bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute renal failure following laparoscopic cholecystectomy
Authors: Briscoe Jessica Helen Rachel , Bahal Vijay
Published: November 2012

A 67-year-old man underwent a laparoscopic cholecystectomy, which was complicated by an empyematous gallbladder. Postoperatively, he was found to have acute renal failure (evidenced by abdominal distension and pain, anuria and vomiting). This was thought to be secondary to pneumoperitoneum, an essential part of the laparoscopic procedure.
Spontaneous gastric perforation in 11-year-old boy with anorexia nervosa: rare presentation with right iliac fossa pain
Authors: Darji Parth , Gandhi Viplav , Banker Hiral , Chaudhari Hemang D
Published: November 2012

This article has been withdrawn.
Syncope in a patient being treated for hepatic and intestinal amoebiasis
Authors: Yelve Kavita , Phatak Sanat , Patil Meenakshi Amit , Pazare Amar R
Published: November 2012

A 63-year-old man presented to our hospital with amoebic liver abscess and was treated successfully for the same. During the course of his treatment, he developed syncopal attacks and was found to have Torsades de Pointes on electrocardiogram. The patient was treated with intravenous magnesium and direct current cardioversion. Hypokalaemia, chloroquine and sepsis were suspected to have precipitated the arrhythmia. The patient remained arrhythmia-free following the correction of these factors.
Hibernoma of the thigh: a lipoma-like variant rare tumour mimicking soft tissue sarcoma
Authors: Gavriilidis Paschalis , Panselinas Grigorios , Zafiriou Georgios
Published: November 2012

A 43-year-old Caucasian woman appeared with painless progressively enlarging tumour of the anterior part of the left thigh of approximately 6 months’ duration. A differential imaging diagnosis of liposarcoma or large lipoma was made. An excisional biopsy was performed with complete removal of a large lobulated and encapsulated grossly ovoid mass. Frozen section diagnosis was unidentified lipomatous tumour with no evidence of malignancy. The final pathological diagnosis was lipoma-like hibernoma. The patient's postoperative course was uneventful and discharged on the seventh postoperative day with full function of the involved leg. Hibernoma is benign tumour and it is not known to recur after complete local excision which is the treatment of choice.
An unusual effect of interferential therapy
Authors: Keramat Keramat Ullah , Gaughran Aisling
Published: November 2012

In this report, a patient with severe shoulder pain was treated with interferential currents, a commonly used modality in physiotherapy for the management of pain. He reported loss of concentration, drowsiness, decreased alertness and gait disturbance, along with analgaesia, for 4–5 h after each treatment. He was regularly taking tramadol HCl for pain relief. Endogenous opioids produced in response to interferential therapy may be excessive or may interact with the tramadol HCl and potentiate its effect. There is no published report of interferential-induced symptoms, as described above, in the authors’ knowledge. The clinician using interferential currents should be aware of this possible effect.
Spontaneous pneumothorax in a patient with granulomatosis with polyangiitis
Authors: Kahraman Hasan , Inci Mehmet Fatih , Tokur Mahmut , Cetin Gozde Yildirim
Published: November 2012

Granulomatosis with polyangiitis (GPA) (Wegener's) is a multiorgan system disease of unknown aetiology characterised by granulomatous inflammation, tissue necrosis and vasculitis. The characteristic lung parenchymal lesions of GPA are firm spherical nodules that may cavitate. Pneumothorax (PX) can develop as a quiet rare complication of cavitary nodules. Our case admitted to our clinic with the diagnosis of GPA showing cavitary pulmonary mass. While taking immunosuppressive treatment, spontaneous PX on left lung was developed. A closed chest tube was inserted to the left lung for expansion of PX. Even after 30 days, the left lung did not re-expand and wedge resection with thoracotomy was conducted and the closed chest tube was still in the left lung. On the seventh day, empyema emerged as a complication and, with appropriate treatment, the patient became well. In GPA patients taking immunosuppressive medication, PX is a serious complication and requires aggressive therapy with broad-spectrum antibiotics.
Varying uses of the ABCD2 scoring system in primary and secondary care: a qualitative study
Authors: Edwards Duncan , Cohn Simon R , Mavaddat Nahal , Virdee Satnam K , Lasserson Daniel , Milner Siobhan , Giles Matthew , McManus Richard , Mant Jonathan
Published: November 2012

Objectives

To explore the usage of the ABCD2 risk stratification score by general practitioners (GPs) and hospital staff during the referral of patients with suspected transient ischaemic attack (TIA) or minor stroke.

Design

Qualitative study using semistructured interviews.

Setting

Nine general practices and two hospital sites in England (Birmingham and Cambridge).

Participants

Nine GPs and nine hospital staff (two consultants, four nurses, two ultrasonographers and one administrator).

Results

In both sites, clinicians used a referral proforma based around the ABCD2 scoring system for a range of purposes including self-education, to assist emphasising urgency to the patient, as a referral pathway facilitator and as a diagnostic tool. Negative views of its role included potential medicolegal threats, that it was a barrier to appropriate care, and led to misdiagnoses. Despite having differing uses by different clinicians, the ABCD2 proforma was the central means of interprofessional communication in TIA referrals across both sites.

Conclusions

Understanding how prediction rules are used in practice is key to determining their impact on processes of care and clinical outcomes. In practice, GPs and their colleagues use the ABCD2 score in subtly different ways and it functions as a ‘boundary object’ by both accommodating these multiple purposes, yet still successfully aiding communication between them.
Does prior coronary artery bypass surgery alter the gender gap in patients presenting with acute coronary syndrome? A 20-year retrospective cohort study
Authors: Al-Aqeedi Rafid Fayadh , Al Suwaidi Jassim , Singh Rajvir , Al Binali Hajar A
Published: November 2012

Objectives

Previous studies demonstrated women presenting with acute coronary syndrome (ACS) have poor outcomes when compared with men ‘the gender gap phenomenon’. The impact of prior coronary artery bypass graft (CABG) on women presenting with ACS is unknown. We hypothesised that the gender gap is altered in ACS patients with prior CABG. The aim of this study was to evaluate patients presenting with ACS according to their gender and history of prior CABG.

Design

Retrospective, observational (cohort) study.

Setting

Data were collected from hospital-based registry of patients hospitalised with ACS in Doha, Qatar, from 1991 through 2010. The data were analysed according to their gender and history of prior CABG.

Participants

A total of 16 750 consecutive patients with ACS were studied. In total, 693 (4.3%) patients had prior CABG; among them 125 (18%) patients were women.

Primary and secondary outcome measures

Comparisons of clinical characteristics, inhospital treatment, and outcomes, including inhospital mortality and stroke were made.

Results

Women with or without prior CABG were older, less likely to be smokers, but more likely to have diabetes mellitus (DM), hypertension and renal impairment than men (p=0.001). Women were less likely to receive reperfusion and early invasive therapies. When compared with men, women without prior CABG carried higher inhospital mortality (11% vs 4.9%; p=0.001) and stroke rates (0.9% vs 0.3%; p=0.001). Female gender was independent predictor of poor outcome. Among prior CABG patients, despite the fact that women had worse baseline characteristics and were less likely to receive evidence-based therapy, there were no significant differences in mortality or stroke rates between the two groups.

Conclusions

Consistent with the world literature, women presenting with ACS and without prior CABG had higher death rates compared with men. Patients with prior CABG had comparable death rates regardless of the gender status.
Prophylactic antibiotic regimens in tumour surgery (PARITY): protocol for a multicentre randomised controlled study
Authors: Ghert Michelle , Deheshi Benjamin , Holt Ginger , Randall R Lor , Ferguson Peter , Wunder Jay , Turcotte Robert , Werier Joel , Clarkson Paul , Damron Timothy , Benevenia Joseph , Anderson Megan , Gebhardt Mark , Isler Marc , Mottard Sophie , Healey John , Evaniew Nathan , Racano Antonella , Sprague Sheila , Swinton Marilyn , Bryant Dianne , Thabane Lehana , Guyatt Gordon , Bhandari Mohit ,   The PARITY Investigators
Published: November 2012

Introduction

Limb salvage with endoprosthetic reconstruction is the standard of care for the management of lower-extremity bone tumours in skeletally mature patients. The risk of deep postoperative infection in these procedures is high and the outcomes can be devastating. The most effective prophylactic antibiotic regimen remains unknown, and current clinical practice is highly varied. This trial will evaluate the effect of varying postoperative prophylactic antibiotic regimens on the incidence of deep infection following surgical excision and endoprosthetic reconstruction of lower-extremity bone tumours.

Methods and analysis

This is a multicentre, blinded, randomised controlled trial, using a parallel two-arm design. 920 patients 15 years of age or older from 12 tertiary care centres across Canada and the USA who are undergoing surgical excision and endoprosthetic reconstruction of a primary bone tumour will receive either short (24 h) or long (5 days) duration postoperative antibiotics. Exclusion criteria include prior surgery or infection within the planned operative field, known colonisation withmethicillin-resistant Staphylococcus aureusorvancomycin-resistant Enterococcusat enrolment, or allergy to the study antibiotics. The primary outcome will be rates of deep postoperative infections in each arm. Secondary outcomes will include type and frequency of antibiotic-related adverse events, patient functional outcomes and quality-of-life scores, reoperation and mortality. Randomisation will be blocked, with block sizes known only to the methods centre responsible for randomisation, and stratified by location of tumour and study centre. Patients, care givers and a Central Adjudication Committee will be blinded to treatment allocation. The analysis to compare groups will be performed using Cox regression and log-rank tests to compare survival functions at α=0.05.

Ethics and dissemination

This study has ethics approval from the McMaster University/Hamilton Health Sciences Research Ethics Board (REB# 12-009). Successful completion will significantly impact on clinical practice and enhance patients’ lives. More broadly, this trial will develop a network of collaboration from which further high-quality trials in Orthopaedic Oncology will follow.
Endoscopic retrograde cholangiopancreatography: is the centre better? The case against centralisation of ERCP services
Authors: Muller A Frank
Published: November 2012

More than 48 000 endoscopic retrograde cholangiopancreatographies (ERCP) are performed in the UK per annum; the majority within district general hospitals. The proposal for centralisation of ERCP services is based on evidence that technical success, length of stay and complication rates are related to the numbers of procedures performed. Local units wishing to continue their ERCP practice, must demonstrate that they are performing sufficient numbers of procedures in a safe, timely and competent fashion.
Does recall of preinjury disability change over time?
Authors: Williamson Owen D , Gabbe Belinda J , Sutherland Ann M , Hart Melissa J ,   on behalf of the Victorian Orthopaedic Trauma Outcome Registry Project Group
Published: November 2012

Background

Pre-injury disability must be determined when assessing whether treatment programs return people to pre-injury status, however there is little empirical evidence to support recommendations that this be done as soon as possible after injury to prevent recall bias.

Objectives

To determine disagreement between recall of pre-injury disability at different time points post-injury and bias towards under- or overestimating pre-injury disability.

Methods

Self-reported pre-injury global disability was assessed within days, 6 months and 12 months post-injury in patients admitted to two level 1 adult trauma centres. Kappa statistics and multiple logistic regression models identified predictors of disagreement between time-points.

Results

Pre-injury disability was measured at all time-points in 801 patients. Pre-injury disability at baseline was rated as none, mild, moderate, marked and severe in 80%, 12%, 5.1%, 1.9% and 1.0% respectively. Absolute agreement between baseline and 6 and 12 months respectively, was 79% and 80%. Corresponding kappa values (95% confidence intervals) were 0.33 (0.26−0.40) and 0.32 (0−25−0.38). Patients over 65 years or not completing high school were more likely to report less pre-injury disability at 6 and 12 months than at baseline with adjusted odds ratios (95% confidence intervals) for these groups being 8.24 (4.32−15.72) and 1.93 (1.03−3.64) respectively.

Conclusions

There was little evidence of recall bias in an adult trauma population if self-reported global pre-injury disability was assessed 6 months post-injury. The recall of pre-injury disability up to 6 months post-injury can be used to determine return to pre-injury status, if assessment is not feasible shortly after injury.
Why more male pedestrians die in vehicle-pedestrian collisions than female pedestrians: a decompositional analysis
Authors: Zhu Motao , Zhao Songzhu , Coben Jeffrey H , Smith Gordon S
Published: November 2012

Objective

Pedestrians account for a third of the 1.2 million traffic fatalities annually worldwide, and men are overrepresented. We examined the factors that contribute to this male-female discrepancy: walking exposure (kilometres walked per person-year), vehicle-pedestrian collision risk (number of collisions per kilometres walked) and vehicle-pedestrian collision case fatality rate (number of deaths per collision).

Design

The decomposition method quantifies the relative contributions (RCs) of individual factors to death rate ratios among groups. The male-female ratio of pedestrian death rates can be expressed as the product of three component ratios: walking exposure, collision risk and case fatality rate. Data sources included the 2008–2009 US Fatality Analysis Reporting System, General Estimates System, National Household Travel Survey and population estimates.

Setting

USA.

Participants

Pedestrians aged 5 years and older.

Main outcome measures

Death rate per person-year, kilometres walked per person-year, collisions per kilometres walked and deaths per collision by sex.

Results

The pedestrian death rate per person-year for men was 2.3 times that for women. This ratio of male to female rates can be expressed as the product of three component ratios: 0.995 for walking exposure, 1.191 for collision risk and 1.976 for case fatality rate. The RCs of these components were 1%, 20% and 79%, respectively.

Conclusions

The majority of the male-female discrepancy in 2008–2009 pedestrian deaths in the US is attributed to a higher fatality per collision rate among male pedestrians.
Vegetative growth response of black cherry (Prunus serotina) to different mechanical control methods in a biosphere reserve
Authors: Annighöfer Peter , Schall Peter , Kawaletz Heike , Mölder Inga , Terwei André , Zerbe Stefan , Ammer Christian
Published: November 2012

We assessed the effectiveness of different management strategies against the non-native invasive tree species black cherry ( Prunus serotina Ehrh.). The species causes substantial management problems in European forest ecosystems, like the Valle del Ticino Biosphere Reserve in Italy, by suppressing the regeneration of native tree species. This can modify ecological key processes and cause biodiversity loss. Since chemical and biological control has mainly been abandoned in European forest ecosystem management, mechanical control measures are presently the preferred option to proceed against the black cherry but have shown very limited results in the reserve. The aim was to control the success of felling the species and to test other mechanical control methods such as girdling and snapping the trees with regard to their efficiency by quantifying the species’ growth reactions. For this purpose, observational studies were conducted in two forest stands of which one was treated in 1996 and the other more recently in 2009. A subsample of resprouting stumps was treated a second time in 2010 to observe the effect of a direct second cutback. An experimental study was implemented in a third forest stand also in 2010 to compare three different mechanical control methods. The results suggest that felling black cherry is ineffective if the objective is to reduce the species’ abundance because resprouts occur on 100% of the treated trees and biomass increment is not reduced in the long term. Girdling proved to be the most effective treatment across the diameter classes considered.
The relative contributions of seed bank, seed rain, and understory vegetation dynamics to the reorganization of Tsuga canadensis forests after loss due to logging or simulated attack by Adelges tsugae
Authors: Farnsworth Elizabeth J. , Barker Plotkin Audrey A. , Ellison Aaron M.
Published: November 2012

Profound changes are occurring in forests as native insects, nonnative insects, or pathogens irrupt on foundation tree species; comprehensive models of vegetation responses are needed to predict future forest composition. We experimentally simulated hemlock woolly adelgid ( Adelges tsugae Annand) infestation (by girdling trees) and preemptive logging of eastern hemlock ( Tsuga canadensis (L.) Carrière) and compared vegetation dynamics in replicate 90 m × 90 m treatment plots and intact hemlock stands from 2004 to 2010. Using Chao–Sørensen abundance-based similarity indices, we assessed compositional similarities of trees, shrubs, forbs, and graminoids among the seed bank, seed rain, and standing vegetation over time and among treatments. Post-treatment seed rain, similar among treatments, closely reflected canopy tree composition. Species richness of the seed bank was similar in 2004 and 2010. Standing vegetation in the hemlock controls remained dissimilar from the seed bank, reflecting suppressed germination. Recruits from the seed rain and seed bank dominated standing vegetation in the logged treatment, whereas regeneration of vegetation from the seed bank and seed rain was slowed due to shading by dying hemlocks in the girdled treatment. Our approach uniquely integrates multiple regeneration components through time and provides a method for predicting forest dynamics following loss of foundation tree species.
Variations in salt expulsion style within the Sable Canopy Complex, central Scotian margin1This article is one of a series of papers published in this CJES Special Issue on the theme ofMesozoic–Cenozoic geology of the Scotian Basin.
Authors: Kendell Kristopher L.
Published: November 2012

There are two allochthonous salt canopies within the central Scotian margin, one on the shelf and another in deeper waters on the Scotian slope. The Sable Shelf Canopy trends southwest–northeast and covers an area approximately 650 km2. Salt thickness within this canopy is generally <1000 m. Reloading of the salt has welded out the margins of the canopy, significantly reducing its extent. Salt tectonics related to this canopy produced many of the exploration targets drilled on the shelf. The Sable Slope Canopy is 50 km basinward on the Scotian slope. This canopy is significantly larger, covering 12 700 km2, and the allochthonous salt is as thick as 3500 m. Although the two canopies are separated by a significant distance, a common detachment surface connects them in multiple locations. Extensional systems detach in the Sable Shelf Canopy, displace strata downdip, and expel salt into the Sable Slope Canopy. The outer shelf and slope region separating these two canopies is dominated by detachment systems. One term, the Sable Canopy Complex, was developed to describe both salt canopies and the zone of detachment that separates them. Interpretation of two-dimensional and three-dimensional seismic data throughout the Sable Canopy Complex has resulted in a detailed allochthonous salt map and all related components including welded systems, salt stocks, faults, sutures, and minibasins. Four distinct expulsion styles are observed to contribute volumes of salt to the canopies: salt-based detachments, counterregional systems, hybrids, and salt stocks. Potential explanations for the variations in expulsion style range from varying volumes of sediment input to paleogeographic positions on the margin to salt sheet length.
Construction and analysis of an SSH cDNA library of early heat-induced genes ofVigna aconitifoliavariety RMO-40
Authors: Rampuria Sakshi , Joshi Uma , Palit Paramita , Deokar Amit A. , Meghwal Raju R. , Mohapatra T. , Srinivasan R. , Bhatt K.V. , Sharma Ramavtar
Published: November 2012

Moth bean ( Vigna aconitifolia (Jacq.) Marechal) is an important grain legume crop grown in rain fed areas of hot desert regions of Thar, India, under scorching sun rays with very little supplementation of water. An SSH cDNA library was generated from leaf tissues of V. aconitifolia var. RMO-40 exposed to an elevated temperature of 42 °C for 5 min to identify early-induced genes. A total of 488 unigenes (114 contigs and 374 singletons) were derived by cluster assembly and sequence alignment of 738 ESTs; out of 206 ESTs (28%) of unknown proteins, 160 ESTs (14%) were found to be novel to moth bean. Only 578 ESTs (78%) showed significant BLASTX similarity (<1 × 10–6) in the NCBI non-redundant database. Gene ontology functional classification terms were retrieved for 479 (65%) sequences, and 339 sequences were annotated with 165 EC codes and mapped to 68 different KEGG pathways. Four hundred and fifty-two ESTs were further annotated with InterProScan (IPS), and no IPS was assigned to 153 ESTs. In addition, the expression level of 27 ESTs in response to heat stress was evaluated through semiquantitative RT–PCR assay. Approximately 20 different signaling genes and 16 different transcription factors have been shown to be associated with heat stress in moth bean for the first time.
DEVELOPING DYNAMIC CAPABILITIES TO MEET SUSTAINABLE DEVELOPMENT CHALLENGES
Authors: CASTIAUX ANNICK
Published: November 2012

Dynamic capabilities are recognized as key factors for the adaptation of the firm to its changing environment. For two decades, a new pressure has been added on the shoulders of firms: they have to integrate sustainable development considerations in their strategy. This paper explores the impact of those new sustainability requirements on the dynamic capabilities that a firm should develop and sustain to remain competitive in turbulent environments. In particular, which new innovation capabilities are required to integrate environmental, social and financial objectives? To answer this question, we first consider the dynamicity levels identified in the literature in relationship with the turbulence of the firm's environment and we study what level is required for which type of sustainable innovation. Secondly, we look at the three fundamental natures of dynamic capabilities (sensing, seizing, transforming) and identify typical new requirements coming from sustainability challenges. We apply this reflection to Green IT innovations.
TRPV2 ion channels expressed in inhibitory motor neurons of gastric myenteric plexus contribute to gastric adaptive relaxation and gastric emptying in mice
Authors: Mihara Hiroshi , Suzuki Nobuhiro , Yamawaki Hidemoto , Tominaga Makoto , Sugiyama Toshiro
Published: November 2012

Gastric adaptive relaxation (GAR) is impaired in ∼40% of functional dyspepsia (FD) patients, and nitric oxide (NO) released from inhibitory motor neurons plays an important role in this relaxation. Although the underlying molecular mechanism of GAR is poorly understood, transient receptor potential channel vanilloid 2 (TRPV2) mechano- and chemoreceptors are expressed in mouse intestinal inhibitory motor neurons and are involved in intestinal relaxation. The aim of this study was to evaluate the distribution of TRPV2 in inhibitory motor neurons throughout the mouse gastrointestinal tract and the contribution of TRPV2 to GAR. RT-PCR and immunohistochemical analyses were used to detect TRPV2 mRNA and protein, respectively. Intragastric pressure was determined with an isolated mouse stomach. Gastric emptying (GE) in vivo was determined using a test meal. TRPV2 mRNA was detected throughout the mouse gastrointestinal tract, and TRPV2 immunoreactivity was detected in 84.3% of neuronal nitric oxide synthase-expressing myenteric neurons in the stomach. GAR, which was expressed as the rate of decline of intragastric pressure in response to volume stimuli, was significantly enhanced by the TRPV2 activator probenecid, and the enhancement was inhibited by the TRPV2 inhibitor tranilast. GE was significantly accelerated by TRPV2 agonist applications, and the probenecid-induced enhancement was significantly inhibited by tranilast coapplication. Mechanosensitive TRPV2 was expressed in inhibitory motor neurons in the mouse stomach and contributed to GAR and GE. TRPV2 may be a promising target for FD patients with impaired GAR.
Reduced ENaC activity and blood pressure in mice with genetic knockout of the insulin receptor in the renal collecting duct
Authors: Li Lijun , Garikepati R. Mayuri , Tsukerman Susanna , Kohan Donald , Wade James B. , Tiwari Swasti , Ecelbarger Carolyn M.
Published: November 2012

To elucidate the role of the insulin receptor (IR) in collecting duct (CD), we bred mice with IR selectively deleted from CD principal cells using an aquaporin-2 promoter to drive Cre-recombinase expression. Young, adult male knockout (KO) mice had altered plasma and electrolyte homeostasis under high- (HS) and low-sodium (LS) diets, relative to wild-type (WT) littermates. One week of LS feeding led to a significant reduction in urine potassium (K+) and sodium (Na+) excretion in KO, and a reduction in the ratio of Na+to chloride (Cl−) in plasma, relative to WT. HS diet (1 wk) increased plasma K+and reduced urine Na+to Cl−ratio in the KO. Furthermore, KO mice had a significantly ( P = 0.025) blunted natriuretic response to benzamil, an epithelial sodium channel (ENaC) antagonist. Western blotting of cortex homogenates revealed modestly, but significantly (∼15%), lower band density for the β-subunit of ENaC in the KO vs. WT mice, with no differences for the α- or γ-subunits. Moreover, blood pressure (BP), measured by radiotelemetry, was significantly lower in KO vs. WT mice under basal conditions (mmHg): 112 ± 5 (WT), 104 ± 2 (KO), P = 0.023. Chronic insulin infusion reduced heart rate in the WT, but not in the KO, and modestly reduced BP in the WT only. Overall, these results support a fundamental role for insulin through its classic receptor in the modulation of electrolyte homeostasis and BP.
Interaction between myoglobin and mitochondria in rat skeletal muscle
Authors: Yamada Tatsuya , Furuichi Yasuro , Takakura Hisashi , Hashimoto Takeshi , Hanai Yoshiteru , Jue Thomas , Masuda Kazumi
Published: November 2012

The mechanisms underlying subcellular oxygen transport mediated by myoglobin (Mb) remain unclear. Recent evidence suggests that, in the myocardium, transverse diffusion of Mb is too slow to effectively supply oxygen to meet the immediate mitochondrial oxygen demands at the onset of muscle contractions. The cell may accommodate the demand by maintaining the distribution of Mb to ensure a sufficient O2supply in the immediate vicinity of the mitochondria. The present study has verified the co-localization of Mb with mitochondria by using biochemical histological and electron microscopy analyses. Immunohistochemical and electron microscopy analysis indicates a co-localization of Mb with mitochondria. Western blotting confirms the presence of Mb colocalizes with the mitochondrial fraction and appears more prominently in slow-twitch oxidative than in fast-twitch glycolytic muscle. In particular, Mb interacts with cytochrome c oxidase-subunit IV. These results suggest that a direct Mb-mediated O2delivery to the mitochondria, which may play a potentially significant role for respiration.
Phasic bursts of the antagonistic jaw muscles during REM sleep mimic a coordinated motor pattern during mastication
Authors: Kato T. , Nakamura N. , Masuda Y. , Yoshida A. , Morimoto T. , Yamamura K. , Yamashita S. , Sato F.
Published: November 2012

Sleep-related movement disorders are characterized by the specific phenotypes of muscle activities and movements during sleep. However, the state-specific characteristics of muscle bursts and movement during sleep are poorly understood. In this study, jaw-closing and -opening muscle electromyographic (EMG) activities and jaw movements were quantified to characterize phenotypes of motor patterns during sleep in freely moving and head-restrained guinea pigs. During non-rapid eye movement (NREM) sleep, both muscles were irregularly activated in terms of duration, activity, and intervals. During rapid eye movement (REM) sleep, clusters of phasic bursts occurred in the two muscles. Compared with NREM sleep, burst duration, activity, and intervals were less variable during REM sleep for both muscles. Although burst activity was lower during the two sleep states than during chewing, burst duration and intervals during REM sleep were distributed within a similar range to those during chewing. A trigger-averaged analysis of muscle bursts revealed that the temporal association between the bursts of the jaw-closing and -opening muscles during REM sleep was analogous to the temporal association during natural chewing. The burst characteristics of the two muscles reflected irregular patterns of jaw movements during NREM sleep and repetitive alternating bilateral movements during REM sleep. The distinct patterns of jaw muscle bursts and movements reflect state-specific regulations of the jaw motor system during sleep states. Phasic activations in the antagonistic jaw muscles during REM sleep are regulated, at least in part, by the neural networks involving masticatory pattern generation, demonstrating that waking jaw motor patterns are replayed during sleep periods.
Task-dependent modulation of SI physiological responses to targets and distractors
Authors: Spingath Elsie , Kang Hyun-Sug , Blake David T.
Published: November 2012

Selective attention experimental designs have shown that neural responses to stimuli in primary somatosensory cortex are stronger when the sensory stimuli are task relevant. Other studies have used animals under no task demands for data collection. The relationship between neural responses in the brain during behavior, and while an animal has no task demands, remains underexplored. We trained two animals to perform somatosensory detection for several weeks, followed by somatosensory discrimination for several weeks. Data in response to physically identical stimuli were collected from cortical implants while the animal was under no task demands before each behavioral session and also during that behavioral session. The Fourier spectra of the field potentials during detection or discrimination compared with the no task condition demonstrated suppression of the somatosensory μ-rhythm that is associated with readiness and anticipation of cognitive use of somatosensory and motor inputs. Responses to the task target were stronger during detection and discrimination than in the no task condition. The amplitude normalized time course of the target evoked response was similar in both cases. Evoked responses to the task distractor were not significantly stronger during behavior than in recordings under no task demands. The normalized time course of the distractor responses showed a suppression that peaks 30–35 ms after the onset of the response. The selectivity of this within trial suppression is the same as the selectivity of enduring suppression evident in studies of sensory cortical plasticity, which suggests the same neural process may be responsible for both.
Short-term plasticity shapes activity pattern-dependent striato-pallidal synaptic transmission
Authors: Kim Juhyon , Kita Hitoshi
Published: November 2012

The cortico-striato (Str)-globus pallidus external segment (GPe) projection plays major roles in the control of neuronal activity in the basal ganglia under both normal and pathological conditions. The present study used rat brain-slice preparations to address our hypothesis that the gain of this disynaptic projection is dynamically controlled by activations of short-term plasticity mechanisms of Str-GPe synapses. The Str-GPe projection neurons fire with very different frequency and firing patterns in vivo depending on the condition of the animal. The results show that the Str-GPe synapses have very strong short-term enhancement mechanisms and that repetitive burst activation of the Str-GPe synapses, which mimic oscillatory burst firing of Str neurons, can sustain enhanced states of synaptic transmission for tens of seconds. The results reveal that the short-term enhancement of Str-GPe synapses contributes to the generation of pauses in the firing of GPe neurons and that signal transfer function in the Str-GPe projection is highly dependent on the firing pattern of Str neurons.
Individuals with cerebellar degeneration show similar adaptation deficits with large and small visuomotor errors
Authors: Schlerf John E. , Xu Jing , Klemfuss Nola M. , Griffiths Thomas L. , Ivry Richard B.
Published: November 2012

The cerebellum has long been recognized to play an important role in motor adaptation. Individuals with cerebellar ataxia exhibit impaired learning in visuomotor adaptation tasks such as prism adaptation and force field learning. Both types of tasks involve the adjustment of an internal model to compensate for an external perturbation. This updating process is error driven, with the error signal based on the difference between anticipated and actual sensory information. This process may entail a credit assignment problem, with a distinction made between error arising from faulty representation of the environment and error arising from noise in the controller. We hypothesized that people with ataxia may perform poorly at visuomotor adaptation because they attribute a greater proportion of their error to their motor control difficulties. We tested this hypothesis using a computational model based on a Kalman filter. We imposed a 20-deg visuomotor rotation in either a single large step or in a series of smaller 5-deg steps. The ataxic group exhibited a comparable deficit in both conditions. The computational analyses indicate that the patients' deficit cannot be accounted for simply by their increased motor variability. Rather, the patients' deficit in learning may be related to difficulty in estimating the instability in the environment or variability in their motor system.
Spectral inputs and ocellar contributions to a pitch-sensitive descending neuron in the honeybee
Authors: Hung Y.-S. , van Kleef J. P. , Stange G. , Ibbotson M. R.
Published: November 2012

By measuring insect compensatory optomotor reflexes to visual motion, researchers have examined the computational mechanisms of the motion processing system. However, establishing the spectral sensitivity of the neural pathways that underlie this motion behavior has been difficult, and the contribution of the simple eyes (ocelli) has been rarely examined. In this study we investigate the spectral response properties and ocellar inputs of an anatomically identified descending neuron (DNII2) in the honeybee optomotor pathway. Using a panoramic stimulus, we show that it responds selectively to optic flow associated with pitch rotations. The neuron is also stimulated with a custom-built light-emitting diode array that presented moving bars that were either all-green (spectrum 500–600 nm, peak 530 nm) or all-short wavelength (spectrum 350–430 nm, peak 380 nm). Although the optomotor response is thought to be dominated by green-sensitive inputs, we show that DNII2is equally responsive to, and direction selective to, both green- and short-wavelength stimuli. The color of the background image also influences the spontaneous spiking behavior of the cell: a green background produces significantly higher spontaneous spiking rates. Stimulating the ocelli produces strong modulatory effects on DNII2, significantly increasing the amplitude of its responses in the preferred motion direction and decreasing the response latency by adding a directional, short-latency response component. Our results suggest that the spectral sensitivity of the optomotor response in honeybees may be more complicated than previously thought and that ocelli play a significant role in shaping the timing of motion signals.
Characterizing the conductance underlying depolarization-induced slow current in cerebellar Purkinje cells
Authors: Kim Yu Shin , Kang Eunchai , Makino Yuichi , Park Sungjin , Shin Jung Hoon , Song Hongjun , Launay Pierre , Linden David J.
Published: November 2012

Brief strong depolarization of cerebellar Purkinje cells produces a slow inward cation current [depolarization-induced slow current (DISC)]. Previous work has shown that DISC is triggered by voltage-sensitive Ca influx in the Purkinje cell and is attenuated by blockers of vesicular loading and fusion. Here, we have sought to characterize the ion channel(s) underlying the DISC conductance. While the brief depolarizing steps that triggered DISC were associated with a large Ca transient, the onset of DISC current corresponded only with the Ca transient decay phase. Furthermore, substitution of external Na with the impermeant cation N-methyl-d-glucamine produced a complete and reversible block of DISC, suggesting that the DISC conductance was not Ca permeant. Transient receptor potential cation channel, subfamily M, members 4 (TRPM4) and 5 (TRPM5) are nonselective cation channels that are opened by Ca transients but do not flux Ca. They are expressed in Purkinje cells of the posterior cerebellum, where DISC is large, and, in these cells, DISC is strongly attenuated by nonselective blockers of TRPM4/5. However, measurement of DISC currents in Purkinje cells derived from TRPM4 null, TRPM5 null, and double null mice as well as wild-type mice with TRPM4 short hairpin RNA knockdown showed a partial attenuation with 35–46% of current remaining. Thus, while the DISC conductance is Ca triggered, Na permeant, and Ca impermeant, suggesting a role for TRPM4 and TRPM5, these ion channels are not absolutely required for DISC.
Targeting Galectin-1 Overcomes Breast Cancer-Associated Immunosuppression and Prevents Metastatic Disease
Authors: Dalotto-Moreno Tomás , Croci Diego O. , Cerliani Juan P. , Martinez-Allo Verónica C. , Dergan-Dylon Sebastián , Méndez-Huergo Santiago P. , Stupirski Juan C. , Mazal Daniel , Osinaga Eduardo , Toscano Marta A. , Sundblad Victoria , Rabinovich Gabriel A. , Salatino Mariana
Published: November 2012

Galectin-1 (Gal1), an evolutionarily conserved glycan-binding protein, contributes to the creation of an immunosuppressed microenvironment at sites of tumor growth. In spite of considerable progress in elucidating its role in tumor-immune escape, the mechanisms underlying the inhibitory functions of Gal1 remain obscure. Here, we investigated the contribution of tumor Gal1 to tumor growth, metastasis, and immunosuppression in breast cancer. We found that the frequency of Gal1+ cells in human breast cancer biopsies correlated positively with tumor grade, while specimens from patients with benign hyperplasia showed negative or limited Gal1 staining. To examine the pathophysiologic relevance of Gal1 in breast cancer, we used the metastatic mouse mammary tumor 4T1, which expresses and secretes substantial amounts of Gal1. Silencing Gal1 expression in this model induced a marked reduction in both tumor growth and the number of lung metastases. This effect was abrogated when mice were inoculated with wild-type 4T1 tumor cells in their contralateral flank, suggesting involvement of a systemic modulation of the immune response. Gal1 attenuation in 4T1 cells also reduced the frequency of CD4+CD25+ Foxp3+ regulatory T (Treg) cells within the tumor, draining lymph nodes, spleen, and lung metastases. Further, it abrogated the immunosuppressive function of Treg cells and selectively lowered the expression of the T-cell regulatory molecule LAT (linker for activation of T cells) on these cells, disarming their suppressive activity. Taken together, our results offer a preclinical proof of concept that therapeutic targeting of Gal1 can overcome breast cancer-associated immunosuppression and can prevent metastatic disease. Cancer Res; 73(3); 1107–17. ©2012 AACR.
Loss of miR-204 Expression Enhances Glioma Migration and Stem Cell-like Phenotype
Authors: Ying Zhe , Li Yun , Wu Jueheng , Zhu Xun , Yang Yi , Tian Han , Li Wei , Hu Bo , Cheng Shi-Yuan , Li Mengfeng
Published: November 2012

Phenotypic similarities have long been recognized between subpopulations of glioma and neural stem cells. Many of these similar properties, including the robust abilities to self-renew, migrate, and invade, are hallmarks of glioma cells that render them extremely aggressive. However, the molecular mechanisms underlying this character, particularly in glioma stem-like cells that drive this disease, remain poorly understood. Here, we report the results of a differential miRNA expression screen that compared glioma and neural stem cells, where we found that miR-204 was markedly downregulated in both types of cells. Mechanistic investigations revealed that miR-204 simultaneously suppressed self-renewal, stem cell-associated phenotype, and migration of glioma cells by targeting the stemness-governing transcriptional factor SOX4 and the migration-promoting receptor EphB2. Restoring miR-204 expression in glioma cells suppressed tumorigenesis and invasiveness in vivo and increased overall host survival. Further evaluation revealed that the miR-204 promoter was hypermethylated and that attenuating promoter methylation was sufficient to upregulate miR-204 in glioma cells. Together, our findings reveal miR-204 as a pivotal regulator of the development of stem cell-like phenotypes and cell motility in malignant glioma cells. Cancer Res; 73(2); 990–9. ©2012 AACR.
Gene Expression Profiles in Peripheral Blood Mononuclear Cells of Chinese Nickel Refinery Workers with High Exposures to Nickel and Control Subjects
Authors: Arita Adriana , Muñoz Alexandra , Chervona Yana , Niu Jingping , Qu Qingshan , Zhao Najuan , Ruan Ye , Kiok Kathrin , Kluz Thomas , Sun Hong , Clancy Hailey A. , Shamy Magdy , Costa Max
Published: November 2012

Background: Occupational exposure to nickel (Ni) is associated with an increased risk of lung and nasal cancers. Ni compounds exhibit weak mutagenic activity, alter the cell's epigenetic homeostasis, and activate signaling pathways. However, changes in gene expression associated with Ni exposure have only been investigated in vitro. This study was conducted in a Chinese population to determine whether occupational exposure to Ni was associated with differential gene expression profiles in the peripheral blood mononuclear cells (PBMC) of Ni-refinery workers when compared with referents.

Methods: Eight Ni-refinery workers and ten referents were selected. PBMC RNA was extracted and gene expression profiling was conducted using Affymetrix exon arrays. Differentially expressed genes (DEG) between both groups were identified in a global analysis.

Results: There were a total of 2,756 DEGs in the Ni-refinery workers relative to the referents [false discovery rate (FDR) adjusted P < 0.05] with 770 upregulated genes and 1,986 downregulated genes. DNA repair and epigenetic genes were significantly overrepresented (P < 0.0002) among the DEGs. Of 31 DNA repair genes, 29 were repressed in the Ni-refinery workers and 2 were overexpressed. Of the 16 epigenetic genes, 12 were repressed in the Ni-refinery workers and 4 were overexpressed.

Conclusions: The results of this study indicate that occupational exposure to Ni is associated with alterations in gene expression profiles in PBMCs of subjects.

Impact: Gene expression may be useful in identifying patterns of deregulation that precede clinical identification of Ni-induced cancers. Cancer Epidemiol Biomarkers Prev; 22(2); 261–9. ©2012 AACR.
Legal Status and Regulation of Complementary and Alternative Medicine in Europe
Authors: Wiesener Solveig , Falkenberg Torkel , Hegyi Gabriella , Hök Johanna , Roberti di Sarsina Paolo , Fønnebø Vinjar
Published: November 2012

Objective: The study aims to review the legal and regulatory status of complementary and alternative medicine (CAM) in the 27 European Union (EU) member states and 12 associated states, and at the EU/European Economic Association (EEA) level. Methods: Contact was established with national Ministries of Health, Law or Education, members of national and European CAM associations, and CAMbrella partners. A literature search was performed in governmental and scientific/non-scientific websites as well as the EUROPA and EUR-lex websites/ databases to identify documents describing national CAM regulation and official EU law documents. Results: The 39 nations have all structured legislation and regulation differently: 17 have a general CAM legislation, 11 of these have a specific CAM law, and 6 have sections on CAM included in their general healthcare laws. Some countries only regulate specific CAM treatments. CAM medicinal products are subject to the same market authorization procedures as other medicinal products with the possible exception of documentation of efficacy. The directives, regulations and resolutions in the EU that may influence the professional practice of CAM will also affect the conditions under which patients are receiving CAM treatment(s) in Europe. Conclusion: There is an extraordinary diversity with regard to the regulation of CAM practice, but not CAM medicinal products. This will influence patients, practitioners and researchers when crossing European borders. Voluntary harmonization is possible within current legislation. Individual states within culturally similar regions should harmonize their CAM legislation and regulation. This can probably safeguard against inadequately justified over- or underregulation at the national level.