bluuebunny/crossref_metadata_2025 huggingface dataset:
The National Institutes of Health Center for Human Immunology, Autoimmunity, and Inflammation: history and progress
Authors: Dickler Howard B. , McCoy J. Philip , Nussenblatt Robert , Perl Shira , Schwartzberg Pamela A. , Tsang John S. , Wang Ena , Young Neil S.
Published: May 2013

The Center for Human Immunology, Autoimmunity, and Inflammation (CHI) is an exciting initiative of the NIH intramural program begun in 2009. It is uniquely trans‐NIH in support (multiple institutes) and leadership (senior scientists from several institutes who donate their time). Its goal is an in‐depth assessment of the human immune system using high‐throughput multiplex technologies for examination of immune cells and their products, the genome, gene expression, and epigenetic modulation obtained from individuals both before and after interventions, adding information from in‐depth clinical phenotyping, and then applying advanced biostatistical and computer modeling methods for mining these diverse data. The aim is to develop a comprehensive picture of the human “immunome” in health and disease, elucidate common pathogenic pathways in various diseases, identify and validate biomarkers that predict disease progression and responses to new interventions, and identify potential targets for new therapeutic modalities. Challenges, opportunities, and progress are detailed.
Improvement in Hemodynamic Response Using a Quadripolar LV Lead
Authors: CABRERA BUENO FERNANDO , ALZUETA RODRÍGUEZ JAVIER , OLAGÜE DE ROS JOSÉ , FERNÁNDEZ‐LOZANO IGNACIO , GARCÍA GUERRERO JUAN JOSÉ , DE LA CONCHA JOAQUÍN FERNÁNDEZ , HERNÁNDEZ MADRID ANTONIO , TOLOSANA VIU JOSE MARÍA , OSCA ASENSI JOAQUÍN , BARRERA CORDERO ALBERTO , LLORENTE HERNANGÓMEZ ELENA
Published: May 2013

Background

The Quartet™ quadripolar lead (St. Jude Medical Inc., St. Paul, MN, USA) offers 10 different left ventricle pacing configurations that may further influence hemodynamic parameters compared to traditional bipolar pacing configurations. The purpose of this study was to evaluate whether pacing from additional quadripolar lead vectors could enhance cardiac output (CO).

Methods

For each patient, CO was measured in “no‐pacing” and in all the 10 configurations available, within 7 days of implantation of the device. Tip‐ring, tip‐right ventricular coil (RVC), and ring‐RVC vectors were considered as traditional vectors. The seven additional configurations available in the quadripolar lead were considered as nontraditional vectors. CO was measured by ECHO. The best configuration was defined as the one presenting the highest CO measurement within configurations, which have a capture threshold <3 V and a safety margin between the capture and the phrenic nerve stimulation thresholds.

Results

Fifty‐one standard cardiac resynchronization therapy patients were enrolled. The mean of each patient's best CO obtained with traditional vectors was higher than the baseline nonpaced CO (4.16 L/min vs 3.64 L/min). The mean of each patient's best CO, including all 10 available configurations, was also higher than the baseline nonpaced CO (4.33 L/min vs 3.64 L/min). In addition, the mean of each patient's best CO obtained with the best configuration available through a quadripolar lead was better than the mean of each patient's best CO obtained with a traditional configuration. In 53% of patients, the best CO was obtained with a nontraditional vector unique to the quadripolar lead.

Conclusions

A quadripolar lead offers multiple additional pacing options to increase CO acutely compared to conventional bipolar leads.
Comparison between two maintenance feeding regimens after successful cow's milk oral desensitization
Authors: Pajno Giovanni B. , Caminiti Lucia , Salzano Giuseppina , Crisafulli Giuseppe , Aversa Tommaso , Messina Maria Francesca , Wasniewska Malgorzata , Passalacqua Giovanni
Published: May 2013

Background

Cow's milk allergy is common in infancy, and total avoidance of this food is the only effective approach. In alternative, oral immunotherapy has been proposed to achieve tolerance. Once desensitization is achieved, daily intake of milk is recommended to maintain it, but this may be impractical for children/parents. We assessed whether a twice weekly maintenance regimen is effective.

Methods

Children who were successfully desensitized with oral immunotherapy were randomized to two maintenance regimens for 1 year: group A had to eat 150–200 ml milk daily, group B had to eat 150–200 ml milk twice weekly. Both regimens were associated to a totally free diet. Maintenance of tolerance and adverse events were recorded during 1 year. Specific IgE, IgG4 and prick‐by‐prick test to milk were carried out before immunotherapy (T0), before maintenance (T1), and after 1 year (T2).

Results

Recorded episodes included asthma, oral itching, urticaria, rhinitis, abdominal pain variously combined, usually associated with concomitant illness or exercise. The episodes were 8 in group A and 9 in group B, with no difference. None of the children discontinued the feeding maintenance. Specific IgG4 increased at T1 and remained high at T2. Specific IgE and skin reactivity significantly decreased at T2. There was no difference in those parameters between the groups.

Conclusion

After achieving desensitization to cow milk with oral immunotherapy, a maintenance regimen with milk given twice weekly is as effective as the daily maintenance.
Role of specific IgE in predicting the clinical course of lentil allergy in children
Authors: Yavuz Suleyman T. , Sahiner Umit M. , Buyuktiryaki Betul , Tuncer Ayfer , Yilmaz Ebru A. , Cavkaytar Ozlem , Karabulut Erdem , Sackesen Cansin
Published: May 2013

Background

Legumes, and particularly lentils, are frequently consumed in Mediterranean, Middle Eastern, and some Asian countries. The aim of this study was to document the demographic features of children with lentil allergy and to determine the role of specific IgE (sIgE) in predicting the risk of clinical reactivity and disease persistence.

Methods

Thirty children were enrolled. The diagnosis of lentil allergy was based on convincing history of symptoms or anaphylaxis after the ingestion of lentils, with positive skin tests and/or sIgE to lentils. To determine the diagnosis and prognosis of lentil allergy, 24 children were evaluated with food challenges.

Results

The median age at the onset of symptoms was 1.5 yr (0.9–2.3) (inter‐quartile range). The most frequent symptoms were immediate cutaneous (97%) and respiratory (30%) reactions, whereas eight patients (27%) reported anaphylactic reactions. The median level of lentil sIgE at the time of diagnosis was 3 kU/l (1.2–9.6). Of the 24 challenges, 12 were positive. Fifteen patients (50%) outgrew the lentil allergy by the age of 3.5 (2.5–11) years. Children with an initial lentil sIgE < 4.9 kU/l had a significantly higher likelihood (68.4% vs. 18.2%) of outgrowing the lentil allergy than children with an initial lentil sIgE ≥ 4.9 k/l (p = 0.008).

Conclusions

Our results suggest that sIgE levels may be important for predicting clinical reactivity and persistence of lentil allergy.
Re‐evaluation of the indications for liver transplantation in Wilson's disease based on the outcomes of patients referred to a transplant center
Authors: Ohya Yuki , Okajima Hideaki , Honda Masaki , Hayashida Shintaro , Suda Hiroko , Matsumoto Shiro , Lee Kwang‐Jong , Yamamoto Hidekazu , Takeichi Takayuki , Mitsubuchi Hiroshi , Asonuma Katsuhiro , Endo Fumio , Inomata Yukihiro
Published: May 2013

The aim of this study was to re‐evaluate the indications and timing of LT for WD. From 2000 to 2009, eight patients with WD who had been referred to our institution for LT were enrolled in this study. The mean patient age was 15.9 yr (range, 7–37 yr). Four patients could not receive LT, because there were no available donors. All four patients were treated with chelating agent medication. Three of them (two of two patients with fulminant WD and one of two with cirrhotic WD) who did not undergo LT are still alive and doing well with stable liver functional tests. Only one of the patients with cirrhotic WD who did not undergo LT died of hepatic failure. Even among the four patients who underwent LT, one with fulminant WD recovered from hepatic encephalopathy with apheresis therapy and chelating agent. He later required LT because of severe neutropenia from d‐penicillamine. The other three patients who underwent LT recovered and have been doing well. Some of the patients with WD can recover and avoid LT with medical treatment. Even when WD has progressed liver cirrhosis and/or fulminant hepatic failure at the time of diagnosis, medical treatment should be tried before considering LT.
Lower respiratory tract viral infections in pediatric abdominal organ transplant recipients: A single hospital inpatient cohort study
Authors: Tran Thy T. , Gonzalez Ivan A. , Tekin Akin , McLaughlin Gwenn E.
Published: May 2013

Respiratory viral infections are a major cause of morbidity and mortality in solid organ transplant recipients. Early detection of a viral etiology of a LRTI in a febrile transplant recipient can theoretically reduce the use of antibiotics, trigger modification of immunosuppression and prompt appropriate isolation procedures to reduce nosocomial infections. We retrospectively evaluated pediatric abdominal organ transplant recipients hospitalized with respiratory illnesses to determine the viral pathogens identified by various methods including multiplex RT‐PCR performed on nasopharyngeal or endotracheal aspirates. Among 30 symptomatic subjects (median age, 2.5 yr) evaluated using this methodology, 25 (83%) were positive for at least one virus. Rhinovirus was the most frequently identified virus (14 subjects). RSV was identified in five subjects with associated mortality of 40%. Parainfluenza, influenza, metapneumovirus, and adenovirus were also identified. This study indicates that rhinovirus is a significant cause of morbidity in this single center cohort of pediatric abdominal organ transplant recipients.
Fibrocartilaginous mesenchymoma arising in the pubic bone: A case report
Authors: Takahashi Yusuke , Oda Yoshinao , Yamamoto Hidetaka , Ishii Takeaki , Setsu Nokitaka , Endo Makoto , Matsuda Shuichi , Iwamoto Yukihide
Published: May 2013

Fibrocartilaginous mesenchymoma (FCM) of the bone is a rare tumor, with only 21 reported cases since 1984. It usually occurs in the long bones of children and adolescents, but in this case, the tumor arose in the pubic bone. The pathological diagnosis of FCM can be challenging, and the treatment should be a wide resection because of its locally aggressive behavior. Histologically, our tumor was composed of a lobular proliferation of spindle cells juxtaposed to the cartilaginous tissue, lacking cytological atypia. Enchondral ossification was observed at the periphery of the cartilaginous nodules, and hypertrophic chondrocytes was recognized, reminiscent of an epiphyseal plate. Intralesional resection followed by phenol and ethanol cauterization was performed in place of the usual wide resection. We report a case of FCM arising in a rare anatomical site, the pubic bone, successfully treated by intralesional resection. One year after the surgery, the patient is free of disease.
Well‐differentiated papillary mesothelioma, possibly giving rise to diffuse malignant mesothelioma: A case report
Authors: Washimi Kota , Yokose Tomoyuki , Amitani Yukiko , Nakamura Mamiko , Osanai Sachie , Noda Hiroko , Kawachi Kae , Takasaki Hirotaka , Akaike Makoto , Kameda Yoichi
Published: May 2013

Well‐differentiated papillary mesothelioma (WDPM) is a distinct subtype of mesothelial tumor from diffuse malignant mesothelioma (DMM), with an uncertain malignant potential. The relationship between WDPM and DMM, with regard to the ability of the former to develop into the latter, is also unknown. A 58‐year‐old woman, diagnosed with a rectal carcinoid tumor, underwent removal of the lymph nodes via the abdomen in 2004. A large number of white miliary nodules were identified on the mesentery and peritoneum, which were histologically diagnosed as WDPM. No further therapy was administered, but the patient was followed‐up using imaging methods. Seven years later, an abdominal wall mass was discovered using positron emission tomography‐computed tomography, and a laparotomy biopsy was performed. DMM was diagnosed, because mesothelioma with extended invasion had been histologically identified. Mesothelioma similar to papillary proliferation was present on the outer layer of the peritoneum, and an infiltrating lesion with continuous restiform or solid‐like structures was noted. WDPM was believed to have undergone malignant transformation. Compared to DMM, WDPM has a good prognosis and is considered a benign or borderline neoplasm. Our findings suggest that WDPM does have malignant potential, however, because histological findings indicated a malignant transformation of WDPM to DMM.
Airspace enlargement with fibrosis shows characteristic histology and immunohistology different from usual interstitial pneumonia, nonspecific interstitial pneumonia and centrilobular emphysema
Authors: Yamada Tsutomu , Nakanishi Yoko , Homma Taku , Uehara Kenji , Mizutani Tomohiko , Hoshi Eishin , Shimizu Yoshihiko , Kawabata Yoshinori , Colby Thomas V.
Published: May 2013

The histologic characteristics of air space enlargement with fibrosis (AEF) are compared with usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP) and centrilobular emphysema (CLE) to determine similarities and differences. Lung specimens from 39 patients were studied; 9 with AEF, 13 with UIP and 5 with CLE identified in lobectomy specimens for cancer and 12 NSIP cases identified on surgical lung biopsies. We determined the characteristics of cystic structures (i.e. abnormal airspace), degree of inflammation and severity of pneumocyte injury semi‐quantitatively. In AEF, the wall thickness of the cystic lesions (0.8 mm) was thinner than in UIP (2.1 mm) and thicker than in CLE (0.07 mm). The degree of inflammation and granulation tissue were milder in AEF than in UIP and NSIP and CLE showed milder inflammatory cells than AEF. As for pneumocyte injury, AEF had fewer erosions (0.1/case) and fewer ubiquitin‐positive pneumocytes than UIP (4.8 cells/slide) and NSIP (9.8 cells/slide). Our data suggested that the histological characteristics of AEF differed significantly from UIP, NSIP and CLE.
Seasonal variation in agar composition and properties from Gracilaria gracilis (Gracilariales, Rhodophyta) of the Patagonian coast of Argentina
Authors: Martín Lucas A. , Rodríguez María C. , Matulewicz María C. , Fissore Eliana N. , Gerschenson Lía N. , Leonardi Patricia I.
Published: May 2013

Seasonal variation of agar from specimens of a commercially exploited population of Gracilaria gracilis (Stackhouse) Steentoft, Irvine & Farnham in the Patagonian coast of Argentina was studied. For each seasonal harvest, random samples of plants were pooled for subsequent polysaccharide extraction at different water temperatures and agar physico‐chemical properties and composition were determined.

Both spring and summer plants yielded 30% and 41% of agar, respectively, which differed slightly in their at rest rheological behavior. Spring and summer plants produced strong gels (238 and 218 g cm−2, respectively), but the latter gels had nil adhesiveness. In autumn plants, agar yield decayed to 19%, though the product still maintained similar gel strength (210 g cm−2). Adhesiveness in this product was at least an order of magnitude higher than in the others, concomitant with a peak in the formation of tetraspores and carpospores. This suggests a biological role for the galactan in the initial attachment of spores to the substrate. But since fall corresponds to the settling of reproductive structures, caution should be taken to harvest the algae once spores have been shed from mother plants.
Physiological ecology of photosynthesis in Prasiola stipitata (Trebouxiophyceae) from the Bay of Fundy, Canada
Authors: Kang Eun Ju , Scrosati Ricardo A. , Garbary David J.
Published: May 2013

The physiological ecology of Prasiola stipitata was examined in situ from two supralittoral sites in the Bay of Fundy (Nova Scotian, Canada) during November 2011, when the population was undergoing major expansion. Photosynthetic parameters (effective quantum yield, ΦPSII, maximum quantum yield, Fv/Fm, and relative electron transport rate, rETR) were evaluated using chlorophyll fluorescence of PSII. A largely shaded and continuously moist population showed no change in ΦPSII from one hour after sunrise to sunset in which natural irradiance varied between 3 and 300 μmol photons m−2 s−1. High irradiance (up to 1800 μmol photons m−2 s−1) had no apparent negative impacts on either quantum yield or rETR, but high desiccation in the field reduced quantum yield to almost zero. When thalli were brought into the laboratory, no change in Fv/Fm was observed up to 60% dehydration; however, there was a steep decline in Fv/Fm between 60% and 85% dehydration. Thalli showed complete recovery of Fv/Fm within one hour of reimmersion in seawater after 2 days of desiccation. After 15 days of desiccation full recovery required 24 h and after 30 days of desiccation thalli showed only partial recovery. These observations confirm the adaptation to photosynthesis in high irradiances and the rapid recovery following extreme desiccation observed in other Prasiola species.
The Functional Role of Oxytocin in the Induction of Oocyte Meiotic Resumption in Cattle
Authors: De Cesaro MP , Trois RL , Gutierrez K , Siqueira L , Rigo ML , Glanzner WG , Oliveira JF , Gonçalves PB
Published: May 2013

Contents

The aim of the present study was to examine the role of oxytocin (OT) in the progesterone (P4) and prostaglandins (PGs) pathway to induce oocyte meiotic resumption. Cumulus–oocyte complexes were co‐cultured with follicular hemisections for 15 h to determine the effects of different doses of OT or atosiban (ATO; oxytocin receptor antagonist) on oocyte meiotic resumption. In another experiment, we examined the effect of the interaction between P4, OT and PGs on the regulatory cascade of the oocyte meiotic resumption. Oxytocin at 1 μm was effective in inducing meiotic resumption in oocytes co‐cultured with follicular cells (84.0%), not differing from the positive control group (74.4%). Atosiban inhibited in a dose‐dependent manner the positive effect of OT on the meiotic resumption (27.6% metaphase I with 10 μm of ATO, which did not differ from the 25.5% of the negative control group). Furthermore, a third experiment showed that P4 was able to induce oocyte meiotic resumption, which was inhibited by ATO. However, the OT positive effect was not blocked by mifepristone (P4 antagonist), but was inhibited by indomethacin (a non‐selective PTGS2 inhibitor). Collectively, these data suggest a sequential role of P4, OT and PGs in the induction of oocyte meiotic resumption.
The Effect of Dose and Type of Cloprostenol on the Luteolytic Response of Dairy Cattle during the Ovsynch Protocol under Different Oestrous Cycle and Physiological Characteristics
Authors: Valldecabres‐Torres X , Larrosa‐Morales P , Cuervo‐Arango J
Published: May 2013

Contents

The objective of this study was to characterize the effect of dose and type of cloprostenol (CLO) on the luteolytic response of dairy cattle during the Ovsynch protocol under different oestrus cycle and physiological characteristics. Twelve non‐lactating dairy cows and 111 lactating dairy cows were used in three experiments. In Experiment I, cows were synchronized so that they had only a 5.5‐ to 6‐day‐old corpus luteum (CL) at the time of the prostaglandin F2α (PGF2α) treatment of Ovsynch. In Experiment II, cows were synchronized so that they had at least a CL of approximately 14 days old at the time of PGF2α treatment and an accessory CL if they had responded to the first GnRH of Ovsynch. Furthermore, in each experiment, cows received either a standard or a double dose of d‐CLO as the luteolytic treatment. In Experiment III, lactating cows were blocked by parity and assigned to one of three luteolytic treatments during Ovsynch: 500 μg d,l‐CLO, 150 or 300 μg of d‐CLO. In Experiment I, the dose of d‐CLO had an effect (p = 0.08) on the percentage of cows with full luteolysis, but not in Experiment II (p > 0.1). More cows in Experiment II had full luteolysis than did cows of Experiment I (87% vs 58%, respectively; p = 0.007). In Experiment III, 87.1%, 84.4% and 86.2% lactating dairy cows had full luteolysis and 37.8%, 36.8% and 36.1% of cows became pregnant after treatment with 500 μg d,l‐CLO, 150 or 300 μg of d‐CLO, respectively (p > 0.05).
In Vitro Development of Bison Embryos Using Interspecies Somatic Cell Nuclear Transfer
Authors: Seaby RP , Alexander B , King WA , Mastromonaco GF
Published: May 2013

Contents

Interspecies somatic cell nuclear transfer (interspecies SCNT) has been explored in many domestic and non‐domestic animal species. However, problems arise during the development of these embryos, which may be related to species‐specific differences in nuclear–cytoplasmic communication. The objectives of this study were to investigate the possibility of producing bison embryos in vitro using interspecies SCNT and assess the developmental potential of these embryos. Treatment groups consisted of cattle in vitro fertilization (IVF) and cattle SCNT as controls and wood bison SCNT, plains bison SCNT and wisent SCNT as experimental groups. Cleavage and blastocyst rates were assessed, and blastocyst quality was determined using total cell number, apoptotic incidence and relative quantification of mitochondria‐related genes NRF1, MT‐CYB and TFAM. These results indicate that embryos can be produced by interspecies SCNT in all bison species/subspecies (13.34–33.54% blastocyst rates). Although increased incidence of apoptosis was observed in bison SCNT blastocysts compared to cattle SCNT controls (10.45–12.69 vs 8.76, respectively) that corresponded with significantly lower cell numbers (80–87 cells vs >100 cells, respectively), no major differences were observed in the expression of NRF1, MT‐CYB and TFAM. This study is the first to report the production of bison embryos by interspecies SCNT. Blastocyst development in all three bison species/subspecies was greater than the rates obtained in previous studies by IVF, which supports the potential role of SCNT for in vitro embryo production in this species. Yet, further investigation of developmental competence and the factors influencing blastocyst quality and viability is required.
Polanyi in Brussels or Luxembourg? Social rights and market regulation in European insurance
Authors: Mabbett Deborah
Published: May 2013

The decision of the Court of Justice of the European Union to ban sex discrimination in insurance has shown the potential reach of the principle of non‐discrimination. This paper discusses the different positions taken by participants in the policy process leading up to the decision, in order to reveal the potential and limitations of non‐discrimination as the basis for market‐regulatory social policy. It is shown that the European Commission's initial support for prohibiting insurance discrimination faltered with the realization that the measure would have little efficacy as a distributive social policy. It was left to the Court to assert that non‐discrimination rights are constitutive for European markets, regardless of their functional and instrumental limitations. The Court's focus was on the market‐integrative potential of rights as sources of norms for the conduct of insurance relationships. It is argued that this form of constitutive regulation is distinct from distributive social policy as it does not require that outcomes are egalitarian, but, rather, that the processes governing market relations should respect fundamental rights.
Successful systemic high‐dose ribavirin treatment of respiratory syncytial virus‐induced infections occurring pre‐engraftment in allogeneic hematopoietic stem cell transplant recipients
Authors: Gueller S. , Duenzinger U. , Wolf T. , Ajib S. , Mousset S. , Berger A. , Martin H. , Serve H. , Bug G.
Published: May 2013

Introduction

Respiratory syncytial virus (RSV) is a frequent cause of respiratory tract infectious disease (RTID) in allogeneic hematopoietic stem cell transplant (HSCT) recipients associated with a high mortality once infection has progressed from upper RTID (URTID) to lower RTID (URTID). Aerosolized ribavirin (RBV) is considered a cornerstone of treatment, but is expensive and has toxic side effects on patients and staff. In this study, RSV infection was detected by polymerase chain reaction (PCR) from routinely collected throat swabs in HSCT patients. Infected individuals were treated according to an institutional protocol using intravenous (IV) RBV for patients with LRTID and oral ribavirin for URTID.

Results

RSV infection was diagnosed in 10 patients (median age 60 years) a median of 15 days after allogeneic HSCT for high‐risk acute myeloid leukemia. Five patients with LRTID received IV RBV within 7 days after HSCT, and 5 with URTID were treated with oral RBV 12–40 days after HSCT. One patient died of septic shock associated with Pseudomonas aeruginosa‐induced pneumonia 28 days after HSCT in prolonged neutropenia. All patients became RSV PCR negative on throat swabs within a median of 22 days from start of RBV. Despite severe lymphopenia, no patient treated for URTID progressed to LRTID. Neutrophil recovery was delayed in 3 patients.

Conclusions

We show that IV and oral RBV were efficacious in preventing progression and reducing mortality of RSV infection in this small series of allogeneic HSCT recipients. Randomized studies are not to be expected for this condition and therefore reporting case series could help in determining optimal RSV treatment.
Evaluation of preoperative and intraoperative red blood cell transfusion practices at Maputo Central Hospital, Mozambique
Authors: Burke Zachary D.C. , Chen James B. , Conceicao Celson , Hoffman Risa M. , Miller Lee T. , Taela Atanasio , DeUgarte Daniel A.
Published: May 2013

Background

The purpose of this study was to evaluate preoperative and intraoperative blood transfusion practices in Hospital Central (Maputo, Mozambique) and estimate the number of potentially avoidable transfusions.

Study Design and Methods

A retrospective cohort study was performed. Age, comorbidities, hemoglobin (Hb), the potential for blood loss, and units of red blood cell (RBC) transfusions were recorded. Preoperative transfusions were evaluated to determine whether they met criteria established by the Mozambican Ministry of Health as well as proposed guidelines based on more restrictive protocols. Avoidable blood transfusions were defined as those preoperative transfusions that were not indicated based on these guidelines. Multivariate logistic regression was used to identify factors that predicted transfusion.

Results

A total of 205 patients (age range, 0.1‐86 years) underwent surgery in the main operating room during the 2‐week study period. Overall, 35 (17%) patients received 68 transfusions. Of these, 36 transfusions were given preoperatively and 32 were given intraoperatively. Thirty‐six percent of preoperative transfusions were avoidable according to national guidelines. Ninety‐two percent were avoidable using more restrictive guidelines. The primary predictors of preoperative blood transfusion were lower Hb (odds ratio [OR], 0.390/1 g/dL; p < 0.0001) and the potential for blood loss (OR, 3.73; p = 0.0410).

Conclusions

Adherence to existing Hb thresholds recommended by national blood transfusion guidelines could significantly reduce the number of transfusions and the association risk of transfusion‐transmissible infections. Adoption of more restrictive guidelines is recommended to further improve blood transfusion utilization and further reduce the transmission risk of human immunodeficiency virus and hepatitis.
Dynamic regulation of glycine–GABA co‐transmission at spinal inhibitory synapses by neuronal glutamate transporter
Authors: Ishibashi Hitoshi , Yamaguchi Junya , Nakahata Yoshihisa , Nabekura Junichi
Published: May 2013

Key points

Inhibition mediated by GABA and glycine is essential for controlling a balance of excitation and inhibition in the spinal cord.

Although these transmitters are known to be co‐released from the same synaptic vesicles, the mechanisms that control the packaging of GABA + glycine into synaptic vesicles have not been fully characterized.

In this study, using paired whole‐cell recording, we found that raised extracellular glutamate levels increased the amplitude of GABAergic IPSCs by enhancing glutamate uptake but reduced glycine release.

High‐frequency trains of stimulation decreased glycinergic IPSCs more than GABAergic IPSCs at GABA/glycine mixed synapses, and repetitive stimulation occasionally failed to evoke glycinergic but not GABAergic IPSCs.

The present results suggest that the use of GABA as a transmitter at GABA/glycine mixed synapses may afford protection against pathophysiological hyperexcitability associated with increased extracellular glutamate concentration.

Abstract  Fast inhibitory neurotransmission in the central nervous system is mediated by γ‐aminobutyric acid (GABA) and glycine, which are accumulated into synaptic vesicles by a common vesicular inhibitory amino acid transporter (VIAAT) and are then co‐released. However, the mechanisms that control the packaging of GABA + glycine into synaptic vesicles are not fully understood. In this study, we demonstrate the dynamic control of the GABA–glycine co‐transmission by the neuronal glutamate transporter, using paired whole‐cell patch recording from monosynaptically coupled cultured spinal cord neurons derived from VIAAT‐Venus transgenic rats. Short step depolarization of presynaptic neurons evoked unitary (cell‐to‐cell) inhibitory postsynaptic currents (IPSCs). Under normal conditions, the fractional contribution of postsynaptic GABA or glycine receptors to the unitary IPSCs did not change during a 1 h recording. Intracellular loading of GABA or glycine via a patch pipette enhanced the respective components of inhibitory transmission, indicating the importance of the cytoplasmic concentration of inhibitory transmitters. Raised extracellular glutamate levels increased the amplitude of GABAergic IPSCs but reduced glycine release by enhancing glutamate uptake. Similar effects were observed when presynaptic neurons were intracellularly perfused with glutamate. Interestingly, high‐frequency trains of stimulation decreased glycinergic IPSCs more than GABAergic IPSCs, and repetitive stimulation occasionally failed to evoke glycinergic but not GABAergic IPSCs. The present results suggest that the enhancement of GABA release by glutamate uptake may be advantageous for rapid vesicular refilling of the inhibitory transmitter at mixed GABA/glycinergic synapses and thus may help prevent hyperexcitability.
Human hypoglossal motor unit activities in exercise
Authors: Walls Clinton E. , Laine Christopher M. , Kidder Ian J. , Bailey E. Fiona
Published: May 2013

Key points

Motor units (MUs) are the fundamental element of force generation. Here we document the MU activities of the airway dilator muscle genioglossus (GG) during breathing at rest and in heavy exercise.

Based on our observations we suggest that tonic MU activity, albeit with varying degrees of respiratory modulation, is the preponderant activity in the GG motoneuron pool of healthy young adults at rest in the upright position.

Second, we show that exercise‐driven increases in respiratory drive are associated with increased GG electromyographic activity principally due to recruitment of previously silent MUs and to a shift in the firing behaviour of already active MUs to inspiratory phase‐dependent bursting.

Such expiration‐related inhibition may arise secondary to an exercise‐related central enhancement of motoneuron excitability that amplifies the response to afferent input.

Abstract  The genioglossus (GG) muscle is considered the principal protruder muscle of the tongue that dilates and stiffens the pharyngeal airway. We recorded whole muscle and single motor unit (MU) activities in healthy adults performing progressive intensity exercise on a cycle ergometer. Tungsten microelectrodes were inserted percutaneously into the GG of 11 subjects (20–40 years) to record electromyographic (EMG) activities and pulmonary ventilation (VI) at rest and at workload increments up to 300 W. Increases in respiratory drive were associated with increases in VI, mean inspiratory flow (Vt/Ti) and tonic and phasic components of the GG EMG activity. In contrast, individual MUs typically showed expiration‐related decreases in firing as exercise intensity increased. We suggest the decrease in MU activity may occur secondary to afferent feedback from lungs/chest wall and that compensation for more negative inspiratory airway pressures generated during heavy exercise occurs primarily via recruitment of previously silent MUs.
Acute exercise induces tumour suppressor protein p53 translocation to the mitochondria and promotes a p53–Tfam–mitochondrial DNA complex in skeletal muscle
Authors: Saleem Ayesha , Hood David A.
Published: May 2013

Key points

p53 is one of several important proteins that regulate the synthesis and function of mitochondria in muscle, and mice lacking p53 have impaired aerobic capacity.

The role of p53 in response to physiological stress such as exercise has not been investigated.

We demonstrate that acute exercise induces the translocation of p53 to mitochondria, and promotes a subsequent interaction with mitochondrial transcription factor A (Tfam) and mitochondrial DNA (mtDNA) to positively affect mtDNA transcription.

This rapid effect on p53 translocation probably represents an early exercise response which can promote long‐term beneficial mitochondrial and metabolic adaptations in muscle.

The results could have clinical implications in light of the growing recognition of exercise as an alternative therapy in cancer treatment, and the central role of p53 in halting tumorigenesis.

Abstract  The major tumour suppressor protein p53 plays an important role in maintaining mitochondrial content and function in skeletal muscle. p53 has been shown to reside in the mitochondria complexed with mitochondrial DNA (mtDNA); however, the physiological repercussions of mitochondrial p53 remain unknown. We endeavoured to elucidate whether an acute bout of endurance exercise could mediate an increase in mitochondrial p53 levels. C57Bl6 mice (n= 6 per group) were randomly assigned to sedentary, acute exercise (AE, 15 m min−1 for 90 min) or acute exercise + 3 h recovery (AER) groups. Exercise concomitantly increased the mRNA content of nuclear‐encoded (PGC‐1α, Tfam, NRF‐1, COX‐IV, citrate synthase) and mtDNA‐encoded (COX‐I) genes in the AE group, and further by ∼5‐fold in the AER group. Nuclear p53 protein levels were reduced in the AE and AER groups, while in contrast, the abundance of p53 was drastically enhanced by ∼2.4‐fold and ∼3.9‐fold in subsarcolemmal and intermyofibrillar mitochondria, respectively, in the AER conditions. Within the mitochondria, the interaction of p53 with mtDNA at the D‐loop and with Tfam was elevated by ∼4.6‐fold and ∼3.6‐fold, respectively, in the AER group. In the absence of p53, the enhanced COX‐I mRNA content observed with AE and AER was abrogated. This study is the first to indicate that endurance exercise can signal to localize p53 to the mitochondria where it may serve to positively modulate the activity of the mitochondrial transcription factor Tfam. Our findings help us understand the mechanisms underlying the effects of exercise as a therapeutic intervention designed to trigger the pro‐metabolic functions of p53.
Molecular basis of activation of the arachidonate‐regulated Ca2+ (ARC) channel, a store‐independent Orai channel, by plasma membrane STIM1
Authors: Thompson Jill L. , Shuttleworth Trevor J.
Published: May 2013

Key points

The two known endogenous Orai channels, the calcium store‐dependent CRAC channel and the store‐independent ARC channel, are both regulated by the protein STIM1.

However, whilst CRAC channel activation is regulated by STIM1 in the endoplasmic reticulum, it is the pool of STIM1 constitutively residing in the plasma membrane that regulates the ARC channels.

Here we show that, although the specific regions of STIM1 critical for the regulation of these channels are largely the same, the actual mechanism of activation is markedly different.

Specifically, STIM1 in the plasma membrane exists in a constitutive association with the ARC channel, only requiring arachidonic acid to induce opening of the channel.

As these channels are known to play critical roles in the generation and modulation of key intracellular calcium signals, such distinct modes of activation are likely to have important implications for the generation and modulation of such signals in diverse cell types.

Abstract  Currently, Orai proteins are known to encode two distinct agonist‐activated, highly calcium‐selective channels: the store‐operated Ca2+ release‐activated Ca2+ (CRAC) channels, and the store‐independent, arachidonic acid‐activated ARC channels. Surprisingly, whilst the trigger for activation of these channels is entirely different, both depend on stromal interacting molecule 1 (STIM1). However, whilst STIM1 in the endoplasmic reticulum membrane is the critical sensor for the depletion of this calcium store that triggers CRAC channel activation, it is the pool of STIM1 constitutively resident in the plasma membrane that is essential for activation of the ARC channels. Here, using a variety of approaches, we show that the key domains within the cytosolic part of STIM1 identified as critical for the activation of CRAC channels are also key for activation of the ARC channels. However, examination of the actual steps involved in such activation reveal marked differences between these two Orai channel types. Specifically, loss of calcium from the EF‐hand of STIM1 that forms the key initiation point for activation of the CRAC channels has no effect on ARC channel activity. Secondly, in marked contrast to the dynamic and labile nature of interactions between STIM1 and the CRAC channels, STIM1 in the plasma membrane appears to be constitutively associated with the ARC channels. Finally, specific mutations in STIM1 that induce an extended, constitutively active, conformation for the CRAC channels actually prevent activation of the ARC channels by arachidonic acid. Based on these findings, we propose that the likely role of arachidonic acid lies in inducing the actual gating of the channel.
Heat Transfer Characteristics of Passive Condensers for Reactor Containment Cooling
Authors: Revankar Shripad T.
Published: May 2013

Passive condensers that are based on gravitational force do not require pumps or blowers to move fluid and, hence, are considered as safety measures in nuclear power plant containment cooling. In this paper vertical tube passive condensers with the tube inside condensation and cooled by a secondary pool of water are discussed as applied to reactor containment heat removal system. Series of experiments were carried out on scaled separate effects test facilities with vertical single tube and four tube bundle condensers. The results of experimental data on the rate of condensation heat transfer, the effects of noncondensable, and parametric effects, such as pressure, tube diameters and lengths, obtained from single tube and tube bundle passive condenser are presented. The data on the tube bundle indicated larger condensation heat transfer due to enhanced heat transfer in the secondary cooling. For tube bundle condensation, the turbulent mixing on the secondary pool side decreases the temperature difference between pool water and condenser tube outer wall, causing an increase in secondary heat transfer. Theoretical models on tube condensation based on heat and mass analogy and boundary layer models were developed. The data were compared with theoretical models and good agreement was observed between theoretical predictions and single tube condensation heat transfer data. For the tube bundle condenser, the theoretical model agreed with data when the secondary side enhancement in heat transfer due to turbulent mixing in the flow boiling was included. Practical heat transfer correlations are presented using available data on passive condensers for reactor application.
Thermodynamics-Based Control of Network Systems
Authors: Berg Jordan M. , Maithripala D. H. S. , Hui Qing , Haddad Wassim M.
Published: May 2013

The zeroth and first laws of thermodynamics define the concepts of thermal equilibrium and thermal energy. The second law of thermodynamics determines whether a particular transfer of thermal energy can occur. Collectively, these fundamental laws of nature imply that a closed collection of thermodynamic subsystems will tend to thermal equilibrium. This paper generalizes the concepts of energy, entropy, and temperature to undirected and directed networks of single integrators, and demonstrates how thermodynamic principles can be applied to the design of distributed consensus control algorithms for networked dynamical systems.
Characterization of Twisted-Tape-Induced Helical Swirl Flows for Enhancement of Forced Convective Heat Transfer in Single-Phase and Two-Phase Flows
Authors: Manglik Raj M. , Bergles Arthur E.
Published: May 2013

By generating helical swirling motion inside a tube with a twisted-tape insert, forced convective heat transfer is significantly enhanced. The primary mechanism entails imparting a centrifugal force component to the longitudinal fluid motion, which superimposes secondary circulation over the main axial flow to promote cross-stream mixing. Based on experimental flow visualization and computational modeling of single-phase laminar flows, a fundamental scaling of the cross-sectional vortex structure and a parametric analysis of the primary enhancement mechanisms in single-phase flows are delineated. Heat transfer coefficient and friction factor correlations for both laminar and turbulent regimes are presented, and the damping effect of swirl on the transition region is highlighted. In flow boiling with net vapor generation, tape-twist-induced helical swirl pushes liquid droplets from the core to the wall to enhance heat transfer and delay dryout. In subcooled boiling, the radial pressure gradient due to the swirl promotes vapor removal from the heated surface to retard vapor blanketing and accommodate higher heat fluxes. The scaling and phenomenological descriptions of the underlying vapor-liquid transport in these different boiling modes and regimes are presented along with any available predictive correlations.
H∞ State-Feedback Control for Semi-Markov Jump Linear Systems With Time-Varying Delays
Authors: Huang Ji , Shi Yang
Published: May 2013

Semi-Markov jump linear systems (S-MJLSs) are more general than Markov jump linear systems in modeling practical systems. This paper investigates the H∞ control problem for a class of semi-Markov jump linear systems with time-varying delays. The sojourn-time partition technique is firstly proposed for the delayed stochastic switching system. A sufficient condition for designing the state feedback controller is then established. Moreover, the sufficient condition is expressed as a set of linear matrix inequalities which can be readily solved. A numerical example illustrates the effectiveness of the proposed controller design technique.
Cross-Species Protein Interactome Mapping Reveals Species-Specific Wiring of Stress Response Pathways
Authors: Das Jishnu , Vo Tommy V. , Wei Xiaomu , Mellor Joseph C. , Tong Virginia , Degatano Andrew G. , Wang Xiujuan , Wang Lihua , Cordero Nicolas A. , Kruer-Zerhusen Nathan , Matsuyama Akihisa , Pleiss Jeffrey A. , Lipkin Steven M. , Yoshida Minoru , Roth Frederick P. , Yu Haiyuan
Published: May 2013

Comparing protein-interaction networks of two species of yeast suggests that network rewiring may enable environmental adaptation.
Sticky Signaling—Adhesion Class G Protein–Coupled Receptors Take the Stage
Authors: Langenhan Tobias , Aust Gabriela , Hamann Jörg
Published: May 2013

Emerging insight on the structural and functional versatility of Adhesion-GPCRs draws a fascinating picture of the multiple signals these molecules transmit.
ATAXIN Clock
Authors: Ray L. Bryan
Published: May 2013

Regulation of protein translation contributes to circadian rhythms.
Stress Inside Out
Authors: Hurtley Stella M.
Published: May 2013

Gram-negative bacteria monitor lipopolysaccharide and outer-membrane protein status to detect and respond to problems.
Nuclear Actin in Action
Authors: Hurtley Stella M.
Published: May 2013

A dynamic polymeric actin structure inside the nucleus is part of the serum response in mammalian tissue culture cells.
Hypoxia Prevents miRNA Processing
Authors: Gough Nancy R.
Published: May 2013

Phosphorylation of a microRNA-processing protein by the EGF receptor inhibits maturation of tumor-suppressing microRNAs.
HIV-1 Resistance Mechanism to an Electrostatically Constrained Peptide Fusion Inhibitor That Is Active against T-20-Resistant Strains
Authors: Shimane Kazuki , Kawaji Kumi , Miyamoto Fusako , Oishi Shinya , Watanabe Kentaro , Sakagami Yasuko , Fujii Nobutaka , Shimura Kazuya , Matsuoka Masao , Kaku Mitsuo , Sarafianos Stefan G. , Kodama Eiichi N.
Published: May 2013

T-20EK is a novel fusion inhibitor designed to have enhanced α-helicity over T-20 (enfuvirtide) through engineered electrostatic interactions between glutamic acid (E) and lysine (K) substitutions. T-20EK efficiently suppresses wild-type and T-20-resistant variants. Here, we selected T-20EK-resistant variants. A combination of L33S and N43K substitutions in gp41 were required for high resistance to T-20EK. While these substitutions also caused resistance to T-20, they did not cause cross-resistance to other known fusion inhibitors.
Discovery of Antivirulence Agents against Methicillin-Resistant Staphylococcus aureus
Authors: Khodaverdian Varandt , Pesho Michelle , Truitt Barbara , Bollinger Lucy , Patel Parita , Nithianantham Stanley , Yu Guanping , Delaney Elizabeth , Jankowsky Eckhard , Shoham Menachem
Published: May 2013

Antivirulence agents inhibit the production of disease-causing virulence factors but are neither bacteriostatic nor bactericidal. Antivirulence agents against methicillin-resistant
Staphylococcus aureus
(MRSA) strain USA300, the most widespread community-associated MRSA strain in the United States, were discovered by virtual screening against the response regulator AgrA, which acts as a transcription factor for the expression of several of the most prominent
S. aureus
toxins and virulence factors involved in pathogenesis. Virtual screening was followed by similarity searches in the databases of commercial vendors. The small-molecule compounds discovered inhibit the production of the toxins alpha-hemolysin and phenol-soluble modulin α in a dose-dependent manner without inhibiting bacterial growth. These antivirulence agents are small-molecule biaryl compounds in which the aromatic rings either are fused or are separated by a short linker. One of these compounds is the FDA-approved nonsteroidal anti-inflammatory drug diflunisal. This represents a new use for an old drug. Antivirulence agents might be useful in prophylaxis and as adjuvants in antibiotic therapy for MRSA infections.