bluuebunny/crossref_metadata_2025 huggingface dataset:
Melatonin regulates the autophagic flux via activation of alpha‐7 nicotinic acetylcholine receptors
Authors: Jeong Jae‐Kyo , Park Sang‐Youel
Published: March 2015

Our previous study suggested that melatonin‐mediated neuroprotective effects are related with the activation of autophagy. However, the mechanism of melatonin‐mediated autophagic activation in prion‐mediated mitochondrial damage is not reported. Alpha‐7 nicotinic acetylcholine receptors (α7nAchR) is a member of nicotinic acetylcholine receptors, and α7nAchR activation regulates via melatonin. Thus, we hypothesized that melatonin‐mediated neuroprotective effect related with to autophagy pathway as a result of α7nAchR regulation. Inactivation of α7nAchR inhibited melatonin‐mediated autophagic activation and protective effect against prion‐mediated mitochondrial neurotoxicity. Also, knockdown of ATG5 blocked the melatonin‐mediated neuroprotection and did not influence to the activation of α7nAchR caused by melatonin. This report is the first study demonstrating that melatonin‐mediated autophagic activation regulates via modulation of α7nAchR signals, and upregulation of α7nAchR signals induced by melatonin plays a pivotal role in neuroprotection of prion‐mediated mitochondrial neurotoxicity. Our results suggested that regulator of α7 nAChR signals including melatonin may have used for neuroprotective strategies for the neurodegenerative disorders including prion diseases.
The value of serum aspartate aminotransferase and gamma‐glutamyl transpetidase as biomarkers in hepatotoxicity
Authors: Robles‐Diaz Mercedes , Garcia‐Cortes Miren , Medina‐Caliz Inmaculada , Gonzalez‐Jimenez Andres , Gonzalez‐Grande Rocio , Navarro Jose M. , Castiella Agustin , Zapata Eva M. , Romero‐Gomez Manuel , Blanco Sonia , Soriano German , Hidalgo Ramon , Ortega‐Torres Maria , Clavijo Encarnacion , Bermudez‐Ruiz Pilar M. , Lucena M. Isabel , Andrade Raúl J.
Published: March 2015

Background & Aims

The current definition of the pattern of liver injury in hepatotoxicity (DILI) is given by the R (ratio) value, dividing alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in upper limits of normal at DILI onset. We aimed to explore the validity of using aspartate aminotransferase (AST) and gamma‐glutamyl transpeptidase (GGT) as biomarkers of hepatocelullar and cholestatic damage, respectively, when calculating the R value.

Methods

Clinical, laboratory and histological data from 588 DILI episodes included in the Spanish DILI Registry were analyzed. Linear regression analysis was performed to establish the most appropriate cut‐off points for hepatocellular and cholestatic patterns when calculating R with AST and GGT.

Results

The overall agreement between ALT/ALP and AST/ALP was 76%, with 96%, 61% and 41% agreement in the hepatocellular (R ≥ 5), cholestatic (R ≤ 2) and mixed groups respectively (P < 0.001). Classified by the causative drug, the agreement was higher (87–95%) among drug classes that mainly present with hepatocellular damage and lower (48–58%) for those in which cholestatic‐mixed injury predominate (P < 0.001)). The overall agreement between ALT/ALP and ALT/GGT was weak (59%), except for in hepatocellular cases that showed a good agreement (94%) (P = 0.001). Pattern of injury according to liver histology demonstrated 65%, 68% and 47% agreement for ALT/ALP, AST/ALP and ALT/GGT ratios respectively.

Conclusions

AST can reliably replace ALT when calculating pattern of liver injury in DILI, while GGT can only substitute ALP when the R value scores as hepatocellular. The biochemical signature of causative drugs does influence the validity of the ratios with AST or GGT.
New dimensions of reservoir sedimentation: a case study of Khodiyar Reservoir, India
Authors: Majumdar Pradeep Kumar
Published: March 2015

Medium and small reservoirs in water‐scarce regions face two extreme hydrological conditions. In years of lesser rainfall, inadequate water storage in the reservoir is a matter of concern. In contrast, flash floods portend disaster in years of better rainfall. There are also other possible hydrological, hydraulic and structural imbalances that may arise because of sedimentation. This study describes these dimensions, citing the example of Khodiyar Reservoir in Gujarat, India. The reservoir capacity was reduced by 36.12%, and a new zero elevation raised by 50% over 41 years. This study indicated the reservoir experienced silting at a much faster rate during the initial inflow years, reaching a regime state after 20 years. During this period, the water evaporation and seepage losses increased because of storage losses. In addition to reducing the flood return periods, sedimentation also could pose structural instability. The analyses of this study indicated the need for evaluating the regime condition in the planning stage to marginalize the effects of reservoir sedimentation on the socio‐economic aspects of water resources development.
Analysis of the tomato leaf transcriptome during successive hemibiotrophic stages of a compatible interaction with the oomycete pathogen Phytophthora infestans
Authors: Zuluaga Andrea P. , Vega‐Arreguín Julio C. , Fei Zhangjun , Matas Antonio J. , Patev Sean , Fry William E. , Rose Jocelyn K. C.
Published: March 2015

The infection of plants by hemibiotrophic pathogens involves a complex and highly regulated transition from an initial biotrophic, asymptomatic stage to a later necrotrophic state, characterized by cell death. Little is known about how this transition is regulated, and there are conflicting views regarding the significance of the plant hormones jasmonic acid (JA) and salicylic acid (SA) in the different phases of infection. To provide a broad view of the hemibiotrophic infection process from the plant perspective, we surveyed the transcriptome of tomato (Solanum lycopersicum) during a compatible interaction with the hemibiotrophic oomycete Phytophthora infestans during three infection stages: biotrophic, the transition from biotrophy to necrotrophy, and the necrotrophic phase. Nearly 10 000 genes corresponding to proteins in approximately 400 biochemical pathways showed differential transcript abundance during the three infection stages, revealing a major reorganization of plant metabolism, including major changes in source–sink relations, as well as secondary metabolites. In addition, more than 100 putative resistance genes and pattern recognition receptor genes were induced, and both JA and SA levels and associated signalling pathways showed dynamic changes during the infection time course. The biotrophic phase was characterized by the induction of many defence systems, which were either insufficient, evaded or suppressed by the pathogen.
Efficacy of combination therapy with probiotics and mosapride in patients with IBS without diarrhea: a randomized, double‐blind, placebo‐controlled, multicenter, phase II trial
Authors: Choi C. H. , Kwon J. G. , Kim S. K. , Myung S.‐J. , Park K. S. , Sohn C.‐I. , Rhee P.‐L. , Lee K. J. , Lee O. Y. , Jung H.‐K. , Jee S. R. , Jeen Y. T. , Choi M.‐G. , Choi S. C. , Huh K. C. , Park H.
Published: March 2015

Background

Probiotics can be beneficial in irritable bowel syndrome (IBS). Mosapride citrate, a selective 5‐HT4 receptor agonist, stimulates gastrointestinal motility. We investigated the efficacy of combination therapy with probiotics and mosapride for non‐diarrheal‐type IBS.

Methods

Two hundred and eighty‐five IBS patients were randomly assigned to either a combination of probiotics (Bacillus subtilis and Streptococcus faecium) and mosapride at one of four different doses or a placebo for 4 weeks. The primary outcome was the proportion of patients experiencing adequate relief (AR) of global IBS symptoms at week 4. The secondary outcomes included subject's global assessment (SGA) of IBS symptom relief, individual symptoms, stool parameters, and IBS‐quality of life.

Key Results

The proportion of AR at week 4 was significantly higher in all treatment groups compared to the placebo group (53.7% in group 1, 55.0% in group 2, 55.2% in group 3, 53.6% in group 4 [the highest dose], and 35.1% in placebo group, respectively, p < 0.05). The proportion of patients reporting ‘completely or considerably relieved’ in the SGA was higher in the treatment groups than in the placebo group. The abdominal pain/discomfort score in the treatment group 4 was more prominently improved compared with that of the placebo group. In patients with constipation‐predominant IBS, the improvements in stool frequency and consistency were significantly higher in the treatment groups 4 and 1, respectively, than those in the placebo group.

Conclusions & Inferences

Combination therapy with probiotics and mosapride is effective for relief of symptoms in patients with non‐diarrheal‐type IBS. The study has been registered in the US National Library of Medicine (http://www.clinicaltrials.gov, NCT01505777).
Population genetics of freeze tolerance among natural populations of Populus balsamifera across the growing season
Authors: Menon Mitra , Barnes William J. , Olson Matthew S.
Published: March 2015

Protection against freeze damage during the growing season influences the northern range limits of plants. Freeze tolerance and freeze avoidance are the two major freeze resistance strategies. Winter survival strategies have been extensively studied in perennials, but few have addressed them and their genetic basis during the growing season.

We examined intraspecific phenotypic variation in freeze resistance of Populus balsamifera across latitude and the growing season. To investigate the molecular basis of this variation, we surveyed nucleotide diversity and examined patterns of gene expression in the poplar C‐repeat binding factor (CBF) gene family.

Foliar freeze tolerance exhibited latitudinal and seasonal variation indicative of natural genotypic variation. CBF6 showed signatures of recent selective sweep. Of the 46 SNPs surveyed across the six CBF homologs, only CBF2_619 exhibited latitudinal differences consistent with increased freeze tolerance in the north. All six CBF genes were cold inducible, but showed varying patterns of expression across the growing season.

Some Poplar CBF homologs exhibited patterns consistent with historical selection and clinal variation in freeze tolerance documented here. However, the CBF genes accounted for only a small amount of the variation, indicating that other genes in this and other molecular pathways likely play significant roles in nature.
PUBLIC VALUE CREATION BY CROSS‐SECTOR COLLABORATIONS: A FRAMEWORK AND CHALLENGES OF ASSESSMENT
Authors: PAGE STEPHEN B. , STONE MELISSA M. , BRYSON JOHN M. , CROSBY BARBARA C.
Published: March 2015

This article proposes ways to assess the public value that cross‐sector collaborations produce. It introduces a framework featuring three dimensions of public value – democratic accountability, procedural legitimacy, and substantive outcomes – that reflect distinct priorities and concerns for public administration. Utilizing examples from research on a multi‐year cross‐sector collaboration in the transportation field, we illustrate the framework's application and identify techniques and challenges for assessing the collaborative creation of public value. The article concludes with questions and propositions to guide future research.
Screening for secondhand smoke in schoolchildren in Japan
Authors: Ino Toshihiro , Kurosawa Kazuo
Published: March 2015

Background

There is no systematic screening for secondhand smoke exposure in children.

Methods

In 2002, we began a secondhand smoke screening (SSS) program for grade 4 elementary schoolchildren with the cooperation of public administration. The SSS program consisted of urinary cotinine measurement in children and a questionnaire survey of their parents.

Results

More than 1200 schoolchildren were enrolled in this program annually. The level of urinary cotinine in 30% of the children was >5 ng/mL, whereas in half of them it was undetectable. The major risk factor affecting cotinine level was mother's smoking. Average cotinine was significantly high in children who had a history of “short stature”, “decayed tooth and/or periodontal disease,” and “frequent stridor”. In addition, the highest level of cotinine was detected in children whose father and/or mother smoked in the living room and the lowest level of cotinine was detected in children whose father and/or mother smoked on the veranda or outside the door. These levels, however, were two–fivefold higher than in children whose parents did not smoke. On follow‐up questionnaire survey 4 years after initial SSS, significant elevated motivation for smoking cessation was noted.

Conclusions

The SSS program is a very simple mass screen that can be done using only a urine test and is very effective for motivating parents to stop smoking with regard to cost benefit.
Clear cell carcinoid of the appendix: Report of two cases with literature review
Authors: Kang Gu Hyum , Lee Byung Seok , Kang Dae Young
Published: March 2015

The clear cell/lipid‐rich change has been described in neuroendocine tumors in several organs, but rarely observed in the appendix. In this study, we describe the morphologic, immunohistochemical features of incidentally discovered appendiceal carcinoids entirely represented by clear cells in a 22‐year‐old man and a 52‐year‐old woman. Ultrastructual examination demonstrated abundant lipid droplets and dense core granules. The mechanism leading to lipid accumulation in the cytoplasm has not been discovered, but degenerative processes following recurrent inflammatory change might be considered. This uncommon variant of appendiceal classic carcinoid tumors may bear a superficial resemblance to goblet carcinoid and/or appendiceal metastases from clear cell carcinoma. Awareness of clear cell carcinoid of the appendix will prevent incorrect diagnosis and unnecessary aggressive management.
Functional diversification of the dehydrin gene family in apple and its contribution to cold acclimation during dormancy
Authors: Falavigna Vítor da Silveira , Miotto Yohanna Evelyn , Porto Diogo Denardi , Anzanello Rafael , Santos Henrique Pessoa dos , Fialho Flávio Bello , Margis‐Pinheiro Márcia , Pasquali Giancarlo , Revers Luís Fernando
Published: March 2015

Dehydrins (DHN) are proteins involved in plant adaptive responses to abiotic stresses, mainly dehydration. Several studies in perennial crops have linked bud dormancy progression, a process characterized by the inability to initiate growth from meristems under favorable conditions, with DHN gene expression. However, an in‐depth characterization of DHNs during bud dormancy progression is still missing. An extensive in silico characterization of the apple DHN gene family was performed. Additionally, we used five different experiments that generated samples with different dormancy status, including genotypes with contrasting dormancy traits, to analyze how DHN genes are being regulated during bud dormancy progression in apple by real‐time quantitative polymerase chain reaction (RT‐qPCR). Duplication events took place in the diversification of apple DHN family. Additionally, MdDHN genes presented tissue‐ and bud dormant‐specific expression patterns. Our results indicate that MdDHN genes are highly divergent in function, with overlapping levels, and that their expressions are fine‐tuned by the environment during the dormancy process in apple.
Differences Between High‐ and Low‐Motility Buffalo Sperm Identified by Comparative Proteomics
Authors: Huang Y‐L , Fu Q , Yang L , Guan J‐L , Pan H , Chen F‐M , Lu K‐L , Zhang M
Published: March 2015

Contents

This study was undertaken to investigate differences in protein expression between high‐ and low‐motility sperm of swamp buffalo. The research used two‐dimensional gel electrophoresis (2DE) coupled to matrix‐assisted laser desorption/ionization time‐of‐flight tandem mass spectrometry (MALDI‐TOF/TOF‐MS) to analyse the different proteins. The results showed 18 different expression protein spots between high‐ and low‐motility buffalo sperm; eight of these proteins were up‐regulated in low‐motility sperm, five were down‐regulated, one deleted and four proteins specifically expressed. Finally, four proteins were successfully identified by MS as belonging to three unique proteins; they are outer dense fibre of sperm tails protein 2 (ODF2), ATP synthase subunit alpha (ATP5A1) and succinyl‐CoA synthetase subunit beta (SUCLG2). In summary, these results help to develop an understanding of the molecular mechanisms associated with low‐motility sperm and provide clues for finding molecular markers associated with sperm motility.
Identification of a Taraxacum brevicorniculatum rubber elongation factor protein that is localized on rubber particles and promotes rubber biosynthesis
Authors: Laibach Natalie , Hillebrand Andrea , Twyman Richard M. , Prüfer Dirk , Schulze Gronover Christian
Published: March 2015

Two protein families required for rubber biosynthesis in Taraxacum brevicorniculatum have recently been characterized, namely the cis‐prenyltransferases (TbCPTs) and the small rubber particle proteins (TbSRPPs). The latter were shown to be the most abundant proteins on rubber particles, where rubber biosynthesis takes place. Here we identified a protein designated T. brevicorniculatum rubber elongation factor (TbREF) by using mass spectrometry to analyze rubber particle proteins. TbREF is homologous to the TbSRPPs but has a molecular mass that is atypical for the family. The promoter was shown to be active in laticifers, and the protein itself was localized on the rubber particle surface. In TbREF‐silenced plants generated by RNA interference, the rubber content was significantly reduced, correlating with lower TbCPT protein levels and less TbCPT activity in the latex. However, the molecular mass of the rubber was not affected by TbREF silencing. The colloidal stability of rubber particles isolated from TbREF‐silenced plants was also unchanged. This was not surprising because TbREF depletion did not affect the abundance of TbSRPPs, which are required for rubber particle stability. Our findings suggest that TbREF is an important component of the rubber biosynthesis machinery in T. brevicorniculatum, and may play a role in rubber particle biogenesis and influence rubber production.
Transforming growth factor‐β released by apoptotic white blood cells during red blood cell storage promotes transfusion‐induced alloimmunomodulation
Authors: Vallion Romain , Bonnefoy Francis , Daoui Anna , Vieille Loredane , Tiberghien Pierre , Saas Philippe , Perruche Sylvain
Published: March 2015

BACKGROUND

Red blood cell (RBC) alloimmunization is a major immunologic risk of transfusion. However, RBC storage facilitates white blood cell (WBC) apoptosis and apoptotic cells have immunomodulatory properties. We investigated the behavior of WBCs, and apoptosis in particular, in RBC units during storage and then studied the impact of WBC apoptosis on the modulation of posttransfusion alloimmunization in RBC products stored short term.

STUDY DESIGN AND METHODS

We used a mouse model of alloimmunization to transfused HEL‐ovalbumin‐Duffy (HOD) surface antigen expressed specifically on RBCs. The presence of circulating anti‐HOD immunoglobulin G detected by flow cytometry confirmed immunization to HOD+ RBCs. WBC apoptosis and factors released by apoptotic WBCs during storage were determined and in particular the role of transforming growth factor (TGF)‐β was assessed on RBC alloimmunization.

RESULTS

In blood stored 72 hours, 30% of WBCs were apoptotic, and transfusion of short‐term‐stored blood resulted in lesser immunization than did fresh blood or stored leukoreduced (LR) RBCs. WBCs undergoing apoptosis released during short‐term storage factors modulating RBC alloimmunization. Indeed apoptotic cell–released factors modulate alloimmunization whereas exogenous apoptotic cells directly transfused with LR RBCs did not. While microparticles released during RBC storage had no immunomodulatory role, TGF‐β found in the supernatant of stored blood demonstrated the capacity to favor Treg polarization of naïve CD4+CD25– T cells in vitro and limited RBC alloimmunization in vivo. Indeed, addition of recombinant TGF‐β to stored LR RBC transfusion strongly limited posttransfusion RBC alloimmunization.

CONCLUSION

Our findings show that short‐term storage of non‐LR blood facilitates WBC apoptosis therefore releasing TGF‐β that modulates posttransfusion RBC alloimmunization.
Molecular signalling pathways in canine gliomas
Authors: Boudreau C. E. , York D. , Higgins R. J. , LeCouteur R. A. , Dickinson P. J.
Published: March 2015

In this study, we determined the expression of key signalling pathway proteins TP53, MDM2, P21, AKT, PTEN, RB1, P16, MTOR and MAPK in canine gliomas using western blotting. Protein expression was defined in three canine astrocytic glioma cell lines treated with CCNU, temozolamide or CPT‐11 and was further evaluated in 22 spontaneous gliomas including high and low grade astrocytomas, high grade oligodendrogliomas and mixed oligoastrocytomas. Response to chemotherapeutic agents and cell survival were similar to that reported in human glioma cell lines. Alterations in expression of key human gliomagenesis pathway proteins were common in canine glioma tumour samples and segregated between oligodendroglial and astrocytic tumour types for some pathways. Both similarities and differences in protein expression were defined for canine gliomas compared to those reported in human tumour counterparts. The findings may inform more defined assessment of specific signalling pathways for targeted therapy of canine gliomas.
Vaginal Microbiota of Adolescent Girls Prior to the Onset of Menarche Resemble Those of Reproductive-Age Women
Authors: Hickey Roxana J. , Zhou Xia , Settles Matthew L. , Erb Julie , Malone Kristin , Hansmann Melanie A. , Shew Marcia L. , Van Der Pol Barbara , Fortenberry J. Dennis , Forney Larry J.
Published: March 2015

Puberty is an important developmental stage wherein hormonal shifts mediate the physical and physiological changes that lead to menarche, but until now, the bacterial composition of vaginal microbiota during this period has been poorly characterized. We performed a prospective longitudinal study of perimenarcheal girls to gain insight into the timing and sequence of changes that occur in the vaginal and vulvar microbiota during puberty. The study enrolled 31 healthy, premenarcheal girls between the ages of 10 and 12 years and collected vaginal and vulvar swabs quarterly for up to 3 years. Bacterial composition was characterized by Roche 454 pyrosequencing and classification of regions V1 to V3 of 16S rRNA genes. Contrary to expectations, lactic acid bacteria, primarily Lactobacillus spp., were dominant in the microbiota of most girls well before the onset of menarche in the early to middle stages of puberty.
Gardnerella vaginalis
was detected at appreciable levels in approximately one-third of subjects, a notable finding considering that this organism is commonly associated with bacterial vaginosis in adults. Vulvar microbiota closely resembled vaginal microbiota but often exhibited additional taxa typically associated with skin microbiota. Our findings suggest that the vaginal microbiota of girls begin to resemble those of adults well before the onset of menarche.

IMPORTANCE
This study addresses longitudinal changes in vaginal and vulvar microbial communities prior to and immediately following menarche. The research is significant because microbial ecology of the vagina is an integral aspect of health, including resistance to infections. The physiologic changes of puberty and initiation of cyclic menstruation are likely to have profound effects on vaginal microbiota, but almost nothing is known about changes that normally occur during this time. Our understanding has been especially hampered by the lack of thorough characterization of microbial communities using techniques that do not rely on the cultivation of fastidious bacteria, as well as a dearth of studies on girls in the early to middle stages of puberty. This study improves our understanding of the normal development of vaginal microbiota during puberty and onset of menarche and may better inform clinical approaches to vulvovaginal care of adolescent girls.
Mediastinal germ cell tumour causing superior vena cava tumour thrombosis
Authors: Karanth Suman S , Vaid Ashok K , Batra Sandeep , Sharma Devender
Published: March 2015

We report a rare case of a 35-year-old man who presented with a 1-week history of retrosternal chest pain of moderate intensity. A positron emission tomography CT (PET-CT) showed a large fluorodeoxy-glucose (FDG)-avid heterogeneously enhancing necrotic mass in the anterosuperior mediastinum with a focal FDG-avid thrombosis of the superior vena cava (SVC) suggestive of tumour thrombus and vascular invasion. α-Fetoprotein levels were raised (5690 IU/L). Image guided biopsy of the mediastinal mass was suggestive of non-seminomatous germ cell tumour (NSGCT). The patient received four cycles of BEP (bleomycin, etoposide and cisplatin) along with therapeutic anticoagulation with low-molecular-weight heparin. Follow-up whole body PET-CT revealed complete resolution of mediastinal mass and SVC tumour thrombosis. The documentation of FDG-PET-avid tumour thrombus resolving with chemotherapy supports the concept of circulating tumour cells being important not only in common solid tumours such as breast and colon cancer but also in relatively less common tumours such as NSGCT. The detection of circulating tumour cells could help deploy aggressive regimens upfront.
Severe hypercalcaemia and colon ischaemia: dehydration as an unusual cause?
Authors: Fernandes Liliana Gil , Ferreira Nuno Ribeiro , Cardiga Rosa , Póvoa Pedro
Published: March 2015

Hypercalcaemia is an emergency with severe consequences. Dehydration can be an uncommon cause of hypercalcaemia, as seen in this case. A 63-year-old woman with type 2 diabetes mellitus, hypothyroidism and osteoporosis, was admitted to the emergency room with abdominal distension and vomiting for 24 h. Initial evaluation was Hg 18.5 g/dL, Htc 56.2%, creatinine 2 mg/dL, metabolic acidaemia, lactate 8.3 mmol/L, anion gap 19, total Ca2+17.7 mg/dL and PO4+ 6.6 mg/dL. CT revealed colonic distension without obstruction or ischaemia. Renal replacement therapy and pamidronate were initiated. The patient's clinical condition deteriorated with septic shock in the context of toxic megacolon and she underwent an emergency subtotal colectomy (10 kg). Hypercalcaemia was corrected in 24 h with aggressive fluid replacement (8 L NaCl 0.9% first 12 h), with a reduction of total Ca2+to 8.2 mg/dL. Other causes of hypercalcaemia were excluded. ‘Hypercalcaemic crisis’ secondary to severe acute dehydration is not mentioned in the literature.
A rare case of fatal stroke after ethylene glycol toxicity
Authors: Garg Deepika , Lim Tanna , Irani Mohamad
Published: March 2015

A 58-year-old man presented to the emergency department with acute left-sided weakness and left visual field defect. His examination was significant for confusion, acetone odour, tachycardia and tachypnoea. Further blood tests revealed an anion gap of 31 mEq/L, serum osmolal gap of 34 mOsm/kg, and creatinine 3.6 mg/dL. Brain MRI revealed acute infarctions scattered throughout the brain along with generalised oedema. The patient deteriorated rapidly and soon thereafter it was reported that a bottle of antifreeze was found near him at home. Haemodialysis was initiated and the patient received fomepizole and bicarbonate. Three days later the patient did not show any neurological improvement and expired later that day. Ethylene glycol toxicity can rarely present with stroke which can be life-threatening when not diagnosed and managed in a timely fashion.
Laparoscopic assistance for primary transanal pull-through in Hirschsprung's disease: a systematic review and meta-analysis
Authors: Thomson David , Allin Benjamin , Long Anna-May , Bradnock Tim , Walker Gregor , Knight Marian
Published: March 2015

Objective

To compare outcomes following totally transanal endorectal pull-through (TTERPT) versus pull-through with any form of laparoscopic assistance (LAPT) for infants with uncomplicated Hirschsprung's disease.

Design

Systematic review and meta-analysis.

Setting

Five hospitals with a paediatric surgical service.

Participants

405 infants with uncomplicated Hirschsprung's disease.

Interventions

TTERPT versus LAPT.

Primary and secondary outcome measures

Primary outcomes: mortality, postoperative enterocolitis, faecal incontinence, constipation, unplanned laparotomy or stoma formation, and injury to abdominal viscera.

Secondary outcomes

Haemorrhage requiring transfusion of blood products, abscess formation, intestinal obstruction, intestinal ischaemia, enteric fistula formation, urinary incontinence or retention, impotency and duration of procedure.

Results

Five eligible studies comprising 405 patients were identified from 2107 studies. All studies were retrospective case series, with variability in outcome assessment quality and length of follow-up. Operative duration was 50.29 min shorter with TTERPT (95% CI 39.83 to 60.74, p<0.00001). There were no significant differences identified between TTERPT and LAPT for incidence of postoperative enterocolitis (OR=0.78, 95% CI 0.44 to 1.38, p=0.39), faecal incontinence (OR=0.44, 95% CI 0.09 to 2.20, p=0.32) or constipation (OR=0.84, 95% CI 0.32 to 2.17, p=0.71).

Conclusions

This meta-analysis did not find any evidence to suggest a higher rate of enterocolitis, incontinence or constipation following TTERPT compared with LAPT. Further long-term comparative studies and multicentre data pooling are needed to determine whether a purely transanal approach offers any advantages over a laparoscopically assisted approach to rectosigmoid Hirschsprung's disease.

Trial registration number

PROSPERO registry- CRD42013005698.
Clinical, ultrasonographic and postmortem findings in a goat with abscessation of the mesenteric lymph nodes
Authors: Braun Ueli , Hilbe Monika , Nuss Karl , Tschoner Theresa
Published: March 2015

This case report describes the clinical, ultrasonographic and pathological findings in a 4.5‐year‐old Grisons striped goat with abscessation of the mesenteric lymph nodes. The goat had a poor appetite, tense abdomen and reduced ruminal motility. There was neutrophilic leukocytosis, and a serological test forCorynebacterium pseudotuberculosiswas positive. Abdominal ultrasonography in the right flank revealed multifocal, circular to oval masses with a diameter of 4–7 cm, heterogeneous content and irregular cavitation. Diagnostic laparotomy revealed multiple mesenteric abscesses. The goat was euthanised, and a diagnosis of severe, multifocal, purulent lymphadenitis involving the mesenteric lymph nodes was made. The onion‐ring appearance of the abscesses and the creamy white to green pus suggested caseous lymphadenitis.
Geography of fields in extra dimensions: String theory lessons for particle physics
Authors: Nilles Hans Peter , Vaudrevange Patrick K. S.
Published: March 2015

String theoretical ideas might be relevant for particle physics model building. Ideally one would hope to find a unified theory of all fundamental interactions. There are only a few consistent string theories in D = 10 or 11 spacetime dimensions, but a huge landscape in D = 4. We have to explore this landscape to identify models that describe the known phenomena of particle physics. Properties of compactified six spatial dimensions are crucial in that respect. We postulate some useful rules to investigate this landscape and construct realistic models. We identify common properties of the successful models and formulate lessons for further model building.
Chebyshev polynomials and the Frohman–Gelca formula
Authors: Queffelec Hoel , Russell Heather M.
Published: March 2015

Using Chebyshev polynomials, C. Frohman and R. Gelca introduced a basis of the Kauffman bracket skein module of the torus. This basis is especially useful because the Jones–Kauffman product can be described via a very simple Product-to-Sum formula. Presented in this work is a diagrammatic proof of this formula, which emphasizes and demystifies the role played by Chebyshev polynomials.
Autonomous Soft-Error Tolerance of FPGA Configuration Bits
Authors: Das Anup , Venkataraman Shyamsundar , Kumar Akash
Published: March 2015

Field-programmable gate arrays (FPGAs) are increasingly susceptible to radiation-induced single event upsets (SEUs). These upsets are predominant in a space environment; however, with increasing use of static RAM (SRAM) in modern FPGAs, these SEUs are gaining prominence even in a terrestrial environment. SEUs can flip SRAM bits of FPGA, potentially altering the functionality of the implemented design. This has motivated FPGA designers to investigate techniques to protect the FPGA configuration bits against such inadvertent bit flips (soft error). Traditionally, triple modular redundancy (TMR) is used to protect the FPGA bit flips. Increasing design complexity and limited battery life motivate for alternative approaches for soft-error tolerance. In this article, we propose a technique to improve autonomous fault-masking capabilities of a design by maximizing the number of zeros or ones in lookup tables (LUTs). The technique analyzes critical configuration bits and utilizes spare resources (XOR gates and carry chains) of FPGAs to selectively manipulate the logic implemented in LUTs using two operations: LUT restructuring and LUT decomposition. We implemented the proposed approach for Xilinx Virtex-6 FPGAs and validated the same with a wide set of designs from the MCNC, IWLS 2005, and ITC99 benchmark suites. Results demonstrate that the proposed logic restructuring maximizes logic 0 (or 1) of LUTs by an average of 20%, achieving 80% fault masking with no area overhead. The fault rate of the entire design is reduced by 60% on average as compared to the existing techniques. Furthermore, the logic decomposition algorithm provides incremental fault-tolerance capabilities and achieves an additional 5% fault masking with an average 7% increase in slice usage.

The complete methodology is implemented into a tool for Xilinx FPGA and is made available online for the benefit of the research community. The algorithms are lightweight, and the whole design flow (including Xilinx Place and Route) was completed in 75 minutes for the largest benchmark in the set.
A Hash Table for Line-Rate Data Processing
Authors: István Zsolt , Alonso Gustavo , Blott Michaela , Vissers Kees
Published: March 2015

FPGA-based data processing is becoming increasingly relevant in data centers, as the transformation of existing applications into dataflow architectures can bring significant throughput and power benefits. Furthermore, a tighter integration of computing and network is appealing, as it overcomes traditional bottlenecks between CPUs and network interfaces, and dramatically reduces latency.

In this article, we present the design of a novel hash table, a fundamental building block used in many applications, to enable data processing on FPGAs close to the network. We present a fully pipelined design capable of sustaining consistent 10Gbps line-rate processing by deploying a concurrent mechanism to handle hash collisions. We address additional design challenges such as support for a broad range of key sizes without stalling the pipeline through careful matching of lookup time with packet reception time. Finally, the design is based on a scalable architecture that can be easily parameterized to work with different memory types operating at different access speeds and latencies.

We have tested the proposed hash table in an FPGA-based memcached appliance implementing a main-memory key-value store in hardware. The hash table is used to index 2 million entries in 24GB of external DDR3 DRAM while sustaining 13 million requests per second, the maximum packet rate that can be achieved with UDP packets on a 10Gbps link for this application.
Design Tradeoffs of SSDs
Authors: Cho Seokhei , Park Changhyun , Won Youjip , Kang Sooyong , Cha Jaehyuk , Yoon Sungroh , Choi Jongmoo
Published: March 2015

In this work, we studied the energy consumption characteristics of various SSD design parameters. We developed an accurate energy consumption model for SSDs that computes aggregate, as well as component-specific, energy consumption of SSDs in sub-msec time scale. In our study, we used five different FTLs (page mapping, DFTL, block mapping, and two different hybrid mappings) and four different channel configurations (two, four, eight, and 16 channels) under seven different workloads (from large-scale enterprise systems to small-scale desktop applications) in a combinatorial manner. For each combination of the aforementioned parameters, we examined the energy consumption for individual hardware components of an SSD (microcontroller, DRAM, NAND flash, and host interface). The following are some of our findings. First, DFTL is the most energy-efficient address-mapping scheme among the five FTLs we tested due to its good write amplification and small DRAM footprint. Second, a significant fraction of energy is being consumed by idle flash chips waiting for the completion of NAND operations in the other channels. FTL should be designed to fully exploit the internal parallelism so that energy consumption by idle chips is minimized. Third, as a means to increase the internal parallelism, increasing way parallelism (the number of flash chips in a channel) is more effective than increasing channel parallelism in terms of peak energy consumption, performance, and hardware complexity. Fourth, in designing high-performance and energy-efficient SSDs, channel switching delay, way switching delay, and page write latency need to be incorporated in an integrated manner to determine the optimal configuration of internal parallelism.
Time- and Space-Efficient Sliding Window Top-k Query Processing
Authors: Pripužić Krešimir , Žarko Ivana Podnar , Aberer Karl
Published: March 2015

A sliding window top-k (
top-k/w
) query monitors incoming data stream objects within a sliding window of size
w
to identify the
k
highest-ranked objects with respect to a given scoring function over time. Processing of such queries is challenging because, even when an object is not a top-k/w object at the time when it enters the processing system, it might become one in the future. Thus a set of potential top-k/w objects has to be stored in memory while its size should be minimized to efficiently cope with high data streaming rates. Existing approaches typically store top-k/w and candidate sliding window objects in a k-skyband over a two-dimensional score-time space. However, due to continuous changes of the k-skyband, its maintenance is quite costly. Probabilistic k-skyband is a novel data structure storing data stream objects from a sliding window with significant probability to become top-k/w objects in future. Continuous probabilistic k-skyband maintenance offers considerably improved runtime performance compared to k-skyband maintenance, especially for large values of
k
, at the expense of a small and controllable error rate. We propose two possible probabilistic k-skyband usages: (
i
) When it is used to process all sliding window objects, the resulting top-k/w algorithm is approximate and adequate for processing random-order data streams. (
ii
) When probabilistic k-skyband is used to process only a subset of most recent sliding window objects, it can improve the runtime performance of continuous k-skyband maintenance, resulting in a novel exact top-k/w algorithm. Our experimental evaluation systematically compares different top-k/w processing algorithms and shows that while competing algorithms offer either time efficiency at the expanse of space efficiency or vice-versa, our algorithms based on the probabilistic k-skyband are both time and space efficient.
Progesterone increases nitric oxide synthesis in human vascular endothelial cells through activation of membrane progesterone receptor-α
Authors: Pang Yefei , Dong Jing , Thomas Peter
Published: March 2015

Progesterone exerts beneficial effects on the human cardiovascular system by inducing rapid increases in nitric oxide (NO) production in vascular endothelial cells, but the receptors mediating these nongenomic progesterone actions remain unclear. Using human umbilical vein endothelial cells (HUVECs) as a model, we show that progesterone binds to plasma membranes of HUVECs with the characteristics of membrane progesterone receptors (mPRs). The selective mPR agonist Org OD 02-0 had high binding affinity for the progesterone receptor on HUVEC membranes, whereas nuclear PR (nPR) agonists R5020 and medroxyprogesterone acetate displayed low binding affinities. Immunocytochemical and Western blot analyses confirmed that mPRs are expressed in HUVECs and are localized on their plasma membranes. NO levels increased rapidly after treatment with 20 nM progesterone, Org OD 02-0, and a progesterone-BSA conjugate but not with R5020, suggesting that this progesterone action is at the cell surface and initiated through mPRs. Progesterone and Org OD 02-0 (20 nM) also significantly increased endothelial nitric oxide synthase (eNOS) activity and eNOS phosphorylation. Knockdown of mPRα expression by treatment with small-interfering RNA (siRNA) blocked the stimulatory effects of 20 nM progesterone on NO production and eNOS phosphorylation, whereas knockdown of nPR was ineffective. Treatment with PI3K/Akt and MAP kinase inhibitors blocked the stimulatory effects of progesterone, Org OD 02-0, and progesterone-BSA on NO production and eNOS phosphorylation and also prevented progesterone- and Org OD 02-0-induced increases in Akt and ERK phosphorylation. The results suggest that progesterone stimulation of NO production in HUVECs is mediated by mPRα and involves signaling through PI3K/Akt and MAP kinase pathways.
Torn ACL: A New Bioengineered Substitute Brought from the Laboratory to the Knee Joint
Authors: Goulet Francine , Rancourt Denis , Cloutier Réjean , Tremblay Pierrot , Belzil Anne-Marie , Lamontagne Jean , Bouchard Marc , Tremblay Julie , Stevens Louis-Mathieu , Labrosse Julie , Langelier Eve , McKee Marc D.
Published: March 2015

Anterior cruciate ligament (ACL) injuries occur at an annual rate of 120 000 in the USA, and many need reconstructive surgery. We report successful results at 1–13 months following implantation of bioengineered ACL (bACL) in goats. A bACL has been developed using autologous ACL cells, a collagen matrix and bone plugs. The extremities of the bACL were fully integrated into the femur and tibia of the host. Vascularisation of the grafts was extensive 1 month post-surgery and improved with time. At 6 months post-grafting, histological and ultrastructural observations demonstrated a highly organised ligamentous structure, rich in type I collagen fibres and fibroblasts. At the implants' insertion sites, characteristic fibrocartilage was observed having well aligned chondrocytes and collagen fibrils. After a year, mechanical rupture of the grafts demonstrated a major gain in strength. Eventual applications of this new technology in humans include multiple uses in orthopaedic, dental and reconstructive surgeries.
Frequency of Temporomandibular Disorders in Asymptomatic Removable Partial and Complete Denture Wearers
Authors: Dulčić N. , Jerolimov V. , Pandurić J.
Published: March 2015

A dogmatic view on occlusion as the main aetiological factor for temporomandibular disorder (TMD) has been present in the literature for a long time, but a direct scientific correlation between occlusal disorders and TMD has never been proven. The purpose of this study was to determine the frequency of TMD signs and tissue-specific diagnoses in a population of 164 asymptomatic participants, 70 removable partial denture wearers and 94 complete denture wearers of an average age of 61.3 years, by means of clinical manual functional analysis. TMD was found in 42.1% of the participants. No statistically significant difference in the occurrence of TMD was found between removable partial and complete denture wearers and between genders (P > 0.05). The most frequent tissue-specific diagnoses were osteoarthrosis (11%), total anterior disc displacement (9.1%) and partial anterolateral disc displacement (8.5%). The frequency of tissue-specific diagnoses was also not influenced by the type of prosthetic replacements.
Limits of Nature and Advances of Technology: What Does Biomimetics Have to Offer to Aquatic Robots?
Authors: Fish F. E.
Published: March 2015

In recent years, the biomimetic approach has been utilized as a mechanism for technological advancement in the field of robotics. However, there has not been a full appreciation of the success and limitations of biomimetics. Similarities between natural and engineered systems are exhibited by convergences, which define environmental factors, which impinge upon design, and direct copying that produces innovation through integration of natural and artificial technologies. Limitations of this integration depend on the structural and mechanical differences of the two technologies and on the process by which each technology arises. The diversity of organisms that arose through evolutionary descent does not necessarily provide all possible solutions of optimal functions. However, in instances where organisms exhibit superior performance to engineered systems, features of the organism can be targeted for technology transfer. In this regard, cooperation between biologists and engineers is paramount.
A Multi-Agent Control Architecture for a Robotic Wheelchair
Authors: Galindo C. , Cruz-Martin A. , Blanco J. L. , Fernńndez-Madrigal J. A. , Gonzalez J.
Published: March 2015

Assistant robots like robotic wheelchairs can perform an effective and valuable work in our daily lives. However, they eventually may need external help from humans in the robot environment (particularly, the driver in the case of a wheelchair) to accomplish safely and efficiently some tricky tasks for the current technology, i.e. opening a locked door, traversing a crowded area, etc. This article proposes a control architecture for assistant robots designed under a multi-agent perspective that facilitates the participation of humans into the robotic system and improves the overall performance of the robot as well as its dependability. Within our design, agents have their own intentions and beliefs, have different abilities (that include algorithmic behaviours and human skills) and also learn autonomously the most convenient method to carry out their actions through reinforcement learning. The proposed architecture is illustrated with a real assistant robot: a robotic wheelchair that provides mobility to impaired or elderly people.
Design and Implementation of NTU Wearable Exoskeleton as an Enhancement and Assistive Device
Authors: Low K. H. , Liu X. , Yu H.
Published: March 2015

This article presents a wearable lower extremity exoskeleton (LEE) developed to enhance the ability of a human’s walking while carrying heavy loads. The ultimate goal of the current research work is to design and control a power assist system that integrates a human’s intellect for feedback and sensory purposes. The exoskeleton system in this work consists of an inner exoskeleton and an outer exoskeleton. The inner exoskeleton measures the movements of the wearer and provides these measurements to the outer exoskeleton, which supports the whole exoskeleton system to walk following the wearer. A special footpad, which is designed and attached to the outer exoskeleton, can measure the zero moment point (ZMP) of the human as well as that of the exoskeleton in time. Using the measured human ZMP as the reference, the exoskeleton’s ZMP is controlled by trunk compensation so that the exoskeleton can walk stably. A simulation platform has first been developed to examine the gait coordination through inner and outer exoskeletons. A commercially available software, xPC Target, together with other toolboxes from MATLAB, has then been used to provide a real-time operating system for controlling the exoskeleton. Real-time locomotion control of the exoskeleton is implemented in the developed environment. Finally, some experiments on different objects showed that the stable walking can be achieved in the real environment.