bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hybrid technique for laparoscopic incisional ventral hernia repair combining laparoscopic primary closure and mesh repair
Authors: Yoshikawa Kozo , Shimada Mitsuo , Kurita Nobuhiro , Sato Hirohiko , Iwata Takashi , Higashijima Jun , Chikakiyo Motoya , Nishi Masaaki , Kashihara Hideya , Takasu Chie , Matsumoto Noriko , Eto Syohei 
Published: July 2014

AbstractIntroductionIncisional ventral hernia is one of the most common surgical complications after laparotomy. Laparoscopic repair of incisional ventral hernia has been conducted recently, and the advantages of this procedure have been reported. However, in large orifice cases, the recurrence rate is increased. To improve recurrence rates in large cases, a hybrid method combining laparoscopic primary closure and mesh repair can be applied.Materials and Surgical TechniqueMonofilament thread was inserted into the abdominal cavity for hernia closure and pulled from the other side of the orifice. The same procedure was performed from the upper side to the lower side without closure, and all thread was placed in line. Both sides of the thread were then introduced to the midline of the incision through a subcutaneous route. This procedure was conducted with an introducer. All threads were tied, and then a mesh was placed.DiscussionHybrid techniques already combine mini‐laparotomy for hernia closure and subsequent laparoscopic intraoperative onlay mesh for reinforcement, but such techniques require laparotomy. In our technique, closure of the linea alba does not require laparotomy. All procedures were performed laparoscopically. This procedure is very easy and safe, and does not require the abdominal cavity to be opened. Thus, hybrid methods are effective for treating cases of incisional hernia involving a large orifice.
Hand‐assisted laparoscopic splenectomy for sclerosing angiomatoid nodular transformation of the spleen complicated by chronic disseminated intravascular coagulation: A case report
Authors: Kakisaka Tatsuhiko , Kamiyama Toshiya , Yokoo Hideki , Orimo Tatsuya , Wakayama Kenji , Tsuruga Yosuke , Kamachi Hirofumi , Harada Taisuke , Kato Fumi , Yamada Yosuke , Mitsuhashi Tomoko , Taketomi Akinobu 
Published: July 2014

AbstractA 36‐year‐old man who presented with a nosebleed and anemia was referred to our hospital. Laboratory test results showed platelet depletion, decreased levels of fibrinogen, and increased fibrinogen degeneration products. CT showed a 13‐cm splenic tumor. T2‐weighted MRI revealed a high‐intensity mass. We preoperatively diagnosed splenic hemangioma with chronic disseminated intravascular coagulation and scheduled an operation to relieve the disseminated intravascular coagulation. We also performed hand‐assisted laparoscopic splenectomy to ensure easy handling of the splenomegaly. The resected specimen microscopically consisted of hemorrhages and hemangiomatous lesions, and multiple angiomatoid nodules were scattered and separated by fibrocollagenous stroma with inflammatory cells. Three types of vessels (capillaries, sinusoids and small veins) were contained in the angiomatoid nodules, and the pathological diagnosis was sclerosing angiomatoid nodular transformation. The results of this case suggest that we should consider sclerosing angiomatoid nodular transformation in the differential diagnosis of patients with splenic tumors, as sclerosing angiomatoid nodular transformation with hemangiomatous features may cause coagulation disorders for which splenectomy should be performed.
The neurosteroid 5β‐pregnan‐3α‐ol‐20‐one enhances actions of etomidate as a positive allosteric modulator of α1β2γ2L GABAA receptors
Authors: Li P , Bracamontes J R , Manion B D , Mennerick S , Steinbach J H , Evers A S , Akk G 
Published: July 2014

Background and PurposeNeurosteroids potentiate responses of the GABAA receptor to the endogenous agonist GABA. Here, we examined the ability of neurosteroids to potentiate responses to the allosteric activators etomidate, pentobarbital and propofol.Experimental ApproachElectrophysiological assays were conducted on rat α1β2γ2L GABAA receptors expressed in HEK 293 cells. The sedative activity of etomidate was studied in Xenopus tadpoles and mice. Effects of neurosteroids on etomidate‐elicited inhibition of cortisol synthesis were determined in human adrenocortical cells.Key ResultsThe neurosteroid 5β‐pregnan‐3α‐ol‐20‐one (3α5βP) potentiated activation of GABAA receptors by GABA and allosteric activators. Co‐application of 1 μM 3α5βP induced a leftward shift (almost 100‐fold) of the whole‐cell macroscopic concentration–response relationship for gating by etomidate. Co‐application of 100 nM 3α5βP reduced the EC50 for potentiation by etomidate of currents elicited by 0.5 μM GABA by about three‐fold. In vivo, 3α5βP (1mg kg‐1) reduced the dose of etomidate required to produce loss of righting in mice (ED50) by almost 10‐fold. In tadpoles, the presence of 50 or 100 nM 3α5βP shifted the EC50 for loss of righting about three‐ or ten‐fold respectively. Exposure to 3α5βP did not influence inhibition of cortisol synthesis by etomidate.Conclusions and ImplicationsPotentiating neurosteroids act similarly on orthosterically and allosterically activated GABAA receptors. Co‐application of neurosteroids with etomidate can significantly reduce dosage requirements for the anaesthetic, and is a potentially beneficial combination to reduce undesired side effects.
Molecular targets of the multifunctional iron‐chelating drug, M30, in the brains of mouse models of type 2 diabetes mellitus
Authors: Mechlovich Danit , Amit Tamar , Bar‐Am Orit , Weinreb Orly , Youdim Moussa B H 
Published: July 2014

Background and PurposeNeurodegenerative diseases are now recognized to be multifunctional, whereby a heterogeneous set of reactions acts independently or cooperatively, leading eventually to the demise of neurons. This has led our group to design and synthesize the multifunctional, nontoxic, brain‐permeable, iron chelator compound M30 with a range of pharmacological properties. Here, we have characterized the molecular targets of M30 in the brains of animal models of type 2 diabetes mellitus (T2DM).Experimental ApproachEffects of M30 on molecular mechanisms associated with neuroprotection in the CNS were investigated‐in the high‐fat diet (HFD) and ob/ob transgenic mouse models of T2DM, using real‐time PCR and Western blotting analyses. Brain monoamine oxidase (MAO) activity and catecholamine levels, and peripheral glucose tolerance were assayed after treatment in vivo.Key ResultsM30 increased cerebral levels of insulin and insulin receptor and phosphorylated‐GSK‐3β in HFD mice, compared with vehicle‐treated HFD mice. In both T2DM mice models, M30 treatment significantly up‐regulated cerebral hypoxia‐inducible factor (HIF)‐1α protein levels and induced the expression of several HIF‐1 target genes involved in neuroprotection, glycolysis, neurogenesis, oxidative stress and anti‐inflammation. Additionally, M30 inhibited MAO‐A and ‐B activities in the cerebellum. Accordingly, M30 administration significantly reduced brain levels of dopamine metabolites and increased levels of 5‐HT and noradrenaline. Glucose tolerance was also improved after M30 treatment in both models of T2DM.Conclusions and ImplicationsIn the brain of HFD and ob/ob transgenic mice, M30 exerted a variety of beneficial neuroprotective regulatory effects that may act synergistically to delay or prevent neurodegenerative processes associated with T2DM.
Simulation with cells in vitro of tamoxifen treatment in premenopausal breast cancer patients with different CYP2D6 genotypes
Authors: Maximov Philipp Y , McDaniel Russell E , Fernandes Daphne J , Korostyshevskiy Valeriy R , Bhatta Puspanjali , Mürdter Thomas E , Flockhart David A , Jordan V Craig 
Published: July 2014

Background and PurposeTamoxifen is a prodrug that is metabolically activated by 4‐hydroxylation to the potent primary metabolite 4‐hydroxytamoxifen (4OHT) or via another primary metabolite N‐desmethyltamoxifen (NDMTAM) to a biologically active secondary metabolite endoxifen through a cytochrome P450 2D6 variant system (CYP2D6). To elucidate the mechanism of action of tamoxifen and the importance of endoxifen for its effect, we determined the anti‐oestrogenic efficacy of tamoxifen and its metabolites, including endoxifen, at concentrations corresponding to serum levels measured in breast cancer patients with various CYP2D6 genotypes (simulating tamoxifen treatment).Experimental ApproachThe biological effects of tamoxifen and its metabolites on cell growth and oestrogen‐responsive gene modulation were evaluated in a panel of oestrogen receptor‐positive breast cancer cell lines. Actual clinical levels of tamoxifen metabolites in breast cancer patients were used in vitro along with actual levels of oestrogens observed in premenopausal patients taking tamoxifen.Key ResultsTamoxifen and its primary metabolites (4OHT and NDMTAM) only partially inhibited the stimulant effects of oestrogen on cells. The addition of endoxifen at concentrations corresponding to different CYP2D6 genotypes was found to enhance the anti‐oestrogenic effect of tamoxifen and its metabolites with an efficacy that correlated with the concentration of endoxifen; at concentrations corresponding to the extensive metabolizer genotype it further inhibited the actions of oestrogen. In contrast, lower concentrations of endoxifen (intermediate and poor metabolizers) had little or no anti‐oestrogenic effects.Conclusions and ImplicationsEndoxifen may be a clinically relevant metabolite in premenopausal patients as it provides additional anti‐oestrogenic actions during tamoxifen treatment.
Selective Na+/Ca2+ exchanger inhibition prevents Ca2+ overload‐induced triggered arrhythmias
Authors: Nagy Norbert , Kormos Anita , Kohajda Zsófia , Szebeni Áron , Szepesi Judit , Pollesello Piero , Levijoki Jouko , Acsai Károly , Virág László , Nánási Péter P , Papp Julius Gy , Varró András , Tóth András 
Published: July 2014

Background and PurposeAugmented Na+/Ca2+ exchanger (NCX) activity may play a crucial role in cardiac arrhythmogenesis; however, data regarding the anti‐arrhythmic efficacy of NCX inhibition are debatable. Feasible explanations could be the unsatisfactory selectivity of NCX inhibitors and/or the dependence of the experimental model on the degree of Ca2+i overload. Hence, we used NCX inhibitors SEA0400 and the more selective ORM10103 to evaluate the efficacy of NCX inhibition against arrhythmogenic Ca2+i rise in conditions when [Ca2+]i was augmented via activation of the late sodium current (INaL) or inhibition of the Na+/K+ pump.Experimental ApproachAction potentials (APs) were recorded from canine papillary muscles and Purkinje fibres by microelectrodes. NCX current (INCX) was determined in ventricular cardiomyocytes utilizing the whole‐cell patch clamp technique. Ca2+i transients (CaTs) were monitored with a Ca2+‐sensitive fluorescent dye, Fluo‐4.Key ResultsEnhanced INaL increased the Ca2+ load and AP duration (APD). SEA0400 and ORM10103 suppressed INCX and prevented/reversed the anemone toxin II (ATX‐II)‐induced [Ca2+]i rise without influencing APD, CaT or cell shortening, or affecting the ATX‐II‐induced increased APD. ORM10103 significantly decreased the number of strophanthidin‐induced spontaneous diastolic Ca2+ release events; however, SEA0400 failed to restrict the veratridine‐induced augmentation in Purkinje‐ventricle APD dispersion.Conclusions and ImplicationsSelective NCX inhibition – presumably by blocking revINCX (reverse mode NCX current) – is effective against arrhythmogenesis caused by [Na+]i‐induced [Ca2+]i elevation, without influencing the AP waveform. Therefore, selective INCX inhibition, by significantly reducing the arrhythmogenic trigger activity caused by the perturbed Ca2+i handling, should be considered as a promising anti‐arrhythmic therapeutic strategy.
Dopamine D1 and corticotrophin‐releasing hormone type‐2α receptors assemble into functionally interacting complexes in living cells
Authors: Fuenzalida J , Galaz P , Araya K A , Slater P G , Blanco E H , Campusano J M , Ciruela F , Gysling K 
Published: July 2014

Background and PurposeDopamine and corticotrophin‐releasing hormone (CRH; also known as corticotrophin‐releasing factor) are key neurotransmitters in the interaction between stress and addiction. Repeated treatment with cocaine potentiates glutamatergic transmission in the rat basolateral amygdala/cortex pathway through a synergistic action of D1‐like dopamine receptors and CRH type‐2α receptors (CRF2α receptors). We hypothesized that this observed synergism could be instrumented by heteromers containing the dopamine D1 receptor and CRF2α receptor.Experimental ApproachD1/CRF2α receptor heteromerization was demonstrated in HEK293T cells using co‐immunoprecipitation, BRET and FRET assays, and by using the heteromer mobilization strategy. The ability of D1 receptors to signal through calcium, when singly expressed or co‐expressed with CRF2α receptors, was evaluated by the calcium mobilization assay.Key ResultsD1/CRF2α receptor heteromers were observed in HEK293T cells. When singly expressed, D1 receptors were mostly located at the cell surface whereas CRF2α receptors accumulated intracellularly. Interestingly, co‐expression of both receptors promoted D1 receptor intracellular and CRF2α receptor cell surface targeting. The heteromerization of D1/CRF2α receptors maintained the signalling through cAMP of both receptors but switched D1 receptor signalling properties, as the heteromeric D1 receptor was able to mobilize intracellular calcium upon stimulation with a D1 receptor agonist.Conclusions and ImplicationsD1 and CRF2α receptors are capable of heterodimerization in living cells. D1/CRF2α receptor heteromerization might account, at least in part, for the complex physiological interactions established between dopamine and CRH in normal and pathological conditions such as addiction, representing a new potential pharmacological target.
Unemployment and product market competition in a Cournot model with efficiency wages
Authors: Chen Zhiqi , Zhao Bo 
Published: July 2014

AbstractThis paper analyzes the impact of product market competition on unemployment, wage and welfare in a model where unemployment is caused by the efficiency wage consideration and oligopolistic firms compete in quantity. It is shown that while more intense competition in the product market increases output and reduces price, it does not necessarily lead to a lower unemployment rate or a higher wage for workers. Depending on the technologies, the relationship between the intensity of competition and the level of employment (respectively, wage, welfare) is not always monotonic, and, in some instances, has an inverted U‐shape.
International trade and directed search unemployment in general equilibrium
Authors: King Ian , Stähler Frank 
Published: July 2014

AbstractWe develop an open economy general equilibrium model, with auction‐based directed search unemployment, to study the interactions of trade and unemployment. The theory ascribes all outcomes purely to the fundamentals of technology and endowment. If countries differ by endowment, trade makes both the unemployment rate and the rental in the capital‐(labour‐) abundant country rise (decline) but does not lead to equalization. If, alternatively, countries differ by technology, trade increases (decreases) the unemployment rate in the country whose technology is relatively superior (inferior) for producing the capital‐intensive good.
Flexible inflation forecast targeting: Evidence from Canada
Authors: Otto Glenn D. , Voss Graham M. 
Published: July 2014

AbstractWe test whether the Bank of Canada pursues a flexible inflation forecast target, one that weights output growth as well as inflation. For the period 1996–2007, we find evidence that the Bank did effectively pursue such a target over the forecast horizon of 12 to 18 months. We find the relative weight that the Bank gives to output growth in its target to be positive and statistically significant within the range of 0.2 to 0.4.
How important are school principals in the production of student achievement?
Authors: Dhuey Elizabeth , Smith Justin 
Published: July 2014

AbstractAs school leaders, principals can influence student achievement in a number of ways, such as hiring and firing of teachers, monitoring instruction and maintaining student discipline, among many others. We measure the effect of individual principals on gains in math and reading achievement between grades 4 and 7 using a value‐added framework. We estimate that a one standard deviation improvement in principal quality can boost student performance by 0.289 to 0.408 standard deviations in reading and math, while the principal at the 75th percentile improves scores by 0.170 to 0.193 relative to the median principal. Our results imply that isolating the most effective principals and allocating them accordingly between schools can have a significant positive effect on reducing achievement gaps.
Post‐secondary attendance by parental income in the U.S. and Canada: Do financial aid policies explain the differences?
Authors: Belley Philippe , Frenette Marc , Lochner Lance 
Published: July 2014

AbstractWe examine the extent to which tuition and needs‐based aid policies explain important differences in the relationship between family income and post‐secondary attendance relationships between Canada and the U.S. Using data from recent cohorts, we estimate substantially smaller attendance gaps by parental income in Canada relative to the U.S., even after controlling for family background, cognitive achievement, and local‐residence fixed effects. We next document that U.S. public tuition and financial aid policies are actually more generous to low‐income youth than are Canadian policies. Equalizing these policies across Canada and the U.S. would likely lead to a greater difference in income‐attendance gradients.
Unemployment and welfare consequences of international outsourcing under monopolistic competition
Authors: Brecher Richard A. , Chen Zhiqi 
Published: July 2014

AbstractThis paper challenges the conventional academic view that international outsourcing is just another form of gainful trade. Contrary to that view, we show that labour‐service outsourcing can reduce the high‐wage country's welfare even when product‐market trade is beneficial, within a model that combines involuntary unemployment and monopolistic competition. Outsourcing's impact on welfare is worsened by a definite loss of jobs and a possible contraction in the range of varieties produced worldwide. While owners of capital benefit from outsourcing under certain conditions, labour's welfare always falls.
Quality of life in a large cohort of adult Brazilian patients with 46,XX and 46,XY disorders of sex development from a single tertiary centre
Authors: Cassia Amaral Rita , Inacio Marlene , Brito Vinicius N. , Bachega Tania A. S. S. , Oliveira Ari A. , Domenice Sorahia , Denes Francisco T. , Sircili Maria Helena , Arnhold Ivo J. P. , Madureira Guiomar , Gomes Larissa , Costa Elaine M. F. , Mendonca Berenice B. 
Published: July 2014

SummaryObjectiveFew studies have focused on the quality of life (QoL) of patients with disorders of sex development (DSD). Our aim was to evaluate QoL in DSD patients with defined diagnoses followed until adulthood in a single tertiary centre.Patients and MethodsAdult patients with DSD (56 patients with 46,XX DSD – 49 with female social sex and 7 with male social sex as well as 88 patients with 46,XY DSD – 54 with female social sex and 34 with male social sex).MeasurementsQoL using WHOQOL‐Bref questionnaire.ResultsBoth patients with 46,XX DSD and patients with 46,XY DSD had similar QoL scores on the WHOQOL‐Bref, comparable to the scores of the Brazilian general population. The chronological age at the start of treatment was negatively and significantly associated with general QoL score. Patients with male social sex DSD had better scores on the psychological domain than patients with female social sex DSD, as found in the Brazilian general population. In addition, among the 46,XY DSD group, the male social sex patients had better QoL compared with the female social sex patients. There was a positive and significant correlation between sexual performance and general QoL, although it explained only 4% of the variability of the general QoL score. The most influencing variables were general health, positive feelings and spirituality, religion and personal beliefs, each of them contributing with 18% of the variability of the general QoL score.ConclusionOur large cohort of adult patients with DSD, which was followed by a multidisciplinary team in a single tertiary centre, had good QoL in adulthood; in addition, late treatment compromised the QoL of patients with DSD, whereas sexual performance has little influence on QoL.
Prioritizing Regions to Conserve a Specialist Folivore: Considering Probability of Occurrence, Food Resources, and Climate Change
Authors: Adams‐Hosking Christine , McAlpine Clive A. , Rhodes Jonathan R. , Moss Patrick T. , Grantham Hedley S. 
Published: July 2014

AbstractFor species that are increasingly threatened by the combined impacts of habitat loss and climate change, the identification of priority regions for conservation planning efforts is urgently required. In the case of specialist folivores, consideration of the effects of climate change on the distributions of their essential food resources should be a key component of conservation planning. The koala (Phascolarctos cinereus) was listed in 2012 as vulnerable under Australian Commonwealth Government law. Here, we incorporate species distribution models for the koala, an arboreal marsupial, and its specialized food resources, to identify broad‐scale priority conservation regions. We demonstrate a spatial prioritization approach that informs conservation planning and that links the shifting distribution of this declining species and its critical food resources under climate change. We find that the inclusion of food plants affected the identification of priority regions for conserving koalas, and that priority regions for the conservation of this species are predicted to shift considerably, often outside the current range of this species, posing additional challenges for its conservation.
FISHing for pancreatobiliary tract malignancy in endoscopic brushings enhances the sensitivity of routine cytology
Authors: Barr Fritcher E. G. , Kipp B. R. , Halling K. C. , Clayton A. C. 
Published: July 2014

Pancreatobiliary tract carcinoma is a lethal disease with low survival rates and limited treatment options. Diagnosis is complicated by benign conditions that can mimic malignancy on radiological studies (e.g. primary sclerosing cholangitis or PSC) and the suboptimal sensitivity of endoscopic biopsy/brushings obtained by endoscopic retrograde cholangiopancreatography (ERCP). The detection of multiple chromosomal gains by fluorescence in situ hybridization (FISH), referred to as polysomy, has demonstrated improved sensitivity over routine cytological evaluation. The evaluation of brushings by both routine cytology and FISH in our cytopathology laboratory has been in clinical practice since 2003. Strong morphological and screening skills enable cytotechnologists to become proficient in the assessment of FISH slides, which translates into cost and time savings. Multiple reports from various institutions have demonstrated the utility of FISH for patients with and without PSC. The incorporation of routine cytology and FISH results into the management algorithm for patients under suspicion for pancreatobiliary malignancy is a testament to the clinical success of these cytological assays.