bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunosuppression with Tacrolimus Improved Reproductive Outcome of Women with Repeated Implantation Failure and Elevated Peripheral Blood Th1/Th2 Cell Ratios
Authors: Nakagawa Koji , Kwak‐Kim Joanne , Ota Kuniaki , Kuroda Keiji , Hisano Michi , Sugiyama Rikikazu , Yamaguchi Koushi
Published: November 2014

Problem

We evaluated the clinical efficacy of immunosuppressive treatment with tacrolimus for repeated implantation failure (RIF) patients who have elevated in T helper (Th1)/Th2 cytokine producing cell ratios.

Method of study

This was a prospective cohort study of treatment for RIF patients (n = 42) with elevated peripheral blood Th1 (CD4+/IFN‐γ+)/Th2 (CD4+/IL‐4+) cell ratios at the Sugiyama clinic between November 2011 and October 2013. Twenty‐five patients were treated with tacrolimus (treatment group) and 17 received no treatment (control group). Treatment group received tacrolimus 2 days before embryo transfer and continued until the day of the pregnancy test, for a total of 16 days. The daily dose of tacrolimus (1–3 mg) was determined based on the degree of the Th1/Th2 cell ratio.

Results

The clinical pregnancy rate of the treatment group was 64.0%, which was significantly higher than that of the control group (0%) (P < 0.0001). In the treatment group, the miscarriage rate was 6.3%, the live birthrate was 60.0% (P < 0.0001). There was no significant side‐effect from tacrolimus in treatment group. No one developed obstetrical complications during pregnancy.

Conclusion

An immunosuppressive treatment using tacrolimus improved pregnancy outcome of repeated implantation failure patients with elevated Th1/Th2 ratios.
Distinct phenotype of hepatotoxicity associated with illicit use of anabolic androgenic steroids
Authors: Robles‐Diaz M. , Gonzalez‐Jimenez A. , Medina‐Caliz I. , Stephens C. , García‐Cortes M. , García‐Muñoz B. , Ortega‐Alonso A. , Blanco‐Reina E. , Gonzalez‐Grande R. , Jimenez‐Perez M. , Rendón P. , Navarro J. M. , Gines P. , Prieto M. , Garcia‐Eliz M. , Bessone F. , Brahm J. R. , Paraná R. , Lucena M. I. , Andrade R. J. ,   the Spanish DILI Registry,   the SLatinDILI Network
Published: November 2014

Background

We have observed an increase in hepatotoxicity (DILI) reporting related to the use of anabolic androgenic steroids (AAS) for bodybuilding.

Aim

To characterise phenotype presentation, outcome and severity of AAS DILI.

Methods

Data on 25 cases of AAS DILI reported to the Spanish (20) and Latin‐American (5) DILI Registries were collated and compared with previously published cases.

Results

AAS DILI increased from representing less than 1% of the total cases in the Spanish DILI Registry in the period 2001–2009 to 8% in 2010–2013. Young men (mean age 32 years), requiring hospitalisation, hepatocellular injury and jaundice were predominating features among the AAS cases. AAS DILI caused significantly higher bilirubin values independent of type of damage when compared to other drug classes (P = 0.001). Furthermore, the cholestatic AAS cases presented significantly higher mean peak bilirubin (P = 0.029) and serum creatinine values (P = 0.0002), compared to the hepatocellular cases. In a logistic regression model, the interaction between peak bilirubin values and cholestatic damage was associated with the development of AAS‐induced acute kidney impairment (AKI) [OR 1.26 (95% CI: 1.035–1.526); P = 0.021], with 21.5 ×ULN being the best bilirubin cut‐off point for predicting AKI risk (AUCROC 0.92). No fatalities occurred.

Conclusions

Illicit recreational AAS use is a growing cause of reported DILI that can lead to severe hepatic and renal injury. AAS DILI is associated with a distinct phenotype, characterised by considerable bilirubin elevations independent of type of damage. Although hepatocellular injury predominates, acute kidney injury develops in cholestatic cases with pronounced jaundice.
Comparison of Systemic Toxicity between Botulinum Toxin Subtypes A1 and A2 in Mice and Rats
Authors: Torii Yasushi , Goto Yoshitaka , Nakahira Shinji , Kozaki Shunji , Kaji Ryuji , Ginnaga Akihiro
Published: November 2014

The adverse events caused by botulinum toxin type A (subtype A1) product, thought to be after‐effects of toxin diffusion after high‐dose administration, have become serious issues. A preparation showing less diffusion in the body than existing drugs has been sought. We have attempted to produce neurotoxin derived from subtype A2 (A2NTX) with an amino acid sequence different from that of neurotoxin derived from subtype A1 (A1NTX). In this study, to investigate whether A2NTX has the potential to resolve these issues, we compared the safety of A2NTX, a progenitor toxin derived from subtype A1 (A1 progenitor toxin) and A1NTX employing the intramuscular lethal dose 50% (im LD50) in mice and rats and the compound muscle action potential (CMAP) in rats. Mouse im LD50 values for A1 progenitor toxin and A2NTX were 93 and 166 U/kg, respectively, and the rat im LD50 values were 117 and 153 U/kg, respectively. In the rat CMAP test, the dose on the contralateral side, which caused a 50% reduction in the CMAP amplitude, that is, CMAP‐TD50, was calculated as 19.0, 16.6 and 28.7 U/kg for A1 progenitor toxin, A1NTX and A2NTX, respectively. The results indicate that A2NTX is safer than A1 progenitor toxin and A1NTX.
Elementary school teachers' ICT use in the classroom and their motivators for using ICT
Authors: Uluyol Çelebi , Şahin Sami
Published: November 2014

Teachers play a significant role in integrating information and communication technology (ICT) in schools, and motivated teachers reflect higher levels of ICT use in their classroom. In this study, we used semistructured interviews to investigate elementary school teachers' ICT use and their motivators for doing so. The participants consisted of 101 elementary school teachers from 24 elementary schools located in the Turkish capital. We discuss and analyze our findings in order to understand the current state of teachers' ICT use and their motivations for using ICT. An overall conclusion from the results is that more concrete encouragement, support and opportunities must be developed to increase teachers' motivation to improve the level and quality of ICT use in classrooms.
Effects of root canal preparation, various filling techniques and retreatment after filling on vertical root fracture and crack formation
Authors: Capar Ismail Davut , Saygili Gokhan , Ergun Hazal , Gok Tuba , Arslan Hakan , Ertas Huseyin
Published: November 2014

Aim

To investigate the incidence of cracks in root dentin after rotary instrumentation and filling with cold lateral condensation (CL), single‐cone obturation (SC), and warm vertical compaction (WV) and retreatment of each filling system.

Methodology

One‐hundred sixty mandibular incisors were selected. Twenty teeth were left unprepared and served as a control, and the remaining 140 teeth were instrumented. Twenty teeth were assigned to an only prepared group. The remaining 120 teeth were assigned to three root canal filling groups and three retreatment groups (n = 20), as follows: CL, WV, SC, and retreatment of each filling system. All the roots were sectioned perpendicular to the long axis at 2, 4, 6, and 8 mm from the apex, and the sections were then observed under a stereomicroscope. The absence/presence of cracks and vertical root fractures were recorded, and the data were analyzed with a Pearson's chi‐square test (P = 0.05).

Results

No complete vertical root fractures were observed in the unprepared and only prepared groups. However, vertical fractures were observed in the filling and retreatment groups. There were significantly more cracks in the retreatment after WV group than the other groups, with the exception of the retreatment after SC, WV, and CL resulted in significantly more cracks than the only prepared and SC.

Conclusions

The filling techniques (except SC) caused more cracks than preparation only. The SC caused fewer cracks compared to the other filling techniques. The retreatment following the different filling techniques (except CL) caused more cracks than the original fillings.
The Efficacy and Safety of Cilostazol in Ischemic Stroke Patients with Peripheral Arterial Disease (SPAD): Protocol of a Randomized, Double-Blind, Placebo-Controlled Multicenter Trial
Authors: Jeng Jiann-Shing , Sun Yu , Lee Jiunn-Tay , Lin Ruey-Tay , Chen Chih-Hung , Po Helen L. , Lin Huey-Juan , Liu Chung-Hsiang , Sun Ming-Hui , Sun Mu-Chien , Chern Chang-Ming , Lien Li-Ming , Chiu Hou-Chang , Hu Han-Hwa , Chiou Hung-Yi , Chen Sien-Tsong , Ma Henry , Hsu Chung Y. ,   the SPAD Study Investigators
Published: November 2014

Rationale

It is not uncommon for patients with ischemic stroke to have peripheral arterial disease (PAD). Patients with polyvascular diseases carry greater burden of atherosclerosis and higher risks of developing vascular events and death. More effective regimens, such as dual antiplatelet agents, may be more effective for controlling progression of atherosclerosis in secondary prevention.

Aim

This study aims to evaluate whether cilostazol plus aspirin is more efficacious than aspirin alone for preventing progression of atherosclerosis in patients with ischemic stroke or transient ischemic attack (TIA) who also have peripheral arterial disease.

Design

The Safety and Efficacy of Cilostazol in Ischemic Stroke Patients with Peripheral Arterial Disease (SPAD) study is a randomized double-blinded placebo-controlled trial. Patients with previous ischemic stroke or TIA who had been taking aspirin (100 mg per day), aged 50 years or older, with PAD in the lower limbs based on ankle-brachial index (ABI) <1·0 will be randomized into the treatment group with cilostazol (200 mg/day) or the placebo group on 1:1 basis.

Study outcomes

Patients will be evaluated at 1, 3, 6, 9 and 12 months after randomization. The primary endpoint is difference in change in ABI between groups. The secondary and tertiary endpoints are the difference between groups in change in carotid intima-media thickness (IMT) and incidence rate of major cardiovascular events, including recurrent stroke, myocardial infarction, unstable angina, other vascular events, and death; and the safety measures, including major bleeding events, hemorrhagic stroke and death of any cause.

Conclusion

The SPAD trial is the first study to evaluate the safety and efficacy of dual antiplatelet agents, aspirin plus cilostazol, in comparison with aspirin alone in patients with both ischemic stroke or TIA and PAD. Results from this trial will provide important information on the merit of adding cilostazol to aspirin for slowing down progression of atherosclerosis in patients with ischemic stroke and PAD.
Parathyroid hormone‐related protein is a developmental regulatory molecule
Authors: Philbrick William M.
Published: November 2014

Parathyroid hormone‐related peptide (PTHrP) was discovered as the tumor product that is responsible for most instances of the syndrome of humoral hypercalcemia of malignancy. It is now known that the PTHrP and PTH genes arose on the basis of an ancient duplication event. One result of this heritage is a short stretch of highly homologous sequence at the N‐terminus of each of the peptides, and another is the fact that these N‐terminal products seem to be serviced by a single G protein‐coupled receptor referred to as the type I receptor. Overexpression and null strategies in mice have recently provided convincing evidence that one such PTHrP function is as a developmental regulatory molecule. For example, overexpression of PTHrP in keratinocytes, mammary epithelial cells and chondrocytes results in a developmental phenotype in each case, while knockout of the gene is associated with a chondrodystrophy that is lethal at birth. Rescue of the PTHrP‐null mouse via a genetic strategy involving a cross between the knockout mouse and a transgenic mouse with targeted PTHrP overexpression in chondrocytes provides a window on previously unappreciated PTHrP developmental regulatory effects in multiple tissues that share a common epithelial‐mesenchymal morphogenetic background.
Perspectives on genetic aspects of dental patterning
Authors: Weiss K. , Stock D. , Zhao Z. , Buchanan A. , Ruddle F. , Shashikant C.
Published: November 2014

Nearly a century of speculation and experimentation has gone into trying to understand the mechanisms that establish the pattern of the differentiated heterodont dentition. Regionally differing qualitative (combinatorial) expression of regulatory genes appears to be involved in this process. Work by our laboratory and others shows that the six members of the mammalian Dlx family of homeobox genes are expressed (a) at multiple times during dental development, (b) differently at different stages, (c) in a way that is related to their genomic organization as gene‐pairs linked to three of the four Hox clusters of positional patterning genes. The expression appears to be involved in jaw regionalization, tooth initiation, and tooth development. However, this expression correlates with no single aspect of dental patterning or tooth development, involves redundant and complementary function, and developmental differences between the maxillary and mandibular dentition suggest that other elements remain to be identified. For example, the possibility that quantitative aspects of gene expression specify developmental fields in the dentition has not yet been investigated. Although the maxilla and mandible develop differently, indirect evidence suggests that, especially in the future midline (incisor) regions, both jaws may be patterned by a consistent process that occurs before neural crest migration takes place, and we hypothesize that signaling factors like Sonic hedgehog and Pax transcription factors may be involved.
NGF, BDNF, NT3, NT4 and GDNF in tooth development
Authors: Nosrat Christopher A. , Fried Kaj , Ebendal Ted , Olson Lars
Published: November 2014

Neurotrophic factors have robust effects on development, differentiation, maintenance and regeneration of neurons. In the present study, we have used in situ hybridization to determine the specific sites of gene activity of five neurotrophic factors during tooth development. Nerve growth factor (NGF) and brain‐derived neurotrophic factor (BDNF) mRNAs were mainly detected in the dental papilla/pulp in postnatal rats, and the pattern of expression correlated with onset of dental innervation. In contrast, neurotrophin 3 (NT3) and 4 (NT4) mRNA expression patterns were predominantly epithelial and were strongest during early developmental stages when teeth are not yet innervated. Glial cell line‐derived neurotrophic factor (GDNF) mRNA was present in dental epithelium at early stages, but later in development, GDNF mRNA expression was mainly mesenchymal and observed in the odontoblast layer and extending into the subodontoblast zone. Our results suggest that both neurotrophins and GDNF may have multiple functions during tooth development. In addition to an influence on the establishment of the dental innervation, neurotrophic substances might have morphogenetic effects such as modulating the proliferation or differentiation of developing epithelial and mesenchymal cells.
EGF does not induce Msx‐1 and Msx‐2 in dental mesenchyme
Authors: Wang Yu‐Hsiung , Kollar Edward J. , Upholt William B. , Mina Mina
Published: November 2014

Previous heterospecific tissue recombinations indicate that mandibular epithelium exerts the first known inductive signal for odontogenesis in mouse embryos. BMP‐4 and EGF are two growth factors implicated as signaling molecules mediating the initial inductive epithelial‐mesenchymal interactions during odontogenesis. The purpose of the present study was to examine and compare the effects of these growth factors and mouse mandibular epithelium on expression of Msx‐1 and Msx‐2 genes in molar‐forming mesenchyme. Agarose beads soaked in growth factors or pieces of mouse mandibular epithelium (E11) were placed in contact with E11 molar‐forming mesenchyme and cultured for 24 h. Whole‐mount in situ hybridization analysis revealed that, in contrast to mouse mandibular epithelium and BMP‐4‐releasing beads, EGF‐releasing beads did not induce the expression of Msx‐1 and Msx‐2 in E11 molar‐forming mesenchyme. These observations suggest that whereas BMP‐4 may be involved in activation of Msx‐1 and Msx‐2 in the underlying mesenchyme, EGF may regulate events involved in the formation of dental lamina.
Effects of aFGF, bFGF, TGFβ1 and IGF‐I on odontoblast differentiation in vitro
Authors: Martín Amaya , Unda Fernando‐José , Bègue‐Kirn Catherine , Ruch Jean‐Victor , Aréchaga Juan
Published: November 2014

In this work, we investigated the effects of aFGF and bFGF alone or combined with TGFβ1 or IGF‐I on odontoblast differentiation. Trypsin‐isolated dental papillae from day 17 mandibular first molar were cultured in semisolid‐agar medium for 6 d. Our results demonstrated that aFGF, bFGF or combinations of these promoted cell polarization at the periphery of the dental Papillae. Moreover, simultaneous addition of aFGF and TGFβ1 to dental Papillae cultures induced both polarization and functional differentiation of odontoblast‐like cells, as well as extracellular matrix deposition. Combination of aFGF or bFGF with IGF‐I caused cell polarization at the surface of dental papillae, but matrix secretion was restricted to a few explants. In the presence of bFGF and TGFβ1, the explants had pronounced cell elongations but no matrix deposition. These results indicate that aFGF or bFGF is not able to induce odontoblast differentiation alone. However, both aFGF and bFGF can act synergistically with TGFβ1 and IGF‐I to strengthen their inductive effects and promote gradients of cytological and functional changes in odontoblast‐like cells.
Dynamic expression of E‐cadherin in ameloblasts and cementoblasts in mice
Authors: Terling C. , Heymann R. , Rozell B. , Öbrink B. , Wroblewski J.
Published: November 2014

During embryonic development, E‐cadherin mediates intercellular adhesion in a variety of epithelia in a spatio‐temporal pattern. We have analyzed the distribution of this cell adhesion molecule in the mouse during odontogenesis, at both mRNA and protein levels, in the mandibular first molars and incisors. E‐cadherin was strongly expressed at the bell stage by the cells of the dental organ, and by the pre‐secretory ameloblasts and the cells of stratum intermedium at the early mineralization stage. At the onset of enamel secretion, E‐cadherin disappeared from the apical pool of the ameloblasts and was later absent from the post‐secretory ameloblasts. E‐cadherin was also found in Hertwig's root sheath and later in the cells producing acellular cementum. These findings indicate that E‐cadherin may be involved in the polarization of the ameloblasts and in the early stages of cementogenesis.
Effect of methotrexate on cell proliferation in developing hamster molar tooth germs in vitro
Authors: Wöltgens Joseph H. M. , Lyaruu Donacian M. , Bronckers Antonius L. J. J. , van Duin Marion A. , Bervoets Theodor J. M.
Published: November 2014

Amongst the most frequently used drugs for the treatment of acute lymphoblastic leukaemia (ALL) belongs methotrexate (MTX), an inhibitor of pyrimidine (thymidine) synthesis. We examined effects of MTX on cell proliferation during tooth morphogenesis in organ culture by exposing hamster molar tooth germs to 10−7 to 10−3 M MTX for 24 h. In the presence of serum, only the highest concentration of MTX (10−3 M) induced a small, non‐significant decrease in cell mass without histological changes but, unexpectedly, increased uptake of [3H]thymidine. In serumless conditions increase in cell mass (dry weight) and incorporation of [3H]thymidine was lower than in serum‐supplemented conditions. Exposure to MTX in serumless conditions reduced the increase in cell mass even further without histological changes and, again, strongly enhanced incorporation of [3H]thymidine to the same proportion as measured in the serum‐supplemented cultures exposed to MTX. The data suggest that only exposure to high levels of MTX reduces proliferation activity, shown by reduction in cell mass. The enhanced [3H]thymidine uptake under MTX exposure was explained by blockage of the internal biosynthesis of thymidine, by which action more radiolabel was taken up from the medium. The data also suggest that serum contains (growth) factors that stimulate cell proliferation, thereby increasing cell mass and [3H]thymidine incorporation.
Analysis of intracellular osteopontin as a marker of osteoblastic cell differentiation and mesenchymal cell migration
Authors: Zohar Ron , Cheifetz Sela , McCulloch Christopher A. G. , Sodek Jaro
Published: November 2014

Formation and repair of the hard and soft connective tissues of teeth and their supporting structures require stem cells to divide, differentiate and migrate to generate specific tissues in a defined temporo‐spatial sequence. We have used antibodies to osteopontin (OPN) and fluorescence‐activated cell sorting (FACS) to determine the relationship between OPN expression and cell differentiation in cultures of fetal rat calvarial cells. At different stages of osteogenic differentiation, OPN was expressed by 60–98% of cells. Populations of small OPN‐negative cells with low cellular granularity (S cells) were isolated and shown to be enriched in stem cells, characterised by a lack of differentiation markers, high proliferative potential, capacity for self renewal and multipotentiality. Within 24 h of plating. S cells attached, spread and started expressing OPN, CD44, and collagens types I, II and III. Confocal microscopy of OPN in differentiating cells revealed two distinct phenotypes; a perinuclear distribution, characteristic of secreted OPN, and an intracellular perimembranous distribution co‐localising with the CD44 receptor, characteristic of migrating cells in which OPN was increased > 10‐fold as measured by immunoblotting. These studies show that OPN is expressed early in mesenchymal cell differentiation and is related to cell migration as well as osteogenesis.
Age‐related prevalence and morphological appearance of facial skin tumours: a prospective, cross‐sectional, observational, multicentre study with special emphasis on melanocytic tumours
Authors: Moscarella E. , Kyrgidis A. , Sperduti I. , Abramavicus A. , Argenziano G. , Cota C. , Eibenschutz L. , De Simone P. , Longo C. , Hofmann‐Wellenhof R. , Zalaudek I.
Published: November 2014

Background

The clinical and histopathological diagnosis of skin tumours arising on the face may be challenging.

Objective

An improved knowledge about the age‐related patterns of facial skin tumours may aid the correct diagnosis and management.

Methods

We conducted a prospective, cross‐sectional morphological study to investigate the age‐related frequency and morphological variability in facial skin tumours in a cohort of consecutive subjects attending two skin lesion clinics in Italy between June and September 2011. A total of 454 consecutive subjects (249 women; 55.5%) presenting with a total of 1866 facial tumours were enrolled in the study. Of the entire cohort, 54 (11.9%) subjects had no facial lesion.

Results

Total body naevus count correlated significantly with the mean number of facial lesions (ρ = 0.289, P < 0.001). The majority of flat lesions were pigmented (1056; 75.70%), compared to palpable (233; 17.40%) and raised lesions (93; 6.90%), the association being statistically significant (Pearson's chi square, P < 0.001. Considering melanocytic tumours only, the frequency of flat lesions significantly decreased with increasing age, while the number of palpable and raised lesions increased with increasing age (chi‐square, P < 0.001). This trend was mainly due to naevi, whereby pigmented melanocytic naevi decreased with increasing age. Conversely, the percentage of non‐ pigmented naevi increased with increasing age (chi‐square, P < 0.001).

Limitations

The study was conducted in skin lesion clinics in Italy, thus any general conclusions with respect to common traits or features based on the phenotypic and genetic diversity within the European population cannot be stated.

Conclusions and relevance

Our study suggests that a high number of facial naevi could predict a high total naevus count. Moreover, naevi present a different morphological appearance during lifetime being initially flat, small and pigmented and becoming later raised, large and hypopigmented. Instead, lentigo maligna is an intraepidermal proliferation that typically presents as flat, large pigmented macule. A given histopathological diagnosis of a junctional naevus of a flat, facial pigmented macule of an elderly should be critically reviewed and treated with caution.
The normal sensibility of the hand declines with age – a proclamation for the use of delta two‐point discrimination values for sensibility assessment after nerve reconstruction
Authors: Schmauss Daniel , Finck Tom , Megerle Kai , Machens Hans‐Guenther , Lohmeyer Joern A.
Published: November 2014

The scores used to evaluate sensibility after digital nerve reconstruction do not take the patient's age into consideration, although there is evidence that the outcome after digital nerve reconstruction is age‐dependent. However, it is not clear if the normal sensibility of the hand is also age‐dependent, as the existing studies have major limitations. We evaluated the normal sensibility of the hand in 232 patients using static and moving two‐point discrimination (2PD) tests and the Semmes–Weinstein‐monofilament test. We found the climax of sensibility in the third decade with age‐dependent deterioration afterwards in all three tests. Mean 2PD values of the radial digital nerve of the index finger (N3) showed to be significantly lower than values of the ulnar digital nerve of the small finger (N10). To overcome shortcomings of classification systems that do not consider the patient's age and inter‐individual differences, we suggest using the difference of the static 2PD values of the injured to the uninjured contralateral nerve (delta 2PD) for assessment of sensibility after digital nerve reconstruction.
Age, Insulin Requirements, Waist Circumference, and Triglycerides Predict Hypogonadotropic Hypogonadism in Patients with Type 1 Diabetes
Authors: Chillarón Juan J. , Fernández-Miró Mercè , Albareda Mercè , Vila Lluís , Colom Cristina , Fontserè Sara , Pedro-Botet Juan ,   on behalf of the TEST-DM1 Study Group, Flores-Le Roux Juana A.
Published: November 2014

Introduction

The prevalence of hypogonadotropic hypogonadism (HH) in patients with type 2 diabetes mellitus is higher than in the general population and leads to detrimental effects on metabolic control, lipid profile, and body composition. Few studies have examined its role in type 1 diabetes mellitus.

Aim

To determine the prevalence of HH in patients with type 1 diabetes and associated risk factors.

Main Outcome Measures

Clinical and biochemical parameters were gathered on initial evaluation. An HH score creating different experimental models was devised to calculate the risk of HH for an individual with type 1 diabetes.

Methods

Cross-sectional study of 181 male patients with type 1 diabetes consecutively admitted to the Diabetes outpatient clinics of three urban hospitals. All participants were Caucasians aged ≥ 18 years with type 1 diabetes duration of more than 6 months.

Results

One hundred and eighty-one male patients with a mean age of 44.2 ± 13.2 years and a type 1 diabetes duration of 18.9 ± 12.7 years were included. Fifteen patients had HH, representing a prevalence of 8.3% (95% confidence interval [CI]: 4.3–12.3%). Age (odds ratio [OR] 1.066 [95% CI: 1.002–1.134]), waist circumference (OR 1.112 [95% CI: 1028–1203]), and insulin requirements ([IU/Kg] ×10 [OR 1.486 {95% CI: 1052–2.098}]) were independently associated with the presence of HH. The model that best predicted HH generated this formula: HH-score = (1.060 × age) + (1.084 × waist circumference) + (14.00 × insulin requirements) + triglycerides, where age was expressed in years, waist circumference in cm, insulin requirements in IU/kg/d, and triglycerides in mg/dL. An HH score > 242.4 showed 100% sensitivity and 53.2% specificity for HH diagnosis; positive and negative predictive values were 17.0 % and 100%, respectively.

Conclusions

One in 10 men with type 1 diabetes presents HH. This condition is associated with age, waist circumference, and insulin requirements. A simple formula based on clinical parameters can rule out its presence.
From Mirroring to World‐Making: Research as Future Forming
Authors: Gergen Kenneth J.
Published: November 2014

After decades of acrimonious debate on the nature of scientific knowledge, researchers in the human or social sciences are reaching a state of relative equanimity, a condition that may be characterized as a reflective pragmatism. Yet, even while the context has favored the development of new forms of research, the longstanding ocular metaphor of inquiry remains pervasive. That is, researchers continue the practice of observing what is the case, with the intent to illuminate, understand, report on, or furnish insight into given states of affairs. And, while selectively useful, such an orientation is not only limited in potential but subject to a receding span of application. As I will propose, when the logics of reflective pragmatism are fully extended, we enter a new territory of understanding, one in which the vision of research is radically altered. We replace the captivating gaze on the world as it is with value based explorations into what it could be. This conception of a future forming orientation to research opens the way to new aims, practices, and reflections.
Eriocaulon vandaanamense sp. nov. (Eriocaulaceae) from Kerala, India
Authors: Sunil C. N. , Ratheesh Narayanan M. K. , Sivadasan M. , Alfarhan A. H. , Abdul Jaleel V.
Published: November 2014

Eriocaulon vandaanamense (Eriocaulaceae), a new species from a marshy coastal area in the Alappuzha District, Kerala, India, is described and illustrated. The new species is similar to E. truncatum and resembles it in having vertically elongated seed coat cells, but differs mainly in having pale black hoary floral bracts, 3‐lobed hoary male sepals, linear‐falcate, non‐conduplicate hoary female sepals, and small, smooth, pale brown seeds without seed coat appendages.
Effect of VRN‐1 and PPD‐D1 genes on heading time in European bread wheat cultivars
Authors: Shcherban Andrey B. , Börner Andreas , Salina Elena A.
Published: November 2014

The variation of the vernalization (VRN‐1) and photoperiod (PPD‐1) genes offers opportunities to adjust heading time and to maximize yield in crop species. The effect of these genes on heading time was studied based on a set of 245 predominantly spring cultivars of bread wheat from the main eco‐geographical regions of Europe. The genotypes were screened using previously published diagnostic molecular markers for detecting the dominant or recessive alleles of the major VRN‐1 loci such as: VRN‐A1, VRN‐B1, VRN‐D1 as well as PPD‐D1. We found that 91% of spring wheat cultivars contain the photoperiod sensitive PPD‐D1b allele. Photoperiod insensitive PPD‐D1a allele has been found mainly in southern region of Europe. For this region the monogenic control of vernalization by VRN‐B1 or VRN‐D1 dominant alleles is common, whereas in the remaining part of Europe, the combination of photoperiod sensitive PPD‐D1b allele with dominant VRN‐A1, VRN‐B1 and recessive vrn‐D1 alleles represents the most frequent genotype. Also, we revealed a significantly later (5–8 days) heading of the monogenically dominant genotypes at VRN‐B1 as compared to the digenic VRN‐A1 VRN‐B1 genotypes.
Influence of flower and flowering characteristics on seed yield in diploid and tetraploid red clover
Authors: Vleugels Tim , Roldán‐Ruiz Isabel , Cnops Gerda
Published: November 2014

Tetraploid red clover (Trifolium pratense L.) often produces insufficient seed to be economically interesting. Numerous studies have identified poor pollination due to long corolla tubes as its cause, but other studies disagree. Therefore, we investigated seed yield, corolla tube length and flowering traits in 244 plants from five diploid and five tetraploid cultivars during 2 years. Tetraploids produced fewer seeds, fewer flower heads and fewer seeds per head, but an equal number of flowers per head when compared to diploids. Although corolla tubes were longer in tetraploid than in diploid red clover (P < 0.001), no correlation between corolla tube length and seed yield was detected. Therefore, the corolla tube length is likely neither the main nor only cause of low seed yield in tetraploid red clover. Instead, three putative causes for low seed yield were identified: tetraploids produced less inflorescences per plant, possessed a lower degree of determinacy and had markedly less seeds per head when compared to diploids. Possible causes for such differences include lower pollen viability and higher rates of embryo abortion.
Beyond Xeroderma Pigmentosum: DNA Damage and Repair in an Ecological Context. A Tribute to James E. Cleaver
Authors: Karentz Deneb
Published: November 2014

The ability to repair DNA is a ubiquitous characteristic of life on Earth and all organisms possess similar mechanisms for dealing with DNA damage, an indication of a very early evolutionary origin for repair processes. James E. Cleaver's career (initiated in the early 1960s) has been devoted to the study of mammalian ultraviolet radiation (UVR) photobiology, specifically the molecular genetics of xeroderma pigmentosum and other human diseases caused by defects in DNA damage recognition and repair. This work by Jim and others has influenced the study of DNA damage and repair in a variety of taxa. Today, the field of DNA repair is enhancing our understanding of not only how to treat and prevent human disease, but is providing insights on the evolutionary history of life on Earth and how natural populations are coping with UVR‐induced DNA damage from anthropogenic changes in the environment such as ozone depletion.
A case of pulmonary hamartoma with distinctive histopathological features: A discussion of its differential diagnosis and histogenesis
Authors: Okudela Koji , Umeda Shigeaki , Otara Misa , Honda Emi , Ohmori Takahiro , Tajari Michihiko , Kameda Yoichi , Ohashi Kenichi
Published: November 2014

We herein describe a case of a benign pulmonary tumor with distinctive histopathological features. A 55‐year‐old Japanese male presented with a well‐demarcated tumor in the left upper lobe of his lung, which gradually increased in size from 18 to 21 mm over 24 months. The resected tumor consisted of an epithelial component of compact irregular glands and mesenchymal component of fascicles between the glands. The differentiation of pneumocytes and smooth muscle cells was immunohistochemically detected in the epithelial component and the mesenchymal component, respectively. No mitosis, necrosis, bleeding, or invasion was observed. A histopathologic diagnosis of fibroleiomyomatous hamartoma was made. We also review previously reported tumors with similar histopathological features and discuss their differential diagnosis and histogenesis.
The clinical application of Doppler ultrasound in obstetrics
Authors: Mone Fionnuala , McAuliffe Fionnuala M , Ong Stephen
Published: November 2014

Key content

Current UK guidance advocates the use of uterine artery Doppler for screening and Doppler of the umbilical artery, middle cerebral artery and ductus venosus for surveillance and timing of delivery of the growth‐restricted fetus.

This article examines available evidence concerning the clinical application of Doppler ultrasound in obstetrics, with the aim of guiding clinicians in its application.

With increasing acceptance of the concept of ‘inversion of the pyramid of antenatal care’, the use of Doppler in the first trimester is also discussed.

Learning objectives

To understand the physiological mechanisms of umbilical artery, middle cerebral artery, uterine artery, ductus venosus and tricuspid valve Doppler assessments.

To appreciate existing clinical evidence for the use of Doppler in specific situations.

To understand the clinical application of Doppler ultrasound in specific clinical situations.

To appreciate the emerging clinical application of Doppler in the first trimester.

Ethical issues

Non‐tertiary centres may not have access to sonographers or equipment required to perform advanced Doppler ultrasound.
Smooth muscle acid‐sensing ion channel 1: pathophysiological implication in hypoxic pulmonary hypertension
Authors: Jernigan Nikki L.
Published: November 2014

New Findings

What is the topic of this review?

An increase in pulmonary arterial smooth muscle cell intracellular Ca2+ levels facilitates the enhanced vasoconstrictor and vascular remodeling responses associated with hypoxic pulmonary hypertension. Identifying the mechanisms of altered Ca2+ homeostasis will advance our understanding of the pathogenesis of pulmonary hypertension and identify potential therapeutic targets.

What advances does it highlight?

Acid sensing ion channel 1 (ASIC1), present in pulmonary arterial smooth muscle cells, contributes to enhanced Ca2+ entry and is an important constituent to the active vasoconstriction, vascular remodeling, and right ventricular hypertrophy associated with hypoxic pulmonary hypertension.

Acid‐sensing ion channels (ASICs) belong to the amiloride‐sensitive, degenerin/epithelial sodium channel superfamily. Acid‐sensing ion channels are voltage‐independent, proton‐gated cation channels, and their activity has been linked to a variety of physiological and pathological functions in the central and peripheral nervous system. Nonetheless, ASICs are expressed in a variety of tissues. In this review, we describe a novel role for ASIC1 in regulating pulmonary arterial smooth muscle cell (PASMC) Ca2+ influx in both physiological and pathophysiological settings. Through a store‐operated mechanism, ASIC1 contributes to pulmonary vasoconstriction elicited by various agonists and alveolar hypoxia. The ASIC1‐mediated Ca2+ entry in PASMCs is a central component of the active vasoconstriction, vascular remodelling and right ventricular hypertrophy associated with the development of hypoxic pulmonary hypertension. Despite the requirement for ASIC1 to enhance Ca2+ influx in the pulmonary hypertensive circulation, these responses are not dependent on an increase in PASMC ASIC1 protein expression, suggesting that hypoxia promotes activation of ASIC1 through other regulatory mechanism(s). Here, I describe some of the correlations between hypoxia‐induced changes in homeostasis of reactive oxygen species with that of ASIC1 function. Ultimately, a better understanding of the molecular mechanisms by which ASICs are regulated will help to elucidate their mechanism of action and identify potential therapeutics that specifically target ASICs.
Antioxidant treatments do not improve force recovery after fatiguing stimulation of mouse skeletal muscle fibres
Authors: Cheng Arthur J. , Bruton Joseph D. , Lanner Johanna T. , Westerblad Håkan
Published: November 2014

Key points

Increased free radical production may contribute to decreased muscle force production during fatiguing exercise, and might delay recovery from fatigue.

We exposed mouse fast‐twitch single fibres to antioxidants targeting specific cellular sites to determine whether these compounds delay fatigue development and/or improve the recovery from fatigue.

Antioxidants had no effect on the fatigue‐induced decrease in contractile force.

During recovery from fatigue, a mitochondria‐targeted antioxidant, SS‐31, restored the fatigue‐induced decrease in sarcoplasmic reticulum Ca2+ release, but did not improve force recovery.

We conclude that antioxidants cannot counteract the force decline during or after induction of muscle fatigue, although they may affect the underlying mechanisms.

The contractile performance of skeletal muscle declines during intense activities, i.e. fatigue develops. Fatigued muscle can enter a state of prolonged low‐frequency force depression (PLFFD). PLFFD can be due to decreased tetanic free cytosolic [Ca2+] ([Ca2+]i) and/or decreased myofibrillar Ca2+ sensitivity. Increases in reactive oxygen and nitrogen species (ROS/RNS) may contribute to fatigue‐induced force reductions. We studied whether pharmacological ROS/RNS inhibition delays fatigue and/or counteracts the development of PLFFD. Mechanically isolated mouse fast‐twitch fibres were fatigued by sixty 150 ms, 70 Hz tetani given every 1 s. Experiments were performed in standard Tyrode solution (control) or in the presence of: NADPH oxidase (NOX) 2 inhibitor (gp91ds‐tat); NOX4 inhibitor (GKT137831); mitochondria‐targeted antioxidant (SS‐31); nitric oxide synthase (NOS) inhibitor (l‐NAME); the general antioxidant N‐acetylcysteine (NAC); a cocktail of SS‐31, l‐NAME and NAC. Spatially and temporally averaged [Ca2+]i and peak force were reduced by ∼20% and ∼70% at the end of fatiguing stimulation, respectively, with no marked differences between groups. PLFFD was similar in all groups, with 30 Hz force being decreased by ∼60% at 30 min of recovery. PLFFD was mostly due to decreased tetanic [Ca2+]i in control fibres and in the presence of NOX2 or NOX4 inhibitors. Conversely, in fibres exposed to SS‐31 or the anti ROS/RNS cocktail, tetanic [Ca2+]i was not decreased during recovery so PLFFD was only caused by decreased myofibrillar Ca2+ sensitivity. The cocktail also increased resting [Ca2+]i and ultimately caused cell death. In conclusion, ROS/RNS‐neutralizing compounds did not counteract the force decline during or after induction of fatigue.
Development of Prediction Technology of Two-Phase Flow Dynamics Under Earthquake Acceleration: (13) Rising Bubble Motion Under Horizontal Vibration
Authors: Arai Rie , Kaneko Akiko , Monji Hideaki , Abe Yutaka , Yoshida Hiroyuki , Takase Kazuyuki
Published: November 2014

An earthquake is one of the most serious phenomena for the safety of a nuclear reactor in Japan. Therefore, structural safety of nuclear reactors has been studied and nuclear reactors ware contracted with structural safety for a big earthquake. However, it is not enough for safety operation of nuclear reactors because thermal-fluid safety is not confirmed under the earthquake. For instance, behavior of gas-liquid two-phase flow is unknown under the earthquake conditions. Especially, fluctuation of void fraction is an important factor for the safety operation of the nuclear reactor. In the previous work, fluctuation of void faction in bubbly flow was studied experimentally and theoretically, to investigate the stability of the bubbly flow. In such studies, flow rate or void fraction fluctuations were given to the steady bubbly flow. In the case of the earthquake, the fluctuation is not only the flow rate, but also a body force on the two-phase flow and a shear force through a pipe wall. Interactions of gas and liquid through their interface also act on the behavior of the two-phase flow. The fluctuation of the void fraction is not clear for such complicated situation under the earthquake.

Therefore, in this research project, the behavior of gas-liquid two-phase flow is investigated experimentally and numerically in the series of study. In this study, to investigate the effects of vibration on bubbly flow in the components and construct an experimental database for validation, we performed visualization experiments of vertical bubbly flow in a rectangular water tank on which a sine wave vibration was applied. In this paper, results of visualized experiment evaluated by the visualization techniques, including positions of bubbles, shapes of bubbles and liquid velocity distributions around bubbles, were shown. And liquid velocity distribution around bubbles by the PIV measurement was also shown. In the results, bubble behaviors were affected by oscillation. And the cycle of the bubble tilt angle was almost same as the cycle of oscillation table velocity.
The AP1000 LBLOCA Analysis Using SCDAP/RELAP5
Authors: Xie Heng
Published: November 2014

In this study, a transient performance simulation model of AP1000 using SCDAP/RELAP5 4.0 is developed. The reactor coolant system (RCS) and passive core cooling system (PXS) are modeled respectively. Various kinds of hydrodynamic component including Volume, Junction, Separator, Accumulator, Branch, Pipe, Valve and Pump are adopted to simulate the fluid system of AP1000. The DECLG (double-end rupture of cold leg) accident is simulated and analyzed. To study the effect of axial heat conduction, two kinds of heat structure with and without reflooding model are employed to simulate the fuel rod respectively. The comparison shows that the 2D heat conduction play important role in the reflooding process.
Analytical Evaluation of Debris Cooling and Spreading Behaviors at Molten Core in Severe Accident
Authors: Kobayashi Akihiro , Miwa Shuichiro , Mori Michitsugu
Published: November 2014

On March 11, 2011, severe accident occurred at Fukushima Daiichi Nuclear Power Plant, and Units 1 to 3 of the plant have led to core melt. That is to say, melted fuel rods and core internals fell to the bottom of the Reactor Pressure Vessel (RPV). It is also believed that molten core has leaked into the reactor containment vessel. In order to plan for a safe molten core removal from the reactor, it is important to estimate the conditions of molten core by conducting analysis. Particular importance of the analysis is to understand the mechanisms of molten core spreading-cooling processes. However, sufficient understanding of this process has not been obtained yet.

The main purpose of this study is to evaluate molten metal spreading-cooling phenomena and subsequently, estimate the conditions of the molten metal. In order to achieve the purpose, the Computational Fluid Dynamics (CFD) for thermal fluid analysis, STAR-CCM+ was utilized. In the simulation of the unsteady two-phase flow, the volume of fluid model was applied for the spreading and interfacial surface formation of molten metal with the surrounding air. The key parameter for the molten metal spreading is the temperature dependent viscosity of molten metal. To assess the validity of this model, the analysis of the VULCANO VE-U7, molten metal spreading experiment, has been compared with simulation results.
A Statistical Model for Accessing Wall Thinning Rate due to Flow Accelerated Corrosion Based on Inspection Data in Nuclear Power Plants
Authors: Zeng Yuyun , Liu Jingquan , Huang Weilin
Published: November 2014

Flow accelerated corrosion (FAC) is a major degradation form of carbon steel and low alloy pipes in the secondary circuit of pressurized water reactor (PWR) plants, which has great impact on plant safety and reliability. For the purpose of effectively monitoring FAC in nuclear power plants, a statistical model for accessing FAC wall thinning rate using plant inspection data is proposed in this paper. The presented model is developed based on Gaussian stochastic process models. Wall thinning rate is considered as a function of key factors that have important influence on the FAC process (i.e., temperature, pH, mass transfer coefficient, etc.). The Kriging method, which has been widely applied in the domain of spatial analysis, is used to model the relationship between wall thinning rate and its impact factors. Model parameters are determined through maximum likelihood estimation using the inspection data. Since the likelihood function of the Kriging model is usually complicated in form, the genetic algorithm is employed to find parameter values that maximize this function. From the presented model, residual lifetime distributions of pipes affected by FAC can be derived, and conditions that may lead to high FAC rate can be found, which provides decision-making support for maintenance strategies optimization in life cycle management of the feed water system. Wall thinning data simulated from a physical-chemical mechanism model presented in literature are used to verify the presented model. Results of validation show that reasonable wall thinning rates and lifetime distributions can be obtained using this model.