UCI Authors in PubMed
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Huckaby MC,Kruse D,Gibbs LH School of Medicine, University of California Irvine, Irvine, CA, USA. |
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MRI findings of bilateral proximal radial physeal injury in a gymnast. Pediatr Radiol. 2012 Jun 20;: Recent advances in imaging techniques shed light on anatomical variants considered normal historically in medical literature. We present an 11-year-old gymnast with unilateral left elbow pain and unusual symmetrical radiographic findings of both elbows that initially raised the question of normal variant cleft epiphysis of the proximal radius. Further imaging with MRI demonstrated bilateral elbow injury that is likely repetitive and chronic rather than an anatomical variant. Post-treatment MRI showed improved changes with rest and non-steroidal anti-inflammatory medications. These findings emphasize the need for vigilance and further investigation when diagnosing a normal variant, particularly in an athlete. PMID: 22714002 |
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Freites JA,Schow EV,White SH,Tobias DJ Department of Chemistry, University of California, Irvine, California. |
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Microscopic origin of gating current fluctuations in a potassium channel voltage sensor. Biophys J. 2012 Jun 6;102(11):L44-6 Voltage-dependent ion channels open and close in response to changes in membrane electrical potential due to the motion of their voltage-sensing domains (VSDs). VSD charge displacements within the membrane electric field are observed in electrophysiology experiments as gating currents preceding ionic conduction. The elementary charge motions that give rise to the gating current cannot be observed directly, but appear as discrete current pulses that generate fluctuations in gating current measurements. Here we report direct observation of gating-charge displacements in an atomistic molecular dynamics simulation of the isolated VSD from the KvAP channel in a hydrated lipid bilayer on the timescale (10-μs) expected for elementary gating charge transitions. The results reveal that gating-charge displacements are associated with the water-catalyzed rearrangement of salt bridges between the S4 arginines and a set of conserved acidic side chains on the S1-S3 transmembrane segments in the hydrated interior of the VSD. PMID: 22713585 |
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Ahdout J,Kotlerman J,Elashoff D,Kim J,Chiu MW Department of Dermatology, University of California, Irvine, CA, USA Department of Medicine Statistics Core Division of Dermatology, Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA Dermatology Service, Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, CA, USA. |
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Modifiable lifestyle factors associated with metabolic syndrome in patients with psoriasis. Clin Exp Dermatol. 2012 Jul;37(5):477-83 Background. Psoriasis is a chronic inflammatory skin disease, which is associated with obesity and with cardiovascular morbidity and mortality. Aim. To evaluate modifiable lifestyle factors including stress level, physical activity and nutrition, which may be associated with metabolic syndrome in patients with psoriasis. Methods. In total, 65 patients with psoriasis and 52 control subjects from our university dermatology clinic were enrolled in this case-control pilot study. The study questionnaire included the Perceived Stress Scale (PSS), the Godin Leisure-Time Exercise Questionnaire (GLTEQ) and the Rapid Eating Assessment for patients (REAP). For subjects with psoriasis, the Psoriasis Area and Severity Index (PASI) was measured. Results. Subjects with psoriasis (mean BMI 27.72) displayed a trend towards a higher BMI compared with controls (mean BMI 25.67). Subjects with psoriasis were not found to have an increased prevalence of self-reported metabolic syndrome-associated diseases including diabetes, heart disease, high cholesterol, hypertension or stroke compared with controls (P = 0.25, P = 0.46, P = 0.96, P = 0.26, and P = 0.16, respectively). There was no significant difference in exercise or stress between patients with psoriasis and controls (P = 0.06 and P = 0.26, respectively). However, compared with controls, subjects with psoriasis (mean REAP score = 2.23) did report poorer overall nutrition as assessed by the REAP score (mean = 2.38, P < 0.01). Among subjects with psoriasis, the factors of stress, smoking and systemic therapy were associated with increased PASI (r = 0.13, r = 3.47 and r = 3.19, respectively). Conclusions. Our study suggests that poor dietary and exercise habits may be factors contributing to obesity and metabolic syndrome in patients with psoriasis. Further studies with larger numbers are needed to confirm these results. PMID: 22712856 |
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Kaplan AG,Abdelshehid C,Alipanah N,Zamansani T,Lee J,Kolla S,Sountoulides P,Graversen JA,Lusch A,Kaufmann O,Louie MK,Clayman R,McDougall EM University of California, Irvine, Urology, 92868, California, United States; kaplana@uci.edu. |
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Genitourinary Exam Skills Training Curriculum for Medical Students: A Follow-up Study of Comfort and Skill Utilization. J Endourol. 2012 Jun 19;: PURPOSE: We developed a Genitourinary skills training curriculum (GUST) for incoming third year medical students (MS3) and performed a follow-up study of comfort with and utilization of these skills. METHODS: GUST consisted of a didactic lecture followed by skills sessions including standardized patient testicular exam (TE) and rectal exam (DRE), male and female Foley catheter placement training (MFC & FFC), suture-knot tying and a faculty-directed small group learning session. Pre & Post-course, and 6 & 18 months after the course, MS3 rated comfort with each skill (Likert scale 0-5), and quantified skill usage. Results were compared to 4th year students (MS4) who had not undergone GUST. RESULTS: 281 MS3 GUST students and 44 MS4 participated. Post-GUST, mean comfort on a Likert scale (0 =uncomfortable) increased for all 4 skills (88.2%-96.9% v. 8.3%-18.5%, p PMID: 22712690 |
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Stephenson ML,Powers BL,Wing DA Department of Obstetrics and Gynecology, University of California, Irvine, CA. |
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Fetal Heart Rate and Cardiotocographic Abnormalities with Varying Dose Misoprostol Vaginal Inserts. J Matern Fetal Neonatal Med. 2012 Jun 19;: Abstract OBJECTIVE: Characterize the incidence and timing of fetal heart rate (FHR) and cardiotocographic abnormalities (CTG) associated with the misoprostol vaginal insert (MVI) during labor induction. METHODS: This secondary analysis of data from the MVI Trial, a multi-site, double-masked, randomized trial of 374 women assigned to MVI 100, 150 or 200 mcg requiring cervical ripening before labor induction evaluated the incidence and clinical outcomes associated with FHR and CTG abnormalities diagnosed using 1997 NICHD definitions. RESULTS: MVI 200 was associated with an increased rate of tachysystole versus MVI 100 (p < 0.001, RR 2.11, 95% CI 1.39, 3.22) but not MVI 150 (p=0.29, RR 1.31, 95% CI 0.82, 2.11). Tachysystole occurred with the drug in situ in 17 (14.4%) and 50 (38.2%) of MVI 100 and 200 subjects, respectively (p PMID: 22712609 |
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Timberlake DS,Wu J,Al-Delaimy WK Program in Public Health, College of Health Sciences, University of California, Irvine, Anteater Instruction & Research Building, Irvine, CA 92697-3957, USA. dtimberl@uci.edu |
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Tribal casinos in California: the last vestige of indoor smoking. BMC Public Health. 2012;12:144 High levels of airborne particles from secondhand smoke have been reported in California Indian casinos. Yet, little is known regarding the smoking status of casino patrons, their avoidance of secondhand smoke while visiting, and their views on a hypothetical smoking ban. PMID: 22364487 |
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Michels TD,Dowling MS,Vanderwal CD 1102 Natural Sciences II, Department of Chemistry, University of California, Irvine, Irvine, CA 92697-2025 (USA) http://chem.ps.uci.edu/~cdv. |
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A Synthesis of Echinopine B. Angew Chem Int Ed Engl. 2012 Jun 18;: In a short synthesis of echinopine B, a guaiane-like intermediate was generated through a methylenecyclopentane annulation onto a substituted cycloheptenone. The resulting bicyclic compound was converted into the natural product by a PtCl(2) -catalyzed enyne cycloisomerization. Several late-stage polycyclic rearrangement products were isolated and characterized. PMID: 22711188 |
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Marshall JF,O'Dell SJ Department of Neurobiology and Behavior, Center for Neurobiology of Learning and Memory, University of California, Irvine, CA 92697, USA. |
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Methamphetamine influences on brain and behavior: unsafe at any speed? Trends Neurosci. 2012 Jun 16;: Methamphetamine damages monoamine-containing nerve terminals in the brains of both animals and human drug abusers, and the cellular mechanisms underlying this injury have been extensively studied. More recently, the growing evidence for methamphetamine influences on memory and executive function of human users has prompted studies of cognitive impairments in methamphetamine-exposed animals. After summarizing current knowledge about the cellular mechanisms of methamphetamine-induced brain injury, this review emphasizes research into the brain changes that underlie the cognitive deficits that accompany repeated methamphetamine exposure. Novel approaches to mitigating or reversing methamphetamine-induced brain and behavioral changes are described, and it is argued that the slow spontaneous reversibility of the injury produced by this drug may offer opportunities for novel treatment development. PMID: 22709631 |
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So L,Fruman DA Department of Molecular Biology and Biochemistry, University of California, Irvine, 92697, USA. |
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PI3K signalling in B- and T-lymphocytes: new developments and therapeutic advances. Biochem J. 2012 Mar 15;442(3):465-81 Activation of PI3K (phosphoinositide 3-kinase) is a shared response to engagement of diverse types of transmembrane receptors. Depending on the cell type and stimulus, PI3K activation can promote different fates including proliferation, survival, migration and differentiation. The diverse roles of PI3K signalling are well illustrated by studies of lymphocytes, the cells that mediate adaptive immunity. Genetic and pharmacological experiments have shown that PI3K activation regulates many steps in the development, activation and differentiation of both B- and T-cells. These findings have prompted the development of PI3K inhibitors for the treatment of autoimmunity and inflammatory diseases. PI3K activation, however, has both positive and negative roles in immune system activation. Consequently, although PI3K suppression can attenuate immune responses it can also enhance inflammation, disrupt peripheral tolerance and promote autoimmunity. An exciting discovery is that a selective inhibitor of the p110δ catalytic isoform of PI3K, CAL-101, achieves impressive clinical efficacy in certain B-cell malignancies. A model is emerging in which p110δ inhibition disrupts signals from the lymphoid microenvironment, leading to release of leukaemia and lymphoma cells from their protective niche. These encouraging findings have given further momentum to PI3K drug development efforts in both cancer and immune diseases. PMID: 22364281 |
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Delisle Milton RC,Milton SC,Chamberlin AR Department of Pharmaceutical Sciences, University of California at Irvine, Irvine, CA 92697, USA. |
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Improving the Fmoc Solid Phase Synthesis of the Cyclic Hexapeptide Complement C5a Antagonist, PMX205. Int J Pept Res Ther. 2011 Dec;17(4):337-342 The anti-inflammatory drug, PMX205, is an antagonist of the C5a complement receptor and has been shown to be effective in rodent models of amyotrophic lateral sclerosis and Alzheimer's disease. This cyclic hexapeptide (c[Arg-Trp-D-Cha-Pro-Orn]-Hca) has been reported to produce relatively low yields for both the linear peptide assembly and the cyclization reaction in solution and solid phase syntheses. During attempts to reproduce the solid phase methodology, a catastrophic loss of substitution was encountered which could be avoided or reduced by the use of 2-chlorotrityl resin. Likewise, the cyclization reaction could be significantly improved by the use of FDPP (pentafluorophenyl diphenylphosphinate) at high dilution (up to 80% purified yield). Both improvements are accomplished with commercially available products. PMID: 22707924 |
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Kaneko TS,Sehgal V,Skinner HB,Al-Ghazi MS,Ramsinghani NS,Marquez Miranda M,Keyak JH Department of Radiological Sciences, B140 Med Sci I, University of California, Irvine, CA 92697, USA. |
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Radioactive bone cement for the treatment of spinal metastases: a dosimetric analysis of simulated clinical scenarios. Phys Med Biol. 2012 Jun 15;57(13):4387-4401 Vertebral metastases are a common manifestation of many cancers, potentially leading to vertebral collapse and neurological complications. Conventional treatment often involves percutaneous vertebroplasty/kyphoplasty followed by external beam radiation therapy. As a more convenient alternative, we have introduced radioactive bone cement, i.e. bone cement incorporating a radionuclide. In this study, we used a previously developed Monte Carlo radiation transport modeling method to evaluate dose distributions from phosphorus-32 radioactive cement in simulated clinical scenarios. Isodose curves were generally concentric about the surface of bone cement injected into cadaveric vertebrae, indicating that dose distributions are relatively predictable, thus facilitating treatment planning (cement formulation and dosimetry method are patent pending). Model results indicated that a therapeutic dose could be delivered to tumor/bone within ∼4 mm of the cement surface while maintaining a safe dose to radiosensitive tissue beyond this distance. This therapeutic range should be sufficient to treat target volumes within the vertebral body when tumor ablation or other techniques are used to create a cavity into which the radioactive cement can be injected. With further development, treating spinal metastases with radioactive bone cement may become a clinically useful and convenient alternative to the conventional two-step approach of percutaneous strength restoration followed by radiotherapy. PMID: 22705967 |
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Kosins AM,Scholz T,Lin M,Evans GR,Keirstead HS Reeve-Irvine Research Center, Irvine, CA, USA. akosins@uci.edu |
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Immunological demyelination enhances nerve regeneration after acute transection injury in the adult rat sciatic nerve. Ann Plast Surg. 2012 Mar;68(3):290-4 Our recent experiments demonstrate that demyelination enhances peripheral nerve regeneration after contusion injury in the adult rat sciatic nerve. The role of demyelination in peripheral nerve regeneration in a sciatic nerve transection model has yet to be elucidated. We hypothesize that (1) axon regeneration within a region of injury increases after experimental, immunologic demyelination, and (2) regenerated axons are partially derived from the proximal motor axons. PMID: 22356781 |
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King CE,Wang PT,Mizuta M,Reinkensmeyer DJ,Do AH,Moromugi S,Nenadic Z Department of Biomedical Engineering, University of California, Irvine, CA 92697, USA. kingce@uci.edu |
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Noninvasive brain-computer interface driven hand orthosis. Conf Proc IEEE Eng Med Biol Soc. 2011;2011:5786-9 Neurological conditions, such as stroke, can leave the affected individual with hand motor impairment despite intensive treatments. Novel technologies, such as brain-computer interface (BCI), may be able to restore or augment impaired motor behaviors by engaging relevant cortical areas. Here, we developed and tested an electroencephalogram (EEG) based BCI system for control of hand orthosis. An able-bodied subject performed contralateral hand grasping to achieve continuous online control of the hand orthosis, suggesting that the integration of a noninvasive BCI with a hand orthosis is feasible. The adoption of this technology to stroke survivors may provide a novel neurorehabilitation therapy for hand motor impairment in this population. PMID: 22255655 |
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Daily K,Patel VR,Rigor P,Xie X,Baldi P Department of Computer Science, University of California Irvine, Irvine, CA 92697, USA. |
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MotifMap: integrative genome-wide maps of regulatory motif sites for model species. BMC Bioinformatics. 2011;12:495 A central challenge of biology is to map and understand gene regulation on a genome-wide scale. For any given genome, only a small fraction of the regulatory elements embedded in the DNA sequence have been characterized, and there is great interest in developing computational methods to systematically map all these elements and understand their relationships. Such computational efforts, however, are significantly hindered by the overwhelming size of non-coding regions and the statistical variability and complex spatial organizations of regulatory elements and interactions. Genome-wide catalogs of regulatory elements for all model species simply do not yet exist. PMID: 22208852 |
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Dervillez X,Gottimukkala C,Kabbara KW,Nguyen C,Badakhshan T,Kim SM,Nesburn AB,Wechsler SL,Benmohamed L Laboratory of Cellular and Molecular Immunology, University of California Irvine, School of Medicine, Irvine, CA 92697. |
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Future of an "Asymptomatic" T-cell Epitope-Based Therapeutic Herpes Simplex Vaccine. Future Virol. 2012 Apr 1;7(4):371-378 Considering the limited success of the recent herpes clinical vaccine trial [1], new vaccine strategies are needed. Infections with herpes simplex virus type 1 and type 2 (HSV-1 & HSV-2) in the majority of men and women are usually asymptomatic and results in lifelong viral latency in neurons of sensory ganglia (SG). However, in a minority of men and women HSV spontaneous reactivation can cause recurrent disease (i.e., symptomatic individuals). Our recent findings show that T cells from symptomatic and asymptomatic men and women (i.e. those with and without recurrences, respectively) recognize different herpes epitopes. This finding breaks new ground and opens new doors to assess a new vaccine strategy: mucosal immunization with HSV-1 & HSV-2 epitopes that induce strong in vitro CD4 and CD8 T cell responses from PBMC derived from asymptomatic men and women (designated here as "asymptomatic" protective epitopes") could boost local and systemic "natural" protective immunity, induced by wild-type infection. Here we highlight the rationale and the future of our emerging "asymptomatic" T cell epitope-based mucosal vaccine strategy to decrease recurrent herpetic disease. PMID: 22701511 |
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Schreiber M,Pfefferbaum B,Sayegh L Center for Disaster Medical Sciences, Department of Emergency Medicine, University of California Irvine School of Medicine, Orange, California (Dr Schreiber); Department of Psychiatry, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma (Dr Pfefferbaum); Office of the Command Surgeon, North American Aerospace Defense Command-US Northern Command, Colorado Springs, Colorado (Dr Sayegh). |
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Toward the Way Forward: The National Children's Disaster Mental Health Concept of Operations. Disaster Med Public Health Prep. 2012 Jun;6(2):174-81 Although increasing evidence suggests that children are at particular risk from disasters and evidence-based practices have been developed to triage and treat them effectively, no strategy or concept of operations linking best practices for disaster response is currently in place. To our knowledge, this report describes the first effort to address this critical gap and outlines a triage-driven children's disaster mental health incident response strategy for seamless preparedness, response, and recovery elements that can be used now. The national children's disaster mental health concept of operations (NCDMH CONOPS) details the essential elements needed for an interoperable, coordinated response for the mental health needs of children by local communities, counties, regions, and states to better meet the needs of children affected by disasters and terrorism incidents. This CONOPS for children proposes the use of an evidence-based, rapid triage system to provide a common data metric to incident response and recovery action and to rationally align limited resources to those at greater need in a population-based approach. PMID: 22700028 |
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Lu P,Blesch A,Graham L,Wang Y,Samara R,Banos K,Haringer V,Havton L,Weishaupt N,Bennett D,Fouad K,Tuszynski MH Department of Neurosciences, University of California, San Diego, La Jolla, California 92093, Veterans Administration Medical Center, San Diego, California 92161, Spinal Cord Injury Center, Heidelberg University Hospital, D-69120 Heidelberg, Germany, Department of Anesthesiology, University of California, Irvine, Irvine, California 92697, and University of Alberta, Centre for Neuroscience, Edmonton, Alberta T6G 2E1, Canada. |
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Motor axonal regeneration after partial and complete spinal cord transection. J Neurosci. 2012 Jun 13;32(24):8208-18 We subjected rats to either partial midcervical or complete upper thoracic spinal cord transections and examined whether combinatorial treatments support motor axonal regeneration into and beyond the lesion. Subjects received cAMP injections into brainstem reticular motor neurons to stimulate their endogenous growth state, bone marrow stromal cell grafts in lesion sites to provide permissive matrices for axonal growth, and brain-derived neurotrophic factor gradients beyond the lesion to stimulate distal growth of motor axons. Findings were compared with several control groups. Combinatorial treatment generated motor axon regeneration beyond both C5 hemisection and T3 complete transection sites. Yet despite formation of synapses with neurons below the lesion, motor outcomes worsened after partial cervical lesions and spasticity worsened after complete transection. These findings highlight the complexity of spinal cord repair and the need for additional control and shaping of axonal regeneration. PMID: 22699902 |
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Ghoniem GM,Miller CJ Department of Urology, University of California, Irvine, Orange, CA, USA, gghoniem@hs.uci.edu. |
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A systematic review and meta-analysis of Macroplastique for treating female stress urinary incontinence. Int Urogynecol J. 2012 Jun 15;: INTRODUCTION AND HYPOTHESIS: Macroplastique® (polydimethylsiloxane injection) is a minimally invasive urethral bulking agent with global clinical literature describing its use over 20 years. This study critically assessed the safety and effectiveness outcomes for adult women treated with Macroplastique for stress urinary incontinence (SUI) through a systematic review and meta-analysis. METHODS: A systematic review of the scientific literature from 1990 to 2010 was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement to quantitatively summarize the safety and effectiveness of Macroplastique for female SUI. A total of 958 patients from 23 cohorts were eligible for inclusion and were analyzed. Random-effects models were used to estimate the improvement and cure rates following treatment at three time periods: short-term (18 months). Expanded models assessed the effect of reinjection rate on successful treatment outcomes. Adverse event rates were aggregated and reported. RESULTS: Improvement rates were 75 % [95 % confidence interval (CI), 69-81] in the short-term, 73 % (95 % CI, 62-83) in the mid-term, and 64 % (95 % CI, 57-71) long-term. Cure/dry rates were 43 % (95 % CI, 33-54), 37 % (95 % CI, 28-46), and 36 % (95 % CI, 27-46) over the same respective follow-up periods. Higher study reinjection rates were associated with improved long-term SUI outcomes. No serious adverse events were reported. CONCLUSIONS: This quantitative review supports Macroplastique as an effective, durable, and safe treatment option for female SUI. Meta-analytic evidence suggests that long-term therapeutic benefit is frequently maintained, with some patients requiring reinjection. PMID: 22699885 |
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Lee MY,Ames BD,Tsai SC Department of Molecular Biology and Biochemistry, University of California, Irvine, California 92697, USA. |
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Insight into the molecular basis of aromatic polyketide cyclization: crystal structure and in vitro characterization of WhiE-ORFVI. Biochemistry. 2012 Apr 10;51(14):3079-91 Aromatic polyketides are biologically active natural products. Many important pharmaceuticals are derived from aromatic polyketides. Especially important in aromatic polyketide biosynthesis is the regiospecific cyclization of a linear, preassembled polyketide chain catalyzed by aromatase/cyclase (ARO/CYC), which serves as a key control point in aromatic ring formation. How different ARO/CYCs promote different cyclization patterns is not well understood. The whiE locus of Streptomyces coelicolor A3(2) is responsible for the biosynthesis of an aromatic polyketide precursor to the gray spore pigment. The WhiE ARO/CYC catalyzes the regiospecific C9-C14 and C7-C16 cyclization and aromatization of a 24-carbon polyketide chain. WhiE ARO/CYC shares a high degree of similarity to another nonreducing PKS ARO/CYC, TcmN ARO/CYC. This paper presents the apo crystal structure of WhiE ARO/CYC, and cocrystal structures of WhiE and TcmN ARO/CYCs bound with polycyclic aromatic compounds that mimic the respective ARO/CYC products. Site-directed mutagenesis coupled with in vitro PKS reconstitution assays was used to characterize the interior pocket residues of WhiE ARO/CYC. The results confirmed that the interior pocket of ARO/CYCs is a critical determinant of polyketide cyclization specificity. A unified ARO/CYC-mediated cyclization mechanism is proposed on the basis of these structural and functional results. PMID: 22432862 |
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Duong S,Youssef J,Pimenta P,Aguigam H,Zhang J,Calantog A,Pilch S,Masters JG,Wilder-Smith P Beckman Laser Institute, University of California, Irvine, California 92612; University of California at Irvine, Irvine, California 92612. |
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An imaging-based approach to the evaluation of xerostomia. Lasers Surg Med. 2012 Jun 12;: BACKGROUND AND OBJECTIVE: Goal was to evaluate the potential of in vivo optical coherence tomography (OCT) imaging to determine the response of patients with xerostomia to a dry mouth toothpaste versus fluoride toothpaste placebo. STUDY DESIGN/MATERIALS AND METHODS: Ten subjects with xerostomia participated in this double-blind, crossover, placebo-controlled study. After examination and OCT imaging, subjects used the first product for 15 days, followed by a 7-day washout period, and then they used the second product for 15 days. Data were acquired at 5-day intervals, also before and after the washout. RESULTS: Visual examination and tongue blade adhesion test did not reflect response to the product. Two imaging-based markers were identified: (i) In OCT images, epithelial thickness increased significantly (P < 0.05) after use of the dry mouth toothpaste, but did not change significantly (P > 0.05) after the use of a fluoride toothpaste and (2) Optical backscattering data showed progressive characteristic changes from baseline with use of the active product. CONCLUSIONS: In this pilot study using in vivo OCT imaging, it was possible to detect and measure oral epithelial response to the dry mouth product versus placebo in patients with xerostomia. CLINICAL IMPLICATIONS: This approach may permit site-specific assessment of xerostomia, individualized treatment planning and monitoring, and sequential mucosal mapping in patients with dry mouth. Lasers Surg. Med. © 2012 Wiley Periodicals, Inc. PMID: 22693075 |
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Limon A,Reyes-Ruiz JM,Miledi R Laboratory of Cellular and Molecular Neurobiology, Department of Neurobiology and Behavior, University of California, Irvine, CA 92697. |
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Loss of functional GABAA receptors in the Alzheimer diseased brain. Proc Natl Acad Sci U S A. 2012 Jun 12;: The cholinergic and glutamatergic neurotransmission systems are known to be severely disrupted in Alzheimer's disease (AD). GABAergic neurotransmission, in contrast, is generally thought to be well preserved. Evidence from animal models and human postmortem tissue suggest GABAergic remodeling in the AD brain. Nevertheless, there is no information on changes, if any, in the electrophysiological properties of human native GABA receptors as a consequence of AD. To gain such information, we have microtransplanted cell membranes, isolated from temporal cortices of control and AD brains, into Xenopus oocytes, and recorded the electrophysiological activity of the transplanted GABA receptors. We found an age-dependent reduction of GABA currents in the AD brain. This reduction was larger when the AD membranes were obtained from younger subjects. We also found that GABA currents from AD brains have a faster rate of desensitization than those from non-AD brains. Furthermore, GABA receptors from AD brains were slightly, but significantly, less sensitive to GABA than receptors from non-AD brains. The reduction of GABA currents in AD was associated with reductions of mRNA and protein of the principal GABA receptor subunits normally present in the temporal cortex. Pairwise analysis of the transcripts within control and AD groups and analyses of the proportion of GABA receptor subunits revealed down-regulation of α1 and γ2 subunits in AD. In contrast, the proportions of α2, β1, and γ1 transcripts were up-regulated in the AD brains. Our data support a functional remodeling of GABAergic neurotransmission in the human AD brain. PMID: 22691495 |
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Koopowitz H,Hawkins BA Department of Ecology and Evolutionary Biology, University of California, Irvine, California, USA. |
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Global climate change is confounding species conservation strategies. Integr Zool. 2012 Jun;7(2):158-64 Most organisms face similar problems with respect to their conservation in the face of global climate change. Here, we examine probable effects of climate change on the hyperdiverse plant family Orchidaceae. In the 20th century, the major concerns for orchid conservation revolved around unsustainable harvest for the orchid trade and, more importantly, land conversion from natural ecosystems to those unable to support wild orchid populations. Land conversion included logging, fire regimes and forest conversions to agricultural systems. Although those forms of degradation continue, an additional suite of threats has emerged, fueled by global climate change. Global climate change involves more than responses of orchid populations to increases in ambient temperature. Increasing temperature induces secondary effects that can be more significant than simple changes in temperature. Among these new threats are extended and prolonged fire seasons, rising sea levels, increases in cyclonic storms, seasonal climate shifts, changes in orthographic wind dew point and increased drought. The long-term outlook for orchid biodiversity in the wild is dismal, as it is for many animal groups, and we need to start rethinking strategies for conservation in a rapidly changing world. PMID: 22691199 |
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Dedeurwaerdere S,Friedman A,Fabene PF,Mazarati A,Murashima YL,Vezzani A,Baram TZ Translational Neuroscience, University of Antwerp, Antwerp, BelgiumDepartments of Physiology and Neurobiology Biomedical Engineering, Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel Department of Neurological, Neuropsychological, Morphological and Motor Sciences, University of Verona, Verona, Italy Departments of Pediatrics, and Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California, U.S.A. Tokyo Metropolitan University, Graduate School of Human Health Science, Tokyo, Japan Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Milan, Italy Departments of Anatomy/Neurobiology and Pediatrics, University of California-Irvine, Irvine, California, U.S.A. |
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Finding a better drug for epilepsy: Antiinflammatory targets. Epilepsia. 2012 Jun 12;: This monograph summarizes one of the sessions of the XI Workshop on Neurobiology of Epilepsy (WONOEP), and provides a critical review of the current state of the field. Speakers and discussants focused on several broad topics: (1) the coexistence of inflammatory processes encompassing several distinct signal-transduction pathways with the epileptogenic process; (2) evidence for the contribution of specific inflammatory molecules and processes to the onset and progression of epilepsy, as well as to epilepsy-related morbidities including depression; (3) the complexity and intricate cross-talk of the pathways involved in inflammation, and the discrete, often opposite roles of a given mediator in neurons versus other cell types. These complexities highlight the challenges confronting the field as it aims to define inflammatory molecules as promising targets for epilepsy prevention and treatment. PMID: 22691043 |
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Hopkins FM,Torn MS,Trumbore SE Department of Earth System Science, University of California, Irvine, CA 92697. |
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Warming accelerates decomposition of decades-old carbon in forest soils. Proc Natl Acad Sci U S A. 2012 Jun 11;: Global climate carbon-cycle models predict acceleration of soil organic carbon losses to the atmosphere with warming, but the size of this feedback is poorly known. The temperature sensitivity of soil carbon decomposition is commonly determined by measuring changes in the rate of carbon dioxide (CO(2)) production under controlled laboratory conditions. We added measurements of carbon isotopes in respired CO(2) to constrain the age of carbon substrates contributing to the temperature response of decomposition for surface soils from two temperate forest sites with very different overall rates of carbon cycling. Roughly one-third of the carbon respired at any temperature was fixed from the atmosphere more than 10 y ago, and the mean age of respired carbon reflected a mixture of substrates of varying ages. Consistent with global ecosystem model predictions, the temperature sensitivity of the carbon fixed more than a decade ago was the same as the temperature sensitivity for carbon fixed less than 10 y ago. However, we also observed an overall increase in the mean age of carbon respired at higher temperatures, even correcting for potential substrate limitation effects. The combination of several age constraints from carbon isotopes showed that warming had a similar effect on respiration of decades-old and younger ( PMID: 22689999 |
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Isaacs AT,Jasinskiene N,Tretiakov M,Thiery I,Zettor A,Bourgouin C,James AA Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, CA 92697-4500. |
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Transgenic Anopheles stephensi coexpressing single-chain antibodies resist Plasmodium falciparum development. Proc Natl Acad Sci U S A. 2012 Jun 11;: Anopheles stephensi mosquitoes expressing m1C3, m4B7, or m2A10 single-chain antibodies (scFvs) have significantly lower levels of infection compared to controls when challenged with Plasmodium falciparum, a human malaria pathogen. These scFvs are derived from antibodies specific to a parasite chitinase, the 25 kDa protein and the circumsporozoite protein, respectively. Transgenes comprising m2A10 in combination with either m1C3 or m4B7 were inserted into previously-characterized mosquito chromosomal "docking" sites using site-specific recombination. Transgene expression was evaluated at four different genomic locations and a docking site that permitted tissue- and sex-specific expression was researched further. Fitness studies of docking site and dual scFv transgene strains detected only one significant fitness cost: adult docking-site males displayed a late-onset reduction in survival. The m4B7/m2A10 mosquitoes challenged with P. falciparum had few or no sporozoites, the parasite stage infective to humans, in three of four experiments. No sporozoites were detected in m1C3/m2A10 mosquitoes in challenge experiments when both genes were induced at developmentally relevant times. These studies support the conclusion that expression of a single copy of a dual scFv transgene can completely inhibit parasite development without imposing a fitness cost on the mosquito. PMID: 22689959 |
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