bluuebunny/crossref_metadata_2025 huggingface dataset:
Skeletal muscle signaling associated with impaired glucose tolerance in spinal cord-injured men and the effects of contractile activity
Authors: Yarar-Fisher Ceren , Bickel C. Scott , Windham Samuel T. , McLain Amie B. , Bamman Marcas M.
Published: June 2013

The mechanisms underlying poor glucose tolerance in persons with spinal cord injury (SCI), along with its improvement after several weeks of neuromuscular electrical stimulation-induced resistance exercise (NMES-RE) training, remain unclear, but presumably involve the affected skeletal musculature. We, therefore, investigated skeletal muscle signaling pathways associated with glucose transporter 4 (GLUT-4) translocation at rest and shortly after a single bout of NMES-RE in SCI ( n = 12) vs. able-bodied (AB, n = 12) men. Subjects completed an oral glucose tolerance test during visit 1 and ≈90 NMES-RE isometric contractions of the quadriceps during visit 2. Muscle biopsies were collected before, and 10 and 60 min after, NMES-RE. We assessed transcript levels of GLUT-4 by quantitative PCR and protein levels of GLUT-4 and phosphorylated- and total AMP-activated protein kinase (AMPK)-α, CaMKII, Akt, and AS160 by immunoblotting. Impaired glucose tolerance in SCI was confirmed by higher ( P < 0.05) plasma glucose concentrations than AB at all time points after glucose ingestion, despite equivalent insulin responses to the glucose load. GLUT-4 protein content was lower ( P < 0.05) in SCI vs. AB at baseline. Main group effects revealed higher phosphorylation in SCI of AMPK-α, CaMKII, and Akt ( P < 0.05), and Akt phosphorylation increased robustly ( P < 0.05) following NMES-RE in SCI only. In SCI, low skeletal muscle GLUT-4 protein concentration may, in part, explain poor glucose tolerance, whereas heightened phosphorylation of relevant signaling proteins (AMPK-α, CaMKII) suggests a compensatory effort. Finally, it is encouraging to find (based on Akt) that SCI muscle remains both sensitive and responsive to mechanical loading (NMES-RE) even ≈22 yr after injury.
Effect of simulated obstructive hypopnea and apnea on thoracic aortic wall transmural pressures
Authors: Clarenbach Christian F. , Camen Giovanni , Sievi Noriane A. , Wyss Christophe , Stradling John R. , Kohler Malcolm
Published: June 2013

Preliminary evidence supports an association between obstructive sleep apnea (OSA) and thoracic aortic dilatation, although potential causative mechanisms are incompletely understood; these may include an increase in aortic wall transmural pressures, induced by obstructive apneas and hypopneas. In patients undergoing cardiac catheterization, mean blood pressure (MBP) in the thoracic aorta and esophageal pressure was simultaneously recorded by an indwelling aortic pigtail catheter and a balloon-tipped esophageal catheter in randomized order during: normal breathing, simulated obstructive hypopnea (inspiration through a threshold load), simulated obstructive apnea (Mueller maneuver), and end-expiratory central apnea. Aortic transmural pressure (aortic MBP minus esophageal pressure) was calculated. Ten patients with a median age (range) of 64 (46–75) yr were studied. Inspiration through a threshold load, Mueller maneuver, and end-expiratory central apnea was successfully performed and recorded in 10, 7, and 9 patients, respectively. The difference between aortic MBP and esophageal pressure (and thus the extra aortic dilatory force) was median (quartiles) +9.3 (5.4, 18.6) mmHg, P = 0.02 during inspiration through a threshold load, +16.3 (12.8, 19.4) mmHg, P = 0.02 during the Mueller maneuver, and +0.4 (−4.5, 4.8) mmHg, P = 0.80 during end-expiratory central apnea. Simulated obstructive apnea and hypopnea increase aortic wall dilatory transmural pressures because intra-aortic pressures fall less than esophageal pressures. Thus OSA may mechanically promote thoracic aortic dilatation and should be further investigated as a risk factor for the development or accelerated progression of thoracic aortic aneurysms.
Effects of prolonged space flight on human skeletal muscle enzyme and substrate profiles
Authors: Fitts R. H. , Colloton P. A. , Trappe S. W. , Costill D. L. , Bain J. L. W. , Riley D. A.
Published: June 2013

Our primary goal was to determine the effects of 6-mo flight on the International Space Station (ISS) on selected anaerobic and aerobic enzymes, and the content of glycogen and lipids in slow and fast fibers of the soleus and gastrocnemius. Following local anesthesia, biopsies were obtained from nine ISS crew members ∼45 days preflight and on landing day (R+0) postflight. We subdivided the crew into those who ran 200 min/wk or more (high treadmill, HT) in-flight from those who ran <100 min/wk (low treadmill, LT). In the LT group, there was a loss of lipid in soleus type I fibers, and muscle glycogen significantly increased in soleus fiber types postflight. Soleus cytochrome oxidase (CO) activity was significantly depressed postflight in the type I fiber. This was attributed to the LT group where CO activity was reduced 59%. Otherwise, there was no change in the crew mean for type I or IIa fiber glycolytic or mitochondrial enzyme activities pre- vs. postflight in either muscle. However, two of the three HT subjects ( Subjects E and H) showed significant increases in both β-hydroxyacyl-CoA dehydrogenase and citrate synthase in the soleus type I fibers, and Subject E, exhibiting the largest increase in soleus oxidative enzymes, was the only subject to show a significant decrease in glycolytic enzyme activity. It is apparent that crew members performing adequate treadmill running can maintain calf muscle enzymes, which suggests that increased fatigue with weightlessness cannot be directly caused by a decline in muscle enzyme capacity.
Effect of airway control by glottal structures on postural stability
Authors: Massery M. , Hagins M. , Stafford R. , Moerchen V. , Hodges P. W.
Published: June 2013

Maintenance of upright posture involves complex neuromotor processes that include control of thoracic and abdominal pressures. Control of airflow by glottal structures is a primary determinant of thoracic pressure and may have a role in control of postural stability. This study aimed to investigate the effect of modulation of airway control on upright postural stability during postural perturbations. Standing balance was gently perturbed in the sagittal plane during 7 breathing/voicing tasks that ranged from completely closed (breath-hold), to partially opened (voicing) or completely open (sigh) glottal conditions in 11 healthy adults. Dependent measures were peak amplitude of displacement of the thorax and center of pressure (CoP). When the glottis was completely open during sigh, thoracic displacement in response to the perturbation was greater than in all other conditions, regardless of direction of perturbation (post hoc, all P < 0.002). The absolute amplitude of CoP displacement was greater with backward perturbation (main effect, Direction P = 0.001) and was greater at both extremes of glottal modulation (glottis closed and completely open) than when the glottis was partially opened during counting out loud (post hoc, all P < 0.04). These results show that airway modulation affects postural control during upright perturbations. The thorax was more stable when the glottis was engaged than when it was required to remain open, whereas control of CoP displacement appeared more optimal during the natural dynamic mid-range airway modulation of voicing. These data suggest that glottal control influences balance, and that glottal control strategies may be an important consideration for patients with breathing and/or balance disorders.
Vandetanib in Children and Adolescents with Multiple Endocrine Neoplasia Type 2B Associated Medullary Thyroid Carcinoma
Authors: Fox Elizabeth , Widemann Brigitte C. , Chuk Meredith K. , Marcus Leigh , Aikin Alberta , Whitcomb Patricia O. , Merino Maria J. , Lodish Maya , Dombi Eva , Steinberg Seth M. , Wells Samuel A. , Balis Frank M.
Published: June 2013

Purpose: Medullary thyroid carcinoma (MTC) is a manifestation of multiple endocrine neoplasia type 2 (MEN2) syndromes caused by germline, activating mutations in the RET (REarranged during Transfection) proto-oncogene. Vandetanib, a VEGF and EGF receptor inhibitor, blocks RET tyrosine kinase activity and is active in adults with hereditary MTC.

Experimental Design: We conducted a phase I/II trial of vandetanib for children (5–12 years) and adolescents (13–18 years) with MTC to define a recommended dose and assess antitumor activity. The starting dose was 100 mg/m2 administered orally, once daily, continuously for 28-day treatment cycles. The dose could be escalated to 150 mg/m2/d after two cycles. Radiographic response to vandetanib was quantified using RECIST (v1.0), biomarker response was measured by comparing posttreatment serum calcitonin and carcinoembryonic antigen (CEA) levels to baseline, and a patient-reported outcome was used to assess clinical benefit.

Results: Sixteen patients with locally advanced or metastatic MTC received vandetanib for a median (range) 27 (2–52) cycles. Eleven patients remain on protocol therapy. Diarrhea was the primary dose-limiting toxicity. In subjects with M918T RET germline mutations (n = 15) the confirmed objective partial response rate was 47% (exact 95% confidence intervals, 21%–75%). Biomarker partial response was confirmed for calcitonin in 12 subjects and for CEA in 8 subjects.

Conclusion: Using an innovative trial design and selecting patients based on target gene expression, we conclude that vandetanib 100 mg/m2/d is a well-tolerated and highly active new treatment for children and adolescents with MEN2B and locally advanced or metastatic MTC. Clin Cancer Res; 19(15); 4239–48. ©2013 AACR.
Systematic Interrogation of 3q26 Identifies TLOC1 and SKIL as Cancer Drivers
Authors: Hagerstrand Daniel , Tong Alexander , Schumacher Steven E. , Ilic Nina , Shen Rhine R. , Cheung Hiu Wing , Vazquez Francisca , Shrestha Yashaswi , Kim So Young , Giacomelli Andrew O. , Rosenbluh Joseph , Schinzel Anna C. , Spardy Nicole A. , Barbie David A. , Mermel Craig H. , Weir Barbara A. , Garraway Levi A. , Tamayo Pablo , Mesirov Jill P. , Beroukhim Rameen , Hahn William C.
Published: June 2013

3q26 is frequently amplified in several cancer types with a common amplified region containing 20 genes. To identify cancer driver genes in this region, we interrogated the function of each of these genes by loss- and gain-of-function genetic screens. Specifically, we found that TLOC1 (SEC62) was selectively required for the proliferation of cell lines with 3q26 amplification. Increased TLOC1 expression induced anchorage-independent growth, and a second 3q26 gene, SKIL (SNON), facilitated cell invasion in immortalized human mammary epithelial cells. Expression of both TLOC1 and SKIL induced subcutaneous tumor growth. Proteomic studies showed that TLOC1 binds to DDX3X, which is essential for TLOC1-induced transformation and affected protein translation. SKIL induced invasion through upregulation of SLUG (SNAI2) expression. Together, these studies identify TLOC1 and SKIL as driver genes at 3q26 and more broadly suggest that cooperating genes may be coamplified in other regions with somatic copy number gain.

Significance: These studies identify TLOC1 and SKIL as driver genes in 3q26. These observations provide evidence that regions of somatic copy number gain may harbor cooperating genes of different but complementary functions. Cancer Discov; 3(9); 1044–57. ©2013 AACR.

This article is highlighted in the In This Issue feature, p. 953
Selective Estrogen Receptor Modulators and Pharmacogenomic Variation in ZNF423 Regulation of BRCA1 Expression: Individualized Breast Cancer Prevention
Authors: Ingle James N. , Liu Mohan , Wickerham D. Lawrence , Schaid Daniel J. , Wang Liewei , Mushiroda Taisei , Kubo Michiaki , Costantino Joseph P. , Vogel Victor G. , Paik Soonmyung , Goetz Matthew P. , Ames Matthew M. , Jenkins Gregory D. , Batzler Anthony , Carlson Erin E. , Flockhart David A. , Wolmark Norman , Nakamura Yusuke , Weinshilboum Richard M.
Published: June 2013

The selective estrogen receptor modulators (SERM) tamoxifen and raloxifene can reduce the occurrence of breast cancer in high-risk women by 50%, but this U.S. Food and Drug Administration-approved prevention therapy is not often used. We attempted to identify genetic factors that contribute to variation in SERM breast cancer prevention, using DNA from the NSABP P-1 and P-2 breast cancer prevention trials. An initial discovery genome-wide association study identified common single-nucleotide polymorphisms (SNP) in or near the ZNF423 and CTSO genes that were associated with breast cancer risk during SERM therapy. We then showed that both ZNF423 and CTSO participated in the estrogen-dependent induction of BRCA1 expression, in both cases with SNP-dependent variation in induction. ZNF423 appeared to be an estrogen-inducible BRCA1 transcription factor. The OR for differences in breast cancer risk during SERM therapy for subjects homozygous for both protective or both risk alleles for ZNF423 and CTSO was 5.71.

Significance: This study identified novel, functionally polymorphic genes involved in the estrogen-dependent regulation of BRCA1 expression, as well as a novel mechanism for genetic variation in SERM therapeutic effect. These observations, and definition of their underlying mechanisms, represent steps toward pharmacogenomically individualized SERM breast cancer prevention. Cancer Discov; 3(7); 812–25. ©2013 AACR.

See related commentary by Machiela and Chanock, p. 728

This article is highlighted in the In This Issue feature, p. 705
Efficacy and Tolerability of Baclofen in Substance Use Disorders: A Systematic Review
Authors: Agabio Roberta , Preti Antonio , Gessa Gian Luigi
Published: June 2013

Background: It has been reported that baclofen, a drug used in the treatment of spasticity, reduces the severity of withdrawal symptoms and substance use disorders (SUDs) for some psychoactive drugs. Aims and Methods: To evaluate the effectiveness and safety of baclofen in the treatment of withdrawal syndrome and/or SUDs, providing (1) an outline of its pharmacological features; (2) a summary of studies that have suggested its possible effectiveness in the treatment of SUDs, and (3) a review of randomized, controlled trials (RCTs) on baclofen and SUDs. Results: Baclofen tolerability is generally considered to be good. Eleven RCTs investigated its effectiveness in the treatment of SUDs. Of these, 5 RCTs found that baclofen is effective, 5 RCTs found that it is ineffective and the results of 1 RCT were not appreciable because it did not achieve the preplanned level of participation. Conclusions: The number of RCTs on baclofen and SUDs is still low, and their results are divergent. Further RCTs should be undertaken, particularly with higher doses of baclofen. Its administration may be suggested in patients who fail to respond to other approved drugs or who are affected by liver disease that prevents their administration, or in patients affected by SUDs for which no approved drugs are available. Treatment should be conducted under strict medical supervision.
The Neural Crest and Cancer: A Developmental Spin on Melanoma
Authors: Kulesa Paul M. , Morrison Jason A. , Bailey Caleb M.
Published: June 2013

Neural crest (NC) cells undergo an epithelial to mesenchymal transition (EMT) in order to exit from the dorsal neural tube. Similarly, ancestrally related melanoma cells employ an EMT-like event during the initial stages of metastasis to dissociate from surrounding keratinocytes. Whether or not the molecular pathogenesis and cellular dynamics of melanoma metastasis resemble the embryonic NC invasion program is unclear. Here, we highlight advances in our understanding of tumor cell behaviors and plasticity, focusing on the relationship between melanoma and the NC invasion programs. We summarize recent discoveries of NC cell guidance and emerging in vivo imaging strategies that permit single cell resolution of fluorescently labeled tumor cells, with a focus on our recently developed in vivo chick embryo transplant model. Crucial to the molecular pathogenesis of metastasis, we highlight advances in gene profiling of small cell numbers, including our novel ability to gather gene expression information during distinct stages of melanoma invasion. Lastly, we present preliminary details of a comparison of specific genetic pathways associated with the early phases of melanoma invasion and known NC induction and migration signals. Our results suggest that malignant melanoma cells hijack portions of the NC program to promote plasticity and facilitate metastasis. In summary, there is considerable power in combining an in vivo model system with molecular analysis of gene expression, within the context of established developmental signaling pathways, to identify and study the molecular mechanisms of metastasis.
RimabotulinumtoxinB versus OnabotulinumtoxinA in the Treatment of Masseter Hypertrophy: A 24-Week Double-Blind Randomized Split-Face Study
Authors: Lee Dong Hun , Jin Seon-Pil , Cho Soyun , Feneran Ashley , Youn Choon Shik , Won Chong Hyun , Park Gyeong-Hun , Kim Byung Wook , An Jeesoo , Chang Sung Eun , Lee Mi Woo
Published: June 2013

Background: Masseter hypertrophy can be ameliorated by botulinum toxin. Objective: To compare the efficacy and safety of RimabotulinumtoxinB (BTX-B) and OnabotulinumtoxinA (BTX-A) in the treatment of masseter hypertrophy. Methods: Sixteen women with bilateral masseter hypertrophy received single injections of BTX-A or BTX-B at a dose ratio of 1:50 or 1:70 in a 24-week double-blind randomized split-face study. Results: Both BTX-A and BTX-B produced significant improvements in masseter hypertrophy. The maximum volume reduction, as determined by computed tomography scanning, at week 12 was comparable between BTX-A and BTX-B at a dose ratio of 1:70 (15.6 and 14.2%, respectively). At week 24, only masseters treated with BTX-A maintained a significant volume reduction. Investigator ratings and patient satisfaction scores paralleled objective computed tomography measurements. Conclusion: Both BTX-A and BTX-B are effective in the treatment of masseter hypertrophy. BTX-B, at a dose ratio of 1:70, has a comparable efficacy but a shorter duration of action than BTX-A.
A Missense Mutation of the α-Galactosidase A Gene in a Chinese Family of Fabry Disease with Renal Failure
Authors: Wang Chunli , Wang Yang , Zhu Feng , Xiong Jing
Published: June 2013

Background: Fabry disease (FD) is a rare disease due to an X-linked recessive inborn error of glycosphingolipid metabolism resulting from the mutations of the α-galactosidase A (α-gal A) gene. FD is rare in Chinese and the data on clinic and genetic features of FD is still limited. Methods: In this study, the α-gal A gene of a Chinese family diagnosed with FD was analyzed for mutations and the genetic features of FD in this family were presented. Results: The α-gal A activity of the proband in this family was 0.03 nmol/ml/h in the whole blood. By PCR amplification and sequencing of the α-gal A gene exons, a single C-to-T transition was identified in codon 112 of exon 2. This C-to-T transition, mapping to position 334 in the cDNA of the α-gal A gene, was a missense mutation predicting a substitution of arginine to cysteine (p.R112C), which disrupts the normal activity of α-gal A enzyme. No further mutations were found in other exons of the α-gal A gene. In contrast to previous reports, in this family, all of the five male patients developed end-stage renal failure due to this missense mutation. Conclusions: These findings suggest that the missense mutation, p.R112C, in α-gal A gene ablates its activity and results in the development of FD with the renal damage.
Saliva Parameters and Erosive Wear in Adolescents
Authors: Zwier N. , Huysmans M.C.D.N.J.M. , Jager D.H.J. , Ruben J. , Bronkhorst E.M. , Truin G.J.
Published: June 2013

The aim of this study was to investigate the relationship between several parameters of saliva and erosive wear in adolescents. (Un-)stimulated saliva was collected from 88 adolescents with erosion and 49 controls (age 16 ± 1 years). Flow rate, pH and buffer capacity were determined immediately. Total protein content, carbonic anhydrase VI, amylase, albumin, calcium, phosphate, urea, sodium, chloride and potassium were measured at a later time. Unstimulated flow rate was found to be significantly lower in subjects with erosive wear (p = 0.016). The chloride concentration in unstimulated saliva was found to be significantly higher in the erosion group (p = 0.019).
Mild Cognitive Impairment, Risk Factors and Magnetic Resonance Volumetry: Role of Probable Alzheimer's Disease in the Family
Authors: Rogne Sigbjørn , Vangberg Torgil , Eldevik Petter , Wikran Gry , Mathiesen Ellisiv B. , Schirmer Henrik
Published: June 2013

Background/Aims: Late-onset Alzheimer's disease (LOAD) comprises sporadic LOAD and familial LOAD. We wanted to determine whether total plasma homocysteine (Hcy), cardiovascular risk factors and volumetric analyses of cerebral magnetic resonance imaging (MRI) were differently associated with mild cognitive impairment (MCI) in subjects from families with aggregation of LOAD (probable familial LOAD) and MCI in subjects from families without LOAD (probable sporadic LOAD). Methods: A total of 103 subjects with MCI without known stroke or other apparent causative diseases were included as cases together with 58 controls. The cases were stratified into 3 groups according to the number of biological relatives with probable LOAD on one side of the family. Cerebral MRI was obtained from all. The case groups were compared to the control group in sex-specific analyses of covariance. Results: Hcy was significantly elevated in all cases compared to controls, except for women with probable familial LOAD. These women also had significantly smaller hippocampal volume and significantly larger lateral ventricles, unlike the women in the other case groups. Conclusions: Our findings suggest that research on Hcy, cardiovascular risk factors and other potential risk factors for LOAD might benefit from distinguishing between sporadic and familial LOAD.
Inactivation of Coxsackievirus B4, Feline Calicivirus and Herpes Simplex Virus Type 1: Unexpected Virucidal Effect of a Disinfectant on a Non-Enveloped Virus Applied onto a Surface
Authors: Thevenin Thomas , Lobert Pierre Emmanuel , Hober Didier
Published: June 2013

Objective: To evaluate the effect of a disinfectant onto viruses in suspension on the one hand and applied onto a surface on the other. Methods: A system combining flocked swabs to recover viruses dried onto stainless steel carriers and gel filtration to eliminate cytotoxic products has been developed to study the virucidal effect of a quaternary ammonium-based disinfectant towards herpes simplex virus type 1 (HSV-1), coxsackievirus B4 (CVB4) and feline calicivirus F9 (FCV). The recovery of FCV has been estimated by RT real-time PCR. Results: HSV-1, CVB4 and FCV had a titer over 104 TCID50 · ml-1 after 2 h drying and were recovered from the carriers using flocked swabs. HSV-1 was inactivated in suspension and on stainless steel carriers by the disinfectant (a reduction factor of 4 and 2.83 log, respectively) whereas CVB4 was resistant. The reduction of infectious titer was moderate, 1.5 log in 30 min, when FCV was in suspension, whereas it was up to 4 log in 10 min when the virus was dried on a carrier. Dried FCV was efficiently recovered from carriers as demonstrated by RT real-time PCR. Conclusion: A non-enveloped virus, FCV, applied on a surface, but not in suspension, was inactivated by a quaternary ammonium-based disinfectant. The resistance of viruses applied onto a surface to the effect of disinfectants should be investigated further.
Control of Myeloid Cell Trafficking in Resolution
Authors: Norling Lucy V. , Perretti Mauro
Published: June 2013

Following tissue injury or microbial invasion, neutrophils are robustly recruited to inflammatory loci, which is a hallmark of the host inflammatory response. This event initiates a series of processes required to activate resolution, including recruitment of monocytes, clearance of microbes, cellular debris and apoptotic neutrophils, the egress of phagocytes and, ultimately, regain of tissue homeostasis. Substantial evidence now signifies that resolution of inflammation is a highly coordinated, active process dictated by the spatial-temporal generation of proresolving mediators that act on specific receptors to modulate cell and tissue reactivity. This review will focus on the mediators, targets and pathways initiated to orchestrate resolution. Importantly, disruption of the key processes involved in inflammatory resolution could result in delayed restoration of tissue homeostasis, leading to fibrosis and/or persistent inflammation.
The CD1d-Natural Killer T Cell Axis in Atherosclerosis
Authors: Bondarenko Sergey , Catapano Alberico Luigi , Norata Giuseppe Danilo
Published: June 2013

A key role for ‘lipid-sensing' CD1-restricted natural killer T (NKT) cells in the pathogenesis of atherosclerosis has been suggested. However, the biology of NKT cells remains poorly characterized, as in different experimental settings their activation was reported to both stimulate and suppress innate and adaptive immune responses. Most of the data from experimental models suggest that NKT cells are proatherogenic; however, it is debated whether the increase in atherosclerosis observed following NKT cell stimulation is a consequence of the inability to induce functional NKT cells rather than the proatherogenic nature of NKT cells. CD1d-expressing antigen-presenting cells and NKT cells were detected in mouse and human atherosclerotic lesions. Furthermore, several lysophospholipids and glycosphingolipids, known to accumulate in atherosclerotic plaques, are antigenic for human NKT cell clones. Lipid transfer proteins, such as apolipoprotein E and microsomal triglyceride transfer protein, are central to NKT cell responses. All these data suggest a profound relation between lipid metabolism, CD1d-NKT cell axis activation and atherosclerosis. In this review, we summarize the advances and gaps in our knowledge of NKT cell biology in the context of atherosclerosis as well as the possibility of influencing NKT cell polarization toward an atheroprotective phenotype.
Rare Types of Rotaviruses Isolated from Children with Acute Gastroenteritis in Patras, Greece
Authors: Kokkinos Petros A. , Ziros Panos G. , Monini Marina , Lampropoulou Petroula , Karampini Anthoula , Papachatzi Eleni , Mantagos Stefanos , Ruggeri Franco M. , Vantarakis Apostolos
Published: June 2013

Background: Acute diarrhea remains a major public health issue worldwide, with gastroenteritis agents associated with a high morbidity, especially in infants and young children. A 1-year study (2009-2010) of rotavirus (RV)-caused pediatric diarrhea was performed on hospitalized children admitted with symptoms of acute diarrhea to the University Hospital of Patras, Greece. Methods: Twenty-nine fecal samples were investigated for RVs, adenoviruses (AdVs), and enteroviruses (EVs) in an attempt to characterize these enteric viruses, which have been implicated in hospitalized diarrhea. Results: A 44.8% (13/29) incidence of viral infection was reported for the viral targets. Monoinfections accounted for 31% (9/29), while bi-infections accounted for 13.4% (4/29). Sequencing of positive samples allowed identification of RVs G4P[8] (2/29), G9P[8] (1/29), and interestingly of the rare type G12P[8] (2/29). AdV types 1, 2, and 6 were also identified in 4/29, 1/29, and 1/29 of the samples, respectively. Regarding the EVs, EV71 (2/29), coxsackievirus A4 (1/29), echovirus 11 (1/29), and EV96 (1/29) were typed. Conclusion: The results of the present study, and specifically the detection of rare RV G12 and EV71 strains, address the need for continuous epidemiological surveys to provide epidemiological pictures of pediatric viral infections circulating in the community.
Histopathology of the Clarion Cochlear Implant Electrode Positioner in a Human Subject
Authors: Seyyedi M. , Burgess B.J. , Eddington D.K. , Gantz B.J. , Nadol Jr. J.B.
Published: June 2013

A Silastic electrode positioner was introduced by the Advanced Bionics Corporation in 1999 and it was designed to achieve a perimodiolar position of the stimulating electrode. The positioner was voluntarily recalled in the United States in July 2002 due to an apparent higher risk of bacterial meningitis in patients in whom the electrode positioner had been placed. A detailed histopathologic study of the positioner in the human has not previously been published. The histopathologic findings in a 74-year-old woman who underwent bilateral cochlear implantation using the positioner are presented. Findings include a large track caused by the combined electrode and its positioner with considerable disruption of the basilar membrane and osseous spiral lamina. Although there was a fibrous sheath around the electrode and positioner at the cochleostomy in both ears, this fibrous sheath did not extend deeply into the cochlea except at the apical end of the electrode beyond the positioner. This resulted in a large fluid space around and between the positioner and electrode within the cochlea and presumably in fluid continuity with the cerebrospinal fluid space. Possible clinical implications are discussed.
Spatiotemporal Expression of Fibroblast Growth Factor 10 in Human Hindgut and Anorectal Development
Authors: Yin Shui Jing , Tang Xiao Bing , Li Fei Fei , Zhang Tao , Yuan Zheng Wei , Wang Wei Lin , Bai Yu Zuo
Published: June 2013

As fibroblast growth factor 10 (FGF-10) gene expression may have a role in anorectal duct formation, this study aimed to assess the spatiotemporal expression pattern of FGF-10 during development of the rectum and hindgut in human embryos. FGF-10 expression was evaluated in human embryos (n = 85) at 3-8 weeks of gestation after immunohistochemical evaluation using antibodies specific for FGF-10. From weeks 4 to 7 of gestation, FGF-10 expression was observed primarily in the apical epithelium of the dorsal urorectal septum, the cloacal membrane (CM) and the hindgut. Following CM rupture (week 7), the epithelium of the anal canal was negative for FGF-10; however, it was present within the urothelium through week 7. FGF-10 expression during the development of the human hindgut and anorectum suggests that it may play a role in hindgut and anorectal morphogenesis.
Ocular Surface Complications after Trabeculectomy: Incidence, Risk Factors, Time Course and Prognosis
Authors: Ono Takeshi , Yuki Kenya , Ozeki Naoki , Shiba Daisuke , Tsubota Kazuo
Published: June 2013

Purpose: To investigate the incidence, risk factors, time course and prognosis of ocular surface complications after trabeculectomy. Procedures: This is a retrospective, case-control study. Data on 399 consecutive patients who underwent trabeculectomy between 1999 and 2009 were evaluated. Cases of postoperative corneal epithelial defects, filamentary keratitis and dellen were evaluated. The risk factors for these ocular surface complications were analyzed with a logistic regression model. Results: Corneal epithelial defects were found in 44 of the 399 patients (11%), filamentary keratitis in 12 patients (3%) and dellen in 7 patients (2%). Dellen required surgical intervention at a statistically significantly higher rate than corneal epithelial defects or filamentary keratitis (p = 0.0001, Fisher's exact test). The significant risk factors for these ocular surface complications were found to be a history of preoperative superficial punctate keratopathy (odds ratio, OR: 2.10, 95% confidence interval, CI: 1.25-3.51, p = 0.005) and a history of diabetes mellitus (OR: 1.69, 95% CI: 1.02-2.81, p = 0.04). Conclusions: Ocular surface complications following trabeculectomy are not rare. The biggest risk factors for these complications were found to be a history of preoperative superficial punctate keratopathy and a history of diabetes mellitus. Surgery is likely to be required for the treatment of dellen.
Rosuvastatin-Induced Acute Interstitial Nephritis
Authors: Londrino Francesco , Zattera Tito , Falqui Valeria , Corbani Valentina , Cavallini Marco , Stefanini Teseo , Chiappini Nadia , Ardini Michela , Martina Valentina , Rombolà Giuseppe
Published: June 2013

We report a case of acute interstitial nephritis (AIN), most likely induced by rosuvastatin, in an 83-year-old male patient. The patient underwent angioplasty of the left internal carotid artery, after which he began a regimen of rosuvastatin (20 mg/day). After 3 weeks the patient was admitted to our unit for acute renal failure with mild proteinuria with negligible urinary sediment. A left kidney biopsy showed dense interstitial infiltrates, mainly composed of lymphocytes with evident tubulitis. Rosuvastatin withdrawal plus prednisolone (1 mg/kg/day) treatment, which was slowly tapered over a period of 4 weeks, allowed for a complete recovery of renal function. To our knowledge, this is the first case report of rosuvastatin-induced AIN. Acute renal failure is associated with a clear increase in morbidity, length of hospital stay and mortality. Moreover, since statins are among the most widely prescribed drugs in Western countries, we think that the risk of AIN should be taken into account as a possible side effect of rosuvastatin.
PKCβ Promotes Vascular Inflammation and Acceleration of Atherosclerosis in Diabetic ApoE Null Mice
Authors: Kong Linghua , Shen Xiaoping , Lin Lili , Leitges Michael , Rosario Rosa , Zou Yu Shan , Yan Shi Fang
Published: June 2013

Objective—

Subjects with diabetes mellitus are at high risk for developing atherosclerosis through a variety of mechanisms. Because the metabolism of glucose results in production of activators of protein kinase C (PKC)β, it was logical to investigate the role of PKCβ in modulation of atherosclerosis in diabetes mellitus.

Approach and Results—

ApoE
−/−
and PKCβ
−/−
/ApoE
−/−
mice were rendered diabetic with streptozotocin. Quantification of atherosclerosis, gene expression profiling, or analysis of signaling molecules was performed on aortic sinus or aortas from diabetic mice. Diabetes mellitus–accelerated atherosclerosis increased the level of phosphorylated extracellular signal-regulated kinase 1/2 and Jun-N-terminus kinase mitogen–activated protein kinases and augmented vascular expression of inflammatory mediators, as well as increased monocyte/macrophage infiltration and CD11c
+
cells accumulation in diabetic ApoE
−/−
mice, processes that were diminished in diabetic PKCβ
−/−
/ApoE
−/−
mice. In addition, pharmacological inhibition of PKCβ reduced atherosclerotic lesion size in diabetic ApoE
−/−
mice. In vitro, the inhibitors of PKCβ and extracellular signal-regulated kinase 1/2, as well as small interfering RNA to Egr-1, significantly decreased high-glucose–induced expression of CD11c (integrin, alpha X 9complement component 3 receptor 4 subunit]), chemokine (C-C motif) ligand 2, and interleukin-1β in U937 macrophages.

Conclusions—

These data link enhanced activation of PKCβ to accelerated diabetic atherosclerosis via a mechanism that includes modulation of gene transcription and signal transduction in the vascular wall, processes that contribute to acceleration of vascular inflammation and atherosclerosis in diabetes mellitus. Our results uncover a novel role for PKCβ in modulating CD11c expression and inflammatory response of macrophages in the development of diabetic atherosclerosis. These findings support PKCβ activation as a potential therapeutic target for prevention and treatment of diabetic atherosclerosis.
Inhibition of Patched-1 Prevents Injury-Induced Neointimal Hyperplasia
Authors: Redmond Eileen M. , Hamm Katie , Cullen John P. , Hatch Ekaterina , Cahill Paul A. , Morrow David
Published: June 2013

Objective—

To determine the role of patched receptor (Ptc)-1 in mediating pulsatile flow-induced changes in vascular smooth muscle cell growth and vascular remodeling.

Approach and Results—

In vitro, human coronary arterial smooth muscle cells were exposed to normal or pathological low pulsatile flow conditions for 24 hours using a perfused transcapillary flow system. Low pulsatile flow increased vascular smooth muscle cell proliferation when compared with normal flow conditions. Inhibition of Ptc-1 by cyclopamine attenuated low flow-induced increases in Notch expression while concomitantly decreasing human coronary arterial smooth muscle cell growth to that similar under normal flow conditions. In vivo, ligation injury–induced low flow increased vascular smooth muscle cell growth and vascular remodeling, while increasing Ptc-1/Notch expression. Perivascular delivery of Ptc-1 small interfering RNA by pluronic gel inhibited the pathological low flow–induced increases in Ptc-1/Notch expression and markedly reduced the subsequent vascular remodeling.

Conclusions—

These results suggest that pathological low flow stimulates smooth muscle cell growth in vitro and vascular remodeling in vivo via Ptc-1 regulation of Notch signaling.
Mechanically Unloading the Left Ventricle Before Coronary Reperfusion Reduces Left Ventricular Wall Stress and Myocardial Infarct Size
Authors: Kapur Navin K. , Paruchuri Vikram , Urbano-Morales Jose Angel , Mackey Emily E. , Daly Gerard H. , Qiao Xiaoying , Pandian Natesa , Perides George , Karas Richard H.
Published: June 2013

Background—

Ischemia/reperfusion injury worsens infarct size, a major determinant of morbidity and mortality after acute myocardial infarction (MI). We tested the hypothesis that reducing left ventricular wall stress with a percutaneous left atrial-to-femoral artery centrifugal bypass system while delaying coronary reperfusion limits myocardial injury in a model of acute MI.

Methods and Results—

MI was induced by balloon occlusion of the left anterior descending artery in adult male swine. In the MI group (n=4), 120 minutes of left anterior descending artery occlusion was followed by 120 minutes of reperfusion without mechanical support. In the mechanically supported group (MI+unload; n=4), percutaneous left atrial–to–femoral artery bypass was initiated after 120 minutes of ischemia, and left anterior descending artery occlusion was prolonged for an additional 30 minutes, followed by 120 minutes of reperfusion with device support. All animals were euthanized after reperfusion, and infarct size was quantified by triphenyltetrazolium chloride staining. Compared with baseline, mean left ventricular wall stress and stroke work were not changed at any point in the MI group but were decreased after reperfusion in the MI+unload group (mean left ventricular wall stress, 44 658 versus 22 963 dynes/cm
2
; stroke work, 2823 versus 655 mm Hg·mL, MI versus MI+unload). Phosphorylation of reperfusion injury salvage kinase pathway proteins from noninfarcted left ventricular tissue was unchanged in the MI group but was increased in the MI+unload group. Compared with the MI group, total infarct size was reduced in the MI+unload group (49% versus 28%, MI versus MI+unload).

Conclusions—

These data support that first unloading the left ventricle despite delaying coronary reperfusion during an acute MI reduces myocardial injury.
Effect of B Vitamins and Lowering Homocysteine on Cognitive Impairment in Patients With Previous Stroke or Transient Ischemic Attack
Authors: Hankey Graeme J. , Ford Andrew H. , Yi Qilong , Eikelboom John W. , Lees Kennedy R. , Chen Christopher , Xavier Denis , Navarro Jose C. , Ranawaka Udaya K. , Uddin Wasim , Ricci Stefano , Gommans John , Schmidt Reinhold , Almeida Osvaldo P. , van Bockxmeer Frank M.
Published: June 2013

Background and Purpose—

High plasma total homocysteine (tHcy) has been associated with cognitive impairment but lowering tHcy with B-vitamins has produced equivocal results. We aimed to determine whether B-vitamin supplementation would reduce tHcy and the incidence of new cognitive impairment among individuals with stroke or transient ischemic attack ≥6 months previously.

Methods—

A total of 8164 patients with stroke or transient ischemic attack were randomly allocated to double-blind treatment with one tablet daily of B-vitamins (folic acid, 2 mg; vitamin B6, 25 mg; vitamin B12, 500 μg) or placebo and followed up for 3.4 years (median) in the VITAmins TO Prevent Stroke (VITATOPS) trial. For this prespecified secondary analysis of VITATOPS, the primary outcome was a new diagnosis of cognitive impairment, defined as a Mini-Mental State Examination (MMSE) score <24 on ≥2 follow-up visits. Secondary outcomes were cognitive decline, and the mean tHcy and MMSE at final follow-up.

Results—

A total of 3089 participants (38%) voluntarily undertook the MMSE >6 months after the qualifying stroke; 2608 participants were cognitively unimpaired (MMSE ≥24), of whom 2214 participants (1110 B-vitamins versus 1104 placebo) had follow-up MMSEs during 2.8 years (median). At final follow-up, allocation to B-vitamins, compared with placebo, was associated with a reduction in mean tHcy (10.2 μmol/L versus 14.2 μmol/L;
P
<0.001) but no change from baseline in the mean MMSE score (−0.22 points versus −0.25 points; difference, 0.03; 95% confidence interval, −0.13 to 0.19;
P
=0.726) and no difference in the incidence of cognitive impairment (5.51% versus 5.47%; risk ratio, 1.01; 95% confidence interval, 0.69–1.48;
P
=0.976), cognitive decline (9.1% versus 10.3%; risk ratio, 0.89; 0.67–1.18;
P
=0.414), or cognitive impairment or decline (11.0% versus 11.3%; risk ratio, 0.98; 0.75–1.27;
P
=0.855).

Conclusions—

Daily supplementation with folic acid, vitamin B6, and vitamin B12 to a self-selected clinical trial cohort of cognitively unimpaired patients with previous stroke or transient ischemic attack lowered mean tHcy but had no effect on the incidence of cognitive impairment or cognitive decline, as measured by the MMSE, during a median of 2.8 years.

Clinical Trial Registration—

URL:
http://www.controlled-trials.com
. Unique identifier: ISRCTN74743444; URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00097669.
Reinventing classroom space to re-energise information literacy instruction
Authors: Julian Suzanne
Published: June 2013

Librarians in academic settings spend a significant amount of time teaching students information literacy skills. Teachers adapt their teaching activities to the constraints of the physical setting of the classroom. Brigham Young University’s Harold B. Lee Library modified a classroom from a traditional lecture room to a room where the seating was mobile. The teachers and students were observed and surveyed to see if the change in physical environment impacted the teaching style or learning activities used. The findings indicate that teachers use familiar routines and lessons in both a traditional lecture-style classroom and a newly-designed flexible learning space as they present information literacy instruction. Teachers who recognised that students benefited from learning activities where they were active participants were more likely to incorporate small changes to their lesson plans. The classroom design can re-energise instruction if the teacher adapts their teaching style to the more flexible learning environment. This article is based on a paper presented at LILAC 2012.
Species delimitation and name application in Deyeuxia abnormis, Agrostis zenkeri, A. pleiophylla and related taxa (Poaceae: Agrostidinae)
Authors: PASZKO BEATA , SORENG ROBERT J.
Published: June 2013

Historically tangled taxonomy and nomenclature of Deyeuxia abnormis, Agrostis zenkeri, A. pleiophylla and their allies is presented. Deyeuxia abnormis is recognized as a distinct species. Previous descriptions of this taxon were entangled with concepts of Agrostis zenkeri and Deyeuxia diffusa. The typification of Deyeuxia abnormis by Noltie is rejected in favor of the lectotype designated by Bor. The name Deyeuxia abnormis is applied to specimens of this species group with a tufted habit and callus hairs between 0.25 and 0.50 percent of their lemma in length. Specimens previously included in D. abnormis that are characterized by scrambling habit, simple or branched culms, and callus hairs between 0.6 and 1.0 percent of the lemma length, are assigned to D. diffusa. The taxonomy of Deyeuxia abnormis and its allies is clarified and new synonyms are provided, along with amended descriptions, and a key to the complex of D. abnormis and its allies. The distributions of Deyeuxia abnormis and D. diffusa in South Asia are updated. The previous typification of Agrostis pleiophylla is rejected and a new lectotype is selected. The names Anisachne gracilis (= Deyeuxia abnormis) and Agrostis continentalis (= Deyeuxia abnormis) are typified.
A Robust C-Band Hydrometeor Identification Algorithm and Application to a Long-Term Polarimetric Radar Dataset
Authors: Dolan Brenda , Rutledge Steven A. , Lim S. , Chandrasekar V. , Thurai M.
Published: June 2013

A new 10-category, polarimetric-based hydrometeor identification algorithm (HID) for C band is developed from theoretical scattering simulations including wet snow, hail, and big drops/melting hail. The HID is applied to data from seven wet seasons in Darwin, Australia, using the polarimetric C-band (C-POL) radar, to investigate microphysical differences between monsoon and break periods. Scattering simulations reveal significant Mie effects with large hail (diameter > 1.5 cm), with reduced reflectivity and enhanced differential reflectivity Zdr and specific differential phase Kdp relative to those associated with S band. Wet snow is found to be associated with greatly depreciated correlation coefficient ρhv and moderate values of Zdr. It is noted that large oblate liquid drops can produce the same electromagnetic signatures at C band as melting hail falling quasi stably, resulting in some ambiguity in the HID retrievals. Application of the new HID to seven seasons of C-POL data reveals that hail and big drops/melting hail occur much more frequently during break periods than during monsoon periods. Break periods have a high frequency of vertically aligned ice above 12 km, suggesting the presence of strong electric fields. Reflectivity and mean drop diameter D0 statistics demonstrate that convective areas in both monsoon and break periods may have robust coalescence or melting precipitation ice processes, leading to enhanced reflectivity and broader distributions of D0. Conversely, for stratiform regions in both regimes, mean reflectivity decreases below the melting level, indicative of evaporative processes. Break periods also have larger ice water path fractions, indicating substantial mixed-phase precipitation generation as compared with monsoonal periods. In monsoon periods, a larger percentage of precipitation is produced through warm-rain processes.