bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reassessment of the pharmacology of Sphingosine‐1‐phosphate S1P3 receptor ligands using the DiscoveRx PathHunter™ and Ca2+ release functional assays
Authors: Riddy DM , Stamp C , Sykes DA , Charlton SJ , Dowling MR 
Published: May 2012

BACKGROUND AND PURPOSE DiscoverRx's PathHunter™ assay measures GPCR agonist potency, via the recruitment of β‐arrestin, independent of the subtype of Gα protein activated. This assay is frequently used in drug discovery although little is known about the agonist pharmacology generated. Here we have compared agonist potency, efficacy and affinity values obtained in PathHunter™ assays with those from more established radioligand binding and functional techniques.EXPERIMENTAL APPROACH Using cells expressing the human sphingosine‐1‐phosphate S1P3 receptor at four different densities, we compared pharmacological affinity and efficacy values of four structurally distinct ligands – FTY720‐P, VPC24191, CYM5442 and the endogenous agonist S1P – obtained from competition binding, functional Ca2+ release and PathHunter™ assays.KEY RESULTS The pKi values for S1P were significantly different (9.34 ± 0.10 and 8.92 ± 0.15) in clones expressing different receptor levels using the binding assay. In the PathHunter™ and Ca2+ assays, S1P and CYM5442 were full agonists, FTY720‐P was a partial agonist, while the efficacy of VPC24191 could not be detected in PathHunter™ assays. VPC23019, previously described as a S1P1/3 receptor antagonist, behaved as an S1P3 receptor partial agonist in the Ca2+ release assay.CONCLUSIONS AND IMPLICATIONS Comparison of data from the PathHunter™ assay with binding and functional Ca2+ assays suggest that PathHunter™ assays measured a different agonist‐bound receptor conformation. While this assay has great utility in drug discovery, care must be taken as high‐efficacy, low‐affinity agonist compounds would not be detected. Therefore highly amplified, more traditional assays are necessary to identify agonists with low efficacy.
Electroclinical pattern in MECP2 duplication syndrome: Eight new reported cases and review of literature
Authors: Vignoli Aglaia , Borgatti Renato , Peron Angela , Zucca Claudio , Ballarati Lucia , Bonaglia Clara , Bellini Melissa , Giordano Lucio , Romaniello Romina , Bedeschi Maria Francesca , Epifanio Roberta , Russo Silvia , Caselli Rossella , Giardino Daniela , Darra Francesca , La Briola Francesca , Banderali Giuseppe , Canevini Maria Paola 
Published: May 2012

SummaryPurpose:  Duplications encompassing the MECP2 gene on the Xq28 region have been described in male patients with moderate to severe mental retardation, absent speech, neonatal hypotonia, progressive spasticity and/or ataxia, recurrent severe respiratory infections, gastrointestinal problems, mild facial dysmorphisms (midface hypoplasia, depressed nasal bridge, large ears) and epilepsy. Epilepsy can occur in >50% of cases, but the types of seizures and the electroclinical findings in affected male individuals have been poorly investigated up to the present. Herein we describe eight patients with MECP2 duplication syndrome and a specific clinical and electroencephalographic pattern.Methods:  Array CGH of genomic DNA from the probands was performed, and an Xq28 duplication ranging from 209 kb to 6.36 Mb was found in each patient. Electroencephalography studies and clinical and seizure features of all the patients were analyzed.Key findings:  We found that epilepsy tended to occur between late childhood and adolescence. Episodes of loss of tone of the head and/or the trunk were the most represented seizure types. Generalized tonic–clonic seizures were rarely observed. The typical interictal EEG pattern showed abnormal background activity, with generalized slow spike and wave asynchronous discharge with frontotemporal predominance. Sleep electroencephalography studies also demonstrated abnormal background activity; spindles and K complex were often abnormal in morphology and amplitude. Response to therapy was generally poor and drug resistance was a significant feature.Significance:  Although these cases and a review of the literature indicate that epilepsy associated with MECP2 duplication syndrome cannot be considered a useful marker for early diagnosis, epilepsy is present in >90% of adolescent patients and shows a peculiar electroclinical pattern. Consequently, it should be considered a significant sign of the syndrome, and an EEG follow‐up of these patients should be encouraged from early childhood. Moreover, the definition of a more specific epileptic phenotype could be useful in order to suspect MECP2 duplication syndrome in older undiagnosed patients.
Distinctive polysomnographic traits in nocturnal frontal lobe epilepsy
Authors: Parrino Liborio , De Paolis Fernando , Milioli Giulia , Gioi Gioia , Grassi Andrea , Riccardi Silvia , Colizzi Elena , Terzano Mario Giovanni 
Published: May 2012

Purpose:  To describe the polysomnographic features and distribution of epileptic motor events, in relation to conventional sleep measures and cyclic alternating pattern (CAP) parameters, in 40 untreated patients with nocturnal frontal lobe epilepsy (NFLE).Methods:  We analyzed the basal polysomnographic recordings of 40 patients (20 male and 20 female; mean age: 31 ± 10 years) with a diagnosis of nocturnal frontal lobe epilepsy. Conventional sleep measures and CAP parameters were assessed. Polysomnographic recordings were subdivided in sleep cycles. The distribution of the epileptic motor events (including minor motor events, paroxysmal arousals, tonic‐dystonic, or hyperkinetic seizures and epileptic nocturnal wandering) was analyzed throughout: total sleep time, non–rapid eye movement (NREM) and REM sleep, light sleep (S1 + S2), slow wave sleep (SWS), each sleep cycle, CAP or non‐CAP sleep, phase A and phase B of CAP. Only clear epileptic motor events supported by video–polysomnographic evidence were taken into consideration. Polysomnographic findings of patients with NFLE were compared with those of 24 age‐ and gender‐balanced healthy subjects without sleep complaints.Key Findings:  Compared to controls, patients with NFLE showed a significant increase in wake after sleep onset, SWS duration, and REM latency, whereas REM sleep duration was significantly lower in NFLE patients. The patients with NFLE showed a significant increase of CAP time, CAP rate (72% vs. 32% in control group), CAP cycles, and mean duration of a CAP sequence. These findings were associated with a significant enhancement of all subtypes of the A phases of CAP (mainly subtype A1). A total of 139 epileptic motor events supported by video‐polysomnographic evidence were counted: 98% of all seizures occurred in NREM sleep and 72% of NREM seizures emerged from SWS, the latter being particularly collected in the first sleep cycles and decreasing in frequency together with the progressive decline of deep sleep. Ninety percent of total NREM seizures occurred during a CAP sequence, and CAP‐related seizures occurred in association with a phase A.Significance:  Significant polysomnographic alterations seem to emerge in patients with NFLE (increased REM latency, epileptic fragmentation of SWS, and increase of CAP rate). The analysis of seizure distribution showed that most epileptic events occurred in SWS, with predominance in the first sleep cycle and decreasing in frequency together with the homeostatic decline of SWS across the night. Within the NREM sleep, CAP is a manifestation of unstable sleep and represents a powerful predisposing condition for the occurrence of nocturnal motor seizures, which arise in concomitance with a phase A.
The association of blood transfusion with mortality after cardiac surgery: cause or confounding? (CME)
Authors: Dixon Barry , Santamaria John D. , Reid David , Collins Marnie , Rechnitzer Thomas , Newcomb Andrew E. , Nixon Ian , Yii Michael , Rosalion Alexander , Campbell Duncan J. 
Published: May 2012

BACKGROUND: Bleeding into the chest is a life‐threatening complication of cardiac surgery. Blood transfusion has been implicated as an important cause of harm associated with bleeding, based largely on studies demonstrating an independent association between transfusion and mortality. These studies did not, however, consider the possibility that bleeding may in itself be harmful, inasmuch as drains are inefficient at clearing blood from the chest and retained blood may compromise cardiac and lung function.STUDY DESIGN AND METHODS: We undertook a multivariate logistic regression analysis of the risk factors associated with mortality in 2599 consecutive patients undergoing cardiac surgery. Unlike previous studies the risk factors examined included the volume of chest tube drainage at 24 hours. A stratified analysis was also undertaken that compared the adjusted risk of death for patients exposed or not exposed to a postoperative blood transfusion.RESULTS: Blood transfusion was not an independent predictor of mortality (p = 0.4). Chest tube drainage was the strongest independent predictor of mortality (p < 0.001). In the stratified analysis, chest tube drainage remained an independent predictor of mortality for patients not exposed to a blood transfusion (p < 0.01). Furthermore, the risk of death of these patients was no different from patients exposed to a blood transfusion (p = 0.7 for interaction).CONCLUSIONS: Our results argue that for patients undergoing cardiac surgery bleeding contributes to mortality through mechanisms unrelated to blood transfusion.
Immediate colposcopic evaluation in postmenopausal women with low‐grade squamous intraepithelial lesion cytology
Authors: AKBAYIR OZGUR , CILESIZ GOKSEDEF BEHIYE PINAR , NUMANOĞLU CEYHUN , CORBACIOGLU AYTUL , ULKER VOLKAN , AKYOL ALPASLAN , GÜRASLAN HAKAN , CETIN AHMET , GULKILIK AHMET 
Published: May 2012

AbstractObjective. To compare the final diagnosis among pre‐ and postmenopausal women with low‐grade squamous intraepithelial lesion (LGSIL) cervical smear results. Design. Retrospective, comparative study. Setting. Departments of obstetrics and gynecology in two teaching and research hospitals. Population. Data were evaluated on 712 women with LGSIL between April 2005 and April 2011. Methods. Results from 129 postmenopausal women with LGSIL were compared with 583 premenopausal women with a similar LGSIL result with respect to sociodemographic data and histopathology. Main outcome measures. Final clinicopathological diagnosis. Results. The mean age of the pre‐ and postmenopausal women was 37.2 and 52.5 years, respectively, and lesions of cervical intraepithelial neoplasia grade 2 or worse were detected by biopsy and/or endocervical curettage in 13.6 and 9.3%, respectively. There was no significant difference between the final diagnosis among pre‐ and postmenopausal women with LGSIL cytology (relative risk 1.43; 95% confidence interval 0.82–2.48; p= 0.19). Invasive cervical cancer was detected in three premenopausal (0.5%) and two postmenopausal women (1.6%). Conclusions. Cervical pre‐invasive and invasive disease rates were similar in pre‐ and postmenopausal women with LGSIL cytology. For this reason, LGSIL in postmenopausal women should be considered more seriously, and colposcopic evaluation may be as acceptable an option in the management of LGSIL in this group of patients as it is with premenopausal women.
Parasitic leiomyomas after laparoscopic surgery with morcellation
Authors: LEREN VIBEKE , LANGEBREKKE ANTON , QVIGSTAD ERIK 
Published: May 2012

Abstract Parasitic leiomyomas after laparoscopic surgery with morcellation are a rare entity, and only a few small series and single case reports have been published in recent years. This was first known as a spontaneously occuring condition, but in recent years it has been observed more frequently as an iatrogenic condition after morcellation, and may occur several years after primary surgery. We present three patients diagnosed in an eight year period, representing an incidence of 0.12% after morcellation procedures in our department. The mechanisms leading to parasitic leiomyomas are discussed, as well as how we should minimize the risk of development of this rare condition.
Human skin cancer stem cells: a tale of mice and men
Authors: Colmont Chantal S. , Harding Keith G. , Piguet Vincent , Patel Girish K. 
Published: May 2012

AbstractCarcinomas, cancers of epithelial tissues, are the commonest malignancies and cause the greatest cancer mortality worldwide. Among these, the incidence of keratinocyte‐derived non‐melanoma skin cancers (NMSC), by far the greatest, is increasing rapidly. Yet despite access to tumor tissue, acceptance of human NMSC as a model carcinoma has been hindered by the lack of a reliable xenograft model. Instead, we have relied on the murine two‐step carcinogenesis protocol as a reproducible squamous cell carcinoma (SCC) model, but this differs from their human counterpart in cause, site, genetic basis and biological behaviour. By xeno‐engraftment of primary human SCC, we were recently successful in demonstrating the presence of primary human SCC cancer stem cells or tumor‐initiating cells. These findings once more align the study human SCC as the archetypal carcinoma model. In this review, we describe the evidence for the existence of tumor‐initiating cells, with emphasis on skin cancer, limiting our discussions to primary human cancer studies where possible.
Comprehensive Analysis of Peripheral Blood Lymphocytes in 76 Women with Recurrent Miscarriage before and after Lymphocyte Immunotherapy
Authors: Liang Peiyan , Mo Meilan , Li Guan‐Gui , Yin Biao , Cai Jing , Wu Tonghua , He Xuebing , Zhang Xu , Zeng Yong 
Published: May 2012

ProblemThe efficacy of lymphocyte immunotherapy (LIT) for unexplained recurrent miscarriage (uRM) remains indefinite. The objective of the present study is to comprehensively evaluate the alterations in the proportions and functions of peripheral blood lymphocytes in patients with uRM before and after LIT.Method of studySeventy‐six women with uRM were included in the present study. Immunophenotype of peripheral blood lymphocytes (76 patients), NK cytotoxicity (62 patients) and Th1 (IFN‐γ and TNF‐α)/Th2 (IL‐10) ratios (73 patients) were assessed during the luteal phase before LIT and after the third LIT by the flow cytometer.ResultsTo date, 29 patients had already delivered or been pregnant more than 20 weeks (successful pregnancy group) and 5 patients experienced subsequent abortion (abortion group). The percentages of CD3+ T cell, CD3+ CD4+ T cell and IL‐10‐producing Th1 cell were significantly increased, whereas the percentages of CD3+ HLA‐DR+ T cell, CD56+ CD3− NK cell and CD56dim CD16+ NK cell, the NK cytotoxicity and the ratios of Th1/Th2 were significantly decreased after LIT in the total patients and in the successful pregnant group. The percentages of CD56+ CD3− NK cell and IFN‐γ‐producing cell, and the ratio of IFN‐γ/IL‐10 were significantly lower after LIT in the successful pregnant group compared to those in the abortion group.ConclusionsLIT alters the proportions and functions of most peripheral blood lymphocyte subsets. Some of these alterations may be beneficial for pregnancy maintenance, whereas some may be potential markers for predicting subsequent abortion.
Consensus in diagnostic definitions for bone or joint infections in children by a Delphi method with European French‐speaking experts
Authors: Mitha Ayoub , Boulyana Mohamed , Hue Valérie , Pruvost Isabelle , Martinot Alain ,   the European French‐speaking expert group, Dubos François 
Published: May 2012

AbstractAim:  Various diagnostic criteria have been proposed for bone or joint infection. This study used a Delphi process to determine the consensual definitions for arthritis, osteomyelitis and bone or joint infections in general in children.Methods:  A group of European French‐speaking experts participated in an email Delphi process. Definitions were identified during a systematic search of the PubMed database. Five definitions of arthritis, eight for osteomyelitis and five for bone or joint infections in general were included in a three‐round process. We sought two sorts of definitions: definitions for ‘definitive’ diagnoses for epidemiological studies and definitions for ‘probable’ diagnoses for clinical or therapeutic studies, considering enlarged criteria.Results:  Ten experts were involved in the Delphi process. A consensus was reached for a definitive diagnosis of arthritis, osteomyelitis and bone or joint infections in general. A consensus was also reached for a probable diagnosis of bone or joint infections in general.Conclusion:  This Delphi process made consensus definitions and criteria available for bone or joint infections that could improve the comparability of both epidemiological and clinical studies. This is a first step to standardise diagnostic criteria and distinguish definitive and probable bone or joint infections in children.
Lactose and fructose malabsorption in children with recurrent abdominal pain: results of double‐blinded testing
Authors: Gijsbers CFM , Kneepkens CMF , Büller HA 
Published: May 2012

AbstractAim:  To investigate malabsorption of lactose and fructose as causes of recurrent abdominal pain (RAP).Methods:  In 220 children (128 girls, mean age 8,8 [4.1–16.0] years) with RAP, hydrogen breath tests (H2BT; abnormal if ΔH2 > 30 ppm) were performed with lactose and fructose. Disappearance of RAP with elimination, recurrence with provocation and disappearance with re‐elimination, followed by a 6‐month pain‐free follow‐up, were considered indicative of a causal relation with RAP. For definite proof, a double‐blinded placebo‐controlled (DBPC) provocation was performed.Results:  Malabsorption of lactose was found in 57 of 210, of fructose in 79 of 121 patients. Pain disappeared upon elimination in 24/38 patients with lactose malabsorption, and in 32/49 with fructose malabsorption. Open provocation with lactose and fructose was positive in 7/23 and 13/31 patients. DBPC provocation in 6/7 and 8/13 patients was negative in all. However, several children continued to report abdominal symptoms upon intake of milk or fructose.Conclusion:  Lactose intolerance nor fructose intolerance could be established as causes of RAP, according to preset criteria including elimination, open provocation and DBPC provocation. However, in clinical practice, persistent feeling of intolerance in some patients should be taken seriously and could warrant extended elimination with repeated challenges.
Maxillary Overdentures Supported by Anteriorly or Posteriorly Placed Implants Opposed by a Natural Dentition in the Mandible: A 1‐Year Prospective Case Series Study
Authors: Slot Wim , Raghoebar Gerry M. , Vissink Arjan , Meijer Henny J. A. 
Published: May 2012

ABSTRACTBackground: For maxillary overdenture therapy, treatment guidelines are missing. There is a need for longitudinal studies.Purpose: The purpose of this 1‐year prospective case series study was to assess the treatment outcome of maxillary overdentures supported by six dental implants opposed by natural antagonistic teeth in the mandible.Materials and Methods: Fifty patients were treated with a maxillary overdenture supported by six dental implants, either placed in the anterior region (n = 25 patients) or in the posterior region (n = 25 patients). Items of evaluation were the following: survival of implants, condition of hard and soft peri‐implant tissues, and patients' satisfaction.Results: One‐year implant survival rate was 98% in the anterior group and 99.3% in the posterior group. Mean radiographic bone loss in the anterior and posterior groups after 1 year of loading was 0.22 and 0.50 mm, respectively. Mean scores for plaque, calculus, gingiva, bleeding, and pocket probing depth were low, and patients' satisfaction was high, with no differences between the groups.Conclusion: Six dental implants placed in either the anterior region or the posterior region of the edentulous maxilla, connected with a bar, and opposed by antagonistic teeth in the mandible supply a proper base for the support of an overdenture.
Dominant Gene cplsr1 Corresponding to Premature Leaf Senescence Resistance in Cotton (Gossypium hirsutum L.)F
Authors: Zhao Jingqing , Jiang Tengfei , Liu Zhi , Zhang Wenwei , Jian Guiliang , Qi Fangjun 
Published: May 2012

AbstractCotton (Gossypium hirsutum L.) premature leaf senescence‐resistant inbred XLZ33 and senescence‐susceptible inbred lines XLZ13 were selected and crossed to produce F1, F1‐reciprocal, F2 and BC1 generations for evaluation of leaf senescence process and inheritance. The results showed that leaf senescence processes for XLZ13 and XLZ33 were obviously different and leaf senescence traits could be distinguished between the two parents at particular periods of cotton growth. Inheritance anlysis for the cotton premature leaf senescence resistant trait further showed that the segregation in the F2 fit a 3:1 ratio inheritance pattern, with resistance being dominant. The backcross of F1 to the susceptible parent produced a 1:1 ratio, confirming that cotton premature leaf senescence resistant trait was from a single gene. The single dominant gene controlling cotton premature leaf senescence resistance in XLZ33 was named as cotton premature leaf senescence resistance 1, with the symbol cplsr1.
Effects of In‐Center Nocturnal Versus Conventional Hemodialysis on Endothelial Dysfunction
Authors: Jin Xiucai , Rong Shu , Mei Changlin , Ye Chaoyang , Chen Jiabin , Chen Xiaoyu 
Published: May 2012

AbstractCardiovascular disease is the leading cause of morbidity and mortality in patients with end‐stage renal disease who undergo hemodialysis and endothelial dysfunction is an early key step in the development of atherosclerosis. The aim of this study was to investigate the effect of thrice‐weekly in‐center nocturnal hemodialysis (INHD, 8 h per session and three sessions per week) and conventional hemodialysis (CHD, 4 h per session and three sessions per week) on endothelial dysfunction in patients with end‐stage renal disease. 32 INHD and 58 matched CHD patients were enrolled, baseline and 12‐month measures of blood pressure (BP), serum calcium and phosphorus, serum intact PTH (iPTH) and brachial artery flow‐mediated dilation (FMD) were collected and analyzed. Baseline characteristics were similar between groups except that serum phosphorus and calcium × phosphorus were higher in the INHD group. At the 12‐month follow‐up, there was a significant increase in FMD (6.0 ± 1.5% to 7.1 ± 1.8%, P < 0.01) in INHD patients. Multivariate analysis showed that FMD was inversely correlated with systolic BP (SBP) (β = −0.485, P < 0.01), diastolic BP (DBP) (β = −0.428, P < 0.01), iPTH (β = −0.405, P < 0.01) and serum phosphorus level (β = −0.375, P < 0.01). There was no significant change in FMD in the CHD group. Compared with CHD, INHD improves endothelial function, and control of serum phosphorus is associated with the improvement of endothelial function.