bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interpreting Stress Responses during Routine Toxicity Studies
Authors: Everds Nancy E. , Snyder Paul W. , Bailey Keith L. , Bolon Brad , Creasy Dianne M. , Foley George L. , Rosol Thomas J. , Sellers Teresa 
Published: March 2013

Stress often occurs during toxicity studies. The perception of sensory stimuli as stressful primarily results in catecholamine release and activation of the hypothalamic–pituitary–adrenal (HPA) axis to increase serum glucocorticoid concentrations. Downstream effects of these neuroendocrine signals may include decreased total body weights or body weight gain; food consumption and activity; altered organ weights (e.g., thymus, spleen, adrenal); lymphocyte depletion in thymus and spleen; altered circulating leukocyte counts (e.g., increased neutrophils with decreased lymphocytes and eosinophils); and altered reproductive functions. Typically, only some of these findings occur in a given study. Stress responses should be interpreted as secondary (indirect) rather than primary (direct) test article–related findings. Determining whether effects are the result of stress requires a weight-of-evidence approach. The evaluation and interpretation of routinely collected data (standard in-life, clinical pathology, and anatomic pathology endpoints) are appropriate and generally sufficient to assess whether or not changes are secondary to stress. The impact of possible stress-induced effects on data interpretation can partially be mitigated by toxicity study designs that use appropriate control groups (e.g., cohorts treated with vehicle and subjected to the same procedures as those dosed with test article), housing that minimizes isolation and offers environmental enrichment, and experimental procedures that minimize stress and sampling and analytical bias. This article is a comprehensive overview of the biological aspects of the stress response, beginning with a Summary (Section 1) and an Introduction (Section 2) that describes the historical and conventional methods used to characterize acute and chronic stress responses. These sections are followed by reviews of the primary systems and parameters that regulate and/or are influenced by stress, with an emphasis on parameters evaluated in toxicity studies: In-life Procedures (Section 3), Nervous System (Section 4), Endocrine System (Section 5), Reproductive System (Section 6), Clinical Pathology (Section 7), and Immune System (Section 8). The paper concludes (Section 9) with a brief discussion on Minimizing Stress-Related Effects (9.1.), and a final section explaining why Parameters routinely measured are appropriate for assessing the role of stress in toxicology studies (9.2.).
The need for thoracic surgery in adult patients receiving extracorporeal membrane oxygenation: a 16-year experience
Authors: Joshi V , Harvey C , Nakas A , Waller DA , Peek GJ , Firmin R 
Published: March 2013

Objectives: Patients on extracorporeal membrane oxygenation (ECMO) are at risk from thoracic complications such as bleeding or pneumothorax, which may subsequently necessitate thoracic surgical intervention. We aimed to: 1) analyse the indication and nature of thoracic surgical intervention in these patients and 2) analyse the effect of a change in the ECMO circuit from roller pump to centrifugal pump on transfusion requirements pre and post thoracotomy. Methods: We retrospectively reviewed a prospectively collected database of 569 adults put on ECMO between 1995 and 2011. Patients undergoing thoracotomy were identified and outcomes were statistically analysed. Results: Forty thoracotomies were performed in 18 patients [61% male, median age 31 (14-56) years, one bilateral procedure]. The indications for ECMO included: pneumonia 14/18 (78%), trauma 2/18 (11%) and other 2/18 (11%). Median duration on ECMO was 13 (1–257) days and the time to initial thoracotomy was 10 (1-183) days. The indications for thoracotomy were: excessive bleeding post chest drain insertion (11/19, 58%), uncontrolled air leak (9/19, 47%) and pleural effusion (4/19, 21%). The primary operations were 12/19 (63%) evacuation of haemothorax, 3/19 (16%) lung repair, 2/19 (11%) diagnostic lung biopsy and 2/19 (11%) other. Ten patients needed a further 21 thoracotomies (3 lobectomies); average 2 (1-5) per patient. In total, 30/40 (75%) thoracotomies were performed for bleeding complication. The change from roller to centrifugal pump trended towards a reduction in mean transfusion requirements in these patients following thoracotomy (11.5 versus 4 units, p=0.14). The in-hospital mortality was 7/18 (39%) patients. There were no statistically significant predictors of poor outcome. Conclusions: The need for thoracotomy whilst on ECMO is 3.2% in this large series. Intervention may be complicated, thus, either ECMO specialists should have thoracic training or thoracic surgeons should be on-site. Potential mortality is high and, although not statistically significant, a difference in transfusion requirements was observed following the change of circuit.
A comparison of benign and inflammatory manifestations of Tolosa-Hunt syndrome
Authors: Hung Chih-Hsien , Chang Kuo-Hsuan , Wu Yi-Ming , Chen Yao-Liang , Lyu Rong-Kuo , Chang Hong-Shiu , Wu Yih-Ru , Chen Chiung-Mei , Huang Chin-Chang , Chu Chun-Che , Liao Ming-Feng , Wai Yau-Yau , Hsu Shih-Pin , Ro Long-Sun 
Published: March 2013

Background Tolosa-Hunt syndrome (THS) manifests as a benign or an inflammatory type disease. The nosography differences between these types remain to be elucidated. We aimed to analyze and compare the clinical presentations of benign and inflammatory THS. Methods The ward patients who presented with THS from January 1990 to May 2011 were retrospectively reviewed. THS was diagnosed according to the recommendations of the International Headache Society. Results Of the 53 THS cases (49 patients), 30 (56.6%) were classified as benign and 23 (43.4%) as inflammatory THS. There were strong similarities between the groups in terms of clinical manifestations, laboratory findings, responses to glucocorticoid treatment, and outcomes. However, patients with inflammatory THS tended to be younger (mean age, 43.4 years; p < 0.05) and have optic nerve dysfunction (56.5%; p < 0.05) and longer disease duration (2.3  ±  1.0 months; p < 0.05) compared to those with benign THS (mean age, 56.4 years; mean disease duration, 1.6  ±  0.7 months). The patients with additional involvement of both the optic nerve and the second division of the trigeminal nerve experienced a longer disease duration ( p < 0.05). Additionally, patients with orbital pseudotumors had diplopia that responded poorly to treatment with glucocorticoids ( p < 0.05). High-dose (>0.5  mg/kg/day) and low-dose (≤0.5  mg/kg/day) prednisolone were equally effective in relieving symptoms in both groups ( p >  0.05). Conclusion Benign and inflammatory THS were highly similar in terms of nosography. The responses to glucocorticoid treatment were generally good except in patients with orbital pseudotumors.
The typical duration of migraine aura: A systematic review
Authors: Viana Michele , Sprenger Till , Andelova Michaela , Goadsby Peter J 
Published: March 2013

Background According to ICHD-II, and as proposed for ICHD-III, non-hemiplegic migraine aura (NHMA) symptoms last between five and 60 minutes whereas hemiplegic migraine aura can be longer. In ICHD-III it is proposed to label aura longer than an hour and less than a week as probable migraine with aura. We tested whether this was appropriate based on the available literature. Methods We performed a systematic literature search identifying articles pertaining to a typical or prolonged duration of NHMA. We also performed a comprehensive literature search in order to identify all population-based studies or case series in which clinical features of NHMA, including but not restricted to aura duration, were reported, in order to gain a complete coverage of the available scientific data on aura duration. Results We did not find any article exclusively focusing on the prevalence of a prolonged aura or more generally on typical NHMA duration. We found 10 articles that investigated NHMA features, including the aura duration. Five articles recorded the proportion of patients in whom whole NHMA lasted for more than one hour, which was the case in 12%–37% of patients. Six articles reported some information on the duration of single NHMA symptoms: visual aura disturbances lasting for more than one hour occurred in 6%–10% of patients, sensory aura in 14%–27% of patients and aphasic aura in 17%–60% of patients. Conclusions The data indicate the duration of NHMA may be longer than one hour in a significant proportion of migraineurs. This seems to be especially true for non-visual aura symptoms. The term probable seems inappropriate in ICHD-III so we propose reinstating the category of prolonged aura for patients with symptoms longer than an hour and less than one week.
Reversible cerebral vasoconstriction syndrome with concurrent bilateral carotid artery dissection
Authors: Bayer-Karpinska Anna , Patzig Maximilian , Adamczyk Christopher , Dimitriadis Konstantinos , Wollenweber Frank A , Dichgans Martin , Jahn Klaus , Opherk Christian 
Published: March 2013

Background The pathophysiological basis of reversible cerebral vasoconstriction syndrome is poorly understood but carotid artery dissection has been discussed as a rare possible cause. So far, only single cases of unilateral carotid artery dissection and reversible cerebral vasoconstriction syndrome have been reported. Case Here, we describe the case of a 54-year old patient presenting to the emergency department with right hemiparesis, hypaesthesia and dysarthria. Furthermore, he reported two episodes of thunderclap headache after autosexual activity. Cerebral imaging showed ischaemic infarcts, slight cortical subarachnoid haemorrhage, bilateral carotid artery dissection and fluctuating intracranial vessel irregularities, compatible with reversible cerebral vasoconstriction syndrome. An extensive diagnostic work-up was normal. No typical trigger factors of reversible cerebral vasoconstriction syndrome could be found. The patient received intravenous heparin and the calcium channel blocker nimodipine. Follow-up imaging revealed no vessel irregularities, the left internal carotid artery was still occluded. Conclusion This case supports the assumption that carotid artery dissection should be considered as a potential trigger of reversible cerebral vasoconstriction syndrome, possibly by altering sympathetic vascular tone.
Repair of Peripheral Vertical Meniscus Lesions in Porcine Menisci
Authors: Lee Yee Han Dave , Nyland John , Burden Robert , Caborn David N.M. 
Published: March 2013

Background: All-inside meniscus repair eliminates the need for an extra incision and decreases neurovascular injury risk. Biomechanical testing can help delineate the efficacy of all-inside device use. Hypothesis: There would be no group differences between 4 peripheral meniscus repair techniques and 3 different devices tested. Study Design: Controlled laboratory study. Methods: Equivalent-sized menisci with attached tibiae were randomly assigned to 1 of 4 test groups (8 specimens each), as follows: group 1, Fast-Fix using No. 0 braided polyester suture; group 2, inside-out repair using 2-0 braided polyester suture; group 3, Sequent using No. 0 ultra–high molecular weight polyethylene (UHMWPE) suture in a continuous “N” configuration; and group 4, Sequent using No. 0 UHMWPE suture in an interrupted configuration. After placement in a clamp, specimens underwent preconditioning from 5 to 20 N for 10 cycles (0.1 Hz), 500 submaximal loading cycles from 5 to 20 N (0.5 Hz), and load-to-failure testing at 12.5 mm/s. A 30-second pause after 10 preconditioning cycles and after 10, 100, and 500 submaximal loading cycles enabled digital photographs to be taken for gapping measurements. Failure mode was recorded. Results: Specimens in group 3 withstood greater failure loads than did those in groups 1 and 4 ( P ≤ .027), and group 3 specimens were stiffer than those in groups 2 and 4 ( P ≤ .048). Displacement during submaximal loading and load-to-failure testing did not differ between groups. Groups 1, 3, and 4 each gapped less than group 2 during submaximal cyclic loading ( P ≤ .05). Groups 1 and 2 failed primarily by suture breakage ( P < .0001), while groups 3 and 4 failed primarily by the suture pulling free from an implant ( P < .0001). Conclusion: Sequent using No. 0 UHMWPE suture in a continuous “N” configuration displayed superior load at failure compared with repairs using Fast-Fix with No. 0 braided polyester suture and displayed greater stiffness and less gapping than inside-out repair using 2-0 braided polyester suture. The suture pulling free from an implant was the primary failure mode for Sequent using No. 0 UHMWPE suture regardless of whether a continuous “N” or an interrupted configuration was used. Study groups that used No. 0 UHMWPE sutures (groups 3 and 4) had more specimens fail by the suture pulling free from an implant. Compared with the weaker braided polyester suture in the inside-out and Fast-Fix groups, the No. 0 UHMWPE suture used in the Sequent groups likely influenced study results, as this suture has stronger material properties. However, the continuous “N” configuration likely also improved the performance of the Sequent with No. 0 UHMWPE suture, as failure load was significantly less with an interrupted configuration. Clinical Relevance: All-inside meniscus repair with continuous suture function may translate into improved patient outcomes.
Effect of nicotine pretreatment on arsenic-induced oxidative stress in male Wistar rats
Authors: Pachauri V. , Flora S.J.S. 
Published: March 2013

Humans are commonly exposed to nicotine, one of the most important lifestyle chemicals. The occurrence of high levels of arsenic in the groundwater of the southeast region of Asia has received much attention in the past decade and has become a global health concern. Predominant occurrence of both these chemicals and ease of their human exposure led us to investigate the effect of nicotine, a major tobacco alkaloid, on arsenic toxicity. Adult male rats were pre-exposed to two different doses of nicotine (0.75 and 3 mg/kg, intraperitoneally) for 7 days followed by 30 days of arsenic exposure (50 ppm sodium arsenite in drinking water). Nicotine pre-exposure resulted in an increased brain arsenic accumulation and a decreased liver arsenic concentration. Arsenic also caused a significant oxidative stress in the blood, brain and liver of the exposed rats. Glutathione- S-transferase, a phase II enzyme, was inhibited by both arsenic and nicotine but no such inhibition was noted in arsenic-treated animals pre-exposed to nicotine. Upon nicotine pre-exposure, brain acetylcholinesterase increased, while monoamine oxidase (MAO) decreased. The toxic effects of MAO significantly attenuated with nicotine pre-exposure. The present study suggests that nicotine may not be the major contributing factor for the previously reported synergistic toxic interaction between tobacco and arsenic. Nicotine pre-exposure in arsenic-exposed animals revealed interesting toxicokinetics and oxidative stress modulating interactions in the brain and liver of rats, which requires further exploration.
Electrophysiological study for comparing the effect of biological activity between type A botulinum toxins in rat gastrocnemius muscle
Authors: Kim C-S. , Jang W.S. , Son I.P. , Nam S.H. , Kim Y.I. , Park K.Y. , Kim B.J. , Kim M.N. 
Published: March 2013

Background: New cosmetic applications and products based on the effects of botulinum toxin (BTX) treatment have stimulated demand for this class of natural compounds. This demand generates the need for appropriate standardized protocols to test and compare the effectiveness of new BTX preparations. Objectives: Based on the previously described electrophysiological methods, we measured and compared the inhibitory effects of two BTX type A (BTX-A) preparations on neuromuscular transmission through split-body test. Methods: The effectiveness was evaluated in terms of the compound muscle action potential (CMAP) and conduction velocity after BTX-A injection. We used a split-body method to compare two different BTX-As in the rat. Results: Based on the changes in the CMAP, the two different BTX-As induced paralytic effect on the rat tibialis anterior muscle. However, the two different BTX-A preparations did not differ significantly in effectiveness and did not induce a delay in conduction velocity. Conclusions: The new BTX-A preparation used in this electrophysiological study had similar effect compared with the previously marketed BTX-A.[AQ: Please approve the edits made to the sentence “The new BTX-A preparation…”) We propose that a split-body electrophysiological protocol will be useful in establishing the comparative effectiveness of new BTX products.
Micro-abrasion study of some dental restorative materials and enamel
Authors: Peña A , Gallardo EA , Morán A , Bravo JA , Vite M 
Published: March 2013

Inside the mouth, tooth wear is a very complex phenomenon that occurs due to physiological, pathological, oral hygiene and orthodontics causes. Abrasion is a type of tooth wear, which causes severe damage compared to attrition, abfraction and erosion wear modes that occur simultaneously; principally on occlusal area during close phase of mastication process when abrasive particles from different sources are located between tooth and tooth or tooth and dental composite contact, designated as three-body abrasion wear in Tribology. ‘In vitro’ wear tests were carried out for three different dental composite restorative base resins, using the Micro-scale TE 66 wear test machine that offers the possibility to reproduce micro-abrasive wear (three-body rolling wear). Two different slurries were used; distillate water and artificial saliva containing SiC abrasive particles, F 1200 4 µm. Three dental composites materials and human enamel were tested at 0.25 N load applied, 0.1 m/s speed ball, 7.98 m sliding distance and 22% of volume containing SiC, at room temperature. Lost volume and wear coefficient, k, were calculated. Scanning electron microscopic and atomic force microscopic images were obtained and wear scars were analysed in order to identify wear mechanisms, such as ploughing, cutting and microcraking. Also, brittle delamination was found only for human enamel.
Primary Repair of Internal Carotid Artery Aneurysm Secondary to Kinking and Cystic Medial Degeneration
Authors: Nenezic Dragoslav , Tanaskovic Slobodan , Radak Djordje , Babic Srdjan , Gajin Predrag 
Published: March 2013

Introduction: In this report, we aim to present a very rare case of internal carotid artery (ICA) aneurysm secondary to kinking and cystic medial degeneration. Case report: A 66-year-old female patient was admitted to our institution for multidetector computed tomography (MDCT) angiography of supra-aortic trunks. On admission, she complained of occasional dizziness; 2 months earlier ascending aorta reconstruction was done for aneurysmal disease. Color Doppler ultrasonography and MDCT arteriography revealed significant right ICA kinking associated with large aneurysm, 24.6 × 24.5 mm2 in diameter. Aneurysm resection was done followed by ICA reconstruction by end-to-end anastomosis. Pathohistological findings of aneurysmal sac revealed cystical medial degeneration with inflammatory infiltrate mostly consisting of lymphocytes and fibrovascular proliferation. Conclusion: This is the first case that describes mutual contribution of cystic medial degeneration and ICA kinking in carotid aneurysm disease etiology successfully treated by aneurysm resection.
Santarus, Inc. v. Par Pharmaceutical, Inc.: Is there a new written description requirement for negative limitations?
Authors: Rein Frederick H , Crystal Joseph B 
Published: March 2013

In Santarus, Inc. et al. v. Par Pharmaceutical, Inc., 694 F.3d 1344 (Fed. Cir. 2012), the Federal Circuit addressed the written description requirement for patent claims containing a negative limitation (i.e., “wherein the composition contains no sucralfate”). This case report presents the context surrounding that issue including the concern by one Federal Circuit judge that a new written description requirement was created for negative claim limitations that would “taint large numbers of issued patents.”
Clinical management of infections caused by multidrug-resistant Enterobacteriaceae
Authors: Delgado-Valverde Mercedes , Sojo-Dorado Jesús , Pascual Álvaro , Rodríguez-Baño Jesús 
Published: March 2013

Enterobacteriaceae showing resistance to cephalosporins due to extended-spectrum β-lactamases (ESBLs) or plasmid-mediated AmpC enzymes, and those producing carbapenemases have spread worldwide during the last decades. Many of these isolates are also resistant to other first-line agents such as fluoroquinolones or aminoglycosides, leaving few available options for therapy. Thus, older drugs such as colistin and fosfomycin are being increasingly used. Infections caused by these bacteria are associated with increased morbidity and mortality compared with those caused by their susceptible counterparts. Most of the evidence supporting the present recommendations is from in vitro data, animal studies, and observational studies. While carbapenems are considered the drugs of choice for ESBL and AmpC producers, recent data suggest that certain alternatives may be suitable for some types of infections. Combined therapy seems superior to monotherapy in the treatment of invasive infections caused by carbapenemase-producing Enterobacteriaceae. Optimization of dosage according to pharmacokinetics/pharmacodynamics data is important for the treatment of infections caused by isolates with borderline minimum inhibitory concentration due to low-level resistance mechanisms. The increasing frequency and the rapid spread of multidrug resistance among the Enterobacteriaceae is a true and complex public health problem.
IL-12 receptor β1 deficiency alters in vivo T follicular helper cell response in humans
Authors: Schmitt Nathalie , Bustamante Jacinta , Bourdery Laure , Bentebibel Salah Eddine , Boisson-Dupuis Stephanie , Hamlin Fran , Tran Mau V. , Blankenship Derek , Pascual Virginia , Savino Daniel A. , Banchereau Jacques , Casanova Jean-Laurent , Ueno Hideki 
Published: March 2013

Key PointsIL-12Rβ1–deficient subjects displayed substantially less circulating memory Tfh and memory B cells than control subjects. The IL-12–STAT4 axis is associated with the development and functions of Tfh cells in vivo in humans.
Soluble vascular endothelial growth factor receptor 3 is essential for corneal alymphaticity
Authors: Singh Nirbhai , Tiem Michelle , Watkins Ryan , Cho Yang Kyung , Wang Ying , Olsen Thomas , Uehara Hironori , Mamalis Christina , Luo Ling , Oakey Zackery , Ambati Balamurali K. 
Published: March 2013

Key Points
Endogenous sVEGFR-3 that is expressed by the cornea binds and sequesters VEGF-C and is critical for corneal alymphaticity. sVEGFR-3 overexpression enhances murine corneal graft transplant survival 5-fold by blocking lymphangiogenesis and hemangiogenesis.
BCL6 breaks occur at different AID sequence motifs in Ig–BCL6 and non-Ig–BCL6 rearrangements
Authors: Lu Zhengfei , Tsai Albert G. , Akasaka Takashi , Ohno Hitoshi , Jiang Yanwen , Melnick Ari M. , Greisman Harvey A. , Lieber Michael R. 
Published: March 2013

Key Points
Chromosomal breaks in BCL6 translocations occur at two distinct DNA sequence motifs associated with AID activity. Motif usage correlates with the type of BCL6 partner gene, suggesting mechanistic differences between Ig–BCL6 and non-Ig–BCL6 rearrangements.
A specific antidote for dabigatran: functional and structural characterization
Authors: Schiele Felix , van Ryn Joanne , Canada Keith , Newsome Corey , Sepulveda Eliud , Park John , Nar Herbert , Litzenburger Tobias 
Published: March 2013

Key Points
We present an antidote for dabigatran that effectively reverses its anticoagulative effect in human plasma in vitro and in rats in vivo. The antidote shares structural features with thrombin in the mode of binding but has no activity in coagulation tests.