise awareness of RMSF in patients who present with a nonspecific febrile illness in tick-endemic areas in the United States. Early diagnosis and treatment with doxycycline before day 5 of illness is essential and can prevent morbidity and mortality.
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Manny T, Krane LS, Hemal AK.
J Endourol. 2013 Feb 26. [Epub ahead of print]
PMID: 23442199
INTRODUCTION: Indocyanine Green (ICG) is emerging as a potential adjunct to robotic partial nephrectomy by its ability to aide in the real-time identification of renal vasculature, renal masses, and the renal mass-parenchymal margin. The fluorescence patterns of renal masses have not been adequately described according to histology and it remains unknown if fluorescence pattern can reliably predict histology or malignancy. We therefore describe the ICG fluorescence pattern of our first 100 robotic partial nephrectomies and correlate with histology. METHODS: We reviewed our prospective robotic partial nephrectomy database and categorized fluoresce pattern as isofluoresent (same as surrounding parenchyma), hypofluorescent (less than surrounding parenchyma, but with uptake), or afluorescent (no visable uptake of dye). Descriptive statistics were applied. RESULTS: All 14 cystic lesions were afluorescent, and comprised 9 malignant and 5 benign masses. Eighty-six lesions were solid, of which 3 were isofluorescent including two clear cell and one translocation tumor. The remaining 83 solid lesions were hypoflurescent and included 65 malignant and 18 benign lesions. Clear cell was the most common histology of which 96% were hypofluorescent and 4% isofluorescent. In determining malignant vs. benign lesions, hypofluorescence had a positive predictive value of 87%, negative predictive value of 52%, sensitivity of 84% and specificity of 57%. CONCLUSIONS: A three grade classification of renal mass ICG fluorescence pattern is correlated with some histologic findings, but unable to reliably predict malignant versus benign lesions.
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Schirillo JA.
Psychon Bull Rev. 2013 Feb 23. [Epub ahead of print]
PMID: 23435628
In studies of lightness and color constancy, the terms lightness and brightness refer to the qualia corresponding to perceived surface reflectance and perceived luminance, respectively. However, what has rarely been considered is the fact that the volume of space containing surfaces appears neither empty, void, nor black, but filled with light. Helmholtz (1866/1962) came closest to describing this phenomenon when discussing inferred illumination, but previous theoretical treatments have fallen short by restricting their considerations to the surfaces of objects. The present work is among the first to explore how we infer the light present in empty space. It concludes with several research examples supporting the theory that humans can infer the differential levels and chromaticities of illumination in three-dimensional space.
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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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Espeland MA, Pettinger M, Falkner KL, Shumaker SA, Limacher M, Thomas F, Weaver KE, Stefanick ML, McQuellon C, Hunt JR, Johnson KC.
Clin Trials. 2013;10(3):463-72.
PMID: 23480899
After clinical trials end, continued follow-up of the assembled cohort often is desirable for additional research. Factors influencing participants' decisions to consent to additional follow-up and how these shape posttrial cohorts have not been broadly studied.
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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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