bluuebunny/crossref_metadata_2025 huggingface dataset:
Cultivating the social–emotional imagination in gifted education: insights from educational neuroscience
Authors: Gotlieb Rebecca , Hyde Elizabeth , Immordino‐Yang Mary Helen , Kaufman Scott Barry
Published: August 2016

Evidence from education, psychology, and neuroscience suggests that investing in the development of the social–emotional imagination is essential to cultivating giftedness in adolescents. Nurturing these capacities may be especially effective for promoting giftedness in students who are likely to lose interest and ambition over time. Giftedness is frequently equated with high general intelligence as measured by IQ tests, but this narrow conceptualization does not adequately capture students’ abilities to utilize their talents strategically to fully realize their future possible selves. The brain's default mode network is thought to play an important role in supporting imaginative thinking about the self and others across time. Because this network's functioning is temporarily attenuated when individuals engage in task‐ and action‐oriented focus (mindsets thought to engage the brain's executive attention network), we suggest that consistently focusing students on tasks requiring immediate action could undermine long‐term cultivation of giftedness. We argue that giftedness—especially in science, technology, engineering, and mathematics (STEM)—can be cultivated by encouraging adolescents’ intellectual curiosity and supporting their ability to connect schoolwork to a larger purpose. Improving STEM and gifted education may depend upon a shift from knowledge transmission and regimented evaluation to creative exploration, intentional reflectiveness, and mindful switching between task focus and imagining.
Intestinal infection at onset of mycophenolic acid‐associated chronic diarrhea in kidney transplant recipients
Authors: von Moos S. , Cippà P.E. , Wüthrich R.P. , Mueller T.F.
Published: August 2016

Background

Chronic diarrhea after kidney transplantation is often attributed to mycophenolic acid (MPA) toxicity. We hypothesize that intestinal infections contribute to the pathogenesis of chronic MPA‐associated diarrhea.

Methods

In this retrospective study, all patients (n = 726) receiving a kidney transplant between 2000 and 2010 at the University Hospital Zurich were followed until July 2014 for occurrence of chronic diarrhea (≥4 weeks). Infectious triggers at diarrhea onset were assessed by reviewing medical history, stool microbiology, and histology of colon biopsies.

Results

In 46 patients (6.3% of the cohort), a total of 51 episodes of chronic diarrhea during MPA treatment were documented. The diarrhea episodes were often severe, as confirmed by significant weight loss. The cumulative incidence of chronic diarrhea was uniformly distributed throughout the post‐transplant period, with 2.0%, 5.1%, and 9.6% at 1, 5, and 10 years, respectively. Evidence was found for intestinal infection at diarrhea onset in 38 episodes (74.5%). Occurrence of diarrhea onset showed a seasonal distribution with peaks in April and October/November. Specific antimicrobial treatment alone was associated with a 19% resolution rate only, whereas combination with dose reduction of MPA or switch from mycophenolate mofetil to enteric‐coated mycophenolate sodium resulted in a 22.7% and 76.5% resolution rate, respectively. Change to an MPA‐free regimen was associated with a 100% resolution rate.

Conclusion

These results provide first evidence for a contribution of intestinal infections in chronic post‐transplant diarrhea associated with MPA treatment.
Perioperative Complications and Outcome of Laparoscopic Cholecystectomy in 20 Dogs
Authors: Scott Jacqueline , Singh Ameet , Mayhew Philipp D. , Brad Case J. , Runge Jeffrey J. , Gatineau Matthieu , Kilkenny Jessica
Published: August 2016

Objective

To report the complications and outcome of dogs undergoing laparoscopic cholecystectomy for uncomplicated gall bladder disease.

Study Design

Multi‐institutional case series.

Animals

Client‐owned dogs (n=20).

Methods

Medical records of dogs that underwent laparoscopic cholecystectomy were reviewed and signalment, history, clinical and ultrasound examination findings, surgical variables, and complications were collated. Laparoscopic cholecystectomy was performed using a multiport approach. Data were compared between dogs with successful laparoscopic cholecystectomy and dogs requiring conversion to open cholecystectomy.

Results

Six dogs (30%) required conversion from laparoscopic to open cholecystectomy due to inability to ligate the cystic duct (3), evidence of gall bladder rupture (1), leakage from the cystic duct during dissection (1), and cardiac arrest (1). Cystic duct dissection was performed in 19 dogs using an articulating dissector (10), right angle forceps (7), and unrecorded (2). The cystic duct was ligated in 15 dogs using surgical clips (5), suture (6), or a combination (4). All dogs were discharged from the hospital and had resolution of clinical signs, although 1 dog developed pancreatitis and 1 dog required revision surgery for bile peritonitis. There was no significant difference in preoperative blood analysis results, surgical technique, or duration of hospitalization between dogs undergoing laparoscopic cholecystectomy and cases converted to open cholecystectomy.

Conclusion

Laparoscopic cholecystectomy can be performed successfully for uncomplicated gall bladder disease in dogs after careful case selection. The surgeon considering laparoscopic cholecystectomy should be familiar with a variety of methods for cystic duct dissection and ligation to avoid difficulties during the procedure.
Dangerous sugar signals
Authors: Wong Wei
Published: August 2016

The glycolytic enzyme hexokinase is a pattern recognition receptor for the NLRP3 inflammasome.
Development of an
In Vitro
Assay for Detection of Drug-Induced Resuscitation-Promoting-Factor-Dependent Mycobacteria
Authors: Loraine Jessica , Pu Feifei , Turapov Obolbek , Mukamolova Galina V.
Published: August 2016

Tuberculosis is a major infectious disease that requires prolonged chemotherapy with a combination of four drugs. Here we present data suggesting that treatment of
Mycobacterium tuberculosis
, the causative agent of tuberculosis, and
Mycobacterium smegmatis
, a model organism widely used for the screening of antituberculosis agents, with first-line drugs resulted in the generation of substantial populations that could be recovered only by the addition of a culture supernatant from growing mycobacteria. These bacilli failed to grow in standard media, resulting in significant underestimation of the numbers of viable mycobacteria in treated samples. We generated
M. smegmatis
strains overexpressing
M. tuberculosis
resuscitation-promoting factors (Rpfs) and demonstrated their application for the detection of Rpf-dependent mycobacteria generated after drug exposure. Our data offer novel opportunities for validation of the sterilizing activity of antituberculosis agents.
Phase 2, Dose-Ranging Study of Relebactam with Imipenem-Cilastatin in Subjects with Complicated Intra-abdominal Infection
Authors: Lucasti Christopher , Vasile Liviu , Sandesc Dorel , Venskutonis Donatas , McLeroth Patrick , Lala Mallika , Rizk Matthew L. , Brown Michelle L. , Losada Maria C. , Pedley Alison , Kartsonis Nicholas A. , Paschke Amanda
Published: August 2016

Relebactam (REL [MK-7655]) is a novel class A/C β-lactamase inhibitor intended for use with imipenem for the treatment of Gram-negative bacterial infections. REL restores imipenem activity against some resistant strains of
Klebsiella
and
Pseudomonas
. In this multicenter, double-blind, controlled trial (NCT01506271), subjects who were ≥18 years of age with complicated intra-abdominal infection were randomly assigned (1:1:1) to receive 250 mg REL, 125 mg REL, or placebo, each given intravenously (i.v.) with 500 mg imipenem-cilastatin (IMI) every 6 h (q6h) for 4 to 14 days. The primary efficacy endpoint was the proportion of microbiologically evaluable (ME) subjects with a favorable clinical response at discontinuation of i.v. therapy (DCIV). A total of 351 subjects were randomized, 347 (99%) were treated, and 255 (73%) were ME at DCIV (55% male; mean age, 49 years). The most common diagnoses were complicated appendicitis (53%) and complicated cholecystitis (17%). Thirty-six subjects (13%) had imipenem-resistant Gram-negative infections at baseline. Both REL doses plus IMI were generally well tolerated and demonstrated safety profiles similar to that of IMI alone. Clinical response rates at DCIV were similar in subjects who received 250 mg REL plus IMI (96.3%) or 125 mg REL plus IMI (98.8%), and both were noninferior to IMI alone (95.2%; one-sided
P
< 0.001). The treatment groups were also similar with respect to clinical response at early and late follow-up and microbiological response at all visits. Pharmacokinetic/pharmacodynamic simulations show that imipenem exposure at the proposed dose of 500 mg IMI with 250 mg REL q6h provides coverage of >90% of carbapenem-resistant bacterial strains.
Phase I Study Assessing the Pharmacokinetic Profile, Safety, and Tolerability of a Single Dose of Ceftazidime-Avibactam in Hospitalized Pediatric Patients
Authors: Bradley John S. , Armstrong Jon , Arrieta Antonio , Bishai Raafat , Das Shampa , Delair Shirley , Edeki Timi , Holmes William C. , Li Jianguo , Moffett Kathryn S. , Mukundan Deepa , Perez Norma , Romero José R. , Speicher David , Sullivan Janice E. , Zhou Diansong
Published: August 2016

This study aimed to investigate the pharmacokinetics (PK), safety, and tolerability of a single dose of ceftazidime-avibactam in pediatric patients. A phase I, multicenter, open-label PK study was conducted in pediatric patients hospitalized with an infection and receiving systemic antibiotic therapy. Patients were enrolled into four age cohorts (cohort 1, ≥12 to <18 years; cohort 2, ≥6 to <12 years; cohort 3, ≥2 to <6 years; cohort 4, ≥3 months to <2 years). Patients received a single 2-h intravenous infusion of ceftazidime-avibactam (cohort 1, 2,000 to 500 mg; cohort 2, 2,000 to 500 mg [≥40 kg] or 50 to 12.5 mg/kg [<40 kg]; cohorts 3 and 4, 50 to 12.5 mg/kg). Blood samples were collected to describe individual PK characteristics for ceftazidime and avibactam. Population PK modeling was used to describe characteristics of ceftazidime and avibactam PK across all age groups. Safety and tolerability were assessed. Thirty-two patients received study drug. Mean plasma concentration-time curves, geometric mean maximum concentration (
C
max
), and area under the concentration-time curve from time zero to infinity (AUC
0–∞
) were similar across all cohorts for both drugs. Six patients (18.8%) reported an adverse event, all mild or moderate in intensity. No deaths or serious adverse events occurred. The single-dose PK of ceftazidime and avibactam were comparable between each of the 4 age cohorts investigated and were broadly similar to those previously observed in adults. No new safety concerns were identified. (This study has been registered at ClinicalTrials.gov under registration no. NCT01893346.)
High Prevalence of Carbapenemase-Producing Enterobacteriaceae among Hospitalized Children in Luanda, Angola
Authors: Kieffer Nicolas , Nordmann Patrice , Aires-de-Sousa Marta , Poirel Laurent
Published: August 2016

This study aimed to evaluate the prevalence of carbapenemase-producing
Enterobacteriaceae
in Luanda, Angola. A total of 157 rectal samples were collected from children visiting a pediatric hospital in Luanda in March 2015. Fifty-seven imipenem-nonsusceptible enterobacterial isolates were recovered, most of which were non-clonally related. The
bla
OXA-181
(50/57) and
bla
NDM-1
(7/57) carbapenemase genes were identified. Notably, OXA-181-producing
Escherichia coli
isolates rarely coproduced extended-spectrum β-lactamases and consequently remained susceptible to broad-spectrum cephalosporins. The
bla
OXA-181
gene was always located on an IncX3 plasmid, while the
bla
NDM-1
gene was located on either IncFIA or IncA/C plasmids. The study identified a high prevalence of OXA-181 among hospitalized children in Angola.
Discovery of Novel Oral Protein Synthesis Inhibitors of Mycobacterium tuberculosis That Target Leucyl-tRNA Synthetase
Authors: Palencia Andrés , Li Xianfeng , Bu Wei , Choi Wai , Ding Charles Z. , Easom Eric E. , Feng Lisa , Hernandez Vincent , Houston Paul , Liu Liang , Meewan Maliwan , Mohan Manisha , Rock Fernando L. , Sexton Holly , Zhang Suoming , Zhou Yasheen , Wan Baojie , Wang Yuehong , Franzblau Scott G. , Woolhiser Lisa , Gruppo Veronica , Lenaerts Anne J. , O'Malley Theresa , Parish Tanya , Cooper Christopher B. , Waters M. Gerard , Ma Zhenkun , Ioerger Thomas R. , Sacchettini James C. , Rullas Joaquín , Angulo-Barturen Iñigo , Pérez-Herrán Esther , Mendoza Alfonso , Barros David , Cusack Stephen , Plattner Jacob J. , Alley M. R. K.
Published: August 2016

The recent development and spread of extensively drug-resistant and totally drug-resistant resistant (TDR) strains of
Mycobacterium tuberculosis
highlight the need for new antitubercular drugs. Protein synthesis inhibitors have played an important role in the treatment of tuberculosis (TB) starting with the inclusion of streptomycin in the first combination therapies. Although parenteral aminoglycosides are a key component of therapy for multidrug-resistant TB, the oxazolidinone linezolid is the only orally available protein synthesis inhibitor that is effective against TB. Here, we show that small-molecule inhibitors of aminoacyl-tRNA synthetases (AARSs), which are known to be excellent antibacterial protein synthesis targets, are orally bioavailable and effective against
M. tuberculosis
in TB mouse infection models. We applied the oxaborole tRNA-trapping (OBORT) mechanism, which was first developed to target fungal cytoplasmic leucyl-tRNA synthetase (LeuRS), to
M. tuberculosis
LeuRS. X-ray crystallography was used to guide the design of LeuRS inhibitors that have good biochemical potency and excellent whole-cell activity against
M. tuberculosis
. Importantly, their good oral bioavailability translates into
in vivo
efficacy in both the acute and chronic mouse models of TB with potency comparable to that of the frontline drug isoniazid.
AraC-Type Regulator Rbf Controls the Staphylococcus epidermidis Biofilm Phenotype by Negatively Regulating the
icaADBC
Repressor SarR
Authors: Rowe Sarah E. , Campbell Christopher , Lowry Colm , O'Donnell Sinead T. , Olson Michael E. , Lindgren Jill K. , Waters Elaine M. , Fey Paul D. , O'Gara James P.
Published: August 2016

Regulation of
icaADBC
-encoded polysaccharide intercellular adhesin (PIA)/poly-
N
-acetylglucosasmine (PNAG) production in staphylococci plays an important role in biofilm-associated medical-device-related infections. Here, we report that the AraC-type transcriptional regulator Rbf activates
icaADBC
operon transcription and PIA production in
Staphylococcus epidermidis
. Purified recombinant Rbf did not bind to the
ica
operon promoter region in electrophoretic mobility shift assays (EMSAs), indicating that Rbf regulates
ica
transcription indirectly. To identify the putative transcription factor(s) involved in Rbf-mediated
icaADBC
regulation, the ability of recombinant Rbf to interact with the promoter sequences of known
icaADBC
regulators was investigated. Recombinant Rbf bound to the
sarR
promoter and not the
sarX
,
sarA
,
sarZ
,
spx
, and
srrA
promoters. Reverse transcription (RT)-PCR demonstrated that Rbf acts as a repressor of
sarR
transcription. PIA expression and biofilm production were restored to wild-type levels in an
rbf sarR
double mutant grown in brain heart infusion (BHI) medium supplemented with NaCl, which is known to activate the
ica
locus, but not in BHI medium alone. RT-PCR further demonstrated that although Rbf does not bind the
sarX
promoter, it nevertheless exerted a negative effect on
sarX
expression. Apparently, direct downregulation of the SarR repressor by Rbf has a dominant effect over indirect repression of the SarX activator by Rbf in the control of
S. epidermidis
PIA production and biofilm formation.

IMPORTANCE
The importance of
Staphylococcus epidermidis
as an opportunistic pathogen in hospital patients with implanted medical devices derives largely from its capacity to form biofilm. Expression of the
icaADBC
-encoded extracellular polysaccharide is the predominant biofilm mechanism in
S. epidermidis
clinical isolates and is tightly regulated. Here, we report that the transcriptional regulator Rbf promotes
icaADBC
expression by negatively regulating expression of
sarR
, which encodes an
ica
operon repressor. Furthermore, Rbf indirectly represses the
ica
operon activator, SarX. The data reveal complicated interplay between Rbf and two Sar family proteins in fine-tuning regulation of the biofilm phenotype and indicate that in the hierarchy of biofilm regulators, IcaR is dominant over the Rbf-SarR-SarX axis.
Small cell neuroendocrine carcinoma of tracheostomy site in a patient with a history of juvenile laryngeal papillomatosis
Authors: Violet Wilmot Victoria , Nixon Iain James , Nixon Ioanna Fragkandrea
Published: August 2016

Juvenile laryngeal papillomatosis is the commonest cause of benign epithelial tumours of the larynx. Following diagnostic biopsy, surgical debulking is the mainstay of therapy. The condition is often recurrent with further papillomas forming after debridement, requiring serial procedures and occasionally demanding tracheostomy. Rarely, the disease can undergo malignant transformation; most commonly to squamous cell carcinoma. We describe the first reported case of small cell neuroendocrine carcinoma occurring in the previous tracheostomy site of a 29-year-old male with a history of juvenile laryngeal papillomatosis. The patient, with a background of multiple treatments for juvenile papillomas, presented with voice change, breathing difficultly and erythema at the site of previous tracheostomy. Induction chemotherapy followed by chemoradiation was used to treat the lesion with a good response to initial therapy.
Pulmonary cavitary lesion and haemoptysis: rare aetiology on biopsy
Authors: Kim John , Thomashow Byron , Saqi Anjali
Published: August 2016

Pleomorphic carcinoma of the lung is a rare form of malignancy that can present similarly to other necrotising cavitary lung diseases. We present a case of a Caucasian woman who presented with recurrent haemoptysis and a right upper lobe cavitary lesion on CT scan. She underwent selective embolisation of the right bronchial artery by interventional radiology to control her haemoptysis. Positron emission tomography/CT scan was performed which showed significant fluorodeoxyglucose uptake in the right upper lobe cavitary lesion. There was a discussion among her providers about the aetiology of this lesion including infection and malignancy. Cultures from bronchoalveolar lavage and blood were negative for infection as the patient underwent right upper lobectomy which showed invasive sarcomatoid pleomorphic carcinoma with a minor component of acinar adenocarcinoma. She was diagnosed with stage IB (T2aN0M0) sarcomatoid pleomorphic carcinoma and underwent adjuvant chemotherapy after her lobectomy with recurrence and metastasis to her stomach and pancreas.
Facilitating mental health research for patients, clinicians and researchers: a mixed-method study
Authors: Robotham D , Waterman S , Oduola S , Papoulias C , Craig T , Wykes T
Published: August 2016

Objectives

Research registers using Consent for Contact (C4C) can facilitate recruitment into mental health research studies, allowing investigators to contact patients based on clinical records information. We investigated whether such a register was useful for mental health research, seeking the perspectives of patients and research investigators.

Setting and design

In 2012, a C4C register was developed in a large secondary mental health provider within the UK; almost 9000 patients have joined. This mixed-method study audited the effectiveness of the register.

Participants

A ‘mystery shopper’ exercise was conducted, and patients (n=21) were recruited to ask clinicians about the availability of research opportunities. Structured interviews were conducted with patients (n=52) about their experiences of being on the register. Similar interviews were conducted with 18 investigators from 19 studies, who had attempted to use the register to recruit participants.

Outcome measures

The impact of C4C on study recruitment, and whether it helped patients learn about research.

Results

So far, the register has provided 928 individuals with 1085 research opportunities (in 60% of cases, the individual agreed to participate in the study). Clinicians were willing to link patients to research opportunities, but often lacked information about studies. For patients, the register provided opportunities which they may not otherwise have; 27 of 52 had participated in studies since joining the register (18 participating for the first time). Most investigators used the register to supplement recruitment to their studies, but described problems in prescreening potential participants from a clinical record for complex studies.

Conclusions

Although the register helped investigators recruit for studies, and provided patients with research opportunities, clinicians' input is still useful for identifying suitable participants. C4C registers should be adapted to provide clinicians with automatically updated information on local studies allowing them to match patients on their caseload with active studies.
Determinants of out-of-hours service users' potentially inappropriate referral or non-referral to an emergency department: a retrospective cohort study in a local health authority, Veneto Region, Italy
Authors: Buja Alessandra , Toffanin Roberto , Rigon S , Sandonà P , Carrara T , Damiani G , Baldo V
Published: August 2016

Background

A growing presence of inappropriate patients has been recognised as one of the main factors influencing emergency department (ED) overcrowding, which is a very widespread problem all over the world. On the other hand, out-of-hours (OOH) physicians must avoid delaying the diagnostic and therapeutic course of patients with urgent medical conditions. The aim of this study was to analyse the appropriateness of patient management by OOH services, in terms of their potentially inappropriate referral or non-referral of non-emergency cases to the ED.

Methods

This was an observational retrospective cohort study based on data collected in 2011 by the local health authority No. 4 in the Veneto Region (Italy). After distinguishing between patients contacting the OOH service who were or were not referred to the ED, and checking for patients actually presenting to the ED within 24 hours thereafter, these patients’ medical management was judged as potentially appropriate or inappropriate.

Results

The analysis considered 22 662 OOH service contacts recorded in 2011. The cases of potentially inappropriate non-referral to the ED were 392 (1.7% of all contacts), as opposed to 1207 potentially inappropriate referrals (5.3% of all contacts). Age, nationality, type of disease and type of intervention by the OOH service were the main variables associated with the appropriateness of patient management.

Conclusions

These findings may be useful for pinpointing the factors associated with a potentially inappropriate patient management by OOH services and thus contribute to improving the deployment of healthcare and the quality of care delivered by OOH services.
Incidence and risk factors for gastrointestinal bleeding among patients admitted to medical intensive care units
Authors: Kumar Shria , Ramos Christopher , Garcia-Carrasquillo Reuben J , Green Peter H , Lebwohl Benjamin
Published: August 2016

Objectives

To identify incidence and risk factors for new-onset gastrointestinal bleeding (GIB) in a medical intensive care unit (ICU), a topic for which there is a paucity of recent studies.

Design

Retrospective cohort study.

Setting

Medical ICUs at our tertiary-care hospital, from 2007 to 2013.

Patients

Patients who developed clinically significant GIB after entering the ICU.

Interventions

Univariable and multivariable analyses.

Main outcome measures

Incidence and risk factors for development of GIB.

Results

4439 patients entered the medical ICU without a pre-existing GIB and 58 (1.3%) developed GIB while in the ICU. Risk factors included length of ICU stay (OR per additional day 1. 06; 95% CI 1.04 to 1.09) and elevated creatinine on ICU admission (OR 2.35; 95% CI 1.18 to 4.68, p=0.02). Elevated bilirubin on ICU admission (OR 2.08; 95% CI 0.97 to 4.47, p=0.06), and elevated aspartate transaminase (AST) on ICU admission (OR 2.20; 95% CI 0.96 to 5.03, p=0.06) trended towards increased risk of GIB that did not meet statistical significance. Age, gender, admission coagulation studies and mechanical ventilation were not predictive of GIB. Among those patients with new-onset GIB in the ICU, 47% died during that hospitalisation, as compared with those 30% of those without a GIB, p<0.01.

Conclusions

Onset of GIB is now an infrequent occurrence in the ICU setting; however those with elevated bilirubin, AST and creatinine upon admission, and with longer length of ICU stay appear at increased risk and may benefit from closer monitoring.
Evidence from randomised controlled trials does not support current dietary fat guidelines: a systematic review and meta-analysis
Authors: Harcombe Zoë , Baker Julien S , DiNicolantonio James J , Grace Fergal , Davies Bruce
Published: August 2016

Objectives

National dietary guidelines were introduced in 1977 and 1983, by the USA and UK governments, respectively, with the ambition of reducing coronary heart disease (CHD) mortality by reducing dietary fat intake. A recent systematic review and meta-analysis by the present authors, examining the randomised controlled trial (RCT) evidence available to the dietary committees during those time periods, found no support for the recommendations to restrict dietary fat. The present investigation extends our work by re-examining the totality of RCT evidence relating to the current dietary fat guidelines.

Methods

A systematic review and meta-analysis of RCTs currently available, which examined the relationship between dietary fat, serum cholesterol and the development of CHD, was undertaken.

Results

The systematic review included 62 421 participants in 10 dietary trials: 7 secondary prevention studies, 1 primary prevention and 2 combined. The death rates for all-cause mortality were 6.45% and 6.06% in the intervention and control groups, respectively. The risk ratio (RR) from meta-analysis was 0.991 (95% CI 0.935 to 1.051). The death rates for CHD mortality were 2.16% and 1.80% in the intervention and control groups, respectively. The RR was 0.976 (95% CI 0.878 to 1.084). Mean serum cholesterol levels decreased in all intervention groups and all but one control group. The reductions in mean serum cholesterol levels were significantly greater in the intervention groups; this did not result in significant differences in CHD or all-cause mortality.

Conclusions

The current available evidence found no significant difference in all-cause mortality or CHD mortality, resulting from the dietary fat interventions. RCT evidence currently available does not support the current dietary fat guidelines. The evidence per se lacks generalisability for population-wide guidelines.
Cold pressor test using strain-gauge plethysmography
Authors: Feliciani Giacomo , Peron Cristiano , La Rocca Augusto , Scuppa Maria Francesca , Malavolta Andrea , Bianchini David , Corazza Ivan , Zannoli Romano
Published: August 2016

This laboratory activity is designed to teach students how to measure forearm muscle blood flow (FBF) to describe the mechanisms of peripheral blood flow thermal regulation in healthy subjects. The cold pressor test (CPT) is the clinical procedure used in the experiment to induce arterial vasoconstriction. Strain-gauge plethysmography is applied on the patient's forearm to noninvasive monitor vasoconstriction effects on local blood perfusion and physiological parameters such as blood pressure (BP) and heart rate (HR). Patients with an altered peripheral vascular resistance (e.g., in hypertension) have different responses to the CPT from healthy subjects. To date, experimental evidence remains unexplained, as we do not know if the BP and HR increase is caused by a decrease in flow rate or an increase in peripheral vascular resistance during the test. To clarify this situation, we have to quantify the parameter we assume is being conditioned by the regulatory physiological intervention, i.e., peripheral vascular resistance. Peripheral vascular resistance quantification can be calculated as the ratio between muscle flow and mean arterial pressure. Students will learn how to apply the instrumental procedure to collect and analyze data before, during, and after the CPT and to describe the physiological responses of the peripheral vascular system to external stressors. They will also learn how to distinguish healthy from pathological responses on the basis of how sympathetic nervous system reactions influence the biomechanics of peripheral vessels.
Formal First Integrals of General Dynamical Systems
Authors: Jiao Jia , Li Wenlei , Zhou Qingjian
Published: August 2016

The goal of this paper is trying to make a complete study on the integrability for general analytic nonlinear systems by first integrals. We will firstly give an exhaustive discussion on analytic planar systems. Then a class of higher dimensional systems with invariant manifolds will be considered; we will develop several criteria for existence of formal integrals and give some applications to illustrate our results at last.
Review on Vertical Twin-Roll Strip Casting: A Key Technology for Quality Strips
Authors: Sahoo Seshadev
Published: August 2016

Nowadays near-net-shape casting technology is an important area of research in the iron and steel industry. Among different kinds of near-net-shape casting process, twin-roll casting process has received much attention among researchers. Twin-roll casting (TRC) has been the subject of extensive research, not only to develop the technology but also to achieve an understanding of microstructural evolution and to produce quality strips. The main issues concerning the design and operation of twin-roll casters are metal-mold heat transfer, metal delivery system, and their possible effects on the solid shell formation and characteristics of the strips. The present review gives an idea about the process aspect, modeling, and quality issues in vertical twin-roll strip casting process and helps to improve the design of twin-roll strip caster.
Mitochondrial Dysfunction Contributes to Hypertensive Target Organ Damage: Lessons from an Animal Model of Human Disease
Authors: Rubattu Speranza , Stanzione Rosita , Volpe Massimo
Published: August 2016

Mechanisms underlying hypertensive target organ damage (TOD) are not completely understood. The pathophysiological role of mitochondrial oxidative stress, resulting from mitochondrial dysfunction, in development of TOD is unclear. The stroke‐prone spontaneously hypertensive rat (SHRSP) is a suitable model of human hypertension and of its vascular consequences. Pathogenesis of TOD in SHRSP is multifactorial, being determined by high blood pressure levels, high salt/low potassium diet, and genetic factors. Accumulating evidence points to a key role of mitochondrial dysfunction in increased susceptibility to TOD development of SHRSP. Mitochondrial abnormalities were described in both heart and brain of SHRSP. Pharmacological compounds able to protect mitochondrial function exerted a significant protective effect on TOD development, independently of blood pressure levels. Through our research efforts, we discovered that two genes encoding mitochondrial proteins, one (Ndufc2) involved in OXPHOS complex I assembly and activity and the second one (UCP2) involved in clearance of mitochondrial ROS, are responsible, when dysregulated, for vascular damage in SHRSP. The suitability of SHRSP as a model of human disease represents a promising background for future translation of the experimental findings to human hypertension. Novel therapeutic strategies toward mitochondrial molecular targets may become a valuable tool for prevention and treatment of TOD in human hypertension.
3Es System Optimization under Uncertainty Using Hybrid Intelligent Algorithm: A Fuzzy Chance-Constrained Programming Model
Authors: Song Jiekun , Zhang Kaixin , Cao Zijian
Published: August 2016

Harmonious development of 3Es (economy-energy-environment) system is the key to realize regional sustainable development. The structure and components of 3Es system are analyzed. Based on the analysis of causality diagram, GDP and industrial structure are selected as the target parameters of economy subsystem, energy consumption intensity is selected as the target parameter of energy subsystem, and the emissions of COD, ammonia nitrogen, SO2, andNOXand CO2emission intensity are selected as the target parameters of environment system. Fixed assets investment of three industries, total energy consumption, and investment in environmental pollution control are selected as the decision variables. By regarding the parameters of 3Es system optimization as fuzzy numbers, a fuzzy chance-constrained goal programming (FCCGP) model is constructed, and a hybrid intelligent algorithm including fuzzy simulation and genetic algorithm is proposed for solving it. The results of empirical analysis on Shandong province of China show that the FCCGP model can reflect the inherent relationship and evolution law of 3Es system and provide the effective decision-making support for 3Es system optimization.
Urinary Lysosomal Enzyme Activities and Albuminuria in Ghanaian Patients with Type 2 Diabetes Mellitus
Authors: Asare-Anane Henry , Twum Felix , Kwaku Ofori Emmanuel , Torgbor Erving L. , Amanquah Seth D. , Osafo Charlotte
Published: August 2016

Renal tubular lysosomal enzyme activities like alanine aminopeptidase (AAP) and N-acetyl-β-D-glucosaminidase (NAG) have been shown to increase in patients developing diabetic nephropathy and nephrosclerosis. This study aimed to determine the activities of N-acetyl-β-D-glucosaminidase and alanine aminopeptidase and albumin concentration in urine samples of patients with type 2 diabetes. One hundred and thirty (65 type 2 diabetic and 65 nondiabetic) subjects participated in this study. Blood samples were drawn for measurements of fasting blood glucose, albumin (Alb), lipids, and creatinine (Cr). Early morning spot urine samples were also collected for activities of alanine aminopeptidase (AAP), N-acetyl-β-D-glucosaminidase (NAG), and concentration of albumin (U-Alb) and creatinine (U-Cr). Both NAG/Cr and AAP/Cr were significantly increased in diabetic subjects compared to controls (p<0.001). There was positive correlation between NAG/Cr and Alb/Cr (r=0.49,p<0.001) and between NAG/Cr and serum creatinine (r=0.441,p<0.001). A negative correlation was found between NAG/Cr and eGFR (r=-0.432,p<0.05). 9.3% and 12% of diabetics with normoalbuminuria had elevated levels of AAP/Cr and NAG/Cr, respectively. We conclude that measuring the urinary enzymes activities (NAG/Cr and AAP/Cr) could be useful as a biomarker of early renal involvement in diabetic complications.
A Novel Energy-Saving Resource Allocation Scheme in LTE-A Relay Networks
Authors: Chen Jen-Jee , Luo Chi-Wen , Chen Zeng-Yu
Published: August 2016

Therelay node(RN) in Long-Term Evolution-Advanced (LTE-A) networks is used to enhance the coverage of high data rate and solve the coverage hole problem. Considering the limited energy nature of User Equipment (UE), connecting to the RN instead of Evolved Node B (eNB) is a better choice for cell-edge UE items. In this paper, on the premise of compatibility to the LTE-A resource allocation specification, we discuss an uplink radio resource, uplink path, modulation and coding scheme (MCS), and transmit power allocation problem for energy conservation in LTE-A relay networks. The objective is to minimize the total energy consumption of UE items while guaranteeing the constraints of UE items’ quality of service (QoS), bit-error-rate (BER), total system resource, and maximum transmit power. Since the problem is NP-complete and the scheduling period in LTE-A is short (the subframe length is only1 ms), we propose an efficient method to solve the problem. The complexity analysis shows the time complexity of the proposed heuristics isO(n2). Simulation results demonstrate that our algorithm can effectively reduce the energy consumption of UE items and guarantee users’ service quality.
Cancer: An Oxidative Crosstalk between Solid Tumor Cells and Cancer Associated Fibroblasts
Authors: Arcucci Alessandro , Ruocco Maria Rosaria , Granato Giuseppina , Sacco Anna Maria , Montagnani Stefania
Published: August 2016

Redox balance is associated with the regulation of several cell signalling pathways and functions. In fact, under physiological conditions, cells maintain a balance between oxidant and antioxidant systems, and reactive oxygen species (ROS) can act as second messengers to regulate cell proliferation, cell death, and other physiological processes. Cancer tissues usually contain higher levels of ROS than normal tissues, and this ROS overproduction is associated with tumor development. Neoplastic tissues are very heterogeneous systems, composed of tumor cells and microenvironment that has a critical role in tumor progression. Cancer associated fibroblasts (CAFs) represent the main cell type of tumor microenvironment, and they contribute to tumor growth by undergoing an irreversible activation process. It is known that ROS can be transferred from cancer cells to fibroblasts. In particular, ROS affect the behaviour of CAFs by promoting the conversion of fibroblasts to myofibroblasts that support tumor progression and dissemination. Furthermore, the wrecking of redox homeostasis in cancer cells and tumor microenvironment induces a metabolic reprogramming in tumor cells and cancer associated fibroblasts, giving advantage to cancer growth. This review describes the role of ROS in tumor growth, by focusing on CAFs activation and metabolic interactions between cancer cells and stromal fibroblasts.
Compressive Behavior and Mechanical Characteristics and Their Application to Stress-Strain Relationship of Steel Fiber-Reinforced Reactive Powder Concrete
Authors: Bae Baek-Il , Choi Hyun-Ki , Lee Bong-Seop , Bang Chang-Hoon
Published: August 2016

Although mechanical properties of concrete under uniaxial compression are important to design concrete structure, current design codes or other empirical equations have clear limitation on the prediction of mechanical properties. Various types of fiber-reinforced reactive powder concrete matrix were tested for making more usable and accurate estimation equations for mechanical properties for ultra high strength concrete. Investigated matrix has compressive strength ranged from 30 MPa to 200 MPa. Ultra high strength concrete was made by means of reactive powder concrete. Preventing brittle failure of this type of matrix, steel fibers were used. The volume fraction of steel fiber ranged from 0 to 2%. From the test results, steel fibers significantly increase the ductility, strength and stiffness of ultra high strength matrix. They are quantified with previously conducted researches about material properties of concrete under uniaxial loading. Applicability of estimation equations for mechanical properties of concrete was evaluated with test results of this study. From the evaluation, regression analysis was carried out, and new estimation equations were proposed. And these proposed equations were applied into stress-strain relation which was developed by previous research. Ascending part, which was affected by proposed equations of this study directly, well fitted into experimental results.
Downregulation of p70S6K Enhances Cell Sensitivity to Rapamycin in Esophageal Squamous Cell Carcinoma
Authors: Lu Zhaoming , Peng Kezheng , Wang Ning , Liu Hong-Min , Hou Guiqin
Published: August 2016

It has been demonstrated that mTOR/p70S6K pathway was abnormally activated in many cancers and rapamycin and its analogs can restrain tumor growth through inhibiting this pathway, but some tumors including esophageal squamous cell carcinoma (ESCC) appear to be insensitive to rapamycin in recent studies. In the present study, we explored the measures to improve the sensitivity of ESCC cells to rapamycin and identified the clinical significance of the expression of phosphorylated p70S6K (p-p70S6K). The results showed that, after downregulating the expression of p70S6K and p-p70S6K by p70S6K siRNA, the inhibitory effects of rapamycin on cell proliferation, cell cycle, and tumor growth were significantly enhancedin vitroandin vivo. Furthermore, p-p70S6K had strong positive expression in ESCC tissues and its expression was closely related to lymph node metastasis and the TNM staging. These results indicated that p-p70S6K may participate in the invasion and metastasis in the development of ESCC and downregulation of the expression of p-p70S6K could improve the sensitivity of cells to rapamycin in ESCC.
Cytotoxicity and Initial Biocompatibility of Endodontic Biomaterials (MTA and Biodentine™) Used as Root-End Filling Materials
Authors: Escobar-García Diana María , Aguirre-López Eva , Méndez-González Verónica , Pozos-Guillén Amaury
Published: August 2016

Objective. The aim of this study was to evaluate the cytotoxicity and cellular adhesion of Mineral Trioxide Aggregate (MTA) and Biodentine (BD) on periodontal ligament fibroblasts (PDL).Methods. PDL cells were obtained from nonerupted third molars and cultured; MTS cellular profusion test was carried out in two groups: MTA and BD, with respective controls at different time periods. Also, the LIVE/DEAD assay was performed at 24 h. For evaluation of cellular adhesion, immunocytochemistry was conducted to discern the expression of Integrinβ1 and Vinculin at 12 h and 24 h. Statistical analysis was performed by the Kruskal-Wallis and Mann-WhitneyUtests.Results. MTA and BD exhibited living cells up to 7 days. More expressions of Integrinβ1 and Vinculin were demonstrated in the control group, followed by BD and MTA, which also showed cellular loss and morphological changes. There was a significant difference in the experimental groups cultured for 5 and 7 days compared with the control, but there was no significant statistical difference between both cements.Conclusions. Neither material was cytotoxic during the time evaluated. There was an increase of cell adhesion through the expression of focal contacts observed in the case of BD, followed by MTA, but not significantly.
Hypotensive Resuscitation among Trauma Patients
Authors: Carrick Matthew M. , Leonard Jan , Slone Denetta S. , Mains Charles W. , Bar-Or David
Published: August 2016

Hemorrhagic shock is a principal cause of death among trauma patients within the first 24 hours after injury. Optimal fluid resuscitation strategies have been examined for nearly a century, more recently with several randomized controlled trials. Hypotensive resuscitation, also called permissive hypotension, is a resuscitation strategy that uses limited fluids and blood products during the early stages of treatment for hemorrhagic shock. A lower-than-normal blood pressure is maintained until operative control of the bleeding can occur. The randomized controlled trials examining restricted fluid resuscitation have demonstrated that aggressive fluid resuscitation in the prehospital and hospital setting leads to more complications than hypotensive resuscitation, with disparate findings on the survival benefit. Since the populations studied in each randomized controlled trial are slightly different, as is the timing of intervention and targeted vitals, there is still a need for a large, multicenter trial that can examine the benefit of hypotensive resuscitation in both blunt and penetrating trauma patients.
New Progress of Epigenetic Biomarkers in Urological Cancer
Authors: Wu Peng , Cao Ziyi , Wu Song
Published: August 2016

Urological cancers consist of bladder, kidney, prostate, and testis cancers and they are generally silenced at their early stage, which leads to the loss of the best opportunity for early diagnosis and treatment. Desired biomarkers are scarce for urological cancers and current biomarkers are lack of specificity and sensitivity. Epigenetic alterations are characteristic of nearly all kinds of human malignances including DNA methylation, histone modification, and miRNA regulation. Besides, the detection of these epigenetic conditions is easily accessible especially for urine, best target for monitoring the diseases of urinary system. Here, we summarize some new progress about epigenetic biomarkers in urological cancers, hoping to provide new thoughts for the diagnosis, treatment, and prognosis of urological cancers.
Anticancer Effects of Targeting Hsp70 in Tumor Stromal Cells
Authors: Gabai Vladimir L. , Yaglom Julia A. , Wang Yongmei , Meng Le , Shao Hao , Kim Geunwon , Colvin Teresa , Gestwicki Jason , Sherman Michael Y.
Published: August 2016

The stress-induced chaperone protein Hsp70 enables the initiation and progression of many cancers, making it an appealing therapeutic target for development. Here, we show that cancer cells resistant to Hsp70 inhibitors in vitro remain sensitive to them in vivo, revealing the pathogenic significance of Hsp70 in tumor stromal cells rather than tumor cells as widely presumed. Using transgenic mouse models of cancer, we found that expression of Hsp70 in host stromal cells was essential to support tumor growth. Furthermore, genetic ablation or pharmacologic inhibition of Hsp70 suppressed tumor infiltration by macrophages needed to enable tumor growth. Overall, our results illustrate how Hsp70 inhibitors mediate the anticancer effects by targeting both tumor cells and tumor stromal cells, with implications for the broad use of these inhibitors as tools to ablate tumor-associated macrophages that enable malignant progression. Cancer Res; 76(20); 5926–32. ©2016 AACR.